Tissue Pathology Research Articles

Bufalin alleviates inflammatory response and oxidative stress in experimental severe acute pancreatitis through activating Keap1-Nrf2/HO-1 and inhibiting NF-κB pathways

Severe acute pancreatitis (SAP) is a prevalent acute inflammatory disease that is clinically manifested by systemic inflammation dysregulation, resulting in a significantly elevated mortality rate. Bufalin has been verified to have potent pharmacological properties, including analgesic, anti-tumor and anti-inflammatory effects. However, it remains unclear whether bufalin inhibits SAP. Thus, we aim to explore the impact of bufalin in SAP rats and to evaluate the potential mechanisms of action. In addition to analyzing serum biochemistry and pancreatic tissue pathology, we elucidated its mechanisms of action through enzyme-linked immunosorbent assay (ELISA), immunohistochemical analysis, Western blot, and quantitative real-time PCR. The results demonstrated that bufalin dose-dependently reversed the elevation of serum Amylase (Amy) and Lipase (LPS) levels in SAP rats, alleviating pancreatic tissue pathological damage. Bufalin exhibited potent antioxidant effects by reducing malondialdehyde (MDA) levels, decreasing Superoxide dismutase (SOD) and glutathione(GSH) consumption, inhibiting the interaction of Keap1-Nrf2, and increasing HO-1 expression. Furthermore, bufalin inhibited TNF-α, IL-6, IL-1β, p-NF-κB-p65, p-IκBα, and NF-κB-p65 expression, while enhancing IκBα expression, ultimately confirming its anti-inflammatory effects on SAP. In summary, our findings suggest that bufalin exerts anti-inflammatory and antioxidant actions in NaT-SAP rats by inhibiting NF-κB and activating the Keap1-Nrf2/HO-1 pathway. This study represents the inaugural application of bufalin in NaT-induced SAP rats, indicating its potential as an effective therapeutic agent for SAP patients.

Thrombospondins: Conserved mediators and modulators of metazoan extracellular matrix.

This review provides a personal overview of significant scientific developments in the thrombospondin field during the course of my career. Thrombospondins are multidomain, multimeric, calcium-binding extracellular glycoproteins with context-specific roles in tissue organisation. They act at cell surfaces and within ECM to regulate cell phenotype and signalling, differentiation and assembly of collagenous ECM, along with tissue-specific roles in cartilage, angiogenesis and synaptic function. More recently, intracellular, homeostatic roles have also been identified. Resolution of structures for the major domains of mammalian thrombospondins has facilitated major advances in understanding thrombospondin biology from molecule to tissue; for example, in illuminating molecular consequences of disease-causing coding mutations in human pseudoachrondroplasia. Although principally studied in vertebrates, thrombospondins are amongst the most ancient of animal ECM proteins, with many invertebrates encoding a single thrombospondin and the thrombospondin gene family of vertebrates originating through gene duplications. Moreover, thrombospondins form one branch of a thrombospondin superfamily that debuted at the origin of metazoans. The super-family includes additional sub-groups, present only in invertebrates, that differ in N-terminal domain organisation, share the distinctive TSP C-terminal region domain architecture and, to the limited extent studied to date, apparently contribute to tissue development and organisation. Finally, major lines of translational research are discussed, related to fibrosis; TSP1, TSP2 and inhibition of angiogenesis; and the alleviation of chronic cartilage tissue pathologies in pseudoachrondroplasia.

H2S alleviated sepsis-induced acute kidney injury by inhibiting PERK/Bax-Bcl2 pathway

To investigate the protective mechanisms of hydrogen sulfide (H2S) in sepsis-induced acute kidney injury (SAKI), we conducted an in vivo study using a SAKI mouse model induced by intraperitoneal lipopolysaccharide (LPS) injection. Following 6 h of LPS injection, levels of tumor necrosis factor-alpha (TNF-α) and blood urea nitrogen (Bun) were significantly elevated in mouse plasma. In the kidneys of SAKI mice, expression of H2S-generating enzymes cysteinyl-tRNA synthetase (CARS), cystathionine γ-lyase (CSE) and cystathionine β-synthase (CBS) was markedly downregulated, while glucose-regulated protein 78 (GRP78), activating transcription factor 6 (ATF6), phosphorylated protein kinase R-like endoplasmic reticulum kinase/protein kinase R-like endoplasmic reticulum kinase (p-PERK/PERK), and B-cell lymphoma-2 recombinant protein X/B-cell lymphoma-2 (Bax/Bcl2) expression was significantly upregulated. H2S improved renal function and attenuated renal histopathological changes in SAKI mice, thereby alleviating LPS-induced endoplasmic reticulum stress (ERS). Additionally, it inhibited the expression of p-PERK/PERK and Bax/Bcl2. After inhibiting CSE activity with dl-propargylglycine (PPG i. p.), the renal tissue pathology in LPS-induced AKI mice was further exacerbated, leading to enhanced activation of the PERK/Bax-Bcl2 pathway. Our findings suggest that endogenous H2S influences the pathogenesis of SAKI, while exogenous H2S protects against LPS-induced AKI by inhibiting the PERK/Bax-Bcl2 pathway involved in ERS.

Inflammasome components as new therapeutic targets in inflammatory disease.

Inflammation drives pathology in many human diseases for which there are no disease-modifying drugs. Inflammasomes are signalling platforms that can induce pathological inflammation and tissue damage, having potential as an exciting new class of drug targets. Small-molecule inhibitors of the NLRP3 inflammasome that are now in clinical trials have demonstrated proof of concept that inflammasomes are druggable, and so drug development programmes are now focusing on other key inflammasome molecules. In this Review, we describe the potential of inflammasome components as candidate drug targets and the novel inflammasome inhibitors that are being developed. We discuss how the signalling biology of inflammasomes offers mechanistic insights for therapeutic targeting. We also discuss the major scientific and technical challenges associated with drugging these molecules during preclinical development and clinical trials.

Optimization of whole slide imaging scan settings for computer vision using human lung cancer tissue.

Digital pathology has become increasingly popular for research and clinical applications. Using high-quality microscopes to produce Whole Slide Images of tumor tissue enables the discovery of insights into biological aspects invisible to the human eye. These are acquired through downstream analyses using spatial statistics and artificial intelligence. Determination of the quality and consistency of these images is needed to ensure accurate outcomes when identifying clinical and subclinical image features. Additionally, the time-intensive process of generating high-volume images results in a trade-off that needs to be carefully balanced. This study aims to determine optimal instrument settings to generate representative images of pathological tissue using digital microscopy. Using various settings, an H&E stained sample was scanned using the ZEISS Axio Scan.Z1. Next, nucleus segmentation was performed on resulting images using StarDist. Subsequently, detections were compared between scans using a matching algorithm. Finally, nucleus-level information was compared between scans. Results indicated that while general matching percentages were high, similarity between information from replicates was relatively low. Additionally, settings resulting in longer scanning times and increased data volume did not increase similarity between replicates. In conclusion, the scan setting ultimately deemed optimal combined consistent and qualitative performance with low throughput time.

Evaluation of peripheral blood inflammation indexes as prognostic markers for colorectal cancer metastasis

The aim of this study was to evaluate the prognostic value of peripheral blood inflammation indexes in patients with metastatic Colorectal Cancer (CRC) and to establish a predictive scoring system. A total of 324 CRC patients diagnosed through pathological examination from January 2017 to July 2022 at the Third Affiliated Hospital of Kunming Medical University were included. The prognosis of patients with metastatic CRC was examined, and the correlation between IL-10 expression in pathological tissues and IL-10 expression in serum was analyzed. The results showed that the prognosis of CRC was poorer when metastasis occurred (P < 0.001). Additionally, IL-10 was highly expressed in the metastatic CRC group (P = 0.018), and the expression of IL-10 in pathological tissues of patients with metastatic CRC was positively correlated with the expression of IL-10 in serum (P = 0.037). The neutrophil-to-lymphocyte ratio (NLR), lymphocyte-to-white blood cell ratio (LWR), aggregate index of systemic inflammation (AISI), monocyte-to-lymphocyte ratio (MLR), systemic inflammatory response index (SIRI), prognostic nutritional index (PNI), advanced lung cancer inflammation index (ALI), and interleukin-10 (IL-10) were calculated and determined by ROC curve. The critical values were 2.135, 3.735, 353.745, 0.265, 1.025, 52.975, 353.635, and 11.25, respectively. Inflammatory indexes with an AUC of more than 0.6 were selected, and each colorectal cancer patient with any of these risk factors was assigned a score of one. The 324 patients were then divided into two groups: 0–4 for the low-risk group and 4–8 for the high-risk group. The occurrence of distant metastases in the two groups was statistically analyzed. The results showed that the OS and PFS of the low-risk group were significantly superior to those of the high-risk group (P < 0.05). These findings indicate that NLR, LWR, AISI, MLR, SIRI, PNI, ALI, and IL-10 are risk factors for distant metastasis in CRC patients. Therefore, the prediction scores of these indexes can be used to effectively evaluate the prognosis of patients with metastatic CRC.

Studies on the Preparation of a Microemulsion Formulation of Matricaria Recutita Essential Oil and the Treatment of 2,4-Dinitro-Chlorobenzene- Induced Eczema in Mice by Inhibiting Inflammation.

Eczema, an inflammatory skin disease causing intense itching, is a function of a range of internal and external factors, impacting individuals of all ages and leading to economic loss. Inflammation is the most important manifestation of eczema, and Matricaria recutita essential oil (MREO) extracted from Matricaria recutita possesses excellent antibacterial and anti-inflammatory properties. In this study, Matricaria recutita microemulsions were prepared by the trans-phase emulsification method and their stability was determined by evaluating the relevant indexes. Establishment of 2,4-dinitro-chlorobenzene-induced AD model in mice. Detection of serum indexes of IL-6, IL-17, and TNF-α, and on pathological tissue sections, the HE staining, toluidine blue staining, immunohistochemistry, and observation were performed. The study obtained optimal conditions for the preparation of microemulsion formulations of Matricaria recutita. Through quality evaluation, it was found that the microemulsion increased stability, reduced irritation, and retained anti-inflammatory activity and therapeutic effects on eczema compared to Matricaria recutita essential oil (MREO). Studies have demonstrated that microemulsion formulations of Matricaria recutita and Matricaria recutita significantly down regulate the proinflammatory factors TNF-α, IL-17, and IL-6. It was shown by hematoxylin-eosin (HE) staining that both Matricaria recutita essential oil (MREO) and Matricaria recutita microemulsion (MRME) improved the inflammatory status of eczematous skin tissues in mice. The number of mast cells expressed in the tissues was decreased in the surface-treated group, as shown by toluidine blue staining. Additionally, the number of mast cells expressed in the tissues in the surface-treated group was reduced, as demonstrated by immunohistochemistry. Furthermore, immunohistochemistry revealed that MREO and MRME have immunomodulatory effects on the tissues. The study showed that microemulsion formulations of Matricaria recutita may serve as a novel remedy for eczema.

Fundamentals of Determination of the Biological Tissue Refractive Index by Ellipsoidal Reflector Method

This paper presents the theoretical fundamentals, prerequisites for creation, and peculiarities of modeling a new method for determining the refractive index of biological tissues. The method uses a mirror ellipsoid of revolution as an optical element to ensure total internal reflection phenomena. This paper thoroughly analyzes the differences in the refractive index of healthy and pathological tissues on a biometric diagnostic basis. The analysis is used to model the measurement setup’s parameters. This paper also considers various methods of determining the refractive index of biological tissues based on different principles of physical optics, such as interferometry, refractometry, ellipsometry, and goniophotometry. It systematizes typical optical elements of total internal reflection that can be used in goniophotometry. It justifies the selection of the element base for the goniometric installation based on the ellipsoidal reflector method. A simulation of the installation operation was carried out for various parameters of the ellipsoidal reflector, ensuring the measurement of the biological tissue refractive index from 1.33 to 1.7. This paper also proposes a constructive solution for manufacturing an ellipsoidal reflector of the required configuration.

Collagen integrity of the annulus fibrosus in degenerative disc disease individuals quantified with collagen hybridizing peptide.

Degenerative disc disease (DDD) is accompanied by structural changes in the intervertebral discs (IVD). Extra-cellular matrix degradation of the annulus fibrosus (AF) has been linked with degeneration of the IVD. Collagen is a vital component of the IVD. Collagen hybridizing peptide (CHP) is an engineered protein that binds to degraded collagen, which we used to quantify collagen damage in AF. This method was used to compare AF samples obtained from donors with no DDD to AF samples from patients undergoing surgery for symptomatic DDD. Fresh AF tissue was embedded in an optimal cutting temperature compound and cryosectioned at a thickness of 8 μm. Hematoxylin and Eosin staining was performed on sections for general histomorphological assessment. Serial sections were stained with Cy3-conjugated CHP and the mean fluorescence intensity and areal fraction of Cy3-positive staining were averaged for three regions of interest (ROI) on each CHP-stained section. Increases in mean fluorescence intensity (p = 0.0004) and percentage of positively stained area (p = 0.00008) with CHP were detected in DDD samples compared to the non-DDD samples. Significant correlations were observed between mean fluorescence intensity and percentage of positively stained area for both non-DDD (R = 0.98, p = 5E-8) and DDD (R = 0.79, p = 0.0012) samples. No significant differences were detected between sex and the lumbar disc level subgroups of the non-DDD and DDD groups. Only tissue pathology (non-DDD versus DDD) influenced the measured parameters. No three-way interactions between tissue pathology, sex, and lumbar disc level were observed. These findings suggest that AF collagen degradation is greater in DDD samples compared to non-DDD samples, as evidenced by the increased CHP staining. Strong positive correlations between the two measured parameters suggest that when collagen degradation occurs, it is detected by this technique and is widespread throughout the tissue. This study provides new insights into the structural alterations associated with collagen degradation in the AF that occur during DDD.

Machine-learning diagnostic models for ovarian tumors

PurposeTo create a diagnostic framework for clinical behavior and pathological tissue prognosis in ovarian cancer by using machine-learning (ML) methods based on multiple biomarkers. Experimental designOverall, 713 patients with ovarian tumors at Sun Yat Sen Memorial Hospital were randomized into training and test cohorts. Four supervised ML classifiers, namely Support Vector Machine, Random Forest, k-nearest neighbor, and logistic regression were used to derive diagnostic and prognostic information from 10 parameters commonly available from pretreatment peripheral blood tests and age. The best prediction model was selected and validated by comparing the accuracy and the area under the ROC curve of each prediction model and by applying the external data of Guangdong Maternal and Child Health Center. ResultsML techniques were superior to conventional regression-based analyses in predicting multiple clinical parameters pertaining to ovarian tumor. Ensemble methods combining weak decision trees and RF showed the best reference in diagnosis, especially for malignant ovarian cancer. The values for the highest accuracy and area under the ROC curve for malignant ovarian cancer from benign or borderline ovarian tumors with RF were 99.82 % and 0.86 (micro-average ROC curve), respectively. The greatest accuracy and AUC for the diagnosis of pathological tissue with logistic regression curve were 78.0 % and 0.95 (micro-average ROC curve), respectively. In external validation, the random forest prediction model had an accuracy of 0.789 for applying data from external centers to verify tumor benignity and malignancy, and the logistic regression model had an accuracy of 0.719 for predicting the nature of the tumor. ConclusionsAn ovarian tumor can be diagnosed and characterized before initial treatment via ML systems to provide critical diagnostic and prognostic information. The use of predictive algorithms can facilitate customized treatment options with patient preprocessing stratification.

RAS, BRAF, and MMR system mutations in metastatic colorectal cancers: an observational study

Introduction: Colorectal cancers (CRCs) are the second cause of malignancy-related deaths and over half of CRCs become metastatic. Genetics plays a critical role in understanding metastatic colorectal cancers (MCRCs), as various genetic mutations influence progression and treatment responses. While there exists plenty of research on genetic mutations in CRCs, few studies have focused on mutations in MCRC patients. The present study aims to provide an overview of the prevalence of KRAS, NRAS, BRAF, and MMR mutations in Iranian MCRC patients. Methods: The present study is a descriptive cross-sectional study on patients with MCRCs referred to a tertiary medical center in Iran from March 2015 to March 2022. Ethics approval was obtained from the ethics committee of the University of Medical Sciences. The patient’s MCRC was confirmed by pathology and Genotyping Assessments of tissue for KRAS, NRAS, BRAF, and MMR mutations. Results: A total of 136 MCRC patients were included in this study; 44 patients (40.7%) had KRAS mutations in their lesions. KRAS mutation status was not significantly related to age or gender (P &gt; 0.05). Only one NRAS mutation was found in one patient. There were no cases of BRAF mutation identified. Among 48 patients assessed for MMRs deficiency, 8 cases (16.7%) were positive, 7 cases (14.6%) were MSI-H, and 1 case (2.1%) was MSI-L. Conclusion: Although no significant relation was found between the KRAS mutation pattern and gender, age, or tumor primary location, the MSI-H mutation-positive tumors were significantly more prevalent in younger patients.

343. DIAGNOSTIC VALUE OF ENDOBRONCHIAL ULTRASOUND-GUIDED TRANSESOPHAGEAL NEEDLE ASPIRATION (EBUS-TENA) IN LESIONS ADJACENT TO BOTH THE TRACHEA/BRONCHUS AND ESOPHAGUS

Abstract Objective To investigate the clinical diagnostic value of endobronchial ultrasound-guided transesophageal needle aspiration (EBUS-TENA) in lesions adjacent to both the trachea/bronchus and esophagus Methods The clinical data of 12 patients who underwent EBUS-TENA from February 2019 to February 2022 were collected. The operative physicians and nurses worked closely with each other and meticulously cared the patients. The vital signs changes were observed and recorded, as well as intraoperative adverse events and the acquired specimens. Results All the 12 patients underwent surgery successfully, and hair-like tissue strips were obtained in each case. There were 8 cases of central lung cancer and 4 cases of mediastinal tumor. The preoperative vital signs scores showed no significant difference with the intraoperative and postoperative scores (P&amp;gt;0.05). A few complications occurred, including 2 case of mild cough, 2 case of nausea and vomiting, with no symptoms of severe cough and dyspnea, haemorrhage, mediastinal infection, pneumothorax, mediastinal emphysema and other complications. Conclusion EBUS-TENA has significant effect in successfully obtaining pathological tissue specimens especially for lesions adjacent to both the trachea/bronchus and esophagus, improving disease positive diagnosis rate, reducing patients discomfort and the risk of surgery.

The Role and Application of Fibroblast Activating Protein.

Fibroblast activation protein-α (FAP), a type-II transmembrane serine protease, is rarely expressed in normal tissues but highly abundant in pathological diseases, including fibrosis, arthritis, and cancer. Ever since its discovery, we have deciphered its structure and biological properties and continue to investigate its roles in various diseases while attempting to utilize it for targeted therapy. To date, no significant breakthroughs have been made in terms of efficacy. However, in recent years, several practical applications in the realm of imaging diagnosis have been discovered. Given its unique expression in a diverse array of pathological tissues, the fundamental biological characteristics of FAP render it a crucial target for disease diagnosis and immunotherapy. To obtain a more comprehensive understanding of the research progress of FAP, its biological characteristics, involvement in diseases, and recent targeted application research have been reviewed. Moreover, we explored its development trend in the direction of clinical diagnoses and treatment.

To introduce a new method of resection of carotid body tumor with preservation of the internal carotid artery ----microscopic coagulation method

Objective:To introduce the surgical experience of carotid body tumor（CBT） resection with preservation of internal carotid artery. Methods:The clinical data of 109 patients with CBT were retrospectively analyzed. The key points of surgical techniques were summarized, the imaging and pathological results were comprehensively analyzed, and the postoperative complications were observed. Results:Of the 109 patients, 28 were Shamblin Ⅰ, 46 were Shamblin Ⅱ, and 35 were Shamblin Ⅲ. Synaptophysin（SYN） and soluble protein-100（S-100） were positive in all cases. There was a positive correlation between the average expression area percentage of S-100 and SYN in pathological tissue of 17 patients（r=0.48）, and the difference was statistically significant（P<0.05）. The average operation time was（148.4±46.2） minutes, the average intraoperative blood loss was（64.7±22.8） mL, and the average hospital stay was（15.2±2.6） days. Three patients underwent tumor resection combined with external carotid artery ligation, 1 patient underwent tumor resection combined with internal carotid artery ligation, and the remaining patients underwent tumor resection alone. The overall rate of intraoperative vascular ligation was 3.7% and the rate of nerve injury was 6.4%. According to preoperative CTA, intraoperative situation and postoperative pathological results, a new classification of CBT was proposed, which could intuitively reflect the gap between the tumor and the carotid artery and the nature of the tumor. Conclusion:Surgical resection of CBT is recommended after diagnosis. The potential gap between the tumor and the blood vessels was found under the microscope. Low energy bipolar electrocoagulation was used to coagulate and cut off the fibrous connective tissue between the tumor and gradually separated along the adventitia of the artery. The carotid artery could be preserved in most cases while the tumor was completely removed, and the amount of intraoperative bleeding and the incidence of complications were reduced. It is particularly important to identify the difficult cases before operation.

Subpectoral Biceps Tenodesis Using an All-Suture Anchor

Background: The long head of the biceps tendon (LHBT) has long been considered an intra-articular pain generator in the shoulder. While nonoperative treatment modalities can be acceptable for less severe presentations of LHBT pathology, surgical treatment options such as tenotomy and tenodesis remain controversial for recalcitrant cases. Open subpectoral biceps tenodesis allows for removal of all pathologic tissue from the bicipital groove, and all-suture anchor fixation utilizes a small caliber unicortical drill hole, which can potentially reduce the risk of a stress riser and iatrogenic fracture. Indications: In this study, we present a male patient with a history of left anterolateral shoulder pain worse overhead activities who has failed extensive physical therapy and other conservative measures. After extensive discussion regarding the treatment options, surgery in the form of shoulder arthroscopy, extensive debridement, rotator cuff repair, and open subpectoral biceps tenodesis was recommended and the patient had opted to proceed. For the purposes of this video, we focus on the open subpectoral biceps tenodesis portion of the procedure. Results: Open subpectoral biceps tenodesis can reduce pain with low complication and high satisfaction rates. Discussion: In this surgical technique study, we underline the importance position of the skin incision in axillary crease as well as skin tensioning when making the incision and retracting the conjoint tendon. We also highlight a locking lasso loop and double luggage tag fixation technique using a double-loaded all-suture anchor for the biceps tenodesis. We also provide technique commentary for appropriate restin tension of the LHBT. Finally, we review outcomes, postoperative management, rehabilitation protocol, and technique pearls and pitfalls. Patient Consent Disclosure Statement: The author(s) attests that consent has been obtained from any patient(s) appearing in this publication. If the individual may be identifiable, the author(s) has included a statement of release or other written form of approval from the patient(s) with this submission for publication.

Cystathionine-β-synthase expression correlates with tumour progression and adverse prognosis in patients with colon cancer.

To investigate the levels of cystathionine-β-synthase (CBS) in colon cancer tissues compared with adjacent control tissues; and to examine the relationship between CBS level and clinical characteristics and prognosis. This retrospective study enrolled patients with primary colon cancer. Paraffin-embedded specimens were used to create pathological tissue microarrays. Immunohistochemistry was performed on the microarray to detect the levels of CBS in colon cancer tissues and normal adjacent tissues. Analyses were undertaken to examine the relationship between the level of CBS and clinical characteristics and prognosis. A total of 216 patients (107 males and 109 females) were included in the study. The level of CBS in cancer tissues was found to be significantly increased compared with normal adjacent control tissues. There were significant differences in tumour location, tumour-node-metastasis stage and survival rate between the CBS-negative and CBS-positive groups. Positive CBS immunostaining was associated with decreased survival in colon cancer patients. The results of multivariate Cox regression analysis revealed that tumour location and positive CBS immunostaining were independent prognostic factors for survival. Positive CBS immunostaining was closely associated with colon cancer and high levels of CBS might accelerate tumour development and affect patient prognosis in colon cancer.

Quercetin Promotes Abdominal Aortic Aneurysm Regression Through the RAGE/PI3K/AKT/mTOR Axis

Objective: Abdominal aortic aneurysms (AAA) are a common critical cardiovascular disease with high morbidity and mortality rates. Quercetin, a flavonoid and a traditional Chinese medicinal ingredient commonly found in vegetables and fruits, has a favorable inhibitory effect on experimental aneurysms without side effects. This study aimed to model elastase AAA and investigate the mechanism of action of quercetin in alleviating AAA. Methods: Quercetin was administered at a dose of 60 mg/kg once daily starting on the day of AAA induction for 5 weeks. The therapeutic effect of quercetin on AAA was demonstrated using biochemical assays, observation of pathological tissue sections, Elastic Van Gieson staining, immunohistochemistry, molecular docking simulations, and Western blot protein validation. Results: Our study showed that quercetin treatment significantly alleviated abdominal aortic vessel wall dilatation, elastin degradation and adhesion to surrounding tissues caused by elastase. Additionally, quercetin significantly inhibited the mRNA and protein expression of the receptor for advanced glycation end products(RAGE)/ phosphatidylinositol 3-kinase (PI3K)/ phosphatidylinositol 3-kinase (AKT) / mammlian target of rapamycin (mTOR) pathway. Conclusion: Quercetin can alleviate abdominal aortic injury caused by elastase via RAGE/PI3K/AKT/mTOR and provide experience in clinical use.

A modified sampling method for the precise detection of prostate cancer tissues using a three-dimensional stereotaxic location technique.

The rapid and accurate acquisition of prostate cancer pathological tissue is critical to prostate cancer research but has traditionally proven challenging. However, the gradual application of three-dimensional (3D) modeling in medical practice has overcome many of the related limitations. This cohort study aimed to compare the difference between a 3D stereotaxic sampling method and traditional cognitive sampling method to clarify the factors affecting sampling. An analysis of 111 men who received radical prostatectomy for prostate cancer at The First Affiliated Hospital of Soochow University between November 2020 and April 2022 was conducted. The positive rate of the cognitive sampling method and the 3D stereotaxic sampling method and their respective influencing factors, such as age, body mass index (BMI), prostate-specific antigen (PSA), PSA density (PSAD), International Society of Urological Pathology (ISUP) grade, tumor volume, number of positive needles from perineal puncture, clinical T stage, and tumor image location, were compared and analyzed, and a cohort study was conducted. Among the 111 patients, there were 57 cases of cognitive sampling and 54 cases of 3D stereotaxic sampling. In this study, the positive rate of cognitive sampling was 29.82% (17/57,), and the positive rate of 3D stereotaxic sampling was 61.11% (33/54), with the positive rate of 3D stereotaxic sampling being significantly higher than that of cognitive sampling (P=0.001). In cognitive sampling, tumor volume [odds ratio (OR) =1.10; 95% confidence interval (CI): 1.02-1.20], number of positive biopsy cores (OR =1.30; 95% CI: 1.06-1.60), Prostate Imaging Report and Data System (PI-RADS) score (OR =5.54; 95% CI: 1.60-19.12), and clinical T stage (OR =2.36; 95% CI: 1.31-4.25) were identified as influencing factors; in 3D stereotaxic sampling, these influencing factors were eliminated, with ORs of 1.22 (95% CI: 0.78-1.90), 0.88 (95% CI: 0.72-1.09), 1.09 (95% CI: 0.62-1.92), and 1.51 (95% CI: 0.86-2.65), respectively, representing a statistically significant difference (P<0.05). The 3D stereotaxic sampling method can accurately obtain the required prostate cancer tissue from the prostate in vitro within a short time, and the factors affecting the positive rate of sampling can be eliminated.

She-Chuang-Si-Wu-Tang Alleviates Inflammation and Itching Symptoms in a Psoriasis Mouse Model by Regulating the Th17/IL-17 Axis via the STAT3/MAPK Pathways.

Psoriasis is an immune-related disorder characterized by silver scales, epidermis thickness, and itching. She-Chuang-Si-Wu-Tang (SSWT), a traditional Chinese medicine decoction, has been used clinically for 400 years. Although it benefits psoriasis treatment, the mechanism of action is still unclear. This study explores SSWT's molecular mechanism in treating psoriasis through network pharmacology analysis and experiments. We identified relevant SSWT and psoriasis targets using network pharmacology and conducted SSWT quality control with high-performance liquid chromatography (HPLC). A mouse model of psoriasis was established using imiquimod (IMQ), with the drug administered continuously for seven days, spanning an eight-day period. During the experiment, we observed spontaneous scratching behaviors and assessed the Psoriasis Area and Severity Index (PASI) scores. At the conclusion of the experiment, we examined skin tissue pathology under an optical microscope and measured epidermal thickness. Additionally, we used enzyme-linked immunosorbent assay (ELISA) and quantitative reverse transcription polymerase chain reaction (qRT-PCR) to measure interleukin (IL)-23, IL-17A, IL-17F, and interferon (IFN)-γ levels in the mice's serum and their mRNA expression in the skin. Western blot analysis was conducted to assess protein levels related to signaling pathways. Results indicate that SSWT may target IL-17 signaling pathways and T helper (Th) 17 cell differentiation, as predicted by network pharmacology. SSWT significantly improved the PASI and Baker scores, reduced epidermal thickness, and decreased spontaneous scratching in IMQ-induced mice. Additionally, SSWT treatment significantly lowered the concentrations of inflammatory factors in the serum and skin lesions, as well as mRNA expression levels, compared to the IMQ group. Furthermore, SSWT significantly inhibited the phosphorylation of both the signal transducer and activator of transcription 3 (STAT3) and mitogen-activated protein kinase (MAPK) pathways. In summary, this study unveiled the potential anti-psoriatic mechanism of SSWT, offering new evidence for its clinical application.

The hemostatic activity and Mechanistic roles of glucosyloxybenzyl 2-isobutylmalate extract (BSCE) from Bletilla striata (Thunb.) Rchb.f. in Inhibiting pulmonary hemorrhage

BackgroundHemorrhagic events cause numerous deaths annually worldwide, highlighting the urgent need for effective hemostatic drugs. The glucosyloxybenzyl 2-isobutylmalates Control Extract (BSCE) from the orchid plant Bletilla striata (Thunb.) Rchb.f. has demonstrated significant hemostatic activity in both in vitro and in vivo studies. However, the effect and mechanism of BSCE on non-traumatic bleeding remain unclear. MethodsPulmonary hemorrhage was induced in 40 Sprague-Dawley rats by administering Zingiber officinale Roscoe. for 14 days. These rats were then randomly divided into five groups: model (Mod), positive control (YNBY), and BSCE low, medium, and high-dose groups. An additional 8 rats served as the control group (Con). The BSCE groups received different doses of BSCE for 10 days, while the YNBY group received Yunnan Baiyao suspension. The effects on body weight, food and water intake, red blood cell count (RBC), hemoglobin concentration (HGB), lung tissue pathology, platelet count, coagulation parameters, and fibrinolytic system markers were evaluated. Network pharmacology and molecular docking analyses were also conducted to identify potential targets and pathways involved in BSCE's effects. ResultsBSCE treatment significantly improved body weight, food intake, and water consumption in rats with pulmonary hemorrhage. RBC and HGB levels increased significantly in the BSCE medium and high-dose groups compared to the Mod group (P < 0.05). Pathological examination revealed that BSCE reduced lung tissue hemorrhage and inflammation, with improvements in alveolar structure. BSCE also positively affected platelet count, thrombin time (TT), activated partial thromboplastin time (APTT), fibrinogen (FIB) levels, and fibrinolytic markers (D-dimer, PAI-1, and t-PA). Network pharmacology and molecular docking identified key targets such as MMPs, CASPs, and pathways including IL-17 and TNF signaling, suggesting BSCE's involvement in hemostasis and anti-inflammatory processes. ConclusionsBSCE exhibits significant hemostatic and protective effects on Z.officinale-induced pulmonary hemorrhage in rats by improving hematological parameters, reducing lung tissue damage, and modulating the coagulation and fibrinolytic systems. The study provides evidence supporting the potential of BSCE as a therapeutic agent for hemorrhagic diseases, with its efficacy linked to multi-target and multi-pathway interactions.