A radiomics nomogram based on multiparametric MRI for diagnosing focal cortical dysplasia and initially identifying laterality.

BACKGROUND: Focal cortical dysplasia (FCD) is the most common epileptogenic developmental malformation. The diagnosis of FCD is challenging. We generated a radiomics nomogram based on multiparametric magnetic resonance imaging (MRI) to diagnose FCD and identify laterality early. METHODS: Forty-three patients treated between July 2017 and May 2022 with histopathologically confirmed FCD were retrospectively enrolled. The contralateral unaffected hemispheres were included as the control group. Therefore, 86 ROIs were finally included. Using January 2021 as the time cutoff, those admitted after January 2021 were included in the hold-out set (n = 20). The remaining patients were separated randomly (8:2 ratio) into training (n = 55) and validation (n = 11) sets. All preoperative and postoperative MR images, including T1-weighted (T1w), T2-weighted (T2w), fluid-attenuated inversion recovery (FLAIR), and combined (T1w + T2w + FLAIR) images, were included. The least absolute shrinkage and selection operator (LASSO) was used to select features. Multivariable logistic regression analysis was used to develop the diagnosis model. The performance of the radiomic nomogram was evaluated with an area under the curve (AUC), net reclassification improvement (NRI), integrated discrimination improvement (IDI), calibration and clinical utility. RESULTS: The model-based radiomics features that were selected from combined sequences (T1w + T2w + FLAIR) had the highest performances in all models and showed better diagnostic performance than inexperienced radiologists in the training (AUCs: 0.847 VS. 0.664, p = 0.008), validation (AUC: 0.857 VS. 0.521, p = 0.155), and hold-out sets (AUCs: 0.828 VS. 0.571, p = 0.080). The positive values of NRI (0.402, 0.607, 0.424) and IDI (0.158, 0.264, 0.264) in the three sets indicated that the diagnostic performance of Model-Combined improved significantly. The radiomics nomogram fit well in calibration curves (p > 0.05), and decision curve analysis further confirmed the clinical usefulness of the nomogram. Additionally, the contrast (the radiomics feature) of the FCD lesions not only played a crucial role in the classifier but also had a significant correlation (r = -0.319, p < 0.05) with the duration of FCD. CONCLUSION: The radiomics nomogram generated by logistic regression model-based multiparametric MRI represents an important advancement in FCD diagnosis and treatment.

The complete chloroplast genome of Swertia davidii (gentianaceae) and its phylogenetic analysis.

To elucidate the genetic information and evolutionary relationships of Swertia, we initiated the sequencing of the complete chloroplast genome of Swertia davidii Franch. 1888, complemented by comparative analyses with closely related species. The chloroplast genome of S. davidii was 153,516 bp in length and exhibited a typical quadripartite structure. It contained two regions with Inverted Repeat lengths of 25,767 bp, located between one Large Single-Copy region (83,617 bp) and one Short Single-Copy region (18,365 bp). The chloroplast genome of S. davidii encoded 132 genes, including 87 protein-coding genes, 37 transfer RNA genes, and 8 ribosomal RNA genes. The overall GC content was 38.15%. Maximum likelihood phylogenetic analysis of Swertia based on 26 available plastomes showed a close relationship between S. davidii and S. kouitchensi. This study will contribute to the genetic preservation of the species and the phylogenetic study of Swertia.

Modulating Elasticity of Liposome for Enhanced Cancer Immunotherapy.

Cancer immunotherapy has emerged as a promising approach to cancer treatment in recent years. The physical and chemical properties of nanocarriers are critical factors that regulate the immune activation of antigen-presenting cells (APCs) in the tumor microenvironment (TME). Herein, we extensively investigated the behavior of liposome nanoparticles (Lipo-NPs) with different elasticities, focusing on their interaction with immune cells and their transport mechanisms from tumors to tumor-draining lymph nodes (tdLNs). Successfully preparing Lipo-NPs with distinct elastic properties, their varied behaviors were observed, concerning immune cell interaction. Soft Lipo-NPs exhibited an affinity to cell membranes, while those with medium elasticity facilitated the cargo delivery to macrophages through membrane fusion. Conversely, hard Lipo-NPs enter macrophages via classical cellular uptake pathways. Additionally, it was noted that softer Lipo-NPs displayed superior transport to tdLNs in vivo, attributed to their deformable nature with lower elasticity. As a result, the medium elastic Lipo-NPs with agonists (cGAMP), by activating the STING pathway and enhancing transport to tdLNs, promoted abundant infiltration of tumor-infiltrating lymphocytes (TILs), leading to notable antitumor effects and extended survival in a melanoma mouse model. Furthermore, this study highlighted the potential synergistic effect of medium elasticity Lipo-NPs with immune checkpoint blockade (ICB) therapy in preventing tumor immune evasion. These findings hold promise for guiding immune-targeted delivery systems in cancer immunotherapy, particularly in vaccine design for tdLNs targeting and eradicating metastasis within tdLNs.

Effect of infarct location and volume on cognitive dysfunction in elderly patients with acute insular cerebral infarction.

BACKGROUND: The aging of the population has become increasingly obvious in recent years, and the incidence of cerebral infarction has shown an increasing trend annually, with high death and disability rates. AIM: To analyze the effects of infarct location and volume on cognitive dysfunction in elderly patients with acute insular cerebral infarction. METHODS: Between January 2020 and December 2023, we treated 98 cases of elderly acute insula, patients with cerebral infarction in the cerebral infarction acute phase (3-4 weeks) and for the course of 6 months in Montreal Cognitive Assessment Scale (MoCA) for screening of cognition. Notably, 58 and 40 patients were placed in the cognitive impairment group and without-cognitive impairment group, respectively. In patients with cerebral infarction, magnetic resonance imaging was used to screen and clearly analyze the MoCA scores of two groups of patients with different infarctions, the relationship between the parts of the infarction volume, and analysis of acute insula cognitive disorder in elderly patients with cerebral infarction and the relationship between the two. RESULTS: The number of patients with cognitive impairment in the basal ganglia and thalamus was significantly higher than that without cognitive impairment (P < 0.05). The total infarct volume in the cognitive impairment group was higher than that in the non-cognitive impairment group, and the difference was statistically significant (P < 0.05). The infarct volumes at different sites in the cognitive impairment group was higher than in the non-cognitive impairment group (P < 0.05). In the cognitive impairment group, the infarct volumes in the basal ganglia, thalamus, and mixed lesions were negatively correlated with the total MoCA score, with correlation coefficients of -0.67, -0.73, and -0.77, respectively. CONCLUSION: In elderly patients with acute insular infarction, infarction in the basal ganglia, thalamus, and mixed lesions were more likely to lead to cognitive dysfunction than in other areas, and patients with large infarct volumes were more likely to develop cognitive dysfunction. The infarct volume in the basal ganglia, thalamus, and mixed lesions was significantly negatively correlated with the MoCA score.

Nutrition-Related Knowledge Graph Neural Network for Food Recommendation.

Food recommendation systems are becoming increasingly vital in modern society, given the fast-paced lifestyle and diverse dietary habits. Existing research and implemented solutions often rely on user preferences and past behaviors for recommendations, which poses significant issues. Firstly, this approach inadequately considers the nutritional content of foods, potentially leading to recommendations that are overly homogeneous and lacking in diversity. Secondly, it may result in repetitive suggestions of the same types of foods, thereby encouraging users to develop unhealthy dietary habits that could adversely affect their overall health. To address this issue, we introduce a novel nutrition-related knowledge graph (NRKG) method based on graph convolutional networks (GCNs). This method not only enhances users' ability to select appropriate foods but also encourages the development of healthy eating habits, thereby contributing to overall public health. The NRKG method comprises two key components: user nutrition-related food preferences and recipe nutrition components. The first component gathers nutritional information from recipes that users show interest in and synthesizes these data for user reference. The second component connects recipes with similar nutritional profiles, forming a complex heterogeneous graph structure. By learning from this graph, the NRKG method integrates user preferences with nutritional data, resulting in more accurate and personalized food recommendations. We evaluated the NRKG method against six baseline methods using real-world food datasets. In the 100% dataset, the five metrics exceeded the performance of the best baseline method by 2.8%, 5.9%, 1.5%, 9.7%, and 6.0%, respectively. The results indicate that our NRKG method significantly outperforms the baseline methods, including FeaStNet, DeepGCN, GraphSAGE, GAT, UniMP, and GATv2, demonstrating its superiority and effectiveness in promoting healthier and more diverse eating habits. Unlike these baseline methods, which primarily focus on hierarchical information propagation, our NRKG method offers a more comprehensive approach by integrating the nutritional information of recipes with user preferences.

Effect of Luhong formula on the cardiac rehabilitation of patients with chronic heart failure.

BACKGROUND: Current treatments for chronic heart failure (CHF) are therapeutically ineffective. The optimization of treatments for this disease needs to be explored and analyzed. AIM: To analyze the effect of using Luhong Formula in the cardiac rehabilitation of patients with CHF and its influence on cardiopulmonary function (CPF) and prognosis. METHODS: In total, 160 patients with CHF admitted between June 2022 and June 2023 were selected, including 75 receiving perindopril (control group) and 85 receiving Luhong Formula (research group). We conducted comparative analyses on the curative effects of traditional Chinese medicine (TCM) syndromes and cardiac function, CPF [oxygen consumption at the anaerobic threshold (VO2 AT) and at peak exercise (peak VO2)], echocardiographic indexes [left atrial volume index (LAVI), left ventricular muscle mass index (LVMI), left ventricular ejection fraction (LVEF)], and prognosis [major adverse cardiovascular events (MACEs) at 6 months follow-up]. RESULTS: The research group showed markedly higher curative effects of TCM syndromes and cardiac function than the control group. In addition, post-treatment VO2 AT, peak VO2, LVMI and LVEF in the research group were significantly higher, whereas LAVI was significantly lower, than those of the control group. Furthermore, fewer patients in the research group developed MACEs at the 6-month follow-up. CONCLUSION: Luhong Formula is more therapeutically effective than perindopril for the cardiac rehabilitation of patients with CHF, specifically in enhancing CPF and prognosis.

Tunable-bias based optical neural network for reinforcement learning in path planning.

Owing to the high integration, reconfiguration and strong robustness, Mach-Zehnder interferometers (MZIs) based optical neural networks (ONNs) have been widely considered. However, there are few works adding bias, which is important for neural networks, into the ONNs and systematically studying its effect. In this article, we propose a tunable-bias based optical neural network (TBONN) with one unitary matrix layer, which can improve the utilization rate of the MZIs, increase the trainable weights of the network and has more powerful representational capacity than traditional ONNs. By systematically studying its underlying mechanism and characteristics, we demonstrate that TBONN can achieve higher performance by adding more optical biases to the same side beside the inputted signals. For the two-dimensional dataset, the average prediction accuracy of TBONN with 2 biases (97.1%) is 5% higher than that of TBONN with 0 biases (92.1%). Additionally, utilizing TBONN, we propose a novel optical deep Q network (ODQN) algorithm to complete path planning tasks. By implementing simulated experiments, our ODQN shows competitive performance compared with the conventional deep Q network, but accelerates the computation speed by 2.5 times and 4.5 times for 2D and 3D grid worlds, respectively. Further, a more noticeable acceleration will be obtained when applying TBONN to more complex tasks. Also, we demonstrate the strong robustness of TBONN and the imprecision elimination method by using on-chip training.

Enhanced anaerobic digestion performance and sludge filterability by membrane microaeration for anaerobic membrane bioreactor application.

Slow dissolution/hydrolysis of insoluble/macromolecular organics and poor sludge filterability restrict the application potential of anaerobic membrane bioreactor (AnMBR). Bubble-free membrane microaeration was firstly proposed to overcome these obstacles in this study. The batch anaerobic digestion tests feeding insoluble starch and soluble peptone with and without microaeration showed that microaeration led to a 65.7-144.8% increase in methane production and increased critical flux of microfiltration membrane via driving the formation of large sludge flocs and the resultant improvement of sludge settleability. The metagenomic and bioinformatic analyses showed that microaeration significantly enriched the functional genes and bacteria for polysaccharide and protein hydrolysis, microaeration showed little negative effects on the functional genes involved in anaerobic metabolisms, and substrate transfer from starch to peptone significantly affected the functional genes and microbial community. This study demonstrates the dual synergism of microaeration to enhance the dissolution/hydrolysis/acidification of insoluble/macromolecular organics and sludge filterability for AnMBR application.

Explosion of research on psychopathology and social media use after COVID-19: A scientometric study.

BACKGROUND: Despite advances in research on psychopathology and social media use, no comprehensive review has examined published papers on this type of research and considered how it was affected by the coronavirus disease 2019 (COVID-19) outbreak. AIM: To explore the status of research on psychopathology and social media use before and after the COVID-19 outbreak. METHODS: We used Bibliometrix (an R software package) to conduct a scientometric analysis of 4588 relevant studies drawn from the Web of Science Core Collection, PubMed, and Scopus databases. RESULTS: Such research output was scarce before COVID-19, but exploded after the pandemic with the publication of a number of high-impact articles. Key authors and institutions, located primarily in developed countries, maintained their core positions, largely uninfluenced by COVID-19; however, research production and collaboration in developing countries increased significantly after COVID-19. Through the analysis of keywords, we identified commonly used methods in this field, together with specific populations, psychopathological conditions, and clinical treatments. Researchers have devoted increasing attention to gender differences in psychopathological states and linked COVID-19 strongly to depression, with depression detection becoming a new trend. Developments in research on psychopathology and social media use are unbalanced and uncoordinated across countries/regions, and more in-depth clinical studies should be conducted in the future. CONCLUSION: After COVID-19, there was an increased level of concern about mental health issues and a changing emphasis on social media use and the impact of public health emergencies.

The development and evolution of the research topic on the mental health of college students: A bibliometric review based on CiteSpace and VOSviewer.

Background: With the advances in society and in response to changing times, college students have had to face multiple challenges. These challenges frequently affect the mental health of college students, leading to significant consequences for their social lives, personal well-being, and academic achievements, thereby attracting extensive societal attention. Therefore, examining the current status of research topics related to the mental health of college students can assist academia in dissecting the influencing factors and seeking solutions at their source or through early intervention. This can contribute to a better understanding of and effectively address this challenge. Method: CiteSpace and VOSviewer were used to conduct a bibliometric analysis of 1609 journal articles indexed in the Web of Science (WoS) database over the past two decades (2000-2022), which helped identify the current state of research and hot topics in the field based on development trends. Furthermore, this study analyzes and discusses the core authors, high-productivity countries and organizations, key journals, and keyword clustering in this field. This study clarifies the current research landscape, analyzes evolving trends based on developmental trajectories, and identifies forefront research hotspots. This study provides scholars with reference research directions and ideas for conducting subsequent studies. Results: Since the beginning of the 21st century, research on college students' mental health has increased, especially in the past three years, and due to the impact of the COVID-19 pandemic and online distance learning, the number of publications has increased rapidly. With the increase in attention and publication volume, the countries and organizations contributing papers as well as core journals have all started to take shape. Cluster and evolution analyses found that several stable research topics have been formed in this research field, and many new and diverse topics are continuously emerging with time. Conclusion: and prospect: The findings prove that the field of college students' mental health has begun to take shape, gradually shifting from conceptual research to the implementation of specific interventions. However, whether specific interventions are effective and how effective they are require further investigation.

Revisiting the antigen markers of vector-borne parasitic diseases identified by immunomics: identification and application to disease control.

INTRODUCTION: Protein microarray is a promising immunomic approach for identifying biomarkers. Based on our previous study that reviewed parasite antigens and recent parasitic omics research, this article expands to include information on vector-borne parasitic diseases (VBPDs), namely, malaria, schistosomiasis, leishmaniasis, babesiosis, trypanosomiasis, lymphatic filariasis, and onchocerciasis. AREAS COVERED: We revisit and systematically summarize antigen markers of vector-borne parasites identified by the immunomic approach and discuss the latest advances in identifying antigens for the rational development of diagnostics and vaccines. The applications and challenges of this approach for VBPD control are also discussed. EXPERT OPINION: The immunomic approach has enabled the identification and/or validation of antigen markers for vaccine development, diagnosis, disease surveillance, and treatment. However, this approach presents several challenges, including limited sample size, variability in antigen expression, false-positive results, complexity of omics data, validation and reproducibility, and heterogeneity of diseases. In addition, antigen involvement in host immune evasion and antigen sensitivity/specificity are major issues in its application. Despite these limitations, this approach remains promising for controlling VBPD. Advances in technology and data analysis methods should continue to improve candidate antigen identification, as well as the use of a multiantigen approach in diagnostic and vaccine development for VBPD control.

Lactic acid bacteria modulate the CncC pathway to enhance resistance to ß-cypermethrin in the oriental fruit fly.

The gut microbiota of insects has been shown to regulate host detoxification enzymes. However, the potential regulatory mechanisms involved remain unknown. Here, we report that gut bacteria increase insecticide resistance by activating the cap "n" collar isoform-C (CncC) pathway through enzymatically generated reactive oxygen species (ROS) in Bactrocera dorsalis. We demonstrated that Enterococcus casseliflavus and Lactococcus lactis, two lactic acid-producing bacteria, increase the resistance of B. dorsalis to ß-cypermethrin by regulating cytochrome P450 (P450) enzymes and α-glutathione S-transferase (GST) activities. These gut symbionts also induced the expression of CncC and muscle aponeurosis fibromatosis. BdCncC knockdown led to a decrease in resistance caused by gut bacteria. Ingestion of the ROS scavenger vitamin C in resistant strain affected the expression of BdCncC/BdKeap1/BdMafK, resulting in reduced P450 and GST activity. Furthermore, feeding with E. casseliflavus or L. lactis showed that BdNOX5 increased ROS production, and BdNOX5 knockdown affected the expression of the BdCncC/BdMafK pathway and detoxification genes. Moreover, lactic acid feeding activated the ROS-associated regulation of P450 and GST activity. Collectively, our findings indicate that symbiotic gut bacteria modulate intestinal detoxification pathways by affecting physiological biochemistry, thus providing new insights into the involvement of insect gut microbes in the development of insecticide resistance.

A functional variant of ALDH1A2 is associated with hand osteoarthritis in the Chinese population.

Genome-wide association study identified common variants within the ALDH1A2 gene as the susceptible loci of hand osteoarthritis (HOA) in UK and Iceland populations. Located in chromosome 15, ALDH1A2 encodes aldehyde dehydrogenase family 1 member A2, which is an enzyme that catalyses the synthesis of retinoic acid from retinaldehyde. Our purposes were to replicate the association of functional variant in ALDH1A2 with the development of HOA in the Chinese population. Variant rs12915901 of ALDH1A2 was genotyped in 872 HOA patients and 1223 healthy controls. Subchondral bone samples were collected from 40 patients who had undergone a trapeziectomy, and the tissue expression of ALDH1A2 was analysed. The chi-square analysis was used to compare the frequency of genotype and risk allele between the HOA cases and controls. The Student t test was used to compare the mRNA expression of ALDH1A2 between patients with genotype AA/AG and those with genotype GG. The frequency of genotype AA was significantly higher in HOA patients than in the controls (7.6% vs. 5.1%, p = .01). The frequency of allele A was significantly higher in the patients than in the controls (28.9% vs. 24.6%, p = .005). The mRNA expression of ALDH1A2 was 1.31-folds higher in patients with genotype GG than in the patients with genotype AA/AG (0.000617 ± 0.000231 vs. 0.000471 ± 0.000198, p = .04). Variant rs12915901 of ALDH1A2 contributed to the susceptibility of HOA in the Chinese population. Allele A of rs12915901 can add to the risk of HOA possibly via down-regulation of ALDH1A2 expression.

Enhancing Soybean and Maize Yields through Improved Nitrogen and Soil Water Use Efficiencies: A 40-Year Study on the Impact of Farmyard Manure Amendment in Northeast China.

The combined application of manure and chemical fertilizers has been recognized as a critical factor driving significant changes in crop yield and nutrient use efficiency, holding the potential to optimize agricultural management to achieve high yields. In this 40-year study, we investigated the effect of manure amendment on soybean and maize yields, water and nitrogen use efficiencies (WUE and NUE), and water and mineral N storage at 0-100 cm soil depths from 2017 to 2018 to explore the optimization of fertilization management strategies for soybean and maize production in Northeast China. To elucidate the impact of chemical fertilizers and manure, twelve treatments-control (CK); single N fertilizer at a low rate (N1) and that at a high rate (N2); N1, phosphorus (P), and potassium (K) fertilizer (N1PK); manure alone at 13.5 and 27 t ha-1 (M1 and M2); and those combined with N, P, or K fertilizer (M1N1, M1N2, and M1N1PK and M2N1, M2N2, and M2N1PK)-were selected and studied. The results showed that long-term amendment with manure significantly increased crop biomass and yield in the soybean-maize-maize rotation system. Combining with manure increased the WUE, the partial factor productivity of N fertilizer (PFPN), and N physiological efficiency (PEN) in both the soybean and maize seasons; conserved soil water (mainly at 40-60 cm); and increased soil N retention (in the upper 60 cm layer), which reduced the risk of N leaching, with a better effect being observed after the application of 13.5 t ha-1 manure. These results provide insight into the potential of using fertilization management strategies that include amendment with 13.5 t ha-1 manure in combination with N, P, and K fertilizer in the maize season and only chemical fertilizer in the soybean season, as these results indicate that such strategies can achieve high yields and be used to implement agricultural sustainable development in brown soil regions in Northeast China.

Atomically dispersed cobalt activator with nitrogen and sulfur co-coordination for high-efficiency Fenton-like catalysis: Insights into density-dependent activity and mechanisms.

Atomically dispersed metal activators (ADMAs) have demonstrated unique advantages in environmental remediation, but how to controllably regulate the active site density and electronic structure of ADMAs to further enhance activation efficiency remains challenging. Here, we introduce a sulfur-atom-doping approach that allows the fine-tuning of atomic Co site content and electronic structure, enabling exploration of density-dependent activation performance of ADMAs for peroxymonosulfate (PMS)-based Fenton-like catalysis. Our investigation reveals a direct correlation between activation capacity and single-Co-site density. The optimal SNC@CoSA-0.05 activator with densely populated Co-N3S1 sites (10.1 wt%) displays exceptional efficacy in eliminating Rhodamine B, with specific activity of 31.0 min-1 g-1 L, outperforming most previously published activators. Moreover, SNC@CoSA-0.05 showed a remarkedly reduced metal leaching (47.4 µg L-1) than its nanocluster counterpart (194 µg L-1) at pH 3.2. Experimental and theoretical analyses unveiled that coordinated sulfur actively modulates the electronic structure of the central Co atom, enhancing the adsorption and activation of PMS, thereby improving decontamination efficiency. Mechanistic studies further elucidate the predominant electron-transfer regime involved in oxidizing micropollutants by SNC@CoSA-0.05/PMS, with Co(IV)=O, •OH, and SO4•- being the auxiliary oxidizing species. This study not only offers a method for concurrent adjustment of active site density and electronic structure in ADMAs but also sheds light on the activation mechanisms of atomic metal sites.

Correlation between serum markers and transjugular intrahepatic portosystemic shunt prognosis in patients with cirrhotic ascites.

BACKGROUND: Individuals with refractory ascites in the context of liver cirrhosis typically face an adverse prognosis. The transjugular intrahepatic portosystemic shunt (TIPS) is an efficacious intervention, but there is a lack of reliable tools for postoperative prognosis assessment. Previously utilized clinical biochemical markers, such as the serum albumin concentration (Alb), sodium (Na+) concentration, and serum creatinine (Scr), have limited predictive value. Therefore, the quest for novel, specific biomarkers to evaluate the post-TIPS prognosis in patients with liver cirrhosis and refractory ascites holds significant practical importance. AIM: To investigate the associations between the Child-Pugh score, model for end-stage liver disease (MELD) score, and serum cystatin C (Cys C) level and post-TIPS prognosis in patients with liver cirrhosis and refractory ascites. METHODS: A retrospective analysis was conducted on 75 patients with liver cirrhosis and refractory ascites who underwent TIPS at our institution from August 2019 to August 2021. These patients were followed up regularly for two years, and the death toll was meticulously documented. The patients were allocated into a survival group (n = 45 patients) or a deceased group (n = 30 patients) based on their prognosis status. The clinical data of the two groups were collected, and Child-Pugh scores and MELD scores were calculated for analysis. Spearman correlation analysis was carried out to evaluate the correlation of prognosis with Child-Pugh grade, MELD score, and Cys C level. Additionally, a multiple-factor analysis utilizing the Cox proportional hazard model was used to identify independent risk factors affecting the post-TIPS prognosis of patients with liver cirrhosis and refractory ascites. The receiver operating characteristic curve (ROC) ascertained the predictive value of the Cys C concentration, Child-Pugh grade, and MELD score for the prognosis of liver cirrhosis with refractory ascites in post-TIPS patients. RESULTS: During a 2-year follow-up period, among 75 patients with liver cirrhosis and refractory ascites who underwent TIPS treatment, 30 patients (40.00%) passed away. The deceased cohort exhibited heightened aspartate aminotransferase, alanine aminotransferase, total bilirubin, Scr, prothrombin time, Cys C, international normalized ratio, Child-Pugh, and MELD scores compared to those of the survival cohort, while Alb and Na+ levels were attenuated in the deceased group (P < 0.05). Spearman analysis revealed moderate to high positive correlations between prognosis and Child-Pugh score, MELD score, and Cys C level (r = 0.709, 0.749, 0.671, P < 0.05). Multivariate analysis using the Cox proportional hazard model demonstrated that the independent risk factors for post-TIPS prognosis in patients with liver cirrhosis and refractory ascites were Cys C (HR = 3.802; 95%CI: 1.313-11.015), Child-Pugh (HR = 3.030; 95%CI: 1.858-4.943), and MELD (HR = 1.222; 95%CI: 1.073-1.393) scores. ROC analysis confirmed that, compared to those of the classic prognostic models for Child-Pugh and MELD scores, the predictive accuracy of Cys C for post-TIPS prognosis in patients with liver cirrhosis and refractory ascites was slightly lower. This analysis yielded sensitivity and specificity values of 83.33% and 82.22%, respectively. The area under the curve value at this juncture was 0.883, with an optimal cutoff value set at 1.95 mg/L. CONCLUSION: Monitoring the serum Cys C concentration is valuable for assessing the post-TIPS prognosis in patients with liver cirrhosis and refractory ascites. Predictive models based on serum Cys C levels, as opposed to Scr levels, are more beneficial for evaluating the condition and prognosis of patients with ascites due to cirrhosis.

Efficacy of transjugular intrahepatic portosystemic shunts in treating cirrhotic esophageal-gastric variceal bleeding.

BACKGROUND: Esophageal-gastric variceal bleeding (EGVB) represents a severe complication among patients with cirrhosis and often culminates in fatal outcomes. Interventional therapy, a rapidly developing treatment modality over the past few years, has found widespread application in clinical practice due to its minimally invasive characteristics. However, whether transjugular intrahepatic portosystemic shunt (TIPS) treatment has an impact on patient prognosis remains controversial. AIM: To probing the efficacy of TIPS for treating cirrhotic EGVB and its influence on the prognosis of patients afflicted by this disease. METHODS: A retrospective study was conducted on ninety-two patients presenting with cirrhotic EGVB who were admitted to our hospital between September 2020 and September 2022. Based on the different modes of treatment, the patients were assigned to the study group (TIPS received, n = 50) or the control group (percutaneous transhepatic varices embolization received, n = 42). Comparative analyses were performed between the two groups preoperatively and one month postoperatively for the following parameters: Varicosity status; hemodynamic parameters [portal vein flow velocity (PVV) and portal vein diameter (PVD); platelet count (PLT); red blood cell count; white blood cell count (WBC); and hepatic function [albumin (ALB), total bilirubin (TBIL), and aspartate transaminase (AST)]. The Generic Quality of Life Inventory-74 was utilized to assess quality of life in the two groups, and the 1-year postoperative rebleeding and survival rates were compared. RESULTS: Following surgical intervention, there was an improvement in the incidence of varicosity compared to the preoperative status in both cohorts. Notably, the study group exhibited more pronounced enhancements than did the control group (P < 0.05). PVV increased, and PVD decreased compared to the preoperative values, with the study cohort achieving better outcomes (P < 0.05). PLT and WBC counts were elevated postoperatively in the two groups, with the study cohort displaying higher PLT and WBC counts (P < 0.05). No differences were detected between the two groups in terms of serum ALB, TBIL, or AST levels either preoperatively or postoperatively (P < 0.05). Postoperative scores across all dimensions of life quality surpassed preoperative scores, with the study cohort achieving higher scores (P < 0.05). At 22.00%, the one-year postoperative rebleeding rate in the study cohort was significantly lower than that in the control group (42.86%; P < 0.05); conversely, no marked difference was observed in the 1-year postoperative survival rate between the two cohorts (P > 0.05). CONCLUSION: TIPS, which has demonstrated robust efficacy in managing cirrhotic EGVB, remarkably alleviates varicosity and improves hemodynamics in patients. This intervention not only results in a safer profile but also contributes significantly to a more favorable prognosis.

Genetic polymorphism of KIAA1217 is functionally associated with lumbar disc herniation in the Chinese population.

BACKGROUND: Genetic polymorphism of KIAA1217 has been reported to be associated with lumbar disc herniation (LDH) in different populations such as Japanese population and Finnish population. This study aimed to explore whether the genetic polymorphism of KIAA1217 is functionally associated with LDH in Chinese population. METHODS: SNP rs16924573 of KIAA1217 was genotyped in 1272 patients and 1248 healthy controls. The mRNA expression of KIAA1217 in the intervertebral disc was analyzed for 84 patients and 32 controls. The differences of genotype and allele distributions between LDH patients and healthy controls were evaluated using the Chi-square test. One-way ANOVA test was used to compare the relationship between genotypes and tissue expression of KIAA1217. RESULTS: Patients were found to have significantly higher frequency of genotype GG of rs16924573 than the controls (64.2% vs. 52.8%, p<0.001). The frequency of allele G was remarkably higher in the patients than in the controls (79.8% vs. 73.2%, p<0.001), with an OR of 1.45 (95% confidential interval=1.27-1.66). Compared with the controls, LDH patients were observed to have significantly decreased expression of KIAA1217. Patients with genotype GG had remarkably lower mRNA expression of KIAA1217 than those with genotype AG or AA (p=0.01). CONCLUSIONS: SNP rs16924573 of KIAA1217 could be functionally associated with LDH in the Chinese population. More in vivo and vitro experiments need to be carried out to further clarify the regulatory mechanism of functional variants in KIAA1217.

SN2 Reaction at the Amide Nitrogen Center Enables Hydrazide Synthesis.

Nucleophilic substitutions are fundamentally important transformations in synthetic organic chemistry. Despite the substantial advances in bimolecular nucleophilic substitutions (SN2) at saturated carbon centers, analogous SN2 reaction at the amide nitrogen atom remains extremely limited. Here we report an SN2 substitution method at the amide nitrogen atom with amine nucleophiles for nitrogen-nitrogen (N-N) bond formation that leads to a novel strategy toward biologically and medicinally important hydrazide derivatives. We found the use of sulfonate-leaving groups at the amide nitrogen atom played a pivotal role in the reaction. This new N-N coupling reaction allows the use of O-tosyl hydroxamates as electrophiles and readily available amines, including acyclic aliphatic amines and saturated N-heterocycles as nucleophiles. The reaction features mild conditions, broad substrate scope (>80 examples), excellent functional group tolerability, and scalability. The method is applicable to late-stage modification of various approved drug molecules, thus enabling complex hydrazide scaffold synthesis.

Genetic polymorphism of WNT9A is functionally associated with thumb osteoarthritis in the Chinese population.

BACKGROUND: In a recent genome-wide association study, novel genetic variations of WNT9A were reported to be involved in the etiopathogenesis of thumb osteoarthritis (TOA) in Caucasians. Our purposes were to replicate the association of WNT9A with the development of TOA in the Chinese population and to further unveil the functional role of the risk variants. METHODS: SNP rs11588850 of WNT9A were genotyped in 953 TOA patients and 1124 healthy controls. The differences of genotype and allele distributions between the patients and healthy controls were evaluated using the Chi-square test. Luciferase Reporter Assay was performed to investigate the influence of variant on the gene expression. RESULTS: There was significantly lower frequency of genotype AA in TOA patients than in the controls 74.9% vs. 81.9%, p < 0.001). The frequency of allele A was remarkably lower in the patients than in the controls (86.3% vs. 90.5%, p < 0.001), with an odds ratio of 0.66 (95% CI = 0.54-0.80). Luciferase Reporter Assay showed that the construct containing mutant allele G of rs11588850 displayed 29.1% higher enhancer activity than the wild allele A construct (p < 0.05). CONCLUSIONS: Allele G of rs11588850 was associated with the increased risk of TOA possibly via up-regulation of WNT9A expression. Further functional analysis into the regulatory role of rs11588850 in WNT9A expression can shed new light on the genetic architecture of TOA.