Prevalence of diverse colorectal polyps and risk factors for colorectal carcinoma in situ and neoplastic polyps.

BACKGROUND: Most colorectal cancers originate from precancerous polyps. This study aimed to determine the prevalence of colorectal polyps with diverse pathological morphologies and to explore the risk factors for colorectal carcinoma in situ (CCS) and neoplastic polyps. METHODS: Inpatients admitted from January 2018 to May 2023 were screened through the hospital information system. Polyps were classified according to pathological morphology. The prevalence of polyps was described by frequency and 95% confidence interval. Univariate and multivariate logistic regression analyses were used to explore the risk factors for CCS and neoplastic polyps. RESULTS: In total, 2329 individuals with 3550 polyps were recruited. Among all patients, 76.99% had neoplastic polyps and 44.31% had advanced adenomas. Tubular adenoma had the highest prevalence at 60.15%, and the prevalence of CCS was 3.86%. Patients with a colorectal polyp diameter ≥ 1.0 cm or number ≥ 3 were 8.07 times or 1.98 times more likely to develop CCS than were those with a diameter < 1.0 cm or number < 3, respectively (OR 8.07, 95%CI 4.48-14.55, p < 0.0001; and OR 1.98, 95%CI 1.27-3.09, p = 0.002). The risk of CCS with schistosome egg deposition was also significantly increased (OR 2.70, 95%CI 1.05-6.98). The higher the levels of carbohydrate antigen (CA) 724 (OR 1.01, 95%CI 1.00-1.02) and CA211 (OR 1.16, 95%CI 1.03-1.32) in patients with colorectal polyps were, the greater the risk of CCS. When colorectal neoplastic polyps were analyzed, we discovered that for each 1-year increase in age, the risk of neoplastic polyps increased by 3% (OR 1.03, 95%CI 1.02-1.04), p < 0.0001. Patients with a polyp diameter ≥ 1.0 cm had a 2.11-fold greater risk of neoplastic polyps compared to diameter < 1.0 cm patients (OR 3.11, 95%CI 2.48-3.92), p < 0.0001. In addition, multiple polyps and CA199 levels are risk factors for neoplastic polyps. CONCLUSION: More than 3/4 of colorectal polyp patients have neoplastic polyps. Patients are more inclined to develop CCS and neoplastic polyps if they have large polyps (> 1.0 cm) or multifocal polyps. The levels of the tumor markers CA724 and CA211 show some potential usefulness for predicting CCS and may be exploited for early identification of high-risk populations.

Bacteremia caused by Nocardia farcinica: a case report and literature review.

BACKGROUND: Nocardia farcinica is one of the most common Nocardia species causing human infections. It is an opportunistic pathogen that often infects people with compromised immune systems. It could invade human body through respiratory tract or skin wounds, cause local infection, and affect other organs via hematogenous dissemination. However, N. farcinica-caused bacteremia is uncommon. In this study, we report a case of bacteremia caused by N. farcinica in China. CASE PRESENTATION: An 80-year-old woman was admitted to Peking Union Medical College Hospital with recurrent fever, right abdominal pain for one and a half month, and right adrenal gland occupation. N. farcinica was identified as the causative pathogen using blood culture and plasma metagenomics next-generation sequencing (mNGS). The clinical considerations included bacteremia and adrenal gland abscess caused by Nocardia infection. As the patient was allergic to sulfanilamide, imipenem/cilastatin and linezolid were empirically administered. Unfortunately, the patient eventually died less than a month after the initiation of anti-infection treatment. CONCLUSION: N. farcinica bacteremia is rare and its clinical manifestations are not specific. Its diagnosis depends on etiological examination, which can be confirmed using techniques such as Sanger sequencing and mNGS. In this report, we have reviewed cases of Nocardia bloodstream infection reported in the past decade, hoping to improve clinicians' understanding of Nocardia bloodstream infection and help in its early diagnosis and timely treatment.

IL1A regulates the inflammation in gout through the Toll-like receptors pathway.

Objective: Gout is a dangerous metabolic condition related to monosodium urate (MSU). Our aim is to study the molecular mechanisms underlying gout and to identify potential clinical biomarkers by bioinformatics analysis and experimental validation. Methods: In this study, we retrieved the overlapping genes between GSE199950-Differential Expressed Genes (DEGs) dataset and key module in Weighted Gene Co-Expression Network Analysis (WGCNA) on GSE199950. These genes were then analyzed by protein-protein interaction (PPI) network, expression and Gene Set Enrichment Analysis to identify the hub gene related to gout. Then, the gene was investigated by peripheral blood mononuclear cells (PBMCs), immunoassay and cell experiments like western blotting to uncover its underlying mechanism in gout cells. Results: From the turquoise module and 83 DEGs, we identified 62 overlapping genes, only 11 genes had mutual interactions in PPI network and these genes were highly expressed in MSU-treated samples. Then, it was found that the IL1A (interleukin 1 alpha) was the only one gene related to Toll-like receptor signaling pathway that was associated with the occurrence of gout. Thus, IL1A was determined as the hub gene in this study. In immunoassay, IL1A was significantly positively correlated with B cells and negatively correlated with macrophages. Moreover, IL1A is highly expressed in gout patients,it has a good clinical diagnostic value. Finally, the results of in vitro experiments showed that after knocking down IL1A, the expressions of pro-inflammatory cytokines and Toll-like receptor signaling pathway-related proteins (TLR2, TLR4, MyD88) were all reduced. Conclusion: It is confirmed that IL1A is a promoting gene in gout with a good diagnostic value, and specifically it affects the inflammation in gout through Toll-like receptor pathway. Our research offers fresh perspectives on the pathophysiology of gout and valuable directions for future diagnosis and treatment.

Classification and Recognition of Building Appearance Based on Optimized Gradient-Boosted Decision Tree Algorithm.

There are high concentrations of urban spaces and increasingly complex land use types. Providing an efficient and scientific identification of building types has become a major challenge in urban architectural planning. This study used an optimized gradient-boosted decision tree algorithm to enhance a decision tree model for building classification. Through supervised classification learning, machine learning training was conducted using a business-type weighted database. We innovatively established a form database to store input items. During parameter optimization, parameters such as the number of nodes, maximum depth, and learning rate were gradually adjusted based on the performance of the verification set to achieve optimal performance on the verification set under the same conditions. Simultaneously, a k-fold cross-validation method was used to avoid overfitting. The model clusters trained in the machine learning training corresponded to various city sizes. By setting the parameters to determine the size of the area of land for a target city, the corresponding classification model could be invoked. The experimental results show that this algorithm has high accuracy in building recognition. Especially in R, S, and U-class buildings, the overall accuracy rate of recognition reaches over 94%.

Hypoxia-induced circWSB1 promotes breast cancer progression through destabilizing p53 by interacting with USP10.

BACKGROUND: Hypoxia has long been considered as a hallmark of solid tumors and is closely associated with tumor progression. Circular RNAs (circRNAs) have been identified as a critical modulator in various cancers. However, the connections between hypoxia and circRNAs are largely unknown. METHODS: Here, we investigated the expression profile of circRNAs in breast cancer (BC) MCF-7 cells under hypoxia and normoxia using microarray. We identified a novel hypoxia-responsive circRNA named circWSB1, whose expression pattern, potential diagnostic value and prognostic significance were assessed by qRT-PCR and in situ hybridization. Loss- and gain-of-function investigations in vivo and in vitro were performed to determine the biological functions of circWSB1. Mechanistically, chromatin immunoprecipitation and dual luciferase reporter assays were carried out to analyze the biogenesis of circWSB1. Furthermore, biotin-labeled RNA pull-down, mass spectrometry, RNA immunoprecipitation, fluorescent in situ hybridization, RNA electrophoretic mobility shift, deletion-mapping, co-immunoprecipitation assays and rescue experiments were applied to investigate the interaction between circWSB1 and Ubiquitin-specific peptidase 10 (USP10) as well as the relationship between USP10 and p53. RESULTS: We found that the expression of circWSB1 was significantly upregulated in BC tissues and correlated with poor clinical outcomes, which might serve as an independent prognostic factor for BC patients. Ectopic expression of circWSB1 promoted the proliferation of BC cell in vitro and in vivo. Mechanistically, circWSB1 was transcriptionally upregulated by HIF1α in response to hypoxia and could competitively bind to deubiquitinase USP10 to prevent the access of p53 to USP10 in BC cells, leading to degradation of p53 and tumor progression of BC. CONCLUSIONS: Taken together, our findings disclose a novel mechanism that hypoxia-inducible circWSB1 could interact with USP10 to attenuate USP10 mediated p53 stabilization and promote the progression of BC, providing an alternative prognostic biomarker and therapeutic target for BC.

Narrative Review of Noninvasive Brain Stimulation in Stroke Rehabilitation.

Stroke is a disease with a high incidence and disability rate, resulting in changes in neural network and corticoid-subcortical excitability and various functional disabilities. The aim of the present study was to discuss the current status of research and limitations and potential direction in the application of noninvasive brain stimulation (NIBS) on post-stroke patients. This literature review focused on clinical studies and reviews. Literature retrieval was conducted in PubMed, Cochrane, Scopus, and CNKI, using the following keywords: Repeated transcranial magnetic stimulation, Transcranial direct current stimulation, Transcranial alternating current stimulation, Transcranial alternating current stimulation, Transcranial focused ultrasound, Noninvasive vagus nerve stimulation, Stroke, and Rehabilitation. We selected 200 relevant publications from 1985 to 2022. An overview of recent research on the use of NIBS on post-stroke patients, including its mechanism, therapeutic parameters, effects, and safety, is presented. It was found that NIBS has positive therapeutic effects on dysfunctions of motor, sensory, cognitive, speech, swallowing, and depression after stroke, but standardized stimulus programs are still lacking. The literature suggests that rTMS and tDCS are more beneficial to post-stroke patients, while tFUS and tVNS are currently less studied for post-stroke rehabilitation, but are also potential interventions.

Exosomal miR-27 negatively regulates ROS production and promotes granulosa cells apoptosis by targeting SPRY2 in OHSS.

Ovarian hyperstimulation syndrome (OHSS) is one of the most dangerous iatrogenic complications in controlled ovarian hyperstimulation (COH). The exact molecular mechanism that induces OHSS remains unclear. In recent years, accumulating evidence found that exosomal miRNAs participate in many diseases of reproductive system. However, the specific role of miRNAs, particularly the follicular fluid-derived exosomal miRNAs in OHSS remains controversial. To identify differentially expressed follicular fluid exosomal miRNAs from OHSS and non-OHSS patients, the analysis based on miRNA-sequence was conducted. The levels of 291 miRNAs were significantly differed in exosomes from OHSS patients compared with normal control, and exosomal miR-27 was one of the most significantly down-regulated miRNAs in the OHSS group. By using MiR-27 mimic, we found it could increase ROS stress and apoptosis by down-regulating the expression of p-ERK/Nrf2 pathway by negatively regulating SPRY2. These data demonstrate that exosomal miRNAs are differentially expressed in follicular fluid between patients with and without OHSS, and follicular fluid exosomal miR-27 may involve in the pathological process of OHSS development.

[Peroxiredoxin 4 protects the testis from heat stress].

OBJECTIVE: To explore the protective effect of Peroxiredoxin 4 (PRDX4) on the testes undergoing heat stress in PRDX4 knockout mice. METHODS: Twenty-four C57BL/6 mice underwent CRISPR/Cas9-mediated total knockout of the PRDX4 gene and another 24 wild-type mice were used as controls. At 9 weeks of age, the rats were subjected to 15-minute testicular heat stress in 43℃ water once a day for 3 days, or in 25℃ water as the control. Before and at 1 day and 5 weeks after treatment, 4 from each group were sacrificed respectively and their testes harvested for observation of histological changes by HE staining, detection of the apoptosis of spermatogenic cells by TUNEL and determination of the expression of PRDX4 by Western blot and those of the oxidative stress factors hydroxynonenal (HNE) and 8-OHdG by immunohistochemistry. RESULTS: No statistically significant differences were observed in testicular histology, the apoptosis rate of spermatogenic cells, and the expressions of HNE and 8-OHdG between the PRDX4 knockout mice and wild-type controls (P > 0.05). After 1-day 43℃ heat stress, the PRDX4 knockout mice showed a significantly increased apoptosis rate of spermatogenic cells as compared with the baseline (ï¼»38.65 ± 2.57ï¼½% vs ï¼»0.46 ± 0.06ï¼½%, P < 0.01), and so did the wild-type controls (ï¼»13.21 ± 1.43ï¼½% vs ï¼»0.33 ± 0.01ï¼½%, P < 0.01), higher in the PRDX4 knockout than in the wild-type control group even at 5 weeks after heat stress (ï¼»3.09 ± 0.16ï¼½% vs ï¼»1.45 ± 0.11ï¼½%, P < 0.01). The PRDX4 knockout mice also exhibited a markedly upregulated expression of 8-OHdG (38.25 ± 1.19 vs 19.54 ± 1.13, P < 0.01), and so did the wild-type controls (24.30 ± 1.65 vs 18.22 ± 1.18, P < 0.01), higher in the PRDX4 knockout than in the wild-type control group even at 5 weeks after heat stress (25.40 ± 1.57 vs 23.25 ± 1.48, P < 0.01). The expression of HNE, however, showed no statistically significant difference before and at 1 day after 43℃ heat stress either in the PRDX4 knockout mice or in the wild-type controls (P > 0.05), though remarkably higher in the former than in the latter group at 5 weeks after treatment (28.57 ± 0.56 vs 19.00 ± 1.35, P < 0.01). The expression of 8-OHdG was also higher in the PRDX4 knockout than in the wild-type control group at 5 weeks, but with no statistically significant difference (P > 0.05). CONCLUSIONS: PRDX4 can effectively protect the testis from heat stress and promote the restoration of its spermatogenic function.

Application of virtual diagnosis and treatment combined with medical record teaching method in standardized training of general practitioner.

The aim of this study was to explore the effect of virtual diagnosis and treatment combined with the medical record teaching method in standardized training of general practitioners. Eighty students who had standardized general practice training, from March 2020 to March 2022, in the grassroots practice base of general practitioner training in the affiliated Hospital of our Medical College were retrospectively analyzed and divided into 2 groups according to the teaching method that they received. The differences in assessment scores, critical thinking, clinical thinking ability, learning autonomy ability, and classroom teaching effectiveness were compared, and the students' satisfaction with teaching was investigated. The scores of theoretical knowledge, skill operation, medical history collection, and case analysis in the study group were notably higher (P < .05). In the study group, scores in truth-seeking, openness to knowledge, analytical ability, systematic ability, self-confidence, curiosity, and cognitive maturity were significantly higher (P < .05). A notable improvement was observed in the study group's scores on systematic thinking ability and evidence-based thinking ability, as well as the scores on critical thinking ability after teaching (P < .05). The scores of learning interest, self-management, plan implementation, and cooperation ability improved notably after teaching (P < .05). Learning target, learning processes, learning effects, classroom environment construction, teaching strategy, and technology application in the study group were significantly higher than those in the control group (P < .05). The satisfaction rate in the study group was significantly higher than that in the control group (P < .05). Virtual diagnosis and treatment combined with case-based learning teaching has a very good effect in the standardized training of general practitioners. Students are generally satisfied with their learning experience, which can improve their critical thinking ability and clinical thinking skills. This teaching method is worth further popularizing.

The activation of HAMP promotes colorectal cancer cell proliferation through zinc-mediated upregulation of SMAD4 expression.

Background: Colorectal cancer (CRC) poses a significant challenge in digestive system diseases, and emerging evidence underscores the critical role of zinc metabolism in its progression. This study aimed to investigate the clinical implications of genes at the intersection of zinc metabolism and CRC. Methods: We downloaded CRC prognosis-related genes and zinc metabolism-related genes from public databases. Then, the overlapping genes were screened out, and bioinformatics analysis was performed to obtain the hub gene associated with CRC prognosis. Subsequently, in vitro assays were carried out to investigate the expression of this hub gene and its exact mechanism between zinc metabolism and CRC. Results: HAMP was identified as the hub CRC prognostic gene from overlapping zinc metabolism-related and CRC prognostic genes. In vitro analysis showed HAMP was over-expressed in CRC, and its knockdown inhibited RKO and HCT-116 cell invasion and migration significantly. ZnSO4 induced HAMP up-regulation to promote cell proliferation, while TPEN decreased HAMP expression to inhibit cell proliferation. Importantly, we further found that ZnSO4 enhanced SMAD4 expression to augment HAMP promoter activity and promote cell proliferation in CRC. Conclusions: HAMP stands out as an independent prognostic factor in CRC, representing a potential therapeutic target. Its intricate regulation by zinc, particularly through the modulation of SMAD4, unveils a novel avenue for understanding CRC biology. This study provides valuable insights into the interplay between zinc metabolism, HAMP, and CRC, offering promising clinical indicators for CRC patients. The findings present a compelling case for further exploration and development of targeted therapeutic strategies in CRC management.

Multi-DECT image-based intratumoral and peritumoral radiomics for preoperative prediction of muscle invasion in bladder cancer.

OBJECTIVES: To assess the predictive value of intratumoral and peritumoral radiomics based on Dual-energy CT urography (DECTU) multi-images for preoperatively predicting the muscle invasion status of bladder cancer (BCa). MATERIAL AND METHODS: This retrospective analysis involved 202 BCa patients who underwent DECTU. DECTU-derived quantitative parameters were identified as risk factors through stepwise regression analysis to construct a DECT model. The radiomic features from the intratumoral and 3 mm outward peritumoral regions were extracted from the 120 kVp-like, 40 keV, 100 keV, and iodine-based material-decomposition (IMD) images in the venous-phase and were screened using Mann-Whitney U test, Spearman correlation analysis, and LASSO. Radiomics models were developed using the Multilayer Perceptron for the intratumoral, peritumoral and intra- and peritumoral (IntraPeri) regions. Subsequently, a nomogram was created by integrating the multi-image IntraPeri radiomics and DECT model. Model performance was evaluated using area-under-the-curve (AUC), accuracy, sensitivity, and specificity. RESULTS: Normalized iodine concentration (NIC) was identified as an independent predictor for the DECT model. The IntraPeri model demonstrated superior performance compared to the intratumoral and peritumoral models both in 40 keV (0.830 vs. 0.766 vs. 0.763) and IMD images (0.881 vs. 0.840 vs. 0.821) in the test cohort. In the test cohort, the nomogram exhibited the best predictability (AUC=0.886, accuracy=0.836, sensitivity=0.737, and specificity=0.881), outperformed the DECT model (AUC=0.763, accuracy=0.754, sensitivity=0.632, and specificity=0.810) in predicting muscle invasion status of BCa with a statistically significant difference (p < 0.05). CONCLUSION: The nomogram, incorporating IntraPeri radiomics and NIC, serves as a valuable and non-invasive tool for preoperatively assessing the muscle invasion status of BCa.

Screening of salt tolerance of maize (Zea mays L.) lines using membership function value and GGE biplot analysis.

Soil salinization is a widely recognized global environmental concern that has a significant impact on the sustainable development of agriculture at a global scale. Maize, a major crop that contributes to the global agricultural economy, is particularly vulnerable to the adverse effects of salt stress, which can hinder its growth and development from germination to the seedling stage. This study aimed to screen highly salt-tolerant maize varieties by using four NaCl concentrations of 0, 60, 120, and 180 mMol/L. Various agronomic traits and physiological and biochemical indices associated with salt tolerance were measured, and salt tolerance was evaluated using principal component analysis, membership function method, and GGE biplot analysis. A total of 41 local maize varieties were assessed based on their D values. The results show that stem thickness, germ length, radicle length, leaf area, germination rate, germination index, salt tolerance index, and seed vigor all decreased as salt concentration increased, while electrical conductivity and salt injury index increased with the concentration of saline solution. Under the stress of 120 mMol/L and 180 mMol/L NaCl, changes in antioxidant enzymes occurred, reflecting the physiological response mechanisms of maize under salt stress. Principal component analysis identified six major components including germination vigor, peroxidase (POD), plant height, embryo length, SPAD chlorophyll and proline (PRO) factors. After calculating the comprehensive index (D value) of each variety's performance in different environments using principal component analysis and the membership function method, a GGE biplot analysis was conducted to identify maize varieties with good salt tolerance stability: Qun Ce 888, You Qi 909, Ping An 1523, Xin Nong 008, Xinyu 66, and Hong Xin 990, as well as varieties with poor salt tolerance: Feng Tian 14, Xi Meng 668, Ji Xing 218, Gan Xin 2818, Hu Xin 712, and Heng Yu 369. Furthermore, it was determined that a 120 mMol/L NaCl concentration was suitable for screening maize varieties during germination and seedling stages. This study further confirmed the reliability of GGE biplot analysis in germplasm selection, expanded the genetic resources of salt-tolerant maize, and provided theoretical references and germplasm utilization for the introduction of maize in saline-alkali areas. These research findings contribute to a better understanding of maize salt tolerance and promote its cultivation in challenging environments.

Combining Deep Learning and Radiomics for Automated, Objective, Comprehensive Bone Mineral Density Assessment From Low-Dose Chest Computed Tomography.

RATIONALE AND OBJECTIVES: To develop an intelligent diagnostic model for osteoporosis screening based on low-dose chest computed tomography (LDCT). The model incorporates automatic deep-learning thoracic vertebrae of cancellous bone (TVCB) segmentation model and radiomics analysis. MATERIALS AND METHODS: A total of 442 participants who underwent both LDCT and quantitative computed tomography (QCT) examinations were enrolled and were randomly allocated to the training, internal testing, and external testing cohorts. The TVCB automatic segmentation model was trained using VB-Net. The accuracy of the segmentation was evaluated using the Dice coefficient. Predictive models for assessing bone mineral density (BMD) were constructed utilizing radiomics analysis based on automatic segmentation (ASeg model) and manual segmentation (MSeg model), respectively. The BMD predictive model based on ASeg and MSeg included the identification of normal and abnormal BMD (first-level model), and osteopenia and osteoporosis (second-level model). The diagnostic performance of the radiomics models were evaluated using the area under the curve (AUC), sensitivity and specificity. RESULTS: The Dice coefficients of the TVCB segmentation model in the internal and external testing cohorts were found to be 0.988 ± 0.014 and 0.939 ± 0.034, respectively. In the first-level model, the AUC of the ASeg model exhibited comparable performance to that of the MSeg model for both the internal (0.985 vs. 0.946, P = 0.080) and external (0.965 vs. 0.955, P = 0.724) testing cohorts. Similarly, in the second-level model, the AUC of the ASeg model was found to be comparable to that of the MSeg model for both the internal (0.933 vs. 0.920, P = 0.794) and external (0.907 vs. 0.892, P = 0.805) testing cohorts. CONCLUSION: A fully automated pipeline for TVCB segmentation and BMD assessment with radiomics analysis can be used for opportunistic BMD screening in chest LDCT.

Impact of virtual monochromatic images of different low-energy levels in dual-energy CT on radiomics models for predicting muscle invasion in bladder cancer.

OBJECTIVE: The purpose of this study was to investigate the impact of different low-energy virtual monochromatic images (VMIs) in dual-energy CT on the performance of radiomics models for predicting muscle invasive status in bladder cancer (BCa). MATERIALS AND METHODS: A total of 127 patients with pathologically proven muscle-invasive BCa (n = 49) and non-muscle-invasive BCa (n = 78) were randomly allocated into the training and test cohorts at a ratio of 7:3. Feature extraction was performed on the venous phase images reconstructed at 40, 50, 60 and 70-keV (single-energy analysis) or in combination (multi-energy analysis). Recursive feature elimination (RFE) and the least absolute shrinkage and selection operator (LASSO) were employed to select the most relevant features associated with BCa. Models were built using a support vector machine (SVM) classifier. Diagnostic performance was assessed through receiver operating characteristic curves, evaluating sensitivity, specificity, accuracy, precision, and the area-under-the curve (AUC) values. RESULTS: In the test cohort, the multi-energy model achieved the best diagnostic performance with AUC, sensitivity, specificity, accuracy, and precision of 0.917, 0.800, 0.833, 0.821, and 0.750, respectively. Conversely, the single-energy model exhibited lower AUC and sensitivity in predicting the muscle invasion status. CONCLUSIONS: By combining information from VMIs of various energies, the multi-energy model displays superior performance in preoperatively predicting the muscle invasion status of bladder cancer.

Identifying potential drug targets for varicose veins through integration of GWAS and eQTL summary data.

Background: Varicose veins (VV) are a common chronic venous disease that is influenced by multiple factors. It affects the quality of life of patients and imposes a huge economic burden on the healthcare system. This study aimed to use integrated analysis methods, including Mendelian randomization analysis, to identify potential pathogenic genes and drug targets for VV treatment. Methods: This study conducted Summary-data-based Mendelian Randomization (SMR) analysis and colocalization analysis on data collected from genome-wide association studies and cis-expression quantitative trait loci databases. Only genes with PP.H4 > 0.7 in colocalization were chosen from the significant SMR results. After the above analysis, we screened 12 genes and performed Mendelian Randomization (MR) analysis on them. After sensitivity analysis, we identified four genes with potential causal relationships with VV. Finally, we used transcriptome-wide association studies and The Drug-Gene Interaction Database data to identify and screen the remaining genes and identified four drug targets for the treatment of VV. Results: We identified four genes significantly associated with VV, namely, KRTAP5-AS1 [Odds ratio (OR) = 1.08, 95% Confidence interval (CI): 1.05-1.11, p = 1.42e-10] and PLEKHA5 (OR = 1.13, 95% CI: 1.06-1.20, p = 6.90e-5), CBWD1 (OR = 1.05, 95% CI: 1.01-1.11, p = 1.42e-2) and CRIM1 (OR = 0.87, 95% CI: 0.81-0.95, p = 3.67e-3). Increased expression of three genes, namely, KRTAP5-AS1, PLEKHA5, and CBWD1, was associated with increased risk of the disease, and increased expression of CRIM1 was associated with decreased risk of the disease. These four genes could be targeted for VV therapy. Conclusion: We identified four potential causal proteins for varicose veins with MR. A comprehensive analysis indicated that KRTAP5-AS1, PLEKHA5, CBWD1, and CRIM1 might be potential drug targets for varicose veins.

Estimation of renal function using iodine maps in dual-energy spectral computed tomography urography: a feasibility and accuracy study.

PURPOSE: To explore the feasibility of measuring glomerular filtration rate (GFR) using iodine maps in dual-energy spectral computed tomography urography (DEsCTU) and correlate them with the estimated GFR (eGFR) based on the equation of creatinine-cystatin C. MATERIALS AND METHODS: One hundred and twenty-eight patients referred for DEsCTU were retrospectively enrolled. The DEsCTU protocol included non-contrast, nephrographic, and excretory phase imaging. The CT-derived GFR was calculated using the above 3-phase iodine maps (CT-GFRiodine) and 120 kVp-like images (CT-GFR120kvp) separately. CT-GFRiodine and CT-GFR120kvp were compared with eGFR using paired t-test, correlation analysis, and Bland-Altman plots. The receiver operating characteristic curves were used to test the renal function diagnostic performance with CT-GFR120kvp and CT-GFRiodine. RESULTS: The difference between eGFR (89.91 ± 18.45 ml·min-1·1.73 m-2) as reference standard and CT-GFRiodine (90.06 ± 20.89 ml·min-1·1.73 m-2) was not statistically significant, showing excellent correlation (r = 0.88, P < 0.001) and agreement (± 19.75 ml·min-1·1.73 m-2, P = 0.866). The correlation between eGFR and CT-GFR120kvp (66.13 ± 19.18 ml·min-1·1.73 m-2) was poor (r = 0.36, P < 0.001), and the agreement was poor (± 40.65 ml·min-1·1.73 m-2, P < 0.001). There were 62 patients with normal renal function and 66 patients with decreased renal function based on eGFR. The CT-GFRiodine had the largest area under the curve (AUC) for distinguishing between normal and decreased renal function (AUC = 0.951). CONCLUSION: The GFR can be calculated accurately using iodine maps in DEsCTU. DEsCTU could be a non-invasive and reliable one-stop-shop imaging technique for evaluating both the urinary tract morphology and renal function.

Impact of multi-parameter images obtained from dual-energy CT on radiomics to predict pathological grading of bladder urothelial carcinoma.

OBJECTIVE: To investigate the effect of radiomics models obtained from dual-energy CT (DECT) material decomposition images and virtual monoenergetic images (VMIs) in predicting the pathological grading of bladder urothelial carcinoma (BUC). MATERIALS AND METHODS: A retrospective analysis of preoperative DECT examination was conducted on 112 patients diagnosed with BUC. This cohort included 76 cases of high-grade urothelial carcinoma and 36 cases of low-grade urothelial carcinoma. DECT can provide material decomposition images of venous phase Iodine maps and Water maps based on the differences in attenuation of substances, as well as VMIs at 40 to 140 keV (interval 10 keV). A total of 13 image sets were obtained, and radiomics features were extracted and analyzed from each set to achieve preoperative prediction of BUC. The best features related to BUC were identified by recursive feature elimination (RFE), the Minimum Redundancy Maximum Relevance (mRMR), and the Least Absolute Shrinkage and Selection Operator (LASSO) in order. A five-fold cross-validation method was used to divide the samples into training and testing sets, and models for pathological prediction of BUC grading were constructed by a random forest (RF) classifier. Receiver operating curves (ROC) were plotted to evaluate the performance of 13 models obtained from each image set. RESULTS: Despite the notable differences in the best radiomics features chosen from each image set, all the features selected from 40 to 100 keV VMIs included the Dependence Variance of the GLDM feature set. There were no statistically significant differences in the area under the curve (AUC) between the training set and the testing set for all 13 models. In the testing set, the AUCs of the models established through 40 keV to 140 keV (interval of 10 keV) image sets were 0.895, 0.874, 0.855, 0.889, 0.841, 0.868, 0.852, 0.847, 0.889, 0.887 and 0.863 respectively. The AUCs for the models established using the Iodine maps and Water maps image sets were 0.873 and 0.852, respectively. CONCLUSION: Despite the differences in the selected radiomic features from DECT multi-parameter images, the performance of radiomics models in predicting the pathological grading of BUC was not affected by the variations in the types of images used for model training.

Comprehensive Evaluation and Selection of 192 Maize Accessions from Different Sources.

In the period 2022-2023, an analysis of fourteen phenotypic traits was conducted across 192 maize accessions in the Aral region of Xinjiang. The Shannon-Wiener diversity index was employed to quantify the phenotypic diversity among the accessions. Subsequently, a comprehensive evaluation of the index was performed utilizing correlation analysis, principal component analysis (PCA) and cluster analysis. The results highlighted significant findings: (1) A pronounced diversity was evident across the 192 maize accessions, accompanied by complex interrelationships among the traits. (2) The 14 phenotypic traits were transformed into 3 independent indicators through principal component analysis: spike factor, leaf width factor, and number of spikes per plant. (3) The 192 materials were divided into three groups using cluster analysis. The phenotypes in Group III exhibited the best performance, followed by those in Group I, and finally Group II. The selection of the three groups can vary depending on the breeding objectives. This study analysed the diversity of phenotypic traits in maize germplasm resources. Maize germplasm was categorised based on similar phenotypes. These findings provide theoretical insights for the study of maize accessions under analogous climatic conditions in Alar City, which lay the groundwork for the efficient utilization of existing germplasm as well as the development and selection of new varieties.

Multicenter comparative genomic study of Klebsiella oxytoca complex reveals a highly antibiotic-resistant subspecies of Klebsiellamichiganensis.

BACKGROUND: The Klebsiella oxytoca complex is an opportunistic pathogen that has been recently identified as an actual complex. However, the characteristics of each species remain largely unknown. We aimed to study the clinical prevalence, antimicrobial profiles, genetic differences, and interaction with the host of each species of this complex. METHODS: One hundred and three clinical isolates of the K. oxytoca complex were collected from 33 hospitals belonging to 19 areas in China from 2020 to 2021. Species were identified using whole genome sequencing based on average nucleotide identity. Clinical infection characteristics of the species were analyzed. Comparative genomics and pan-genome analyses were performed on these isolates and an augmented dataset, including 622 assemblies from the National Center for Biotechnology Information. In vitro assays evaluating the adhesion ability of human respiratory epithelial cells and survivability against macrophages were performed on randomly selected isolates. RESULTS: Klebsiella michiganensis (46.6%, 48/103) and K. oxytoca (35.92%, 37/103) were the major species of the complex causing human infections. K. michiganensis had a higher genomic diversity and larger pan-genome size than did K. oxytoca. K. michiganensis isolates with blaoxy-5 had a higher resistance rate to various antibiotics, antimicrobial gene carriage rate, adhesion ability to human respiratory epithelial cells, and survival rate against macrophages than isolates of other species. CONCLUSION: Our study revealed the genetic diversity of K. michiganensis and firstly identified the highly antimicrobial-resistant profile of K. michiganensis carrying blaoxy-5.

The protective effects of Zhi-Gan-Cao-Tang against diabetic myocardial infarction injury and identification of its effective constituents.

ETHNOPHARMACOLOGICAL RELEVANCE: Cardiovascular complications are highly prevalent in patients with diabetes. Zhi-Gan-Cao-Tang (ZGCT), a famous traditional Chinese medicine (TCM) prescription, can be used for the treatment of diabetes with cardiovascular disease complications. ZGCT is composed of nine Chinese herbs: the radix and rhizoma of Glycyrrhiza uralensis Fisch. (Gancao in Chinese, 12 g), the radix of Rehmannia glutinosa Libosch. (Dihuang in Chinese, 50 g), the radix and rhizoma of Panax ginseng C. A. Mey. (Renshen in Chinese, 6 g), the radix of Ophiopogon japonicus (L. f.) Ker-Gawl. (Maidong in Chinese, 10 g), the fructus of Ziziphus jujuba Mill. (Dazao in Chinese, 18 g), the fructus of Cannabis sativa L. (Maren in Chinese, 10 g), Donkey-hide gelatine (Ejiao in Chinese, 6 g), the ramulus of Cinnamomum cassia Presl (Guizhi in Chinese, 9 g), and the fresh rhizoma of Zingiber officinale Rosc. (Shengjiang in Chinese, 9 g). Many of these Chinese herbs are also used in other systems of medicine (Japan, India, European, etc.). However, the effects and effective constituents of ZGCT against diabetic cardiovascular disease remain unclear. AIM OF THE STUDY: This study aimed to investigate the protective effect of ZGCT against diabetic myocardial infarction (DMI) injury in vivo and in vitro and to identify the effective constituents of ZGCT. MATERIALS AND METHODS: The in vivo effect on DMI injury was evaluated in a DMI mouse model. The in vitro effect and effective constituent screening experiments were conducted in an H9c2 cardiomyocyte injury model induced by high glucose and hypoxia. RESULTS: It was found that ZGCT significantly reduced myocardial infarction size and serum lactate dehydrogenase (LDH) levels in DMI mice. Myocardial histopathological experiments showed that ZGCT alleviated the disordered arrangement and fracture of muscle fibers and cell disappearance and reduced inflammatory cell infiltration. Cellular experiments showed that ZGCT inhibited cardiomyocyte apoptosis by decreasing the expression of the proapoptotic factor Bax. In addition, it inhibited inflammatory reactions by suppressing the activation of the IκBα/NF-κB pathway and the expression of iNOS. Eight constituents from six Chinese herbs in the recipe of ZGCT were found to enhance the viability of injured cardiomyocytes, and six effective constituents played protective roles through anti-apoptotic and/or anti-inflammatory activities. In addition, one of the effective constituents, glycyrrhizic acid, was verified in vivo to have cardioprotective effect on DMI mice. CONCLUSIONS: The TCM prescription ZGCT protects against DMI by inhibiting cardiomyocyte apoptosis and reducing inflammatory reactions. Eight effective constituents of ZGCT were identified. This study provides a scientific basis for the clinical application of ZGCT and is valuable for quality marker research on this prescription.