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A two-year long-term workshop centered around a phenotypic whole-cell screening strategy for integrating cutting-edge knowledge and discovery-based laboratory experiences was developed to serve as a preparatory course for enhancing the teaching quality of the upper-level discovery-based research internship curriculum for pharmacy major undergraduates. The workshop comprises four modules that integrate lessons and experiments into a genuine research project, which initiates with a medicinal-chemistry course, run concurrently in the second year and culminates with the discovery-based research internship curriculum for pharmacy major students as a corequisite in the last year. The effective implementation of the featured pedagogical approaches in the modules is detailed as described. A group of students (N = 4) passed the instructor-student two-way choice and were enrolled in the senior-level phenotypic hit discovery laboratory project. The students synthesized a small library of molecules, tested them in an antibacterial assay, and further designed new compounds to analyze structure-activity relationships. Furthermore, positive feedback from students revealed that the phenotypic hit discovery oriented workshop enabled them to gain in-depth cutting-edge knowledge and provided an understanding of how medicinal chemists engage in new drug discovery research. The student's early exposure to troubleshooting or exploring unexpected results in an authentic scientific environment inspired them with ambition and confidence to engage with new drug discovery. We hope that this workshop will serve as a springboard for those wishing to educate medicinal chemists at an undergraduate level with modern strategies that are relevant to the current and future drug discovery landscape.

Abstract To investigate the relationship between Leisure time physical activity (LTPA) patterns and PhenoAgeAccel in patients with Type 2 diabetes (T2D), emphasizing the role of regular LTPA in mitigating biological aging. This study utilized data from the National Health and Nutrition Examination Survey (NHANES) from 1999 to 2018, including 4,134 adults with T2D. Multivariable linear regression models and restricted cubic spline (RCS) methods were employed to assess the relationship between LTPA and Phenotypic age acceleration (PhenoAgeAccel), with segmented likelihood ratio tests to detect nonlinear thresholds. Stratified regression and interaction tests were conducted for robust analysis. Compared to individuals with no LTPA patterns, those with regular LTPA patterns had significantly lower PhenoAgeAccel scores (β = -1.164, 95% CI: -1.651 to -0.677, P

Abstract Reliable traffic flow data is not only crucial for traffic management and planning, but also the foundation for many intelligent applications. However, the phenomenon of missing traffic flow data often occurs, so we propose an imputation model for missing traffic flow data to overcome the randomness and instability bands of traffic flow. First, k-means clustering is used to classify road segments with traffic flow belonging to the same pattern into a group to utilize the spatial characteristics of roads fully. Then, the LSTM networks optimized with an attention mechanism are used as the base learner to extract the temporal dependence of the traffic flow. Finally, the AdaBoost algorithm is used to integrate all the LSTM-attention networks into a reinforced learner to impute the missing data. To validate the effectiveness of the proposed model, we use the PeMS dataset for validation, we impute the data with missing data rate from 10 to 60% under three missing modes, and we use multiple baseline models for comparison, which confirms that our proposed model improves the stability and accuracy of imputing the missing data of the traffic flow with different scenarios.

Objective To investigate the efficacy and safety of 4-week cluster immunotherapy with house dust mite extracts in patients allergic to house dust mites. Methods From August 2022 to May 2024， 80 patients with house dust mite-induced allergic rhinitis， complicated with or without asthma， were recruited from multiple centers （including Peking Union Medical College， et al） to undergo 4-week dose-escalation subcutaneous cluster immunotherapy with house dust mites. Patient symptoms， medication use， quality of life， asthma control test （ACT） results， as well as local and systemic adverse reactions were recorded at 0， 1， 6， and 12 months， respectively. Results Significant differences were observed in the daily total symptom scores （P < 0.001）， daily nasal scores （P < 0.001）， daily ocular scores （P = 0.009）， and total symptom and medication scores （P = 0.003） across different time points during cluster immunotherapy， respectively. Significant differences were also found in the activity RQLQ （P < 0.001）， sleep RQLQ （P = 0.002）， non-eye/nose symptom RQLQ （P = 0.032）， practical problems RQLQ （P < 0.001）， nasal symptom RQLQ （P < 0.001）， emotional RQLQ （P = 0.011）， total RQLQ （P < 0.001）， and children’s ACT scores （P < 0.001）， respectively. The longer the time， the lower the score. During the dose-escalation period， 22 patients （27.5%） experienced local adverse reactions， and 5 patients （6.3%） experienced systemic adverse reactions. A total of 35 （3.6%） injections resulted in adverse reactions， including 27 （2.8%） injections with local reactions and 8 （0.8%） injections with systemic reactions. Conclusion Four-week cluster immunotherapy with house dust mites shows significant efficacy in patients allergic to house dust mites.

COVID-19 posed a major challenge to the healthcare system and resources worldwide. The popularization of vaccines and the adoption of numerous prevention and control measures enabled the gradual end of the COVID-19 pandemic. However, successive occurrence of autoimmune diseases in patients with COVID-19 cannot be overlooked. Long COVID has been the major focus of research due to the long duration of different symptoms and the variety of systems involved. Autoimmunity may play a crucial role in the pathogenesis of long COVID. Here, we reviewed several autoimmune disorders occurring after COVID-19 infection and the pathogenesis of long COVID.

Abstract Many observational studies and experiments have found a strong association between lipid levels and adipokines and multiple myeloma (MM), but the causal relationship between lipid levels, adipokines and MM remains to be determined. We performed a two-sample and multivariate MR analysis to investigate the causal relationship between lipid levels, adipokines and MM. Total cholesterol(TC), high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), and triglycerides (TG) were used to represent lipid levels, and adiponectin, leptin, and resistin were used to represent adipokines. Genetic data for each index and MM were obtained from the Integrated Epidemiology Unit (IEU) Genome-Wide Association Study (GWAS) database, and two-sample MR analyses were performed, as well as multivariate MR analyses of adipokines for causality of MM using BMI as an adjusting factor. In the analyzed results, no significant causal association was found between adipokines, lipid levels and multiple myeloma, and after adjusting for BMI, an association between adipokines and MM was still not found. The results of this MR study do not support an association between genetically predicted adipokines, lipid levels, and risk of MM, but we cannot rule out the existence of a weak association. The mechanisms need to be further investigated.

Abstract Saposhnikovia divaricata is commonly used in clinical practice as a heat-clearing and detoxifying traditional Chinese medicine. Current research on Saposhnikovia divaricata has mostly focused on chromones, while studies on its lipophilic parts remain scarce. In this study, samples of the lipophilic components of Saposhnikovia divaricata (SDL) from different regions in China were collected to establish an HPLC fingerprint. The quality of SDL was evaluated through chemical pattern recognition and multi-component content determination. Furthermore, using the Caenorhabditis elegans (C. elegans) model, the anti-aging ability of SDL was preliminarily studied. In the HPLC fingerprints of 11 batches of SDL, 19 common peaks were identified, and 4 components were characterized as follows: peak 14, linolenic acid (ALA); peak 15, docosahexaenoic acid (DHA); peak 16, linoleic acid (LA); peak 17, oleic acid (OA). The similarity of the fingerprint ranged from 0.704 to 0.929. The results indicate that the content of ALA, DHA, LA, and OA are 0.040–0.440 mg/g, 0.003–0.116 mg/g, 1.047–6.460 mg/g, and 0.040–0.294 mg/g, respectively. HCA analysis divided 11 batches of SDL into two categories, and PCA analysis extracted 6 principal components with a cumulative contribution rate of 85.91%. The anti-aging ability of the SDL was proved by measuring the lifespan, reproductive capacity, body length, mobility, lipofuscin content, and heat stress resistance of C. elegans. The combination of high-performance liquid chromatography fingerprint and chemical pattern recognition for multi-component content determination is a reliable, comprehensive, and promising evaluation of the quality of SDL. The confirmation of SDL’s anti-aging ability provides the possibility for the research of Saposhnikovia divaricata in the field of healthy food and cosmetics.

Abstract Background: The use of immune checkpoint inhibitors (ICIs) as neoadjuvant therapy is a promising novel approach in resectable non-small-cell lung cancer (NSCLC). This study aimed to investigate the prognostic value of PD-L1 in patients with NSCLC receiving neoadjuvant immune checkpoint inhibitor plus chemotherapy (CT). Materials and methods: Several databases (PubMed, Embase, and cochrane central register of controlled trials [CENTRAL]) were systematically searched. Randomized controlled trials (RCTs) investigating pathological and survival outcomes with neoadjuvant ICI + CT versus CT alone in NSCLC were analyzed. Results: Overall, eight RCTs (n = 3,404) were included. The analyses showed neoadjuvant ICI + CT significantly improved complete pathological response (pCR) and event-free survival (EFS) in either tumor PD-L1

Age-related macular degeneration (AMD) is the first permanent cause of vision loss in developed countries, which is also a disease with high incidence and blindness rate in China. Studies have demonstrated that lipid metabolism is one of the key mechanisms of AMD. However, the precise mechanism remains unclear and medications for AMD treatments based on this mechanism have not yet been established. In this review, we critically review relevant studies to examine the associations between lipid metabolism and AMD from the perspectives of lipoproteins, lipid metabolism-related molecular, and lipid metabolism-related treatments, aiming to help understand the roles that lipid metabolism mechanisms play in the development and progression of AMD and to provide ideas for future targeted lipid metabolism therapies.

Abstract Accurate identification of animals and the verification of their parentage can be used to pedigree populations and support selective breeding. The International Society for Animal Genetics recommended 16 cattle STRs for individual identification and parentage testing in cattle, but no multiplex STR typing system contains these 16 STRs. Here, we develop an efficient 17-plex multiplex typing system for cattle that contains the 16 ISAG recommend STRs and a sex-determining marker. Compared to the Bovine Parenting Typing Kit (containing 11 of the 16 ISAG recommend STRs), our new typing system not only increases the number of molecular markers, but also simplifies the PCR operation and shortens the time for the typing procedure (from 4.5 h to 1 h 37 min). Profile can be generated from a single PCR reaction using as little as 1 ng of DNA. The combined probabilities of paternity exclusion CPEduo and CPEtrio were 0.999804697 and 0.999999260, respectively. These results indicate that our 17-plex typing system is a fast, sensitive and species-specific method for the identification of individuals and their parentage for cattle. The application of this system will improve the efficiency of the identification of cattle individuals and their paternity, supporting population genetic research and the selective breeding of cattle.

Abstract The aim of this study is to perform proteomic and metabolomic analyses in bilateral renal pelvis urine of patients with unilateral uric acid kidney stones to identify the specific urinary environment associated with uric acid stone formation. Using cystoscopy-guided insertion of ureteral catheters, bilateral renal pelvis urine samples are collected. Liquid chromatography-tandem mass spectrometry (LC-MS/MS) is employed to identify differentially expressed proteins and metabolites in the urine environment. Differentially expressed proteins and metabolites are further analyzed for their biological functions and potential metabolic pathways through Gene Ontology (GO) analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis. In the urine from the stone-affected side, eight differential proteins were significantly upregulated, and six metabolites were dysregulated. The uric acid stone urinary environment showed an excess of α-ketoisovaleric acid and 3-methyl-2-oxovaleric acid, which may contribute to the acidification of the urine. Functional and pathway analyses indicate that the dysregulated metabolites are mainly associated with insulin resistance and branched chain amino acid metabolism.

Abstract The Industrial Internet of Things (IIoT) is recognized as one of the revolutionary technologies driving smart manufacturing and improving productivity. As manufacturing processes grow increasingly intricate, the entire manufacturing ecosystem encompasses multiple managed IoT domains. Within this highly interconnected environment, devices from diverse domains must collaborate, leading to considerable apprehensions about the security and privacy of device-to-device communications. Current authentication methods encounter several challenges. Traditional authentication schemes overly rely on trusted third parties, rendering them susceptible to external attacks or internal spoofing. This susceptibility gives rise to a range of security and privacy concerns. In response to these challenges, this paper aims to contribute to a more secure and efficient service scheme for smart factories by devising a blockchain-based distributed IoT architecture. The proposed scheme introduces a federated blockchain to establish trust among different domains, thereby enabling secure connections between devices in distinct domains. Through security analysis, it is proved that the proposed authentication scheme has integrity, mutual authentication, scalability, and resistance to four attacks. Furthermore, efficiency analysis experiments show that our scheme is feasible for smart factories, and as the number of peer nodes increases, the performance and efficiency of the blockchain network become better.

Abstract Based on the innovation-driven theory and the ability-motivation-opportunity (AMO) perspective, we explore the role of intellectual property protection (IPP) in enhancing the radical technological innovation (RTI) of national research project teams (NRPT). Survey data from 336 national research project team members from universities and enterprises were used to analyze the theoretical model of this study, bringing in the chain-mediated effects of innovation milieu (IM) and group potential (GP) for analysis, as well as two-stage hybrid partial least squares structural equation modeling (PLS-SEM) and artificial neural network techniques (ANN) to evaluate the hypotheses. The empirical findings of this paper show that the strength of IPP has a positive relationship with RTI of NRPT, and that IPP is the most important predictor of this. These new findings expand the scope of innovation-driven theory and AMO theory, and provide a constructive model for NRPT to provide suggestions for the improvement of IPP system as a way to improve the realization of RTI. The results of this study can guide policymakers in strengthening IPP systems to encourage research teams to explore innovation more proactively and to facilitate the reasonable sharing and transfer of innovative outcomes. By creating a supportive innovation environment and maximizing the potential of research teams, technological breakthroughs can be achieved more effectively.

Abstract In recent observational studies, a potential link between prostatitis and prostate cancer (PCa) has been hinted at, yet the causality remains ambiguous. In our endeavor to scrutinize the conceivable causal nexus between prostatitis and PCa, we embarked upon a Mendelian randomization (MR) study. MR circumvents arbitrary groupings by employing genetic variations that have a strong association with the exposure as instrumental variables to infer causal relationships between exposures and outcomes. The etiology of PCa remains elusive. Given that prostatitis and prostate cancer occupy the same anatomical region, MR can more effectively delineate their relationship by mitigating confounding variables. This method can indirectly elucidate disease correlations, thereby contributing to cancer prevention strategies. FinnGen Consortium data were used for the prostatitis genome-wide association study (GWAS), including 74,658 participants. UK biobank baseline data (ncase = 3436, ncontrol = 459574), European Bioinformatics Institute Database (ncase = 79148, ncontrol = 61106), and IEU openGWAS database (ncase = 79148, ncontrol = 61106) were used for PCa outcomes, mostly for European population samples. Data from the GWSAs for prostatitis were compared with data from the three GWASs for PCa, respectively, in an analysis of an MR. Utilizing the inverse variance weighting (IVW) methodology as our primary analytical framework, we delved into a meticulous exploration of the conceivable causal association between prostatitis and PCa. Furthermore, we deployed supplementary methodologies, including Maximum Likelihood, MR-Egger, weighted median, and MR-PRESSO, to thoroughly assess and scrutinize the causality aspect comprehensively. Cochran’s Q statistic is employed as a metric to quantify the heterogeneity inherent in instrumental variables. The inverse variance weighted analysis revealed no discernible effect of prostatitis on PCa in the three PCa GWAS databases (odds ratio [OR]: 1.001, 95% Confidence Interval [CI]: 0.999–1.002, p = 0.28), (OR: 1.015, 95% CI: 0.981–1.050, p = 0.40), (OR: 1.015, 95% CI: 0.981–1.050, p = 0.40). Similarly, employing MR-Egger did not yield substantial evidence (OR: 0.999, 95% CI: 0.999–1.002, p = 0.89), (OR: 1.103, 95% CI: 1.006–1.209, p = 0.07), (OR: 1.103, 95% CI: 1.006–1.209, p = 0.07). The weighted median analysis also failed to provide convincing support for the impact of prostatitis on the incidence of PCa (OR: 1.001, 95% CI: 1.000-1.002, p = 0.064), (OR: 0.989, 95% CI: 0.946–1.034, p = 0.64), (OR: 0.989, 95% CI: 0.945–1.036, p = 0.65). The results of the MR showed no causality from prostatitis to PCa.

Abstract Unilateral Nephrectomy is one of the most common treatments for surgical diseases of the kidney but often results in postsurgical acute kidney injury (AKI). In the current study, we aimed to investigate the risk factors for AKI in patients who have received Unilateral Nephrectomy. We retrospectively analysed 528 patients who underwent Unilateral Nephrectomy for different etiologies between January 2013 and December 2018 at the Affiliated Hospital of Qingdao University. We recorded the prevalence and severity of AKI, age, gender, diabetes, body mass index (BMI), hypertension, preoperative renal function, etiology, performed surgically, anaemia, albumin, coagulation, lactate dehydrogenase, nitrogen (BUN), and uric acid. Univariate and multivariate logistic regression analyses were used to investigate the predictors of AKI in patients with Unilateral Nephrectomy. Overall, 218 of the 528 patients (41.2%) developed AKI during their hospitalisation. Univariate analysis showed that AKI was significantly associated with gender (male, OR = 1.866, P = 0.001), overweight (OR = 2.19, P = 0.0002), and surgical approach (OR = 1.7, P = 0.018), while multivariate logistic regression analysis showed that male gender (OR = 1.953, P = 0.001), overweight (OR = 2.176, P = 0.001), and preoperative renal function (OR = 0.507, P = 0.001) were independent factors for AKI. Regression analysis among different etiologies showed significant differences in postoperative AKI. After Unilateral nephrectomy, AKI is more likely to occur in overweight male patients with normal kidney function. AKI occurred more frequently in patients who are kidney donors, but rarely in those with non-function kidneys.

Abstract The leaves of Cyclocarya paliurus (Batalin) Iljinskaja, an endemic tree with a scattered distribution in subtropical China, are rich in flavonoids with beneficial, health-promoting properties. To understand the impact of environment and genetic similarity on the variation pattern of flavonoids in this species, we analyzed C. paliurus germplasm resources from 26 different populations previously sampled from the main distribution area. Environmental, genetic and biochemical data was associated by genetic structure analysis, non-parametric tests, correlation analysis and principal component analysis. We found that populations with higher flavonoid contents were distributed at higher elevations and latitudes and fell into two groups with similar genetic diversities. Significant accumulations of isoquercitrin and kaempferol 3-O-glucoside were detected in the higher flavonoid-content resources. In addition, the genetic clusters with higher flavonoid contents exhibited broader environmental-adaptive capacities. Even in the presence of environmental factors promoting C. paliurus flavonoid accumulation, only those populations having a specific level of genetic similarity were able to exploit such environments.

Objective To investigate the expression of trophoblast cell-surface antigen 2 (TROP2) in salivary adenoid cystic carcinoma (SACC) in order to analyze its relationship with TROP2 expression and clinicopathological features, as well as to clarify the correlation between TROP2 expression and the prognosis of patients with SACC. Methods With approval from the ethics committee, the expression of TROP2 in 85 SACC and paracancer tissue samples was detected by using the immunohistochemical method, and the relationship between TROP2 expression and clinicopathological characteristics was analyzed. The Kaplan-Meier method was used to analyze the relationship between TROP2 protein expression and 5-year disease-free survival (DFS) in 40 patients with SACC. Furthermore, the logistic regression model was used to analyze the prognostic factors of patients with SACC. Results The low or no expression rate of TROP2 in SACC tissues was significantly higher than that in paracancer tissues (PPPOR = 5.37; 95% CI: 1.03-28.08; P = 0.046) and Ⅲ-Ⅳ clinical staging (OR = 6.89; 95%CI: 1.37~34.77; P = 0.019) were risk factors affecting the prognosis of patients with SACC. Conclusion Low or no expression of TROP2 protein in SACC tissues leads to poor prognosis of patients and is positively correlated with tumor growth and clinical staging. In addition, low or no expression of TROP2 can be used as an independent prognostic risk factor for poor prognosis in patients with SACC, and TROP2 is a marker of poor prognosis in patients with SACC.

Abstract Previous studies have yielded inconsistent results regarding the association between chronic kidney disease (CKD) and the risk of cognitive impairment (CI). This study aimed to investigate the longitudinal association of CKD with CI risk in the Chinese middle-aged and older population. A total of 16,515 CI-free participants 45 years of age or older including 15,595 without CKD and 920 with CKD were followed from 2011 until 2018 (median [interquartile range]: 7 [5.5-7]) to detect incident CI. Over the follow-up, 648 participants developed CI. Data were analyzed using multi-adjusted Cox proportional hazard regression and Laplace regression. The incidence rate (IR) of CI was significantly higher in individuals with CKD at 11.46 per 1,000 person-years (95% confidence interval [CI], 8.90 to 14.76) than in those without CKD at 6.38 per 1,000 person-years (95% CI, 5.89 to 6.92). Compared to those without CKD, the hazard ratios of those with CKD was 1.56 (95% CI, 1.19 to 2.04) for CI. Participants with CKD in the middle-aged group (45–54 years) exhibited a heightened risk of CI in age-stratified analyses. CKD accelerated the onset of CI by 1.24 years (10th percentile difference [PD]; 95% CI, -2.03 to -0.43, p

Abstract Background Premature ovarian insufficiency (POI) is a reproductive disorder characterized by the cessation of ovarian function before the age of 40. Although mitochondrial dysfunction and immune disorders are believed to contribute to ovarian damage in POI, the interplay between these factors remains understudied. Methods In this research, transcriptomic data related to POI were obtained from the NCBI GEO database. Hub biomarkers were identified through the construction of a protein‒protein interaction (PPI) network and further validated using RT‒qPCR and Western blot. Moreover, their expression across various cell types was elucidated via single-cell RNA sequencing analysis. A comprehensive investigation of the mitochondrial and immune profiles of POI was carried out through correlation analysis. Furthermore, potential therapeutic agents were predicted utilizing the cMap database. Results A total of 119 mitochondria-related differentially expressed genes (MitoDEGs) were identified and shown to be significantly enriched in metabolic pathways. Among these genes, Hadhb, Cpt1a, Mrpl12, and Mrps7 were confirmed both in a POI model and in human granulosa cells (GCs), where they were found to accumulate in GCs and theca cells. Immune analysis revealed variations in macrophages, monocytes, and 15 other immune cell types between the POI and control groups. Notably, strong correlations were observed between seven hub-MitoDEGs (Hadhb, Cpt1a, Cpt2, Mrpl12, Mrps7, Mrpl51, and Eci1) and various functions, such as mitochondrial respiratory complexes, dynamics, mitophagy, mitochondrial metabolism, immune-related genes, and immunocytes. Additionally, nine potential drugs (calyculin, amodiaquine, eudesmic acid, cefotaxime, BX-912, prostratin, SCH-79797, HU-211, and pizotifen) targeting key genes were identified. Conclusions Our results highlight the crosstalk between mitochondrial function and the immune response in the development of POI. The identification of MitoDEGs could lead to reliable biomarkers for the early diagnosis, monitoring, and personalized treatment of POI.

Abstract Axis inhibition protein 1 (AXIN1), a scaffold protein interacting with various critical molecules, plays a vital role in determining cell fate. However, its impact on the antiviral innate immune response remains largely unknown. Here, we identify that AXIN1 acts as an effective regulator of antiviral innate immunity against both DNA and RNA virus infections. In the resting state, AXIN1 maintains the stability of the transcription factor interferon regulatory factor 3 (IRF3) by preventing p62-mediated autophagic degradation of IRF3. This is achieved by recruiting ubiquitin-specific peptidase 35 (USP35), which removes lysine (K) 48-linked ubiquitination at IRF3 K366. Upon virus infection, AXIN1 undergoes a phase separation triggered by phosphorylated TANK-binding kinase 1 (TBK1). This leads to increased phosphorylation of IRF3 and a boost in IFN-I production. Moreover, KYA1797K, a small molecule that binds to the AXIN1 RGS domain, enhances the AXIN1-IRF3 interaction and promotes the elimination of various highly pathogenic viruses. Clinically, patients with HBV-associated hepatocellular carcinoma (HCC) who show reduced AXIN1 expression in pericarcinoma tissues have low overall and disease-free survival rates, as well as higher HBV levels in their blood. Overall, our findings reveal how AXIN1 regulates IRF3 signaling and phase separation-mediated antiviral immune responses, underscoring the potential of the AXIN1 agonist KYA1797K as an effective antiviral agent.

Abstract The pore-throat structure is a crucial parameter for evaluating reservoir characteristics and assessing the potential of oil and gas resources. Understanding the relationship between reservoir pore-throat variations and oil-bearing properties is essential. Through a combination of techniques, including thin-section casting, scanning electron microscopy (SEM), micro-computed tomography (micro-CT), and high-pressure mercury injection (HPMI), we examined the tight sandstone reservoirs from the Chang 4 + 5 members of the Yanchang Formation in the study area. This analysis elucidates the relationship between the pore-throat structure and fractal characteristics of the samples and their oil-bearing properties. The results show that : (1) The tight sandstone reservoirs in the study area mainly develop three types of pores: dissolution pores, residual intergranular pores, and microfractures. Residual intergranular pores are primarily controlled by early compaction processes, while dissolution processes easily form secondary pores, increasing the porosity of the reservoir. Microfractures can significantly enhance both the permeability of the reservoir. (2) Using the characteristic parameters of HPMI, the reservoir is classified into four categories, labeled as type I to type IV. As the categories progress from type I to type IV, pore-throat size decreases, porosity and permeability decrease, and reservoir properties deteriorate. The overall fractal dimension of pores decreases, while the fractal dimensions of individual pore types increase. Pore connectivity becomes more complex, and heterogeneity strengthens. (3) Reservoir porosity shows a strong positive correlation with permeability. As reservoir properties improve, the number of macropores increases, leading to a higher Reservoir Quality Index (RQI) and better oil-bearing characteristics.

Abstract Background Epilepsy is a prevalent neurological disorder in which seizures cause recurrent episodes of unconsciousness or muscle convulsions, seriously affecting the patient’s work, quality of life, and health and safety. Timely prediction of seizures is critical for patients to take appropriate therapeutic measures. Accurate prediction of seizures remains a challenge due to the complex and variable nature of EEG signals. The study proposes an epileptic seizure model based on a multidimensional Transformer with recurrent neural network(LSTM-GRU) fusion for seizure classification of EEG signals. Methodology Firstly, a short-time Fourier transform was employed in the extraction of time-frequency features from EEG signals. Second, the extracted time-frequency features are learned using the Multidimensional Transformer model. Then, LSTM and GRU are then used for further learning of the time and frequency characteristics of the EEG signals. Next, the output features of LSTM and GRU are spliced and categorized using the gating mechanism. Subsequently, seizure prediction is conducted. Results The model was tested on two datasets: the Bonn EEG dataset and the CHB-MIT dataset. On the CHB-MIT dataset, the average sensitivity and average specificity of the model were 98.24% and 97.27%, respectively. On the Bonn dataset, the model obtained about 99% and about 98% accuracy on the binary classification task and the tertiary upper classification task, respectively. Conclusion The findings of the experimental investigation demonstrate that our model is capable of exploiting the temporal and frequency characteristics present within EEG signals.

Abstract Background The growing body of research on kidney disease in children has identified a broad spectrum of genetic etiologies. Methods We conducted a prospective study to evaluate the efficacy of an optimized genetic test and subclinical changes in a real-world context before kidney transplantation. All cases involved recipients under the age of 18 who underwent whole exome sequencing (ES) between 2013 and 2022. Results The study population included 244 children, with a median age of 13.1 years at transplantation. ES provided a molecular genetic diagnosis in 114 (46.7%) probands with monogenic variants in 15 known disease-causing genes. ES confirmed the suspected clinical diagnosis in 74/244 (30.3%) cases and revised the pre-exome clinical diagnoses in 40/244 (16.4%) cases. ES also established a specific underlying cause for kidney failure for 19 patients who had previously had an unknown etiology. Genetic diagnosis influenced clinical management in 88 recipients (36.1%), facilitated genetic counseling for 18 families (7.4%), and enabled comprehensive assessment of living donor candidates in 35 cases (14.3%). Conclusions Genetic diagnosis provides critical insights into the pathogenesis of kidney disease, optimizes clinical strategies concerning risk assessment of living donors, and enhances disease surveillance of recipients.

Objective To investigate the effect of different antibacterial agents combined with tigecycline in patients with multidrug-resistant Acinetobacter baumannii (MDRAB)-related ventilator-associated pneumonia (VAP), and to provide options for better treatment of the disease in clinical practice. Methods A retrospective analysis was performed for the clinical data of the patients with MDRAB-related VAP who were admitted from January 2016 to August 2023 in Qingdao municipal Hospital, and according to the treatment regimen, they were divided into tigecycline group (group A) with 56 patients, cefoperazone-sulbactam combination therapy group (B group) with 42 patients, and carbapenem combination therapy group (group C) with 24 patients. The three groups were compared in terms of infection and related outcome measures. Results There were no significant diffe-rences in the type of pathogene infected and infection sites between the three groups (P>0.05). Groups B and C had a significantly higher bacterial clearance rate than group A (χ2=5.38,4.48,P0.05). Conclusion Tigecycline combined with cefoperazone-sulbactam or carbapenem achieves a higher bacterial clearance rate than tigecycline alone in MDRAB-related VAP, and combined medication is a relatively good treatment option.

Background The number of migrant elderly in China and abroad is rising, and their mental health problems can no longer be ignored due to mobility-related adversities. Objective To analyze the current situation, research hotspots and trends in the field of mental health of migrant elderly at home and abroad in the past 10 years based on CiteSpace, and provide reference for research in related fields. Methods CNKI, Wanfang Data, VIP, CBM, Scopus, PubMed and Web of Science Core Collection were used as data sources, and CiteSpace was used for visualization and analysis, including publication volume, authors, institutions and keywords. Results A total of 1 023 papers were obtained, 726 in English and 297 in Chinese. Domestic authors mainly collaborated with the same institution, while there were more inter-institutional collaborations abroad. The current research hotspots mainly focused on the elderly with migration, elderly immigrants, old migrants, depression, psychological distress and social support. Conclusion Compared with abroad, there are fewer publications in China currently, with looser cooperation among research authors and institutions, and a lack of core authors, needing more diversification of disciplines and research methods. Focusing on hotspots and cutting-edge content, exploring the mechanism of the role of mental health of migrant elderly, implementing psychological interventions, strengthening health education, and improving the psychological resilience and subjective well-being of migrant elderly are the main trends of future research.

Abstract Background The epidemiology of fungi identified via next-generation sequencing in bronchoalveolar lavage fluid among patients with COVID-19 is unknown. Methods De-identified information, including age, SARS-CoV-2 reads and fungi from bronchoalveolar lavage fluid, were used to analysis. Results A total of 960 patients with COVID-19 were included. Gender was unknown in 38 patients, and 648 (70.3%) of the rest patients were male. For 876 patients with information on age, their mean ± standard age was 63.4 ± 21.3 years, with the minimum being 0.2 years and the maximum being 101 years. For all the patients, their median [interquartile range] SARS-CoV-2 reads were 26,038 [4421.5, 44,641.5]. The Aspergilli were identified in 159 (16.6%) patients, with Aspergillus fumigatus, Aspergillus flavus and Aspergillus niger in 103 (10.7%), 81 (8.4%) and 17 (1.8%), respectively. The Mucoraceae were identified in 14 (1.5%) patients. Pneumocystis jirovecii was identified in 65 (6.8%) patients, among whom 12 (18.5%) patients also had Aspergilli. The Cryptococcaceae and the Dematiaceae were also identified in some patients, including Cryptococcus in 11 (1.1%) patients. Conclusions In bronchoalveolar lavage fluid among patients with COVID-19, the Aspergilli were very commonly identified, as were the Mucoraceae, Pneumocystis jirovecii and Cryptococcus via next-generation sequencing.

Abstract Diabetes mellitus (DM) is a chronic metabolic disease that is highly susceptible to kidney injury. Di’ao XinXueKang capsules (DXXK) is a novel Chinese herbal medicine that has been used in clinical trials for the therapy of DM and kidney disease, but the underlying pharmacological mechanism remains unclear. This study aims to integrate network pharmacology, molecular docking and in vivo experiments to explore the potential mechanisms of DXXK in the treatment of diabetic kidney injury. The chemical constituents of DXXK were extracted from the ETCM and Batman-TCM databases, and then evaluated for their pharmacological activity via the Swiss ADME platform. Multiple disease databases were searched and integrated for DM-related targets. Overlapping targets were then collected to construct a protein–protein interaction (PPI) network. KEGG and GO enrichment analyses were performed based on the Metascape database, and molecular docking was performed using AutoDock Vina software. The main components in DXXK were analyzed by HPLC. The results of network pharmacology and molecular docking were validated in an animal model of DM induced by the combination of a high-fat diet (HFD) and streptozotocin (STZ). We screened and obtained 7 ingredients and identified dioscin, protodioscin, and pseudoprotodioscin as the major components of DXXK by HPLC. A total of 2,216 DM-related pathogenic genes were obtained from DrugBank, GeneCards, OMIM, and DisGeNET databases. KEGG and GO enrichment analyses indicated that the TGF-beta signaling pathway is a critical pathway associated with DM therapy. Molecular docking revealed that the ingredients in DXXK bind to the pivotal targets TGFβ1, Smad2, and Smad3. In diabetic mice, we found that DXXK alleviated diabetic symptoms, lowered blood glucose, improved insulin tolerance, and modulated lipid metabolism. Furthermore, DXXK attenuated renal lesions and fibrosis by downregulating TGFβ1, Smad2, and Smad3. Collectively, our results suggest that DXXK has the potential to regulate glucolipid metabolism in DM, and it may serve as a viable therapeutic option for renoprotection by inhibiting of the TGF-β1/Smad2/3 pathway.

Abstract Medullary thyroid carcinoma (MTC) is a rare type of thyroid malignancy that accounts for approximately 1–2% of all thyroid cancers (TCs). MTC include hereditary and sporadic cases, the former derived from a germline mutation of rearrangement during transfection (RET) proto-oncogene, whereas somatic RET mutations are frequently present in the latter. Surgery is the standard treatment for early stage MTC, and the 10-year survival rate of early MTC is over 80%. While for metastatic MTC, chemotherapy showing low response rate, and there was a lack of effective systemic therapies in the past. Due to the high risk (ca. 15–20%) of distant metastasis and limited systemic therapies, the 10-year survival rate of patients with advanced MTC was only 10–40% from the time of first metastasis. Over the past decade, targeted therapy for RET has developed rapidly, bringing hopes to patients with advanced and progressive MTC. Two multi-kinase inhibitors (MKIs) including Cabozantinib and Vandetanib have been shown to increase progression-free survival (PFS) for patients with metastatic MTC and have been approved as choices of first-line treatment. However, these MKIs have not prolonged overall survival (OS) and their utility is limited due to high rates of off-target toxicities. Recently, new generation TKIs, including Selpercatinib and Pralsetinib, have demonstrated highly selective efficacy against RET and more favorable side effect profiles, and gained approval as second-line treatment options. Despite the ongoing development of RET inhibitors, the management of advanced and progressive MTC remains challenging, drug resistance remains the main reason for treatment failure, and the mechanisms are still unclear. Besides, new promising therapeutic approaches, such as novel drug combinations and next generation RET inhibitors are under development. Herein, we overview the pathogenesis, molecular genetics and current management approaches of MTC, and focus on the recent advances of RET inhibitors, summarize the current situation and unmet needs of these RET inhibitors in MTC, and provide an overview of novel strategies for optimizing therapeutic effects.

Diffuse midline glioma (DMG), H3K27-altered, is lethal pediatric-type, high-grade, localized to the midline region of the central nervous system. Effective treatment guidelines are absent, and clinical trials are preferred for primary or recurrent DMG patients. Recently, epigenetic agent-based immunotherapy has exhibited promising therapeutic effects in the clinical setting. However, the underlying mechanisms remain a mystery. The rare DMG tumor samples from biopsy or resection largely impede basic research, by using patient-derived tumor cells which better recapitulate the parental tumor's heterogeneity compared to established cell lines. As an epigenetic reprogramming disease, DMG exhibits a global loss of H3K27 trimethylation (H3K27me3) and a gain of H3K27 acetylation (H3K27ac). Analysis of multiple epigenetic marks is fundamentally necessary. However, traditional techniques cannot allow ultra-low input and high-throughput. Herein we have developed a new method called high-throughput in situ tagged immunoprecipitation sequencing (HiTIP-seq), which uses an integrated superhydrophobic microwell array technology (InSMART). We were able to perform 100 parallel assays from as few as 100 cells per microwell on a single chip. We applied the technology to profile epigenetic alterations of three-dimensional (3D) cell cultures derived from DMG patients. Our HiTIP-seq integrated with RNA sequencing (RNA-seq) analysis revealed that the combination of epigenetic agents (panobinostat and tazemetostat), reprogrammed histone modifications and drove transcriptome changes. Among them, Wnt inhibitory factor 1 (WIF1) has a gain of H3K27ac and a loss of H3K27me3, which leads to the upregulated expression. Altogether, HiTIP-seq is a versatile method for high-throughput analysis of histone modifications, suitable for both DMG research and studying rare 3D models.

Abstract Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease characterized by motor neuron degeneration. Dysregulation of long non-coding RNAs (lncRNAs) has been implicated in ALS pathogenesis but their roles remain unclear. Previous studies found lnc-ABCA12-3 was downregulated in ALS patients. We aim to characterize the expression and function of lnc-ABCA12-3 in ALS and explore its mechanisms of action. Lnc-ABCA12-3 expression was analyzed in PBMCs from ALS patients and correlated with clinical outcomes. Effect of modulating lnc-ABCA12-3 expression was assessed in cell models using assays of apoptosis, protein homeostasis and pathway analysis. RNA pull-down and interaction studies were performed to identify lnc-ABCA12-3 binding partners. Lnc-ABCA12-3 was downregulated in ALS patients, correlating with faster progression and shorter survival. Overexpression of lnc-ABAC12-3 conferred protection against oxidative stress-induced apoptosis, while knockdown lnc-ABCA12-3 enhanced cell death. Lnc-ABCA12-3 maintained protein quality control pathways, including ubiquitination, autophagy and stress granule formation, by regulating the ubiquitin shuttle protein UBQLN1. This study identified lnc-ABCA12-3 as a novel regulatory lncRNA implicated in ALS pathogenesis by modulating cellular survival and stress responses through interactions with UBQLN1, influencing disease progression. Lnc-ABCA12-3 may influence ALS through regulating protein homeostasis pathways.

Abstract The aim of this study was to investigate the effect of zoledronic acid (ZA) on postoperative healing and functional rehabilitation in osteoporotic patients with rotator cuff (RC) injury. 96 Patients were divided into three groups according to bone mineral density and ZA use (Group A: normal BMD; Group B: osteoporosis and intravenous ZA use; Group C: osteoporosis, without ZA use). Radiologic, functional and Serological outcomes were evaluated 6 months after surgery. The functional scores in all groups exhibited significant improvement 6 months after surgery. Inter-group comparison showed that Constant Shoulder joint function Score (CSS) of group A not significantly differing from that of group B, the other indicators were significantly better than those of group B and C. There were no significant differences in shoulder forward flexion, abductive Range of Motion between group B and C. Other indicators of group B were significantly improved compared to group C. The retear rate in group C (30.3%, 10/33) was higher than group A (6.1%, 2/33) and group B (13.3%, 4/30). In conclusion, the application of ZA can significantly reduce the rate of RC retear in elderly patients with osteoporosis after surgery, which is significant for postoperative shoulder joint functional rehabilitation.

Abstract Abnormal expression of circRNAs has been observed in different types of carcinomas, and they play significant roles in the biology of these cancers. Nevertheless, the clinical relevance and functional mechanisms of the majority of circRNAs implicated in breast cancer progression remain unclear. The primary objective of our investigation is to uncover new circRNAs in breast cancer and elucidate the underlying mechanisms by which they exert their effects. The circRNA expression profile data for breast cancer and RNA-sequencing data were acquired from distinct public databases. Differentially expressed circRNAs and mRNA were identified through fold change filtering. The establishment of the competing endogenous RNAs (ceRNAs) network relied on the interplay between circular RNAs, miRNAs, and mRNAs. The hub genes were identified from the protein–protein interaction (PPI) regulatory network using the CytoHubba plugin in Cytoscape. Moreover, the expression levels and prognostic value of these hub genes in the PPI network were assessed using the GEPIA and Kaplan–Meier plotter databases. Fluorescence in situ hybridization (FISH) was used to identified the expression and intracellular localization of hsa_circ_0059665 by using the tissue microarray. Transwell analysis and CCK-8 analysis were performed to assess the invasion, migration, and proliferation abilities of breast cancer cells. Additionally, we investigated the interactions between hsa_circ_0059665 and miR-602 through various methods, including FISH, RNA-binding protein immunoprecipitation (RIP), and luciferase reporter assay. Rescue experiments were conducted to determine the potential regulatory role of hsa_circ_0059665 in breast cancer progression. A total of 252 differentially expressed circRNAs were identified. Among them, 246 circRNAs were up-regulated, while 6 circRNAs were down-regulated. Based on prediction and screening of circRNA-miRNA and miRNA-mRNA binding sites, we constructed a network consisting of circRNA-miRNA-mRNA interactions. In addition, we constructed a Protein–Protein Interaction (PPI) network and identified six hub genes. Moreover, the expression levels of these six hub genes in breast cancer tissues were found to be significantly lower. Furthermore, the survival analysis results revealed a significant correlation between low expression levels of KIT, FGF2, NTRK2, CAV1, LEP and poorer prognosis in breast cancer patients. The FISH experiment results indicated that hsa_circ_0059665 exhibits significant downregulation in breast cancer, and its decreased expression is linked to poor prognosis in breast cancer patients. Functional in vitro experiments revealed that overexpression of hsa_circ_0059665 can inhibit proliferation, migration and invasion abilities of breast cancer cells. Further molecular mechanism studies showed that hsa_circ_0059665 exerts its anticancer gene role by acting as a molecular sponge for miR-602. In our study, we constructed and analyzed a circRNA-related ceRNA regulatory network and found that hsa_circ_0059665 can act as a sponge for miR-602 and inhibit the proliferation, invasion and migration of breast cancer cells.

Abstract The aim of this study was to explore the related factors linked to the development and infectivity of tuberculosis. This was achieved by comparing the clinical characteristics of patients with pulmonary tuberculosis (TB) who tested positive in smear Mycobacterium tuberculosis tests with this who tested negative in smear mycobacterium tests but positive in sputum Gene Xpert tests. We gathered clinical data of 1612 recently hospitalized patients diagnosed with pulmonary tuberculosis who tested positive either in sputum Gene-Xpert test or sputum smear Mycobacterium tuberculosis tests. The data was collected from January 1, 2018 to August 5, 2023, at Sichuan Provincial People's Hospital. We conducted separately analyzes and comparisons of the clinical characteristics between the two groups of patients, aiming to discussed the related factors influencing the development and infectivity of tuberculosis. In comparison to the GeneXpert positive group, the sputum smear positive group exhibited a higher proportion of elderly patients (aged 75–89) and individuals classified as underweight (BMI

Abstract Even though the capability of aircraft manufacturing has improved, human factors still play a pivotal role in flight accidents. For example, fatigue-related accidents are a common factor in human-led accidents. Hence, pilots’ precise fatigue detections could help increase the flight safety of airplanes. The article suggests a model to recognize fatigue by implementing the convolutional neural network (CNN) by implementing flight trainees' face attributions. First, the flight trainees’ face attributions are derived by a method called the land-air call process when the flight simulation is run. Then, sixty-eight points of face attributions are detected by employing the Dlib package. Fatigue attribution points were derived based on the face attribution points to construct a model called EMF to detect face fatigue. Finally, the proposed PSO-CNN algorithm is implemented to learn and train the dataset, and the network algorithm achieves a recognition ratio of 93.9% on the test set, which can efficiently pinpoint the flight trainees’ fatigue level. Also, the reliability of the proposed algorithm is validated by comparing two machine learning models.

Abstract Investigate the impact of remnant cholesterol (RC) levels on carotid artery intima thickness (CIT) in type 2 diabetes mellitus (T2DM) patients. From September 2021 to September 2023, a prospective multicenter study involved 158 T2DM patients. They were divided into a higher RC group (n = 80) and a lower RC group (n = 78) based on median RC levels. Additionally, 92 healthy volunteers served as the control group. CIT, carotid media thickness (CMT), and carotid intima-media thickness (CIMT) were measured. General clinical data, lab results, CIMT, CIT, and CMT differences among the three groups were compared. Multiple regression analysis explored CIT factors in T2DM patients. 1. No significant sex, age, BMI, high-density lipoprotein cholesterol (HDL-C), T2DM duration, fasting blood glucose, or glycated hemoglobin differences were found among the groups (p > 0.05). 2. CIMT and CIT were significantly higher in T2DM than the control group (p 0.05). Multiple linear regression analysis showed RC as an influencing CIT factor in T2DM patients (β = 0.473, p = 0.005). CIT is significantly thicker in T2DM patients with higher RC than in those with lower RC, and RC is the influence factor of CIT, which suggests that more attention should be paid to the detection of RC in T2DM patients.

Background The effective evaluation of scientific and technological achievements in traditional Chinese medicine (TCM) is of great significance in promoting the innovative development of TCM. Previous evaluations of scientific and technological achievements in TCM often used a generalized evaluation method, leading to problems such as inappropriate indicators and limited dimensions, which is not conducive to reflecting the multiple values of achievements in a scientific and comprehensive way. Consequently, there is an urgent need to establish categorized and multi-dimensional evaluation index system for the evaluation of scientific and technological achievements in TCM in the new period. Objective To establish a scientific, categorized, reliable and comprehensive evaluation index system that reflects the principles of TCM and highlights its unique advantages aiming at the scientific and technological achievements in TCM, in accordance with the contemporary requirements for scientific and technological evaluation in China. Methods This study began in November 2022 and was completed in May 2023. A preliminary index framework was developed through literature review and focus group discussions. Delphi expert consultation was then conducted over two rounds to determine the evaluation indexes and points. The hierarchical analysis method was used to calculate the weight of each index. Results The final evaluation index system of scientific and technological achievements in TCM clinical research comprised 10 threshold indicators, 4 primary indicators, 17 secondary indicators, and 17 evaluation points. After testing, the positive coefficient of experts in both rounds of Delphi method implementation was 100%, the authority coefficient was 0.94 and 0.93, respectively. The Kendall's W consistency test for each level of indicators yielded two-tailed significance (P

ObjectiveTo compare the application value of three image post-processing techniques volume rendering （VR）, multiplanar reformation （MPR） and curved planar reformation （CPR） in the identification of rib fracture malunion.MethodsThe types and numbers of rib fracture malunion in 75 patients were recorded, and the sensitivity, specificity, accuracy and Youden index of VR, MPR and CPR in the diagnosis of rib fracture malunion were compared. Receiver operator characteristic （ROC） curve was drawn and area under the curve （AUC） was calculated, and the detection rates of three image post-processing techniques for different types of rib fracture malunion were compared.ResultsA total of 243 rib fractures were malunion in 75 patients. The diagnostic sensitivity of VR, MPR and CPR for rib fracture malunion was 52.67%, 79.84% and 91.36%, the specificity was 99.58%, 97.89% and 99.15%, the accuracy was 83.66%, 91.76% and 96.51%, the Youden index was 0.52, 0.78 and 0.91, the AUC was 0.761, 0.889 and 0.953, respectively. Compared with VR, there were statistically significant differences in the number of broken rib end misalignment over 1/3, broken rib end overlap, broken rib end angulation and intercostal bridge detected in MPR （P

Abstract Researchers have investigated the potential of leveraging pre-trained language models, such as CodeBERT, to enhance source code-related tasks. Previous methodologies have relied on CodeBERT’s ‘[CLS]’ token as the embedding representation of input sequences for task performance, necessitating additional neural network layers to enhance feature representation, which in turn increases computational expenses. These approaches have also failed to fully leverage the comprehensive knowledge inherent within the source code and its associated text, potentially limiting classification efficacy. We propose CodeClassPrompt, a text classification technique that harnesses prompt learning to extract rich knowledge associated with input sequences from pre-trained models, thereby eliminating the need for additional layers and lowering computational costs. By applying an attention mechanism, we synthesize multi-layered knowledge into task-specific features, enhancing classification accuracy. Our comprehensive experimentation across four distinct source code-related tasks reveals that CodeClassPrompt achieves competitive performance while significantly reducing computational overhead.

Abstract This study addresses the growing anxiety and depression among Chinese university students by evaluating and ranking music education strategies to alleviate these issues. We integrates Fuzzy Analytic Hierarchy Process (FAHP) and Fuzzy Technique for Order of Preference by Similarity to Ideal Solution (TOPSIS). FAHP was utilized to determine the weight of factors such as academic pressures, social relationships, and cultural norms, while fuzzy TOPSIS ranked the effectiveness of music education interventions based on these weights. The results revealed that ‘Mental health stigma’ and ‘Academic Pressures and Rigidity’ are among the highest weighted factors, significantly impacting student anxiety. ‘Music Appreciation and Music-Based Self-Care’ emerged as the most effective strategy. These results highlight the importance of direct involvement in music-related activities for improving student mental health.

Objective To investigate risk factors for the development of post-transplant diabetes mellitus (PTDM) in patients undergoing orthotopic liver transplantation. Methods We included 293 patients who underwent orthotopic liver transplantation at The Affiliated Hospital of Qingdao University from July 1, 2017 to January 31, 2023. According to whether PTDM occurred, the patients were divided into PTDM group (n=66) and non-PTDM group (n=227). Significantly different clinical para-meters between the two groups were included in a multivariable logistic regression model to determine independent risk factors for PTDM. The impact of PTDM on the survival rate of the patients was analyzed using a Kaplan-Meier survival curve. Results The incidence rate of PTDM among the patients was 22.5%. The PTDM group and non-PTDM group differed significantly in age, the percentage of patients with a history of hypertension, preoperative fasting blood glucose level, preoperative serum total cholesterol level, preoperative serum low-density lipoprotein level, the percentage of patients treated with cyclosporine after surgery, and the percentage of patients treated with anti-rejection regimen C (cyclosporine alone or combined with mycophenolate or sirolimus) or D (mycophenolate or sirolimus alone) after surgery (t=-3.191,U=-5.668--2.559,χ2=3.922-5.689,P46 years, a history of hypertension, preoperative fasting blood glucose level >6.1 mmol/L, preoperative serum low-density lipoprotein level >3.12 mmol/L, postoperative use of anti-rejection regimen C (cyclosporine alone or combined with mycophenolate or sirolimus) were independent risk factors for the occurrence of PTDM (P46 years, a history of hypertension, preoperative fasting blood glucose level >6.1 mmol/L, preoperative serum low-density lipoprotein level >3.12 mmol/L, and postoperative anti-rejection treatment with cyclosporine alone or combined with mycophenolate or sirolimus are independent risk factors for adult PTDM.

Abstract Atrial fibrillation (A-fib) is the most common type of heart arrhythmia, typically treated with radiofrequency catheter ablation to isolate the heart from abnormal electrical signals. Monitoring the formation of ablation-induced lesions is crucial for preventing recurrences and complications arising from excessive or insufficient ablation. Existing imaging modalities lack real-time feedback, and their intraoperative usage is in its early stages. A critical need exists for an imaging-based lesion indexing (LSI) method that directly reflects tissue necrosis formation. Previous studies have indicated that spectroscopic photoacoustic (sPA) imaging can differentiate ablated tissues from their non-ablated counterparts based on PA spectrum variation. In this paper, we introduce a method for detecting ablation lesion boundaries using sPA imaging. This approach utilizes ablation LSI, which quantifies the ratio between the signal from ablated tissue and the total tissue signal. We enhance boundary detection accuracy by adapting a regression model-based compensation. Additionally, the method was cross-validated with clinically used intraoperative monitoring parameters. The proposed method was validated with ex vivo porcine cardiac tissues with necrotic lesions created by different ablation durations. The PA-measured lesion size was compared with gross pathology. Statistical analysis demonstrates a strong correlation (R > 0.90) between the PA-detected lesion size and gross pathology. The PA-detected lesion size also exhibits a moderate to strong correlation (R > 0.75) with local impedance changes recorded during procedures. These results suggest that the introduced PA imaging-based LSI has great potential to be incorporated into the clinical workflow, guiding ablation procedures intraoperatively.

Abstract Pre-treatment host and viral factors may affect serum ferritin levels in patients with hepatitis C virus (HCV) infection. We delineated pre-treatment factors associated with hyperferritinemia in these patients. 1682 eligible patients underwent pre-treatment assessment for serum ferritin and various host/viral factors. Univariate and multivariate logistic regression analyses were conducted to evaluate factors associated with hyperferritinemia. Multivariate logistic regression analyses revealed that age > 50 years (adjusted odds ratio [OR]: 1.38 (95% confidence interval [CI] 1.09–1.74), p = 0.008), fibrosis stage ≥ F3 (adjusted OR: 1.36 (95% CI 1.04–1.77), p = 0.02), fibrosis index based on four parameters (FIB-4) > 3.25 (adjusted OR: 1.46 (95% CI 1.11–1.92), p = 0.01), presence of metabolic dysfunction-associated steatotic liver disease (MASLD) (adjusted OR: 1.43 (95% CI 1.21–1.76), p = 0.001), and alanine transaminase (ALT) > 2 folds upper limit of normal (ULN) (adjusted OR: 2.87 (95% CI 2.20–3.75), p

Abstract Plants are affected by many environmental factors during their various stages of growth, among which salt stress is a key factor. WRKY transcription factors play important roles in the response to stress in plants. In this study, SmWRKY40 from eggplant (Solanum melongena L.) was found to belong to the subfamily of WRKY transcription factor group II, closely related to the evolution of wild tomato ScWRKY40 (Solanum chilense). The expression of SmWRKY40 could be induced by several abiotic stresses (drought, salt, and high temperature) and ABA to different degrees, with salt stress being the most significant. In Arabidopsis thaliana, the seed germination rate of SmWRKY40 overexpression seedlings was significantly higher than those of the wild type under high concentrations of NaCl and ABA, and root elongation of overexpression lines was also longer than wild type under NaCl treatments. SmWRKY40 overexpression lines were found to enhance Arabidopsis tolerance to salt with lower ROS, MDA, higher soluble protein, proline accumulation, and more active antioxidant enzymes. The expression level of genes related to stress and ABA signaling displayed significant differences in SmWRKY40 overexpression line than that of WT. These results indicate that SmWRKY40 regulates ABA and salt stress responses in Arabidopsis.

Abstract Background The relationship between periodontitis and cardiovascular disease (CVD) has been extensively studied, but the role of biological aging in this relationship remains poorly understood. This study is dedicated to investigating the effect of periodontitis on the incidence of CVD and to elucidating the potential mediating role of biological aging. Furthermore, this study will seek to elucidate the causal association between periodontitis, CVD, and biological aging. Methods We included 3269 participants from the National Health and Nutrition Examination Survey (2009–2014) with diagnostic information on periodontitis and composite CVD events. Biological aging was evaluated by utilizing both the Klemera–Doubal method’s calculated biological age (KDMAge) and phenotypic age (PhenoAge). Logistic regression, restricted cubic spline (RCS) analysis, and subgroup analysis were used for data analysis. Mediation analysis was employed to explore the mediating role of biological aging. Subsequently, Mendelian randomization (MR) analyses were performed using genome-wide association study databases to explore potential causal relationships between periodontitis, CVD, and biological aging. Results Periodontitis was associated with a higher risk of CVD. Participants with periodontitis were found to have increased levels of biological aging, and elevated levels of biological aging were associated with increased CVD risk. Mediation analyses showed a partial mediating effect of biological aging (PhenoAge: 44.6%; KDMAge: 22.9%) between periodontitis and CVD risk. MR analysis showed that periodontitis played a causal role in increasing the risk of small vessel stroke, while myocardial infarction was found to increase the risk of periodontitis. In addition, reverse MR analysis showed that phenotypic aging can increase the risk of periodontitis, and there is a two-way causal relationship between CVD and biological aging. Conclusions Periodontitis is associated with an increased CVD risk, partially mediated by biological aging, with a complex causal interrelationship. Targeted interventions for periodontal health may slow the biological aging processes and reduce CVD risk.

Abstract Background The attentional network test (ANT) is widely used to evaluate the performance of three attentional networks: alerting, orienting and executive attention networks. This study aimed to investigate the characteristics of attention functions in HIV-negative patients with early forms of neurosyphilis (NS) and their correlation with abnormalities in brain magnetic resonance imaging (MRI). Methods Thirty patients with early forms of NS, 31 patients with syphilis but without NS (Non-NS) and 35 healthy controls were recruited from an HIV-negative cohort between September 2020 and November 2022. The participants were evaluated with the ANT and the Mini-Mental State Examination (MMSE). Brain MRI was performed in NS and Non-NS patients. Results No significant differences were observed in the MMSE scores among the three groups. However, patients with early forms of NS showed poorer performance in orienting and alerting functions than Non-NS group (F = 6.952, P = 0.011 and F = 8.794, P = 0.004, respectively); No significant difference was observed in executive function between the two groups (F = 0.001, P = 0.980). Multivariate analysis of variance using the Bonferroni post hoc test indicated that patients with NS exhibited less efficient orienting function (P = 0.023), and alerting function (P = 0.003) but not executive function (P = 0.99), compared to Non-NS patients. Additionally, a significant difference was found in orienting function between patients with NS and healthy controls (P

Abstract Adverse events (AEs) are a significant concern for healthcare systems. However, it is difficult to evaluate their influence because of the complexity of various medical services. This study aimed to assess the influence of AEs on the outcomes of hospitalized patients using a diagnosis-related group (DRG) database. We conducted a case–control study of hospitalized patients at a multi-district tertiary hospital with 2200 beds in China, using data from a DRG database. An AE refers to an unintended physical injury caused or contributed to by medical care that requires additional hospitalization, monitoring, treatment, or even death. Relative weight (RW), a specific indicator of DRG, was used to measure the difficulty of diagnosis and treatment, disease severity, and medical resources utilized. The primary outcomes were hospital length of stay (LOS) and hospitalization costs. The secondary outcome was discharge to home. This study applied DRG-based matching, Hodges–Lehmann estimate, regression analysis, and subgroup analysis to evaluate the influence of AEs on outcomes. Two sensitivity analyses by excluding short LOS and changing adjustment factors were performed to assess the robustness of the results. We identified 2690 hospitalized patients who had been divided into 329 DRGs, including 1345 patients who experienced AEs (case group) and 1345 DRG-matched normal controls. The Hodges–Lehmann estimate and generalized linear regression analysis showed AEs led to prolonged LOS (unadjusted difference, 7 days, 95% confidence interval [CI] 6–8 days; adjusted difference, 8.31 days, 95% CI 7.16–9.52 days) and excess hospitalization costs (unadjusted difference, $2186.40, 95% CI: $1836.87-$2559.16; adjusted difference, $2822.67, 95% CI: $2351.25-$3334.88). Logistic regression analysis showed AEs were associated with lower odds of discharge to home (unadjusted odds ratio [OR] 0.66, 95% CI 0.54–0.82; adjusted OR 0.75, 95% CI 0.61–0.93). The subgroup analyses showed that the results for each subgroup were largely consistent. LOS and hospitalization costs increased significantly after AEs in complex diseases (RW ≥ 2) and in relation to high degrees of harm subgroups (moderate harm and above groups). Similar results were obtained in sensitivity analyses. The burden of AEs, especially those related to complex diseases and severe harm, is significant in China. The DRG database serves as a valuable source of information that can be utilized for the evaluation and management of AEs.