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Abstract Breast cancer, characterized by unique epidemiological patterns and significant heterogeneity, remains one of the leading causes of malignancy-related deaths in women. The increasingly nuanced molecular subtypes of breast cancer have enhanced the comprehension and precision treatment of this disease. The mechanisms of tumorigenesis and progression of breast cancer have been central to scientific research, with investigations spanning various perspectives such as tumor stemness, intra-tumoral microbiota, and circadian rhythms. Technological advancements, particularly those integrated with artificial intelligence, have significantly improved the accuracy of breast cancer detection and diagnosis. The emergence of novel therapeutic concepts and drugs represents a paradigm shift towards personalized medicine. Evidence suggests that optimal diagnosis and treatment models tailored to individual patient risk and expected subtypes are crucial, supporting the era of precision oncology for breast cancer. Despite the rapid advancements in oncology and the increasing emphasis on the clinical precision treatment of breast cancer, a comprehensive update and summary of the panoramic knowledge related to this disease are needed. In this review, we provide a thorough overview of the global status of breast cancer, including its epidemiology, risk factors, pathophysiology, and molecular subtyping. Additionally, we elaborate on the latest research into mechanisms contributing to breast cancer progression, emerging treatment strategies, and long-term patient management. This review offers valuable insights into the latest advancements in Breast Cancer Research, thereby facilitating future progress in both basic research and clinical application.

Abstract Objective Neuroendocrine cervical carcinoma (NECC) is a rare but highly aggressive tumor. The clinical management of NECC follows neuroendocrine neoplasms and cervical cancer in general. However, the diagnosis and prognosis of NECC remain dismal. The aim of this study was to identify a specific protein signature for the diagnosis of NECC. Methods Protein and gene expression data for NECC and other cervical cancers were retrieved or downloaded from self-collected samples or public resources. Eleven machine-learning algorithms were packaged into 66 combinations, of which we selected the optimal algorithm, including randomForest, SVM-RFE, and LASSO, to select key NECC specific dysregulated proteins (kNsDEPs). The diagnostic effect of kNsDEPs was validated by a set of predictive models and immunohistochemical staining method. The dysregulation patterns of kNsDEPs were further investigated in other neuroendocrine carcinomas. Results Our results showed that NECC displays distinctive biological characteristics, such as HPV18 infection, and exhibits unique molecular features, particularly an enrichment in cytoskeleton-related functions. Furthermore, secretagogin (SCGN), adenylyl cyclase-associated protein 2 (CAP2), and calcyclin-binding protein (CACYBP) were identified as kNsDEPs. These kNsDEPs play a central role in cytoskeleton protein binding and showcase robust diagnostic ability and specificity for NECC. Moreover, the concurrent upregulation of SCGN and CACYBP, along with the downregulation of CAP2, represents a unique feature of NECC, distinguishing it from other neuroendocrine carcinomas. Conclusions This study uncovers the significance of kNsDEPs and elucidates their regulated networks in the context of NECC. It highlights the pivotal role of kNsDEPs in NECC diagnosis, thus offering promising prospects for the development of diagnostic biomarkers for NECC.

Abstract Background To assess the clinical utility of PCA3 in the diagnostic accuracy, the correlation between PCA3 and biopsy or pathological characteristics and the performance of PCA3 to reduce the unnecessary biopsies in Chinese population. Methods A prospective study including patients with indication of prostate biopsies from 4 centers was conducted. All patients underwent PCA3 urine tests and prostate biopsies. The PCA3 score was analyzed by PCA3 gene expression Detection Kit (Fluorescent RT-PCR) (York biotech, Cat.#YDM-B01, China). Base model (clinical information) and PCA3 model (PCA3 scores and clinical information) were constructed via multivariate logistic regression. Discrimination, calibration and decision curve analysis were evaluated. Results In 1117 patients, 587 men with positive biopsy results had higher median PCA3 scores than those with negative biopsy results (p

Objective To analyze the prognosis and risk factors of the anterior and posterior circulation tandem lesions (TLs) patients after recanalization treatment. Methods The general and clinical data of 42 patients with TLs who received recanalization treatment in Shijiazhuang People's Hospital from April 2019 to August 2022 were retrospectively collected. The prognosis of 90 d after surgery was evaluated by the modified Rankin Scale (mRS). Univariate and multivariate stepwise Logistic regression analyses were used to investigated the risk factors of poor prognosis of TLs. Results According to mRS scores at the 90 d after surgery, the patients were divided into good prognosis group (mRS ≤ 2, n = 21) and poor prognosis group (mRS > 2, n = 21). The National Institutes of Health Stroke Scale (NIHSS) score at admission (Z = ⁃ 2.916, P = 0.004), time from onset to recanalization (Z = ⁃ 2.048, P = 0.041), mechanical thrombectomy times ≥ 3 (χ2 = 4.725, P = 0.030) and the proportion of hematoma type hemorrhagic transformation (χ2 = 8.400, P = 0.004) in the poor prognosis group were higher than those in good prognosis group. Logistic regression analysis showed that high NIHSS score at admission (OR = 12.457, 95%CI: 2.066-75.120; P = 0.006), mechanical thrombectomy times ≥ 3 (OR = 9.387, 95%CI: 1.222-72.140; P = 0.031) and postoperative hemorrhagic transformation (OR = 7.237, 95%CI: 1.019-51.403; P = 0.048) wererisk factors of poor prognosis of TLs. Conclusions Anterior and posterior circulation TLs patients with lower NHISS score at admission, mechanical thrombectomy times < 3 and without postoperative hemorrhagic transformation may have good prognosis.

Abstract Background Stent dislodgement is a rare but particularly challenging complication. However, current treatment strategies are suboptimal. Objective This study sought to preliminarily assess the feasibility of a novel self-expanding basket (SEB) catheter to successfully retrieve dislodged stent during percutaneous coronary intervention (PCI). Method The novel SEB catheter is designed as a self-expanding basket tip made of superelastic shape nitinol memory alloy, which could automatically expand to tightly wrap and flatten the deformed struts regardless of whether the stent come off the guidewire. Consecutive patients with coronary artery disease who experienced stent dislodgement during PCI were included. The primary outcome was procedure success defined as completely removing the stent without surgical incision of blood vessels, or hemostatic forceps, or injury of access vessels. Results From May 2020 to May 2023, a total of 6 patients encountering stent dislodgment were enrolled. Five presented as stent dislodgment with the guidewire in situ and the rest one as total stent and guidewire loss. Successful retrieving of dislodged stent with SEB catheter was achieved in 100% (6 of 6) subjects. After retracting lost stent, 5 of 6 patients received new stent implantation, and one only underwent balloon angioplasty with acceptable imaging results. No safety events were observed. Conclusions This preliminary report of the novel stent retrieving device presents favorable efficacy and safety profile. Further multicenter study is required to confirm these findings. Clinical trial number Not applicable.

Abstract Wearable sensors have attracted considerable interest due to their ability to detect a variety of information generated by human physiological activities through physical and chemical means. The performance of wearable sensors is limited by their stability, and endowing wearable sensors with superhydrophobicity is one of the means to enable them to maintain excellent performance in harsh environments. This review emphasizes the imperative progress in flexible superhydrophobic sensors for wearable devices. Besides, the wettability principle and the mechanism of wearable sensors are briefly introduced to propose the combination of superhydrophobicity and wearable sensors. Next, superhydrophobic substrates for wearable sensors, including but not limited to, polydimethylsiloxane, polyurethane, gel, rubber, and fabric, are described in depth, and also the respective fabrication processes and performances. Moreover, the utility of superhydrophobic wearable sensors in a normal intelligent environment is described, highlighting their application in monitoring physiological signals, such as physical movement, pulse, vibration, temperature, perspiration, respiration, and so on. Finally, this review evaluates the challenges and dilemmas that wearable sensors must be overcome for further development and improve the functional performance of wearable sensors, paving the way for their expansion into advanced wearable sensing systems.

Obesity-related glomerulopathy (ORG) represents an escalating public health with no effective treatments currently available. Abnormal lipid metabolism and lipid droplet deposition in the kidneys are key contributors to ORG. Cyanidin-3-glucoside (C3G) has shown potential in regulating lipid metabolism and may offer reno-protective effects; however, its therapeutic efficacy and underlying mechanisms in ORG remain unclear. An ORG mouse model was established, followed by an 8-week C3G intervention. The mice were divided into three groups: normal control (CT) group, ORG group, and C3G treatment group. Fecal 16S rRNA sequencing, metabolomics of feces-serum-kidney, and kidney single-cell RNA sequencing (scRNA-seq) were performed to investigate the effects and mechanisms of C3G. Compared to CT mice, ORG mice exhibited elevated serum CHO, TG, Cys-C, UACR, urinary Kim-1, and NAG levels, along with glomerular hypertrophy and tubular injury. These biochemical and pathological indicators improved following C3G treatment. Fecal 16S analysis revealed reduced gut microbiota diversity in ORG mice compared to CT mice, while C3G intervention increased gut microbiota diversity. Metabolic profiling of feces, serum, and kidney indicated reprogramming of glycerophospholipid metabolism in ORG mice, ameliorated by C3G treatment. Further analysis demonstrated that abnormal glycerophospholipid metabolites correlated with blood lipids, urinary protein, urinary tubular injury markers, and gut microbiota, specifically Lachnospiraceae and Blautia. Additionally, scRNA-seq analysis identified activation of the PPARγ/CD36 pathway in proximal tubule cells (PTCs) of ORG mice. C3G improved abnormal glycerophospholipid metabolism and alleviated injury in PTCs by inhibiting the PPARγ/CD36 pathway. C3G reduces lipid droplet accumulation in the PTCs of ORG mice by modulating the gut microbiota and inhibiting the PPARγ/CD36 pathway. These findings offer new insights and therapeutic targets for ORG.

IntroductionIn order to enhance the quality of cigar tobacco leaves (CTLs), a gradient variable temperature fermentation approach was employed.MethodsThe temperature gradient demonstrated a gradual increase from low temperature (35 ± 2°C) to moderate temperature (45 ± 2°C), and then to high temperature (55 ± 2°C). Each temperature gradient underwent a 10-day fermentation process, resulting in a total duration of 30 days. Changes in sensory evaluation, chemical composition, and bacterial absolute quantitative structure and function were examined throughout the process of gradient variable temperature fermentation.ResultsCompared to constant temperature fermentation, gradient variable temperature fermentation improved the sensory quality of CTLs, reduced total sugar and cembrane degradation products, and increased the amino acid contents. It resulted in significant changes in bacterial quantity and function of CTLs, but had no significant effects on the richness and diversity of bacterial communities. The results of correlation analyses showed that sensory quality had significant correlation with chemical composition, which effected by predominant microbes. The gradient variable temperature fermentation process underwent a three-phase model to characterize the alterations of CTLs. Phase I (35°C) was the microbial stage, during which there was a significant decrease in both the total number and function of microorganisms. The dominant genera shifted from Acinetobacter to Staphylococcus and Corynebacterium, and with high reducing sugar, polyphenol compound and low sensory score. Phase II (45°C) marked a chemical stage, with an enhancement in sensory evaluation. A total of 17 chemicals significantly decreased and six increased, and the decline of microbial populations persisted. The enhanced relative abundances of four microecological hubs, namely Staphylococcus, Corynebacterium, Oceanobacillus, and Bacillus, had the potential to produce protease and lipase to the production of peptides, amino acids, and organic acid, catabolizing sugars and polyphenol compounds, through carbohydrate metabolism and amino acid metabolism, resulted an increase in sensory quality of CTLs. Phase III (55°C) indicated a relative mature stage with the highest score of sensory evaluation. Eight compositions from plamochromic pigments and polyphenol compounds exhibited gradual decreases, while relative contents of carbohydrate metabolism and amino acid metabolism increased.ConclusionThe gradient variable temperature fermentation had demonstrated a significant positive influence on the quality of CTL by providing optimal fermentation temperature for microbial growth, metabolism, and the generation of quality-related chemical compositions.

IntroductionFermentation plays a significant role in improving the quality of cigar tobacco leaves. Particularly, fermentation with characteristic additives has been identified as an effective approach to enhance the fermentation process. The objective of this study was to develop new additives and investigate their influence on cigar tobacco leaves.MethodsThe active ingredients extracted from three citrus species were obtained by ultrasonic-assisted extraction followed by solid phase purification. The effects of these ingredients as fermentation additives on the primary chemical components, microbial communities, and sensory quality of cigar tobacco leaves were subsequently analyzed.ResultsResults showed that: (1) Flavonoids were the main components of the prepared citrus extracts. (2) The addition of citrus extracts resulted in a reduced content of amino acids, oxalic acid, and unsaturated fatty acids in cigar tobacco leaves, while increasing the content of citric acid. Besides, the total amount of aroma substances in cigar tobacco leaves increased by 38.15% with the addition of citrus extracts, with notable enhancements in the levels of D-limonene, β-dihydroionone, dihydroactiniolactone, and other representative aroma components. (3) The addition of citrus extracts promoted the succession of the microbial community in cigar tobacco leaves and promoted the enrichment of Pseudomonas and Corynebacterium. (4) The addition of citrus extracts effectively reduced the irritation and improved the aroma richness of cigar tobacco leaves.DiscussionIn this study, the influence of citrus-derived active ingredients on cigar quality was systematically analyzed, providing a reference for the development of characteristic fermentation additives for cigars and the extension of cigar quality enhancement technologies.

ObjectOsteosarcoma is a malignant tumor originating from the bones, commonly found in children and adolescents, especially in rapidly growing bone areas such as the knees and upper arms. In this study, we aim to delineate the evolution and convergence of research themes in osteosarcoma metabolomics over the past decade, identify major contributors, and forecast emerging trends that could direct future research efforts.MethodThe bibliometric method has been applied to systematically analyze the literature in the field of osteosarcoma metabolomics. The relevant literatures were collected from the Web of Science Core Collection, spanning from January 1, 2014, to December 31, 2023. Tools such as CiteSpace, Bibliometrix, and VOSviewer were used for the visual analysis of the collected literatures. The focused information includes institutions, journals, countries, authors, keywords, and citations.ResultVarious aspects in the field of osteosarcoma metabolism were analyzed. Shanghai Jiao Tong University has published the most papers in the past ten years, followed by Central South University and Zhejiang University. Among the sources, the international journal of molecular sciences publishes the most articles, and oncotarget is the journal with the highest H index. According to Bradford’s law, there are 34 core journals identified. A total of 5501 authors participated in the creation of papers in this field. The distribution of authors follows Lotka`s Law, and 85.3% of authors have only one article. 46% of the corresponding authors are from China, but most of these corresponding authors are not good at international cooperation. China also has the largest number of publications, followed by the United States. It can be confirmed that China dominates this field. Among the keywords, “expression” is the keyword that has received the most attention in the past ten years. All keywords can be divided into 9 clusters. Based on the explosive words and hot topics each year, we speculate that future research will focus on the tumor microenvironment, molecular mechanisms and autophagy, targeted therapies and inhibitors.ConclusionIn summary, this study comprehensively analyzed the current state of research in the field of osteosarcoma metabolism through bibliometric methods. The findings revealed the development trends and research hotspots in this field, which may provide valuable references for future research directions.

Abstract Background Circulating tumor DNA (ctDNA) has emerged as a promising biomarker for noninvasive cancer diagnostics, particularly in the context of metastatic non‐small‐cell lung cancer (NSCLC). Detecting targetable variants through ctDNA analysis offers the potential to guide treatment decisions, especially in cases where tissue samples are insufficient or unavailable. Method In this study, we developed and validated a next‐generation sequencing panel targeting 101 cancer‐related genes (101‐test) to detect somatic variants in ctDNA from a large cohort of Chinese patients with metastatic NSCLC. The performance of the 101‐test was assessed by evaluating its limit of detection (LOD), accuracy, and precision in identifying molecular variants. Additionally, the concordance between ctDNA and tissue samples for detecting targetable variants was analyzed in 904 patients. Results The 101‐test demonstrated a LOD of 0.38% for single‐nucleotide variants (SNVs), 0.33% for insertions and deletions (InDels), and 0.33% for fusions. Sensitivity was 98.3% for SNVs, 100% for InDels, and 100% for fusions when compared to digital droplet PCR (ddPCR)/breakpoint PCR reference methods. The by‐variant sensitivity for somatic variants was 97.5%, with a specificity of 99.9% between tumor‐only and tumor‐normal analyses. In a real‐world cohort, the concordance between ctDNA and tissue samples for identifying targetable variants was 72.2% (457/633). Notably, the EGFR S768I variant, recently recommended by clinical guidelines, achieved an 80% concordance rate. Furthermore, 4.3% of patients (27/633) with targetable variants were identified exclusively through ctDNA testing. Conclusion The ctDNA‐based 101‐test is a highly sensitive and specific tool for detecting targetable variants in metastatic NSCLC, particularly in cases with insufficient tissue samples. The findings support the use of ctDNA testing as a reliable and complementary method to traditional tissue‐based molecular analysis, enhancing the precision of treatment strategies for NSCLC patients.

ObjectiveTo explore the functional characteristics of a patient of Bartter syndrome type III and compound heterozygous mutations in CLCNKB gene and explore the rescue effect of cystic fibrosis transmembrane conductance regulator modulator compound VX-809 on CLCNKB gene missense variant.MethodsA retrospective analysis was conducted for a hospitalized patient of Bartter syndrome type III on September 2, 2019. Clinical characteristics, growth and development status, laboratory findings and genetic data were reviewed. Wild-type and variant CLCNKB genes were separately transfected into human embryonic kidney 293 cells (HEK293) and the expression levels of ClC-Kb protein in each group detected by Western blot. The differences in protein expression between wild-type and variant type were compared by unpaired t-test. Additionally, immunofluorescent stain was utilized for examining the subcellular localization of ClC-Kb protein. And cystic fibrosis transmembrane conductance regulator modulator compound VX-809 was employed for treating cells after transfecting with a over-expressing variant in CLCNKB gene.ResultsThis 32-month-old girl presented with hypokalemia, hypochloremia, metabolic alkalosis, renal salt wasting and normal blood pressure in all four extremities. Genetic testing results revealed compound heterozygous variations in CLCNKB gene. Transfection of two variant plasmids (p.F213C & p. Y466Mfs13) into HEK293 cells indicated that the expression of variant ClC-Kb protein was significantly lower than that of wild-type (P

Abstract Background Immunosuppression is a leading cause of septic death. Therefore, it is necessary to search for biomarkers that can evaluate the immune status of patients with sepsis. We assessed the diagnostic and prognostic value of low-density neutrophils (LDNs) and myeloid-derived suppressor cells (MDSCs) subsets in the peripheral blood mononuclear cells (PBMCs) of patients with sepsis. Methods LDNs and MDSC subsets were compared among 52 inpatients with sepsis, 33 inpatients with infection, and 32 healthy controls to investigate their potential as immune indicators of sepsis. The percentages of LDNs, monocytic MDSCs (M-MDSCs), and polymorphonuclear MDSCs (PMN-MDSCs) in PBMCs were analyzed. Sequential organ failure assessment (SOFA) scores, C-reactive protein (CRP), and procalcitonin (PCT) levels were measured concurrently. Results The percentages of LDNs and MDSC subsets were significantly increased in infection and sepsis as compared to control. MDSCs performed similarly to CRP and PCT in diagnosing infection or sepsis. LDNs and MDSC subsets positively correlated with PCT and CRP levels and showed an upward trend with the number of dysfunctional organs and SOFA score. Non-survivors had elevated M-MDSCs compared with that of patients who survived sepsis within 28 days after enrollment. Conclusions MDSCs show potential as a diagnostic biomarker comparable to CRP and PCT, in infection and sepsis, even in distinguishing sepsis from infection. M-MDSCs show potential as a prognostic biomarker of sepsis and may be useful to predict 28-day hospital mortality in patients with sepsis.

BackgroundOsteosarcoma (OS), a bone tumor with high ability of invasion and metastasis, has seriously affected the health of children and adolescents. Many studies have suggested a connection between OS and the epithelial-mesenchymal transition (EMT). We aimed to integrate EMT-Related genes (EMT-RGs) to predict the prognosis, immune infiltration, and therapeutic response of patients with OS.MethodsWe used consensus clustering to identify potential EMT-Related OS molecular subtypes. Somatic mutation, tumor immune microenvironment, and functional enrichment analyses were performed for each subtype. We next constructed an EMT-Related risk signature and evaluated it by Kaplan-Meier (K-M) analysis survival and receiver operating characteristic (ROC) curves. Moreover, we constructed a nomogram to more accurately predict OS patients’ clinical outcomes. Response effects of immunotherapy in OS patients was analyzed by Tumor Immune Dysfunction and Exclusion (TIDE) analysis, while sensitivity for chemotherapeutic agents was analyzed using oncoPredict. Finally, the expression patterns of hub genes were investigated by single-cell RNA sequencing (scRNA-seq) data analysis.ResultsA total of 53 EMT-RDGs related to prognosis were identified, separating OS samples into two separate subgroups. The EMT-high subgroup showed favourable overall survival and more active immune response. Significant correlations were found between EMT-Related DEGs and functions as well as pathways linked to the development of OS. Additionally, a risk signature was established and OS patients were divided into two categories based on the risk scores. The signature presented a good predictive performance and could be recognized as an independent predictive factor for OS. Furthermore, patients with higher risk scores exhibited better sensitivity for five drugs, while no significant difference existed in immunotherapy response between the two risk subgroups. scRNA-seq data analysis displayed different expression patterns of the hub genes.ConclusionWe developed a novel EMT-Related risk signature that can be considered as an independent predictor for OS, which may help improve clinical outcome prediction and guide personalized treatments for patients with OS.

PurposeThis study aimed to investigate the impact of paternal age > 40 years on clinical pregnancy and perinatal outcomes among patients undergoing in vitro fertilization treatment.MethodsWe selected 75 male patients (aged > 40 years) based on predefined inclusion and exclusion criteria. Propensity score matching was performed in a 1:3 ratio, resulting in a control group (aged ≤ 40 years) of 225 individuals. Various statistical tests, including the Mann-Whitney U test, Chi-square test, Fisher’s exact test, and binary logistic regression, were used to analyze the association between paternal age and clinical outcomes.ResultsWe found no statistically significant differences in semen routine parameters, clinical pregnancy outcomes, and perinatal outcomes between paternal aged > 40 and ≤ 40 years. However, in the subgroup analysis, the live birth rate significantly decreased in those aged ≥ 45 compared to those aged 41–42 and 43–44 years (31.25% vs. 69.23% and 65%, respectively; all p < 0.05). Additionally, the clinical pregnancy rate was significantly lower among those aged ≥ 45 than among those aged 41–42 (43.75% vs. 74.36%; p=0.035).ConclusionPaternal age ≥ 45 years was associated with lower live birth and clinical pregnancy rates.