Association Between Prediabetes and Risk, Mortality of Hepatocellular Carcinoma: A Meta-Analysis.

BACKGROUND: As the high-risk stage of diabetes, the role of prediabetes in the development of hepatocellular carcinoma (HCC) remains unclear. To address this knowledge gap, we undertook a meta-analysis to investigate the potential association between the prediabetic stage and HCC. METHODS: In this study, two independent investigators conducted a comprehensive search for relevant articles published up until May 2023 in several databases, including PubMed, Web of Science, Medline, EMBASE, and Google Scholar. The results were then summarized using STATA 12.0 software. RESULTS: Our analysis included a total of 6 cohort studies involving 1,490,752 participants, as well as 1 case-control study with 220 participants. The research aimed to examine the association between prediabetes and the risk of HCC. Our meta-analysis revealed that prediabetes was significantly associated with an elevated risk of HCC (odds ratio (OR)/relative risk (RR) = 1.25, 95% confidence interval (CI) 1.06 to 1.48, I2 = 57.2%, p = 0.012), using a random-effects model. Moreover, four cohort studies, encompassing 1,362,847 participants, explored the relationship between prediabetes and HCC mortality. The meta-analysis showed that prediabetes was associated with a higher mortality rate of HCC, also utilizing a random-effects model (hazard ratio (HR) = 1.36, 95% CI 1.02 to 1.81, I2 = 55.8%, p = 0.060). CONCLUSIONS: Overall, our findings highlight a significant association between prediabetes and an increased risk of HCC and suggest that prediabetes may also contribute to higher mortality rates among HCC patients.

Flavomycin restores colistin susceptibility in multidrug-resistant Gram-negative bacteria.

Polymyxin is used as a last resort antibiotics for infections caused by multi-drug resistant (MDR) Gram-negative bacteria and is often combined with other antibiotics to improve clinical effectiveness. However, the synergism of colistin and other antibiotics remains obscure. Here, we revealed a notable synergy between colistin and flavomycin, which was traditionally used as an animal growth promoter and has limited activity against Gram-negative bacteria, using checkerboard assay and time-kill curve analyses. The importance of membrane penetration induced by colistin was assessed by examining the intracellular accumulation of flavomycin and its antimicrobial impact on Escherichia coli (E. coli) strains with truncated lipopolysaccharides. Besides, a mutation in the flavomycin binding site was created to confirm its role in the observed synergy. This synergy is manifested as an augmented penetration of the E. coli outer membrane by colistin, leading to increased intracellular accumulation of flavomycin and enhanced cell killing thereafter. The observed synergy was dependent on the antimicrobial activity of flavomycin, as mutation of its binding site abolished the synergy. In vivo studies confirmed the efficacy of colistin combined with flavomycin against MDR E. coli infections. This study is the first to demonstrate the synergistic effect between colistin and flavomycin, shedding light on their respective roles in this synergism. Therefore, we propose flavomycin as an adjuvant to enhance the potency of colistin against MDR Gram-negative bacteria. IMPORTANCE: Colistin is a critical antibiotic in combating multi-drug resistant Gram-negative bacteria, but the emergence of mobilized colistin resistance (mcr) undermines its effectiveness. Previous studies have found that colistin can synergy with various drugs; however, its exact mechanisms with hydrophobic drugs are still unrevealed. Generally, the membrane destruction of colistin is thought to be the essential trigger for its interactions with its partner drugs. Here, we use clustered regularly interspaced palindromic repeats (CRISPR)-CRISPR-associated protein 9 (Cas9) for specifically mutating the binding site of one hydrophobic drug (flavomycin) and show that antimicrobial activity of flavomycin is critical for the synergy. Our results first give the evidence that the synergy is set off by colistin's membrane destruction and operated the final antimicrobial function by its partner drugs.

The genetics and clinical outcomes in 151 cases of fetal growth restriction: A Chinese single-center study.

OBJECTIVE: To determine the detection rate of chromosomal abnormalities and pregnancy outcomes in fetuses with intrauterine growth restriction. Study design A total of 151 fetal samples with intrauterine growth restriction were divided into the isolated fetal growth restriction (FGR) group, FGR group with structural malformation, and FGR group with non-structural malformation, according to ultrasound abnormalities. The enrolled patients were divided into an early onset FGR group (<32 weeks) and a late-onset FGR group (≥32 weeks). Chromosomal karyotype and microarray analyses were performed and pregnancy outcomes were monitored. Results The karyotypes of 122 patients were analyzed. Four patients exhibited abnormal chromosome numbers or structures. Variations in copy number were detected in 151 cases; 19 cases were found to have chromosomal abnormalities, with a positivity rate of 12.6 %. There was one trisomy in 18 cases, one trisomy in 21 cases, eight pathogenic copy number variations (CNVs), and nine CNVs of unknown clinical significance. The detection rate of FGR combined with structural malformation was significantly higher than that of isolated FGR group. The detection rate of FGR with structural malformations was significantly higher than that with non-structural malformations. The positive detection rate in the FGR group was similar to that in the FGR group with non-structural malformations, with no statistical significance. Chromosomal abnormalities were detected in 17 patients with early onset FGR, with a positivity rate of 13.8 %. Two cases of chromosomal abnormalities were detected in the late-onset FGR group, with a positive rate of 7.1 %, with no statistical significance. A total of 151 fetuses with FGR were followed up for pregnancy outcomes, resulting in 36 cases of pregnancy termination and 13 cases of loss to follow-up. Among the 102 delivered fetuses, six exhibited delayed growth and development, one presented with hypospadias, and another failed the hearing screening. The remaining 94 fetuses demonstrated normal growth and development. Conclusions This study confirms the value of CNV detection in fetuses and dynamic ultrasound monitoring for fetuses with intrauterine growth restriction.

A Case Report of Pregnancy Complicated with Primary Hemophagocytic Lymphohistiocytosis.

Background: Hemophagocytic lymphohistiocytosis (HLH) is a severe hyperinflammatory syndrome characterized by excessive activation of NK cells and cytotoxic T lymphocytes, subsequently leading to macrophage activation and increased cytokine production. Misdiagnosis due to nonspecific clinical presentations and inadequate understanding of the disease can significantly jeopardize the safety of both the mother and the infant. We report a case of pregnancy combined with HLH and conduct a literature review to provide insights into the diagnosis and treatment of pregnancy-related HLH. Case Presentation: We discussed a case of a pregnant woman with persistent postpartum fever, serum ferritin, and elevated liver function, who failed to respond to repeated anti-infective therapy and was diagnosed with HLH after multidisciplinary diagnostic treatment. We gave dexamethasone treatment, and the patient's temperature and blood cells quickly returned to normal. Finally, exome sequencing revealed heterozygous variation in UNC13D gene, so we considered this case as pregnancy combined with primary HLH (pHLH). Conclusion: We report the case of HLH diagnosed during pregnancy and show that early diagnosis and timely intervention can prevent rapid disease progression, reduce maternal mortality rates, and improve survival rates. Additionally, molecular genetic testing can confirm pathogenic gene mutations, providing essential genetic counseling for patients with pHLH who plan to conceive a healthy child.

Revealing Lithium Nitrate-Mediated Solid-Electrolyte Interphase of Lithium Metal Anode via Cryogenic Transmission Electron Microscopy.

The cycle stability of lithium metal anode (LMA) largely depends on solid-electrolyte interphase (SEI). Electrolyte engineering is a common strategy to adjust SEI properties, yet understanding its impact is challenging due to limited knowledge on ultrafine SEI structures. Herein, using cryogenic transmission electron microscopy, we reveal the atomic-level SEI structure of LMA in ether-based electrolytes, focusing on the role of LiNO3 additives in SEI modulation at different temperature (25 and 50 °C). Poor cycle stability of LMA in the baseline electrolyte without LiNO3 additives stems from the Li2CO3-rich mosaic-type SEI. Increased LiNO3 content and elevated operating temperature enhance cyclic performance by forming bilayer or multilayer SEI structures via preferential LiNO3 decomposition, but may thicken the SEI, leading to reduced initial Coulombic efficiency and increased overpotential. The optimal SEI features a multilayer structure with Li2O-rich inner layer and closely packed grains in the outer layer, minimizing electrolyte decomposition or corrosion.

Obesity-associated metabolic inflammation promotes triple-negative breast cancer progression through the interleukin-6/STAT3/pentraxin 3/matrix metalloproteinase 7 axis.

BACKGROUND: This study aimed to investigate the regulatory mechanism of the adipose factor interleukin (IL)-6 in promoting pentraxin 3 (PTX3) expression in triple-negative breast cancer (TNBC). METHODS: We established an in vitro coculture model of mature adipocytes and TNBC cells using a Transwell system. Cell scratch, Transwell migration, and matrix invasion assays were used to evaluate the migration and invasion abilities of TNBC cells cocultured with adipocytes. Next, we used lentivirus-mediated functional depletion experiments to study PTX3's role in the adipocyte-dependent migration of TNBC cells. RESULTS: After coculturing TNBC cells with adipocytes, PTX3 expression was upregulated, which accompanied enhanced cell migration and invasion. Using GEO data and RNA-seq analysis, we identified PTX3 as a key target gene influenced by the adipose TNBC microenvironment. IL-6 upregulation in the conditioned medium of mature adipocytes and in the serum of high-fat diet mice was associated with this effect, and the recombinant protein IL-6 significantly promoted the migration and invasion of TNBC cells along with the phosphorylation of intracellular STAT3 and the upregulation of PTX3. PTX3 knockdown inhibited TNBC cell migration and eliminated the enhanced migration caused by coculturing with adipocytes. Furthermore, in vivo experiments confirmed that the PTX3 knockdown reduced obesity-induced lung metastasis. Subsequent experiments with cytokines and drug inhibitors confirmed that adipocyte-derived IL-6 promoted PTX3 expression by activating the STAT3 signaling pathway. Additionally, bioinformatic analysis indicated that PTX3 promotes TNBC metastasis by regulating the matrix metalloproteinase (MMP) family. CONCLUSION: Our study elucidated Obesity-related metabolic inflammation promotes the progression via the IL-6/STAT3/PTX3/MMP7 axis.

Early-onset and later-onset cancer: trends, risk factors, and prevention in Northern China.

The characteristics of early-onset (onset age <50 years) and later-onset (onset age ≽ 50 years) cancers differ significantly. Identifying novel risk factors for both types of cancer is crucial for increasing awareness of cancer prevention and for reducing its burden. This study aimed to analyze the trends in incidence and risk factors for early-onset and late-onset cancers. We conducted a prospective study by drawing data from the Kailuan Study. This study included 6,741 participants with cancer (624 with early-onset cancer and 6,117 with later-onset cancer) and 6,780 matched controls among the 186,249 participants who underwent Kailuan health examinations from 2006 to 2019. The primary outcomes were cancer incidence rates, and associated risk factors for early- and later-onset cancer. Weighted Cox regression was used to calculate hazard ratios and 95% confidence intervals of each exposure factor for early- and later-onset cancer by cancer type. Population-attributable risk proportions were used to estimate the number of cases that could be prevented by eliminating a risk factor from the population. Except for liver cancer, incidence rates for nearly all types of cancer increased during the study period. Smoking, alcohol consumption, lipid metabolism disorders, hypertension, diabetes mellitus, fatty liver, and inflammation were associated with a significantly increased risk of cancer at multiple sites, but risk factors for cancer incidence differed by site. Smoking, alcohol consumption, inflammation, and hypertension were the major contributors to preventable cancer. The incidence of several different types of cancer, including early-onset cancer, is increasing in northeastern China. Differences in risk factors between early-onset and later-onset malignancies may contribute to the divergence in the observed changes in incidence trends between these two specific types of cancer.

Clinical treatment patterns, molecular characteristics and survival outcomes of ROS1-rearranged non-small cell lung cancer: A large multicenter retrospective study.

BACKGROUND: Non-small cell lung cancer (NSCLC) harboring ROS1 rearrangements is a molecular subset that exhibits favorable responses to tyrosine kinase inhibitor (TKI) treatment than chemotherapy. This study investigated real-world treatment patterns and survival outcomes among patients with ROS1-rearranged advanced NSCLC. METHODS: We conducted a retrospective analysis of patients with ROS1-rearranged advanced NSCLC treated in four different hospitals in China from August 2018 to March 2022. The study analyzed gene fusion distribution, resistance patterns, and survival outcomes. RESULTS: ROS1 rearrangement occurs in 1.8 % (550/31,225) of our study cohort. CD74 was the most common ROS1 fusion partner, accounting for 45.8 %. Crizotinib was used in 73.9 % of patients in the first-line treatment, and an increased use of chemotherapy, ceritinib, and lorlatinib was seen in the second-line setting. Lung (43.2 %) and brain (27.6 %) were the most common sites of progression in first-line setting, while brain progression (39.2 %) was the most common site of progression in second-line. Median overall survival was 46 months (95 % confidence intervals: 39.6-52.4). First-line crizotinib use yielded significantly superior survival outcomes over chemotherapy in terms of progression-free (18.5 vs. 6.0; p < 0.001) and overall survival (49.8 vs. 37; p = 0.024). The choice of treatment in the latter line also had survival implications, wherein survival outcomes were better when first-line crizotinib was followed by sequential TKI therapy than first-line chemotherapy followed by TKI therapy. CONCLUSIONS: Our study provided insights into the real-world treatment, drug resistance patterns, and survival outcomes among patients with ROS1-rearranged NSCLC. This information serves as a valuable reference for guiding the treatment of this molecular subset of NSCLC.

Plasma triglyceride is associated with the recurrence of atrial fibrillation after radiofrequency catheter ablation: A retrospective study.

BACKGROUND: The purpose of this study was to explore the association between triglycerides (TGs) and the risk of atrial fibrillation (AF) recurrence. METHODS AND RESULTS: Included were adult patients with AF who underwent radiofrequency catheter ablation in the Affiliated Changzhou Second People's Hospital of Nanjing Medical University. The enrolled patients were divided into the AF recurrence group and the sinus rhythm (SR) maintenance group. The univariate Cox regression analysis and Kaplan-Meier survival curve were performed estimate the association between TG and the risk of AF recurrence. Of the 402 patients, 79 (19.7%) experienced recurrence of AF after ablation. The TG level was significantly higher in the AF recurrence group than in the SR-maintaining group. Patients were grouped by quartile of TG levels, with Quartile 1 and Quartile 2 defined as the low concentration group, Quartile 3 as the moderate concentration group, and Quartile 4 as the high concentration group. Multivariate Cox regression analysis showed that the moderate concentration group (p = .02, hazard ratio [HR]: 2.331, 95% confidence interval [CI]: 1.141-4.762) and high concentration group (p = .007, HR: 2.873, 95% CI: 1.332-6.199) were associated with an increased risk of AF recurrence compared with the low concentration group. The median follow-up was 1.17 years, it is indicated that a higher risk of recurrent AF was observed in the moderate concentration and high concentration group (log-rank: χ2 = 7.540, p = .023). CONCLUSION: Our data suggest that an elevated TG level measured before catheter ablation is associated with an increased risk of AF recurrence.

Gradient gyroid Ti6Al4V scaffolds with TiO2 surface modification: Promising approach for large bone defect repair.

Large bone defects, particularly those exceeding the critical size, present a clinical challenge due to the limited regenerative capacity of bone tissue. Traditional treatments like autografts and allografts are constrained by donor availability, immune rejection, and mechanical performance. This study aimed to develop an effective solution by designing gradient gyroid scaffolds with titania (TiO2) surface modification for the repair of large segmental bone defects. The scaffolds were engineered to balance mechanical strength with the necessary internal space to promote new bone formation and nutrient exchange. A gradient design of the scaffold was optimized through Finite Element Analysis (FEA) and Computational Fluid Dynamics (CFD) simulations to enhance fluid flow and cell adhesion. In vivo studies in rabbits demonstrated that the G@TiO2 scaffold, featuring a gradient structure and TiO2 surface modification, exhibited superior healing capabilities compared to the homogeneous structure and TiO2 surface modification (H@TiO2) and gradient structure (G) scaffolds. At 12 weeks post-operation, in a bone defect representing nearly 30 % of the total length of the radius, the implantation of the G@TiO2 scaffold achieved a 27 % bone volume to tissue volume (BV/TV) ratio, demonstrating excellent osseointegration. The TiO2 surface modification provided photothermal antibacterial effects, enhancing the scaffold's biocompatibility and potential for infection prevention. These findings suggest that the gradient gyroid scaffold with TiO2 surface modification is a promising candidate for treating large segmental bone defects, offering a combination of mechanical strength, bioactivity, and infection resistance.

Anthropometrics and cancer prognosis: a multicenter cohort study.

BACKGROUND: Anthropometric indicators have been shown to be associated with the prognosis of patients with cancer. However, any single anthropometric index has limitation in predicting the prognosis. OBJECTIVES: This study aimed to observe the predictive role of 7 anthropometric indicators based on body size on the prognosis of patients with cancer. METHODS: A principal component analysis (PCA) on 7 anthropometric measurements: height, weight, BMI, hand grip strength (HGS), triceps skinfold thickness (TSF), mid-upper arm circumference (MAC), and calf circumference (CAC) was conducted. Principal components (PCs) were derived from this analysis. Cox regression analysis was used to investigate the association between the prognosis of patients with cancer and the PCs. Subgroups and sensitivity analyses were also conducted. RESULTS: Through PCA, 4 distinct PCs were identified, collectively explaining 88.3% of the variance. PC1, primarily characterized by general obesity, exhibited a significant inverse association with risk of cancer-related death (adjusted hazard ratio [HR]: 0.86; 95% confidence interval [CI]: 0.83, 0.88). PC2 (short stature with high TSF) was not significantly associated with cancer prognosis. PC3 (high BMI coupled with low HGS) demonstrated a significant increase with risk of cancer-related death (adjusted HR: 1.08; 95% CI: 1.05, 1.11). PC4 (tall stature with high TSF) exhibited a significant association with increased cancer risk (adjusted HR: 1.05; 95% CI: 1.02, 1.07). These associations varied across different cancer stages. The stability of the results was confirmed through sensitivity analyses. CONCLUSIONS: Different body sizes are associated with distinct prognostic outcomes in patients with cancer. The impact of BMI on prognosis is influenced by both HGS and subcutaneous fat. This finding may influence the clinical care of cancer and improve the survival of cancer patients.

Guidelines for the clinical application of the Xihuang pill for the prevention and treatment of breast hyperplasia diseases.

CONTEXT: The Xihuang pill (XHP) is a traditional Chinese medicine formulation that has been historically used in the prevention and treatment of proliferative breast diseases. However, there is a lack of guidelines that offer recommendations for its clinical use. OBJECTIVE: The task force from the Chinese Guangdong Pharmaceutical Association aims to develop evidence-based guidelines for XHP to prevent and treat proliferative breast diseases. METHODS: We searched six Chinese and English electronic databases, including the China National Knowledge Infrastructure, the Chinese Scientific Journal Database, the Wanfang Medical Database, PubMed, and Embase, up to November 1, 2022. Publications (case reports, clinical observation, clinical trials, reviews) on using XHP to treat proliferative breast diseases were manually searched. The search terms were Xihuang pill, hyperplasia of the mammary gland, breast lump, and mastalgia. The writing team developed recommendations based on the best available evidence. RESULTS: Treatment should be customized based on syndrome identification. We recommend using XHP for the prevention and treatment of breast hyperplasia disease when a patient presents the following syndromes: concurrent blood stasis syndrome, concurrent phlegm-stasis syndrome, and concurrent liver fire syndrome. Safety indicators, including blood analysis and liver and kidney function monitoring, should be performed regularly during treatment. CONCLUSIONS: Current clinical evidence suggests that XHP can be used as a standalone treatment or in conjunction with other medications to prevent and manage breast hyperplasia diseases. More randomized controlled studies are warranted to establish high-quality evidence of its use.

Complex genotype-phenotype correlation of MYH11: new insights from monozygotic twins with highly variable expressivity and outcomes.

BACKGROUND: Thoracic aortic aneurysm/dissection (TAAD) and patent ductus arteriosus (PDA) are serious autosomal-dominant diseases affecting the cardiovascular system. They are mainly caused by variants in the MYH11 gene, which encodes the heavy chain of myosin 11. The aim of this study was to evaluate the genotype-phenotype correlation of MYH11 from a distinctive perspective based on a pair of monozygotic twins. METHODS: The detailed phenotypic characteristics of the monozygotic twins from the early fetal stage to the infancy stage were traced and compared with each other and with those of previously documented cases. Whole-exome and Sanger sequencing techniques were used to identify and validate the candidate variants, facilitating the analysis of the genotype-phenotype correlation of MYH11. RESULTS: The monozygotic twins were premature and presented with PDA, pulmonary hypoplasia, and pulmonary hypertension. The proband developed heart and brain abnormalities during the fetal stage and died at 18 days after birth, whereas his sibling was discharged after being cured and developed normally post follow-up. A novel variant c.766 A > G p. (Ile256Val) in MYH11 (NM_002474.2) was identified in the monozygotic twins and classified as a likely pathogenic variant according to the American College of Medical Genetics/Association for Molecular Pathology guidelines. Reviewing the reported cases (n = 102) showed that the penetrance of MYH11 was 82.35%, and the most common feature was TAAD (41.18%), followed by PDA (22.55%), compound TAAD and PDA (9.80%), and other vascular abnormalities (8.82%). The constituent ratios of null variants among the cases with TAAD (8.60%), PDA (43.8%), or compound TAAD and PDA (28.6%) were significantly different (P = 0.01). Further pairwise comparison of the ratios among these groups showed that there were significant differences between the TAAD and PDA groups (P = 0.006). CONCLUSION: This study expands the mutational spectrum of MYH11 and provides new insights into the genotype-phenotype correlation of MYH11 based on the monozygotic twins with variable clinical features and outcomes, indicating that cryptic modifiers and complex mechanisms beside the genetic variants may be involved in the condition.

Interstitial Fluid Shear Stress Induces the Synthetic Phenotype Switching of VSMCs to Release Pro-calcified Extracellular Vesicles via EGFR-MAPK-KLF5 Pathway.

Phenotypic switching (from contractile to synthetic) of vascular smooth muscle cells (VSMCs) is essential in the progression of atherosclerosis. The damaged endothelium in the atherosclerotic artery exposes VSMCs to increased interstitial fluid shear stress (IFSS). However, the precise mechanisms by which increased IFSS influences VSMCs phenotypic switching are unrevealed. Here, we employed advanced numerical simulations to calculate IFSS values accurately based on parameters acquired from patient samples. We then carefully investigated the phenotypic switching and extracellular vesicles (EVs) secretion of VSMCs under various IFSS conditions. By employing a comprehensive set of approaches, we found that VSMCs exhibited synthetic phenotype upon atherosclerotic IFSS. This synthetic phenotype is the upstream regulator for the enhanced secretion of pro-calcified EVs. Mechanistically, as a mechanotransducer, the epidermal growth factor receptor (EGFR) initiates the flow-based mechanical cues to MAPK signaling pathway, facilitating the nuclear accumulation of the transcription factor krüppel-like factor 5 (KLF5). Furthermore, pharmacological inhibiting either EGFR or MAPK signaling pathway blocks the nuclear accumulation of KLF5 and finally results in the maintenance of contractile VSMCs even under increased IFSS stimulation. Collectively, targeting this signaling pathway holds potential as a novel therapeutic strategy to inhibit VSMCs phenotypic switching and mitigate the progression of atherosclerosis.

Practical Synthesis of Chiral α-Aminophosphonates with Weak Bonding Organocatalysis at ppm Loading.

α-Aminophosphonic acids as an important class of bioisosteres of α-amino acids demonstrate various biologically important activities. We report here the development of a highly enantioselective isomerization of α-iminophosphonates enabled by an extraordinarily efficient organocatalyst. This organocatalyst afforded a total turnover number (TON) of 20,000-1,000,000 for a wide range of α-alkyl iminophosphonates. Even at a parts-per-million (ppm) loading, this catalyst achieved a complete reaction in greater than 93% enantiomeric excess (ee). Computational studies revealed that this small-molecule catalyst achieved enzyme-like efficiency via a network of weak bonding interactions that effectively preorganized the substrate and catalyst toward a transition-state-like complex. Considering the substrate tolerance, catalytic efficiency, and mechanism, this organocatalyst could be regarded as a small-molecule isomerase.

A non-invasive preoperative prediction model for predicting axillary lymph node metastasis in breast cancer based on a machine learning approach: combining ultrasonographic parameters and breast gamma specific imaging features.

BACKGROUND: The most common route of breast cancer metastasis is through the mammary lymphatic network. An accurate assessment of the axillary lymph node (ALN) burden before surgery can avoid unnecessary axillary surgery, consequently preventing surgical complications. In this study, we aimed to develop a non-invasive prediction model incorporating breast specific gamma image (BSGI) features and ultrasonographic parameters to assess axillary lymph node status. MATERIALS AND METHODS: Cohorts of breast cancer patients who underwent surgery between 2012 and 2021 were created (The training set included 1104 ultrasound images and 940 BSGI images from 235 patients, the test set included 568 ultrasound images and 296 BSGI images from 99 patients) for the development of the prediction model. six machine learning (ML) methods and recursive feature elimination were trained in the training set to create a strong prediction model. Based on the best-performing model, we created an online calculator that can make a linear predictor in patients easily accessible to clinicians. The receiver operating characteristic (ROC) and calibration curve are used to verify the model performance respectively and evaluate the clinical effectiveness of the model. RESULTS: Six ultrasonographic parameters (transverse diameter of tumour, longitudinal diameter of tumour, lymphatic echogenicity, transverse diameter of lymph nodes, longitudinal diameter of lymph nodes, lymphatic color Doppler flow imaging grade) and one BSGI features (axillary mass status) were selected based on the best-performing model. In the test set, the support vector machines' model showed the best predictive ability (AUC = 0.794, sensitivity = 0.641, specificity = 0.8, PPV = 0.676, NPV = 0.774 and accuracy = 0.737). An online calculator was established for clinicians to predict patients' risk of ALN metastasis ( https://wuqian.shinyapps.io/shinybsgi/ ). The result in ROC showed the model could benefit from incorporating BSGI feature. CONCLUSION: This study developed a non-invasive prediction model that incorporates variables using ML method and serves to clinically predict ALN metastasis and help in selection of the appropriate treatment option.

Systemic immune inflammation index and system inflammation response index on the third postoperative day predict poor prognosis of aneurysmal subarachnoid hemorrhage patients.

The inflammatory response is involved in the progression of aneurysmal subarachnoid hemorrhage (aSAH). We sought to investigate the relationships of inflammatory indicators including blood cell counts and the ratios of different blood cells counts with the prognosis of aSAH patients. We performed a retrospective study including 140 patients with aSAH and aneurysm surgeries. The relationships of neutrophils, lymphocytes, monocytes, platelets, systemic immune inflammation index (SII), system inflammation response index (SIRI), neutrophil-lymphocyte ratio and platelet-lymphocyte ratio with prognosis were investigated by univariable analysis and multivariable logistic regression model. The patient with Modified Rankin Scale (mRS) score＜3 was defined as having a good prognosis, while with mRS score ≥3 was defined as having a poor prognosis. Among 140 patients included, there were 108 cases with good prognosis and 32 cases with poor prognosis after follow-up. On the 3rd postoperative day, the neutrophils counts, SIRI level and SII level in cases with poor prognosis were significantly higher than cases with good prognosis, P < .05. After adjusting for baseline differences in Hunt-Hess grade, Glasgow Coma Scale score, combination with intraventricular hemorrhage and maximum diameter of aneurysm, the levels of SIRI (odds ratio = 3.968, 95% CI: 1.432-10.992, P = .008) and SII (odds ratio = 3.313, 95% CI: 1.029-10.665, P = .045) on the 3rd postoperative day could predict poor prognosis. SII and SIRI on the 3rd postoperative day could independently predict the poor prognosis in aSAH. However, the cutoff values for predicting prognosis needs to be validated in larger-sample studies.

Genome-wide association study and development of molecular markers for yield and quality traits in peanut (Arachis hypogaea L.).

BACKGROUND: This study aims to decipher the genetic basis governing yield components and quality attributes of peanuts, a critical aspect for advancing molecular breeding techniques. Integrating genotype re-sequencing and phenotypic evaluations of seven yield components and two grain quality traits across four distinct environments allowed for the execution of a genome-wide association study (GWAS). RESULTS: The nine phenotypic traits were all continuous and followed a normal distribution. The broad heritability ranged from 88.09 to 98.08%, and the genotype-environment interaction effects were all significant. There was a highly significant negative correlation between protein content (PC) and oil content (OC). The 10× genome re-sequencing of 199 peanut accessions yielded a total of 631,988 high-quality single nucleotide polymorphisms (SNPs), with 374 significant SNP loci identified in association with the nine traits of interest. Notably, 66 of these pertinent SNPs were detected in multiple environments, and 48 of them were linked to multiple traits of interest. Five loci situated on chromosome 16 (Chr16) exhibited pleiotropic effects on yield traits, accounting for 17.64-32.61% of the observed phenotypic variation. Two loci on Chr08 were found to be strongly associated with protein and oil contents, accounting for 12.86% and 14.06% of their respective phenotypic variations, respectively. Linkage disequilibrium (LD) block analysis of these seven loci unraveled five nonsynonymous variants, leading to the identification of one yield-related candidate gene and two quality-related candidate genes. The correlation between phenotypic variation and SNP loci in these candidate genes was validated by Kompetitive allele-specific PCR (KASP) marker analysis. CONCLUSIONS: Overall, molecular markers were developed for genetic loci associated with yield and quality traits through a GWAS investigation of 199 peanut accessions across four distinct environments. These molecular tools can aid in the development of desirable peanut germplasm with an equilibrium of yield and quality through marker-assisted breeding.

Remnant cholesterol is an effective biomarker for predicting survival in patients with breast cancer.

BACKGROUND: Breast cancer is the most common malignancy in women worldwide. The relationship between remnant cholesterol (RC) and the prognosis of patients with breast cancer has not been clearly reported. This study investigated the prognostic value of RC in predicting mortality in patients with breast cancer. METHODS: This study prospectively analysed 709 women patients with breast cancer from the Investigation on Nutrition Status and Clinical Outcome of Common Cancers (INSCOC) project. Restricted cubic splines were used to analyse the dose-response relationship between RC and breast cancer mortality. The Kaplan-Meier method was used to evaluate the overall survival of patients with breast cancer. A Cox regression analyses was performed to assess the independent association between RC and breast cancer mortality. Inverse probability of treatment weighting (IPTW) using the propensity score was used to reduce confounding. Sensitivity analysis was performed after excluding patients with underlying diseases and survival times shorter than one year. RESULTS: A linear dose-response relationship was identified between RC and the risk of all-cause mortality in patients with breast cancer (p = 0.036). Kaplan-Meier survival analysis and log-rank test showed that patients with high RC levels had poorer survival than those with low RC levels (p = 0.007). Univariate and multivariate Cox regression analyses showed that RC was an independent risk factor for mortality in women patients with breast cancer. IPTW-adjusted analyses and sensitivity analyses showed that CR remained a prognostic factor. CONCLUSIONS: RC is an independent risk factor for the prognosis of patients with breast cancer, and patients with higher RC levels have poorer survival.