Sesquilignans PD from Zanthoxylum nitidum var. tomentosum exerts antitumor effects via the ROS/MAPK pathway in liver cancer cells.

Sesquilignans PD is a natural phenylpropanoid compound that was isolated from Zanthoxylum nitidum var. tomentosum. In this study, we assessed the antitumor effect of PD on SK-Hep-1 and HepG2 cells and the underlying molecular mechanisms. The results revealed that PD markedly inhibited the proliferation and migration of both liver cancer cells. Moreover, PD induced apoptosis, autophagy, and reactive oxygen species (ROS) production in liver cancer cells. Notably, PD increased the protein levels of p-p38 MAPK and p-ERK1/2 in liver cancer cells. This is the first report on the anticancer effect of PD, which is mediated via increased ROS production and MAPK signaling activation.

Rapid Determination of Tetracyclines in Drinking and Environmental Waters Using Fully Automatic Solid-Phase Extraction with Ultra-Performance Liquid Chromatography-Tandem Mass Spectrometry.

The abuse and irrational use of tetracyclines (TCs) in human medicine and animal husbandry has become a serious concern, affecting the ecological environment and human health. The aim of this study was to develop a sensitive and selective method using fully automatic solid-phase extraction coupled with ultra-performance liquid chromatography-tandem mass spectrometry for the determination of twelve TCs in water. Four isotope-labeled internal standards for TCs were used to correct matrix effects. Several parameters affecting extraction efficiency were systematically optimized, and the optimum experimental conditions found were 1.0 L water sample with 0.5 g/L Na2EDTA (pH 3.0) extracted and enriched by CNW HLB cartridge and eluted by 4 mL of acetone:methanol (v/v, 1:1). The enrichment factors were up to 798-1059 but only requiring about 60 min per six samples. Under the optimized conditions, the linearity of the method ranged from 0.2 to 100 µg/L for 12 TCs, the detection limits were as low as 0.01-0.15 ng/L, and the recoveries were in the range of 70%-118%, with relative standard deviations less than 15%. The developed method can be successfully utilized for the determination of 12 TCs in pure water, tap water, river water, and mariculture seawater. In summary, three and six TCs were detected in river water and mariculture seawater, respectively, with total concentrations of 0.074-0.520 ng/L (mean 0.248 ng/L) and 0.792-58.369 ng/L (12.629 ng/L), respectively. Tetracycline (TC) and oxytetracycline (OTC) were the dominant TCs in river water, while doxytetracycline (DXC) and OTC were dominant in mariculture seawater.

Single-cell RNA-seq reveals the effects of the FecB mutation on the transcriptome profile in ovine cumulus cells.

Genetic variations in the ovine ovulation rate, which are associated with the FecB mutation, provide useful models by which to explore the mechanisms regulating the development of mammalian antral follicles. In order to study the effects of the FecB mutation on cumulus cell differentiation, preovulatory follicles were aspirated and cumulus cells were isolated from three FecB genotypes (homozygous, heterozygous and wild type) of Small Tail Han (STH) sheep superstimulated with FSH. Transcriptome information from tens of thousands of cumulus cells was determined with the 10 × Genomics single-cell RNA-seq technology. Under the superovulation treatment, the observed number of preovulatory follicles in the ovaries of FecB carriers was still significantly higher than that in the wild-type (P < 0.05). The expression patterns of cumulus cells differed between FecB carriers and wild-type ewes. The screened cumulus cells could also be further divided into different cell clusters, and the differentiation states and fates of each group of cumulus cells also remained different, which supports the notion that heterogeneity in gene expression is prevalent in single cells. The oxidative phosphorylation pathway was significantly enriched in differentially expressed genes among the cell differentiation branch nodes of cumulus cells and among the differentially expressed genes of cumulus cells from the three genotypes. Combined with the important role of oxidative phosphorylation in the maturation of COCs, we suggest that the oxidative phosphorylation pathway of cumulus cells plays a crucial role in the differentiation process of cumulus cells and the mutation effect of the FecB gene.

The influence of near-infrared carbon dots on the conformational variation and enzymatic activity of glucose oxidase: A multi-spectroscopic and biochemical study with molecular docking.

In recent years, the exceptional biocatalytic properties of glucose oxidase (GOx) have spurred the development of various GOx-functionalized nanocatalysts for cancer diagnosis and treatment. Carbon dots, renowned for their excellent biocompatibility and distinctive fluorescence properties, effectively incorporate GOx. Given the paramount importance of GOx's enzymatic activity in therapeutic efficacy, this study conducts a thorough exploration of the molecular-level binding dynamics between GOx and near-infrared carbon dots (NIR-CDs). Utilizing various spectrometric and molecular simulation techniques, we reveal that NIR-CDs form a ground-state complex with GOx primarily via hydrogen bonds and van der Waals forces, interacting directly with amino acid residues in GOx's active site. This binding leads to conformational change and reduces thermal stability of GOx, slightly inhibiting its enzymatic activity and demonstrating a competitive inhibition effect. In vitro experiments demonstrate that NIR-CDs attenuate the GOx's capacity to produce H2O2 in HeLa cells, mitigating enzyme-induced cytotoxicity and cellular damage. This comprehensive elucidation of the intricate binding mechanisms between NIR-CDs and GOx provides critical insights for the design of NIR-CD-based nanotherapeutic platforms to augment cancer therapy. Such advancements lay the groundwork for innovative and efficacious cancer treatment strategies.

Role of long non-coding RNA in inflammatory bowel disease.

Inflammatory bowel disease (IBD) is a group of recurrent chronic inflammatory diseases, including Crohn's disease (CD) and ulcerative colitis (UC). Although IBD has been extensively studied for decades, its cause and pathogenesis remain unclear. Existing research suggests that IBD may be the result of an interaction between genetic factors, environmental factors and the gut microbiome. IBD is closely related to non-coding RNAs (ncRNAs). NcRNAs are composed of microRNA(miRNA), long non-coding RNA(lnc RNA) and circular RNA(circ RNA). Compared with miRNA, the role of lnc RNA in IBD has been little studied. Lnc RNA is an RNA molecule that regulates gene expression and regulates a variety of molecular pathways involved in the pathbiology of IBD. Targeting IBD-associated lnc RNAs may promote personalized treatment of IBD and have therapeutic value for IBD patients. Therefore, this review summarized the effects of lnc RNA on the intestinal epithelial barrier, inflammatory response and immune homeostasis in IBD, and summarized the potential of lnc RNA as a biomarker of IBD and as a predictor of therapeutic response to IBD in the future.

A Lactobacillus Combination Ameliorates Lung Inflammation in an Elastase/LPS-induced Mouse Model of Chronic Obstructive Pulmonary Disease.

Chronic obstructive pulmonary disease (COPD) is the world's leading lung disease and lacks effective and specific clinical strategies. Probiotics are increasingly used to support the improvement of the course of inflammatory diseases. In this study, we evaluated the potential of a lactic acid bacteria (LAB) combination containing Limosilactobacillus reuteri GMNL-89 and Lacticaseibacillus paracasei GMNL-133 to decrease lung inflammation and emphysema in a COPD mouse model. This model was induced by intranasal stimulation with elastase and LPS for 4 weeks, followed by 2 weeks of oral LAB administration. The results showed that the LAB combination decreased lung emphysema and reduced inflammatory cytokines (IL-1ß, IL-6, TNF-α) in the lung tissue of COPD mice. Microbiome analysis revealed that Bifidobacterium and Akkermansia muciniphila, reduced in the gut of COPD mice, could be restored after LAB treatment. Microbial α-diversity in the lungs decreased in COPD mice but was reversed after LAB administration, which also increased the relative abundance of Candidatus arthromitus in the gut and decreased Burkholderia in the lungs. Furthermore, LAB-treated COPD mice exhibited increased levels of short-chain fatty acids, specifically acetic acid and propionic acid, in the cecum. Additionally, pulmonary emphysema and inflammation negatively correlated with C. arthromitus and Adlercreutzia levels. In conclusion, the combination of L. reuteri GMNL-89 and L. paracasei GMNL-133 demonstrates beneficial effects on pulmonary emphysema and inflammation in experimental COPD mice, correlating with changes in gut and lung microbiota, and providing a potential strategy for future adjuvant therapy.

[Quantitative study on the acupoint effects based on complex network analysis: with the examples of the textbook networks formed by Chinese Acupuncture and Moxibustion Therapy and Practical Acupuncture and Moxibustion].

By extracting the acupoint names and their main indications from cases in Chinese Acupuncture and Moxibustion Therapy and Practical Acupuncture and Moxibustion, the acupoints and their main indications are represented in a reduced dimension, establishing an "acupoint-indication" linkage. Using complex network detection results (node degree values), the specificity of acupoints was assessed. The small-world characteristics of the "acupoint-indication" network are utilized to analyze the consistency of acupoint selection in acupuncture prescriptions and strategies to avoid redundant acupoints. The results show that the "acupoint-indication" network formed by both texts exhibited an approximate "long-tail" distribution, with a large number of node degree values concentrated between 0 and 4 000, while a few nodes have degree values exceeding 10 000. There are significant differences in the number and distribution of nodes with degree values> 10 000 between the two texts. Chinese Acupuncture and Moxibustion Therapy includes 11 acupoints with multiple edges across the body, whereas Practical Acupuncture and Moxibustion contains only 2 such acupoints, located in the lower limbs. Clinically, some acupoints have a broad therapeutic effect and appear in numerous prescriptions. The division of acupoints based on node degree values can coarsely evaluate the body region specificity of acupoints' regulatory effects. The "acupoint-indication" network of Chinese Acupuncture and Moxibustion Therapy has a higher number of edges than that of Practical Acupuncture and Moxibustion, which might be related to the different historical contexts of the two texts. In the future, diagnostic and therapeutic patterns with historical continuity can be utilized to optimize acupuncture prescriptions.

Brain Gene Regulatory Networks Coordinate Nest Construction in Birds.

Nest building is a vital behavior exhibited during breeding in birds, and is possibly induced by environmental and social cues. Although such behavioral plasticity has been hypothesized to be controlled by adult neuronal plasticity, empirical evidence, especially at the neurogenomic level, remains limited. Here, we aim to uncover the gene regulatory networks that govern avian nest construction and examine whether they are associated with circuit rewiring. We designed an experiment to dissect this complex behavior into components in response to pair bonding and nest material acquisition by manipulating the presence of mates and nest materials in 30 pairs of zebra finches. Whole-transcriptome analysis of 300 samples from five brain regions linked to avian nesting behaviors revealed nesting-associated gene expression enriched with neural rewiring functions, including neurogenesis and neuron projection. The enriched expression was observed in the motor/sensorimotor and social behavior networks of female finches, and in the dopaminergic reward system of males. Female birds exhibited predominant neurotranscriptomic changes to initiate the nesting stage, while males showed major changes after entering this stage, underscoring sex-specific roles in nesting behavior. Notably, major neurotranscriptomic changes occurred during pair bonding, with minor changes during nest material acquisition, emphasizing social interactions in nest construction. We also revealed gene expression associated with reproductive behaviors and tactile sensing for nesting behavior. This study presents novel neurogenomic evidence supporting the hypothesis of adult neural plasticity underlying avian nest-construction behavior. By uncovering the genetic toolkits involved, we offer novel insights into the evolution of animals' innate ability to construct nests.

Triblock polyadenine-based electrochemical aptasensor for ultra-sensitive detection of carcinoembryonic antigen via exonuclease III-assisted target recycling and hybridization chain reaction.

Carcinoembryonic antigen (CEA), a key colon biomarker, demands a precise detection method for cancer diagnosis and prognosis. This study introduces a novel electrochemical aptasensor using a triblock polyadenine probe for ultra-sensitive detection of CEA. The method leverages Exonuclease III (Exo III)-assisted target recycling and hybridization chain reaction. The triblock polyadenine probe self-assembles on the bare gold electrode through the strong affinity between adenine and gold electrode, blocking CEA diffusion and providing a large immobilization surface. CEA binding to hairpin probe 1 (HP1), followed by the hybridization between HP1 and hairpin probe 2 (HP2), triggers DNA cleavage by Exo III, amplifying the signal via a hybridization chain reaction and producing numerous dsDNA walkers that generates a dramatic electrochemical impedance signal. Under optimized conditions, the aptasensor achieved two ultra-low detection limits: 0.39 ag∙mL-1 within the concentration range of 5 ag∙mL-1 to 5 × 106 ag∙mL-1, and 1.5 ag∙mL-1 within the concentration range of 5 × 106 ag∙mL-1 to 1 × 1010 ag∙mL-1. Its performance in human serum samples meets the practical standards, offering a promising new tool for ultrasensitive tumor marker detection, potentially revolutionizing early cancer diagnosis.

Multispectral Imaging-Based System for Detecting Tissue Oxygen Saturation With Wound Segmentation for Monitoring Wound Healing.

OBJECTIVE: Blood circulation is an important indicator of wound healing. In this study, a tissue oxygen saturation detecting (TOSD) system that is based on multispectral imaging (MSI) is proposed to quantify the degree of tissue oxygen saturation (StO2) in cutaneous tissues. METHODS: A wound segmentation algorithm is used to segment automatically wound and skin areas, eliminating the need for manual labeling and applying adaptive tissue optics. Animal experiments were conducted on six mice in which they were observed seven times, once every two days. The TOSD system illuminated cutaneous tissues with two wavelengths of light - red ([Formula: see text] nm) and near-infrared ([Formula: see text] nm), and StO2 levels were calculated using images that were captured using a monochrome camera. The wound segmentation algorithm using ResNet34-based U-Net was integrated with computer vision techniques to improve its performance. RESULTS: Animal experiments revealed that the wound segmentation algorithm achieved a Dice score of 93.49%. The StO2 levels that were determined using the TOSD system varied significantly among the phases of wound healing. Changes in StO2 levels were detected before laser speckle contrast imaging (LSCI) detected changes in blood flux. Moreover, statistical features that were extracted from the TOSD system and LSCI were utilized in principal component analysis (PCA) to visualize different wound healing phases. The average silhouette coefficients of the TOSD system with segmentation (ResNet34-based U-Net) and LSCI were 0.2890 and 0.0194, respectively. CONCLUSION: By detecting the StO2 levels of cutaneous tissues using the TOSD system with segmentation, the phases of wound healing were accurately distinguished. This method can support medical personnel in conducting precise wound assessments. Clinical and Translational Impact Statement-This study supports efforts in monitoring StO2 levels, wound segmentation, and wound healing phase classification to improve the efficiency and accuracy of preclinical research in the field.

Effectiveness of early palliative care in patients with head and neck cancer in Taiwan.

BACKGROUND: Early palliative care (EPC) benefits some cancers, but its clinical outcomes differ depending on patients' racial and ethnic disparities, and customs. To determine whether EPC improves symptoms, emotional distress, and quality of life among Taiwanese patients with early or advanced-stage head and neck cancer (HNC). METHODS: Based on participants' pathological stages, they were categorized as having early and advanced-stage HNC. Those willing and unwilling to undergo EPC were assigned to the EPC and standard groups, respectively. Their daily cancer-related symptoms were assessed using the Distress Thermometer (DT) and MD Anderson Symptom Inventory (MDASI), whose scores' concurrent validity was evaluated using the European Organization for Research and Treatment of Core Quality of Life (EORTC-QLQ-C30) and Head and Neck 35 (EORTC-QLQ-H&N35) questionnaires. RESULTS: Patients (n = 93) diagnosed with HNC at Taiwan's Chia-Yi Christian Hospital from November 2020 to October 2022 were recruited. The patients voluntarily split into two groups: EPC groups and standard groups (23 and 11 in early-stage; 46 and 13 in advanced-stage, respectively). DT assessment showed significant emotional distress improvements for all patients with HNC who received EPC. The EORTC-QLQ-C30 questionnaire indicated that, compared to standard interventions, EPC groups significantly improved the quality of life and some symptoms for both early and advanced-stage HNC patients. However, the EORTC-QLQ-H&N35 questionnaire found no significant difference between the two groups. Furthermore, advanced-stage patients' anticancer treatment completion rates with EPC and standard interventions were 95.35% and 75%, respectively. CONCLUSION: EPC improves symptoms, emotional distress, quality of life, and treatment completion rates in Taiwanese patients with early or advanced-stage HNC. Nonetheless, further extensive clinical studies are required for validation.

Identification of early events in serrated pathway colorectal tumorigenesis by using digital spatial profiling.

INTRODUCTION: The colorectal serrated pathway involves precursor lesions known as sessile serrated lesions (SSL) and traditional serrated adenomas (TSA). Mutations in BRAF or KRAS are crucial early events in this pathway. Additional genetic and epigenetic changes contribute to the progression of these lesions into high-grade lesions and, eventually, invasive carcinoma. METHODS: We employed digital spatial profiling to investigate the transcriptional changes associated with SSL and TSA. The genes identified are confirmed by immunohistochemical (IHC) staining. Colorectal (CRC) cell lines with CEACAM6 overexpression and knockdown were established to study the roles of CEACAM6 on tumorigenesis of CRC. RESULTS: Ten genes were upregulated in SSL and TSA, and seven were upregulated in both types of lesions. IHC staining confirmed overexpression of CEACAM6, LCN2, KRT19, and lysozyme in SSL and TSA. CEACAM6 expression is an early event in the serrated pathway but a late event in the conventional pathway. Using cell line models, we confirmed that CEACAM6 promotes CRC cells' proliferation, migration, and invasion abilities. CONCLUSION: These results highlight that the transcriptional changes in the early stages of tumorigenesis exhibit relative uniformity. Identifying these early events may hold significant promise in elucidating the mechanisms behind tumor initiation.

Empagliflozin attenuates doxorubicin-induced cardiotoxicity by inhibiting the JNK signaling pathway.

BACKGROUND: Sodium-glucose cotransporter-2 inhibitors, such as empagliflozin, are pivotal therapies for heart failure. However, the effect of empagliflozin on doxorubicin-related cardiac dysfunction remains unclear. METHODS: Human induced pluripotent stem cell- and embryonic stem cell-derived cardiomyocytes were used to investigate the direct effect of empagliflozin on human cardiomyocytes. Then, the c-Jun amino-terminal kinases (JNK) inhibitor SP600125 was administered to the doxorubicin cardiotoxicity model in vitro and in vivo to investigate the role of JNK in empagliflozin. RESULTS: In human stem cell-derived cardiomyocytes, pretreatment with empagliflozin attenuated doxorubicin-induced cleavage of caspase 3 and other apoptosis markers. Empagliflozin significantly attenuated doxorubicin-induced phosphorylation of JNK and p38. Inhibiting the phosphorylation of JNK (SP600125) or STAT3 attenuated doxorubicin-induced apoptosis, but inhibiting the phosphorylation of p38 did not. SP600125 inhibits the phosphorylation of STAT3 (S727), and a STAT3 (Y705) inhibitor also inhibits the phosphorylation of JNK. Empagliflozin and SP600125 attenuated doxorubicin-induced increases in reactive oxygen species (ROS) and decreases in oxidized nicotinamide adenine dinucleotide (NAD+). In animal studies, empagliflozin and SP600125 attenuated doxorubicin-induced cardiac dysfunction and fibrosis. CONCLUSIONS: Empagliflozin attenuated doxorubicin-induced apoptosis by inhibiting the phosphorylation of JNK and its downstream signaling pathways, including ROS and NAD+.

Biomarker-triggered, spatiotemporal controlled DNA nanodevice simultaneous assembly and disassembly.

Despite many advances in the use of DNA nanodevices as assembly or disassembly modules to build various complex structures, the simultaneous assembly and disassembly of DNA structures in living cells remains a challenge. In this study, we present a modular engineering approach for assembling and disassembling DNA nanodevices in response to endogenous biomarkers. As a result of pairwise prehybridization of original DNA strands, the DNA nanodevice is initially inert. In an effort to bind one of the paired strands and release its complement, nucleolin competes. Assembly of the DNA nanodevice is initiated when the released complement binds to it, and disassembly is initiated when APE1 shears the assembled binding site of the DNA nanodevice. Spatial-temporal logic control is achieved through our approach during the assembly and disassembly of DNA nanodevices. Furthermore, by means of this assembly and disassembly procedure, the sequential detection and imaging of two tumor markers can be achieved, thereby effectively reducing false-positive signal results and accelerating the detection time. This study emphasizes the simultaneous assembly and disassembly of DNA nanodevices controlled by biomarkers in a simple and versatile manner; it has the potential to expand the application scope of DNA nanotechnology and offers an idea for the implementation of precision medicine testing.

Trends in cancer-related suicide in the United States: a population-based epidemiology study spanning 40 years of data.

Large cohort studies examining trends in cancer-related suicide are lacking. We analyzed data from the Surveillance, Epidemiology, and End Results (SEER) database, encompassing a total of 4,870,410 patients diagnosed with cancer from 1975 to 2017 in the United States. Joinpoint regression was used to estimate the annual percent change (APC) and average annual percentage change (AAPC) of age-adjusted rates of suicide. In the past 40 years, we revealed a gradual increase in cancer-related suicide rates from 1975 to 1989, followed by a gradual decrease from 1989 to 2013, and a marked decrease from 2013 to 2017. These trends suggested the potential impact of advancements in psychosocial care for patients with cancer in contributing to the observed decrease in suicide rates.

The Mediator Med23 controls a transcriptional switch for muscle stem cell proliferation and differentiation in muscle regeneration.

Muscle stem cells (MuSCs) contribute to a robust muscle regeneration process after injury, which is highly orchestrated by the sequential expression of multiple key transcription factors. However, it remains unclear how key transcription factors and cofactors such as the Mediator complex cooperate to regulate myogenesis. Here, we show that the Mediator Med23 is critically important for MuSC-mediated muscle regeneration. Med23 is increasingly expressed in activated/proliferating MuSCs on isolated myofibers or in response to muscle injury. Med23 deficiency reduced MuSC proliferation and enhanced its precocious differentiation, ultimately compromising muscle regeneration. Integrative analysis revealed that Med23 oppositely impacts Ternary complex factor (TCF)-targeted MuSC proliferation genes and myocardin-related transcription factor (MRTF)-targeted myogenic differentiation genes. Consistently, Med23 deficiency decreases the ETS-like transcription factor 1 (Elk1)/serum response factor (SRF) binding at proliferation gene promoters but promotes MRTF-A/SRF binding at myogenic gene promoters. Overall, our study reveals the important transcriptional control mechanism of Med23 in balancing MuSC proliferation and differentiation in muscle regeneration.

Association between a metabolic score for insulin resistance and hypertension: results from National Health and Nutrition Examination Survey 2007-2016 analyses.

Background: The Metabolic Score for Insulin Resistance (METS-IR) offers a promising and reliable non-insulin-based approach to assess insulin resistance and evaluate cardiometabolic risk. However, evidence for the association between METS-IR and hypertension was still limited. Methods: Participants from the National Health and Nutrition Examination Survey (NHANES) database from 2007-2016 were selected for weighted multivariable regression analyses, subgroup analyses and restricted cubic spline (RCS) modeling to assess the association between the METS-IR and hypertension, as well as systolic blood pressure (SBP) and diastolic blood pressure (DBP). Results: This study enrolled 7,721 adults aged ≥20 years, 2,926 (34.03%) of whom was diagnosed as hypertension. After adjusting for all potential covariates, an increased METS-IR (log2 conversion, denoted as log2METS-IR) was independently associated with a higher prevalence of hypertension (odd ratio [OR] 3.99, 95% confidence interval [CI] 3.19~5.01). The OR for hypertension in subjects with the highest quartile of METS-IR was 3.89-fold (OR 3.89, 95% CI 3.06~4.94) higher than that in those with the lowest quartile of METS-IR. This positive correlation became more significant as METS-IR increased (p for trend < 0.001). Log2METS-IR was significantly correlated with increase in SBP (ß 6.75, 95% CI 5.65~7.85) and DBP (ß 5.59, 95% CI 4.75~6.43) in a fully adjusted model. Consistent results were obtained in subgroup analyses. Hypertension, SBP and DBP all exhibited a non-linear increase with the rise in METS-IR. The minimal threshold for the beneficial association of METS-IR with hypertension, SBP and DBP were all identified to be 46.88. Conclusion: The findings of this study revealed a significant positive association between METS-IR and hypertension among US adults, suggesting METS-IR as a potential tool for assessing hypertension risk.

Ultrasound-guided core needle biopsy combined with immunohistochemistry and molecular testing improve the diagnostic accuracy of bone metastases from follicular thyroid carcinoma, two case reports and analyses.

Key Clinical Message: Ultrasound-guided core needle biopsy combined with immunohistochemistry and molecular testing could improve the diagnostic accuracy of bone metastases from follicular thyroid carcinoma, help to predict distant metastasis and prognosis. Abstract: Metastatic thyroid follicular carcinoma presenting initially with bone lesion is uncommon, its prime symptom is gradual onset, localized pain. Patient with bone metastasis who were diagnosed before thyroidectomy had a higher rate of mortality, clinician should be cautious in eliciting the clinical history and this insidious symptom in middle age group, carry out further examination. We are presenting two case reports of a follicular thyroid carcinoma with bone metastasis, ultrasound-guided core needle biopsy combined with immunohistochemistry (IHC) were carried out by our clinical team to determine the source and nature of the tumor, relevant literature was reviewed, molecular testing was discussed, we believe core needle biopsy combined with IHC and molecular testing improve the diagnostic accuracy of bone metastases from follicular thyroid carcinoma.

Tumor budding is an optimal indictor of occult cervical metastasis in clinical early-stage buccal mucosa squamous cell carcinoma.

BACKGROUND: Buccal mucosa squamous cell carcinoma (BMSCC) is an aggressive disease. This study investigated the clinicopathological significance of tumor budding (TB), depth of invasion (DOI), and mode of invasion (MOI) on occult cervical metastasis (CM) of BMSCC. METHODS: Seventy-one cT1-2N0 BMSCC patients were included in this retrospective study. TB, DOI, MOI, and other clinicopathological features were reviewed. Risk factors for occult CM, locoregional recurrence-free survival (LRRFS), and overall survival (OS) were analyzed using logistic regression and Cox's proportional hazard models, respectively. RESULTS: Multivariate analysis with the logistic regression model revealed that MOI, DOI, and TB were significantly associated with occult CM in early-stage BMSCC after adjusting for variates. However, multivariate analysis with the Cox's proportional hazard model found only TB to be a prognostic factor for LRRFS (hazard ratio 15.03, 95% confidence interval [CI] 1.94-116.66; p = 0.01; trend test p = 0.03). No significant association was found between MOI, DOI, or TB and OS. CONCLUSIONS: The optimal predictor of occult CM and prognosis of early-stage BMSCC is TB, which may assist clinicians in identifying patients at high risk of cervical metastasis.

Seminal plasma S100A8/A9 as a potential biomarker of genital tract inflammation.

ABSTRACT: Infections and inflammatory reactions in the male genital tract are the leading causes of male infertility with a prevalence of 6%-10%, primarily affecting testicular and epididymal function and ultimately compromising sperm quality. However, most infertile patients with genital infection/inflammation are asymptomatic and easily overlooked. Traditional indicators, including white blood cells, elastase, and other components in semen, can reflect inflammation of the genital tract, but there is still a lack of a uniform standard method of detection. Therefore, it is necessary to explore reliable markers in semen that reflect the inflammatory status of the genital tract. Using the experimental autoimmune orchitis (EAO) model to simulate noninfectious chronic orchitis, we successfully collected ejaculated seminal fluid from EAO rats using optimized electrical stimulation devices. Proteomic analysis was performed using isobaric tags for relative and absolute quantification (iTRAQ). Compared to the control group, 55 upregulated and 105 downregulated proteins were identified in seminal plasma samples from the EAO group. In a preliminary screening, the inflammation-related protein S100A8/A9 was upregulated. We further verified that S100A8/A9 was increased in seminal plasma and highly expressed in testicular macrophages of the EAO model. In patients with oligoasthenospermia and genital tract infections, we also found that S100A8/A9 levels were remarkably increased in seminal plasma and testicular macrophages. S100A8/A9 in semen may be a potential biomarker for chronic genital inflammation. Our study provides a new potential biomarker for early diagnosis and further understanding of male infertility caused by genital inflammation.