Pathological Analysis Research Articles

Visual pathology reports for communication of final margin status in laryngeal cancer surgery

BackgroundPositive margins are frequently observed in total laryngectomy (TL) specimens. Effective communication of margin sampling sites and final margin status between surgeons and pathologists is crucial. In this study, we evaluate the utility of multimedia visual pathology reports to facilitate interdisciplinary discussion of margin status in laryngeal cancer surgery. MethodsEx vivo laryngeal cancer surgical specimens were three-dimensional (3D) scanned before standard of care pathological analysis. Using computer-aided design software, the 3D model was annotated to reflect inking, sectioning, and margin sampling sites, generating a visual pathology report. These reports were distributed to head and neck surgeons and pathologists postoperatively. ResultsFifteen laryngeal cancer surgical specimens were 3D scanned and virtually annotated from January 2022 to December 2023. Most specimens (73.3%) were squamous cell carcinomas (SCCs). Among the cases, 26.7% had final positive surgical margins, whereas 13.3% had close margins, defined as <5 mm. The visual pathology report demonstrated sites of close or positive margins on the 3D specimens and was used to facilitate postoperative communication between surgeons and pathologists in 85.7% of these cases. Visual pathology reports were presented in multidisciplinary tumor board discussions (20%), email correspondences (13.3%), and teleconferences (6.7%), and were referenced in the final written pathology reports (26.7%). Conclusions3D scanning and virtual annotation of laryngeal cancer specimens for the creation of visual pathology reports is an innovative approach for postoperative pathology documentation, margin analysis, and surgeon–pathologist communication.

Swertia cincta and its main active ingredients regulate the PPAR-α pathway in anti-cholestatic liver injury

Ethnopharmacological relevanceSwertia cincta is a traditional remedy for cholestasis commonly utilised in Yunnan, China. Despite its widespread use, the specific active components and underlying mechanisms of action remain poorly understood. Aim of this studyThis study aimed to investigate the therapeutic properties, mechanisms, and active compounds of Swertia cincta in an animal model of cholestasis induced by alpha-naphthylisothiocyanate (ANIT). Materials and methodsUHPLC/Q-TOF-MS and high-performance liquid chromatography (HPLC) were utilised to analyse the blood components of Swertia cincta. An ANIT-induced cholestatic liver injury animal model was established, and metabolomics was employed to explore the potential mechanisms of Swertia cincta in treating cholestatic liver injury. Hepatocellular injury induced by taurochenodeoxycholic acid was evaluated in vitro, and key bioactive components of Swertia cincta for cholestatic liver injury treatment were identified and confirmed using the ANIT-induced mouse model. ResultsThe established HPLC method demonstrates good specificity and reproducibility, enabling the simultaneous determination of six components in Swertia cincta. Results from serum biochemical indicators and liver pathology analysis indicated that Swertia cincta exhibits promising anti-cholestasis liver injury effects. Specifically, gentiopicroside, loganic acid, and isoorientin were identified as key active ingredients in treating cholestatic liver injury. Their mechanism of action primarily involves regulating PPAR-α, FXR, CYP3A4, NTCP, CAR, and CPT2. By modulating PPAR-α and bile acid metabolism-related proteins, reducing pro-inflammatory factors, enhancing bile acid transport, and promoting fatty acid oxidation to reduce lipid accumulation, Swertia cincta exerts protective and therapeutic effects against cholestatic liver injury. Notably, gentian bitter glycosides appear to be the most critical components for this effect. ConclusionSwertia cincta may improve cholestatic liver injury by activating the peroxisome proliferator-activated receptor alpha pathway, and the key active compounds were gentiopicroside, loganic acid, and isoorientin.

ECMTrans-net: Multi-Class Segmentation Network Based on Tumor Tissue in Endometrial Cancer Pathology Images

Endometrial cancer has the second highest incidence of malignant tumors in the female reproductive system, and accurate and efficient endometrial cancer pathology image analysis is one of the important research components of computer-aided diagnosis. However, endometrial cancer pathologic images have the challenges of smaller solid tumors, lesion areas varying in morphology, and difficulty distinguishing solid and non-solid tumors, which would impact the accuracy of subsequent pathological analyses. Therefore, an Endometrial Cancer Multi-class Transformer Network (ECMTrans-net) is proposed to improve the segmentation accuracy of endometrial cancer pathology images. On the one hand, an ECM-Attention is proposed, which can sequentially infer attention maps along three separate dimensions: channel, local spatial, and global spatial, and multiply the attention maps and the input feature map for adaptive feature refinement, solving the problems of the small size of solid tumors and similar characteristics of solid tumors to non-solid tumors and further improving the accuracy of segmentation of solid tumors. On the other hand, an ECM-Transformer is proposed, which can fuse multi-class feature information and dynamically adjust the receptive field, solving the issue of complex tumor features. Experiments on the solid tumor endometrial cancer pathological (ST-ECP) dataset show that the ECMTrans-net performs superior to state-of-the-art image segmentation methods, and the average values of Accuracy, MIoU, Precision, and Dice were 0.952, 0.927, 0.931 and 0.901, respectively.

Inter-reader reliability and diagnostic accuracy of PI-RADS scoring between academic and community care networks: How wide is the gap?

ImportanceThe Prostate Imaging Reporting & Data System (PI-RADS) scoring guidelines were developed to address the substantial variation in interpretation and reporting of prostate cancer (PCa) multiparametric MRI (mpMRI) results, and subsequent updates have sought to further improve inter-reader reliability. Nonetheless, the variability of PI-RADS scoring in real-world settings may represent a continuing challenge to the widespread standardization of prostate mpMRI and limit its overall clinical benefit. ObjectiveTo assess variability in mpMRI interpretation and reporting of PCa, we evaluated the discrepancies in PI-RADS scoring between community practices and a tertiary academic care center. Design, setting, and participantsWe identified 262 mpMRI studies from nonacademic facilities, reinterpreted by radiologists at our institution between January 2016 and July 2022. Results of targeted MRI fusion biopsy were identified for 193 of these patients, totaling 302 lesions. PI-RADS scoring from both community and academic interpreters were recorded in addition to presence of clinically significant PCa (csPCa) on pathological analysis of targeted cores. Main Outcome and measuresThe primary outcome was inter-reader reliability via intraclass correlation (ICC) and the kappa statistic. We also assessed the diagnostic accuracy of PI-RADS scoring for detecting csPCa for both cohorts via receiver operator characteristics (ROC) analysis and compared these findings using paired-sample area difference under curve analysis. ResultsInter-reader agreement and reliability of PI-RADS scoring per lesion was generally poor (absolute agreement ICC = 0.393, 95% CI: 0.288–0.488; consistency ICC = 0.407, 95% CI: 0.308–0.497; kappa = 0.336, 95% CI: 0.267–0.406). Reliability results from studies obtained after the publication of PI-RADSv2.1 were similar to those of the overall analysis. No agreement was observed in the subgroup of lesions scored as PIRADS 3 by community interpreters. No statistically significant difference in diagnostic accuracy was observed between cohorts (ROC area under curve [AUC]: 0.759 vs. 0.785, respectively; P = 0.337). PI-RADS 3 was determined to be the optimal cutoff for detecting clinically significant disease in both cohorts. Conclusions and relevanceOur results suggest that mpMRI diagnostic accuracy for detecting csPCa is not significantly different between academic and community practices. However, significantly poor reliability of mpMRI was observed between cohorts, suggesting the risk of introducing practice variation for community prostate cancer management. Variability, particularly for PI-RADS 3 lesions, can lead to inconsistent biopsy recommendations, which may result in missed csPCa or unnecessary biopsies.

Case study: May human norovirus infection be associated with premature delivery?

Human norovirus (HuNoV) is the leading cause of acute gastroenteritis. The varying severity of chronic infection in patients with underlying immune deficiencies poses additional burdens on public health. However, the potential effects of HuNoV infection during pregnancy, a specific immune perturbed state, have been rarely reported. Recently, four cases of HuNoV-infected patients in the late stages of pregnancy were admitted to the Guangzhou Women and Children's Medical Center, and premature rupture of membranes as primary adverse outcome was observed in these cases. Samples of fetal accessory tissue were collected from two of these cases at delivery to explore the potential pathogenesis. Pathological analysis showed placental malperfusion in both maternal and fetal vascular, while a decrease in vessels was not observed in villi of placenta. There was obvious pathological change in the chorion of fetal membrane, accompanied by a tendency of Th-1 immune bias. Notably, aggregation of M2 macrophages was observed in the chorion of the fetal membrane, potentially recruited for tissue repair. Next-generation sequencing showed minimal changes in immune pathways within placenta tissue. A gene panel associated with immunosuppression was identified in the fetal membrane of HuNoV-infected women compared to those of normal parturient. Taken together, this study provides clues for the association between the HuNoV and premature delivery, which requires the attention of the clinicians.

Efficient, gigapixel-scale, aberration-free whole slide scanner using angular ptychographic imaging with closed-form solution.

Whole slide imaging provides a wide field-of-view (FOV) across cross-sections of biopsy or surgery samples, significantly facilitating pathological analysis and clinical diagnosis. Such high-quality images that enable detailed visualization of cellular and tissue structures are essential for effective patient care and treatment planning. To obtain such high-quality images for pathology applications, there is a need for scanners with high spatial bandwidth products, free from aberrations, and without the requirement for z-scanning. Here we report a whole slide imaging system based on angular ptychographic imaging with a closed-form solution (WSI-APIC), which offers efficient, tens-of-gigapixels, large-FOV, aberration-free imaging. WSI-APIC utilizes oblique incoherent illumination for initial high-level segmentation, thereby bypassing unnecessary scanning of the background regions and enhancing image acquisition efficiency. A GPU-accelerated APIC algorithm analytically reconstructs phase images with effective digital aberration corrections and improved optical resolutions. Moreover, an auto-stitching technique based on scale-invariant feature transform ensures the seamless concatenation of whole slide phase images. In our experiment, WSI-APIC achieved an optical resolution of 772 nm using a 10×/0.25 NA objective lens and captures 80-gigapixel aberration-free phase images for a standard 76.2 mm × 25.4 mm microscopic slide.

Integrated multi-omics approach and pathological analyses provide new insights into the hepatic injury and metabolic alterations in Saanen goats after dietary exposure to aflatoxin B1

Exploring the toxicity and metabolic mechanisms of Aflatoxin B1 (AFB1) in ruminants can help to develop strategies to prevent or reduce the transfer of the toxin and its metabolites to milk and meat. This study aimed to explore the effects of 3 concentrations of dietary AFB1 (0, 50, and 500 μg/kg) on hepatic injury and metabolism in Saanen goats via histological examination, Western blot analysis, as well as integrated multi-omics techniques. Eighteen Saanen goats were assigned to 1 of 3 treatments and the AFB1 challenge lasted for 14 d. Results showed that the liver tissue was enlarged and the relative organ index of the liver was linearly increased with elevated AFB1 levels. The hepatocyte apoptosis rate was significantly increased after AFB1 exposure and the Western blotting results revealed that both the external apoptotic pathway and mitochondrial-mediated intrinsic apoptotic pathway might be involved in AFB1-induced hepatocyte apoptosis. There were 251, 269, 154 significant differentially expressed genes (DEGs) and 340, 596, 127 significant differential metabolites for the control (C; 0 μg/kg) and low-dose (L; 50 μg/kg), C and high-dose (H; 500 μg/kg), L and H comparisons. The DEGs annotated were mainly involved in the cell part, cell, single-organism process, cellular process, binding, and other functional categories. The identified metabolites primarily belonged to glycerophospholipids, prenol lipids, carboxylic acids and derivatives. Integrative analysis of transcriptomics and metabolomics revealed that glycerophospholipids metabolism and choline metabolism in cancer were the most affected pathways related to AFB1 exposure. The identified differential metabolites, DEGs, and pathways might have played a crucial role in the hepatic injury induced by AFB1 in goats.

TCT-424 Pathologic Analysis of Fibrin Deposition Around Stent Struts Within 1 Month After Placement of Circumferentially Coated Durable Polymer Drug-Eluting Stents and Abluminally Coated Biodegradable Polymer Drug-Eluting Stents for Acute Coronary Syndrome

TCT-424 Pathologic Analysis of Fibrin Deposition Around Stent Struts Within 1 Month After Placement of Circumferentially Coated Durable Polymer Drug-Eluting Stents and Abluminally Coated Biodegradable Polymer Drug-Eluting Stents for Acute Coronary Syndrome

Multiple Primary Cavernous Hemangiomas of the Skull.

Multiple primary cavernous hemangiomas of the skull are exceedingly rare, with surgery often being the treatment of choice. The complexity of radiologic diagnosis means that the identification of these hemangiomas still largely depends on pathologic analysis. This article outlines the diagnostic and therapeutic journey of a 52-year-old female patient afflicted with multiple primary cavernous hemangiomas of the skull. Although the occurrence of multiple cavernous hemangiomas in this patient may seem fortuitous, the authors aim to contribute to understanding the pathogenesis of such conditions through this case report.

Algorithm for Processing X-ray Images Using Fuzzy Logic

Introduction. To improve the diagnostics of knee joint diseases, it is necessary to enhance the quality of processing radiographic images, i.e., to provide experts with more accurate information for pathology analysis. The objective of the study is to demonstrate the capabilities of fuzzy logic in improving the algorithm for determining reference lines and knee flexion angles. This requires a program that analyzes X-ray images. The methods known today, described in scientific and applied literature, are not sufficiently automated. In some cases, orthopedists and surgeons have to manually refine images and adjust lines. This gap is filled by the presented work. The algorithm developed by the author is described. It does not involve human participation and automatically identifies the lines and angles of knee flexion. Based on the result issued by the system, the doctor can, firstly, judge the presence of pathology. Secondly, the information provided by the program allows for more accurate planning, performing operations, and prescribing therapy.Materials and Methods. Images from two X-ray machines operating in Al-Basel Hospital (Latakia, Syria) were used. The Python language was used for the software implementation of the algorithm. The solution was tested on 500 patients at Al-Basel Hospital. The results generated by the new system and previous versions of X-ray image processing programs were compared.Results. An algorithm for constructing reference lines and angles for processing knee joint X-ray images is created, described, and implemented in practice. The capabilities of fuzzy logic in automating double threshold detection when identifying bone boundaries in images are shown. The operation of an improved Gaussian filter designed for processing X-ray images is described. The modified method of knee bone X-ray analysis includes the development of an algorithm for automatic detection of structures and anomalies in knee joints, determination and measurement of anatomical parameters, assessment of the degree of damage, etc. The method for determining the contour boundaries on radiographs combined the Canny detector, the watershed algorithm, and fuzzy logic. The program has been implemented in medical practice and shows 98% accuracy, spending less than 20 seconds to process the image.Discussion and Conclusion. The new system provides high accuracy, acceptable efficiency, and does not require manual correction of images. Experts are now able to identify subtle indicators of disorders. In addition, the new method makes it possible to understand complex cases when several factors are combined, indicating potential pathology. Widespread implementation of the method will improve the quality of medical services in orthopedics. Scientific research in this direction should be continued to expand the set of strategies for the treatment of diseases of the musculoskeletal system. It is necessary to create solutions with absolute accuracy, higher processing efficiency, as well as methods suitable for analyzing other joints.

Successful rapid improvement of acute respiratory distress syndrome induced by EGFR-mutated non-small cell lung cancer with almonertinib: a case report

BackgroundAcute respiratory distress syndrome (ARDS) is a life-threatening condition frequently encountered in critically ill patients, including those with advanced non-small cell lung cancer (NSCLC). Almonertinib, a third-generation epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor (TKI), has shown promise as a first-line treatment for NSCLC with classical EGFR mutations. However, its efficacy in NSCLC patients suffering from ARDS has not been well-documented.Case PresentationWe report the case of a 63-year-old Chinese Han female with severe NSCLC complicated by ARDS. Upon hospital admission, the patient exhibited progressive dyspnea and required intubation to maintain oxygenation. Pathological analysis of bronchoalveolar lavage fluid sediment confirmed lung adenocarcinoma, and genetic testing of blood identified an EGFR E19 mutation. The patient was treated with almonertinib, resulting in significant clinical improvement and successful extubation after nine days. Radiographic imaging showed substantial reduction in pulmonary lesions, highlighting the efficacy of almonertinib.ConclusionThis case represents the first documented successful treatment of ARDS induced by EGFR E19 mutated NSCLC using almonertinib. The favorable clinical response observed in this critically ill patient suggests that almonertinib may be a viable therapeutic option for managing severe complications in NSCLC. Further research is necessary to corroborate these findings and optimize dosage and toxicity management strategies for broader clinical application.

Laparoscopic endoscopic cooperative surgery for gastric subepithelial lesion during laparoscopic sleeve gastrectomy for severe obesity

BackgroundThe frequency of pathologies detected incidentally before, during, and after a bariatric surgery, such as subepithelial lesion (SEL) of the stomach, is likely to rise as bariatric surgery becomes more common.Case presentationA 49-year-old female patient presented with severe obesity, for which laparoscopic sleeve gastrectomy (LSG) was planned. During a preoperative examination, endoscopy revealed a 10 mm SEL in the posterior wall of the upper body of the stomach. Excision of the SEL was performed simultaneously with the LSG. Endoscopy demonstrated that the SEL was situated on the remnant side of the stomach. Endoscopic resection using laparoscopic endoscopic cooperative surgery was performed for the SEL, and the thinned gastric wall was closed by hand-sewing. Thereafter, LSG was performed. Pathological analysis of the SEL led to a diagnosis of leiomyoma. The patient was discharged on postoperative day 6.ConclusionSurgeons should be prepared to manage incidentally detected pathologies before, during, and after bariatric surgery and to choose the surgical method most suitable to the individual patient.

Loss of TREM2 diminishes CAA despite an overall increase of amyloid load in Tg-SwDI mice.

The microglial receptor triggering receptor expressed on myeloid cells 2 (TREM2) is a major risk factor for Alzheimer's disease (AD). Experimentally, Trem2 deficiency affects parenchymal amyloid beta (Aβ) deposition. However, the role of TREM2 in cerebrovascular amyloidosis, especially cerebral amyloid angiopathy (CAA), remains unexplored. Tg-SwDI (SwDI) mice, a CAA-prone model of AD, and Trem2 knockout mice were crossed to generate SwDI/TWT, SwDI/THet, and SwDI/TKO mice, followed by pathological and biochemical analyses at 16 months of age. Loss of Trem2 led to a dramatic decrease in CAA and microglial association, despite a marked increase in overall brain Aβ load. Single nucleus RNA sequencing analysis revealed that in the absence of Trem2, microglia were activated but trapped in transition to the fully reactive state, with distinct responses of vascular cells. Our study provides the first evidence that TREM2 differentially modulates parenchymal and vascular Aβ pathologies, offering significant implications for both TREM2- and Aβ-targeting therapies for AD. Triggering receptor expressed on myeloid cells 2 (TREM2) differentially modulates brain parenchymal and vascular amyloidosis. Loss of Trem2 markedly reduces cerebral amyloid angiopathy despite an overall increase of amyloid beta load in Tg-SwDI mice. Microglia are trapped in transition to the fully reactive state without Trem2. Perivascular macrophages and other vascular cells have distinct responses to Trem2 deficiency. Balanced TREM2-targeting therapies may be required for optimal outcomes.

Malignant Perivascular epithelioid cell tumour of the uterus without TFE3 gene rearrangement: a case report

BackgroundPerivascular epithelioid cell tumours (PEComas) are soft tissue tumours. These neoplasms belong to the family of mesenchymal tumours, which include angiomyolipomas, clear-cell sugar tumours of the lung, and PEComas not otherwise specified (NOS). The probability of a perivascular epithelioid cell tumour (PEComa) occurring in the uterus is low, and the incidence, diagnosis, treatment, and outcomes of such tumours are still unclear.Case presentationA 51-year-old woman presented a 4-year history of natural menopause. An intrauterine mass was detected via ultrasound examination; the mass showed a tendency to increase but caused no symptoms. The levels of tumour markers were within the normal range. Pathological analysis of the curettage revealed perivascular epithelioid differentiation of the endometrial tumour. Consequently, a laparoscopic total hysterectomy with bilateral adnexectomy was performed. No distant metastasis was detected via whole-body positron emission computed tomography (PETCT) after the operation. Fluorescence in situ hybridization (FISH) revealed no TFE3 gene rearrangement. Next-generation sequencing of bone and soft tissue revealed negative TSC1/2 and TP53 expression. No recurrence or metastasis was observed during the 18-month follow-up period.ConclusionPEComa of the gynecologic tract is a rare and challenging entity. Diffuse HMB-45 expression, TSC alterations and TFE3 rearrangement are characteristic of uterine PEComas. Surgical resection is the first choice. Genetic testing is helpful for determining the nature of the mass and for choosing targeted therapy. Further research is needed to establish treatment protocols.

Application of Magnetic Resonance Imaging Report Combined With VI-RADS Bi-Parametric and Multi-Parametric Scoring Systems in Bladder Cancer Diagnosis

To verify by retrospective analysis the performance of applying dual-parametric (T2 weighted image [T2WI] and diffusion weighted image [DWI]) and multi-parametric (T2WI, DWI, and dynamic contrast enhance [DCE]) evaluation systems of Vesical Imaging-Reporting and Data System (VI-RADS) in the magnetic resonance imaging (MRI) diagnosis of bladder cancer. The imaging and clinical data of bladder cancer patients who underwent bladder MRI examination in the Department of Urology of our hospital between January 2020 and December 2021 were collected. A total of 215 bladder cancer patients, among whom there were 183 males and 32 females with an average age of (67.60±11.42) years, were included. The bladder cancer diagnosis of all the cases was verified by pathology analysis of tissue samples. Two radiologists, who were double-blinded, scored multiple sequences separately. Then, a comparative analysis was made on the diagnostic performance of dual-parametric and multi-parametric VI-RADS diagnostic scores. The diagnostic test with receiver operator characteristic (ROC) curves and Cohen's Kappa were used to evaluate the diagnostic efficacy and consistency. The area under the curve (AUC) and 95% confidence interval (CI) of the multi-parametric VI-RADS evaluation system by the two radiologists in the overall population were 0.878 (0.830-0.925) and 0.856 (0.805-0.907), while those for the bi-parametric VI-RADS evaluation system were 0.889 (0.844-0.934) and 0.856 (0.805-0.907), showing no statistically significant difference. No significant difference was observed in the subgroup analysis of patients who underwent transurethral resection of bladder tumor (TURBT). Furthermore, the Kappa values for inter-rater agreement between of the two radiologists were 0.694 and 0.546 (with the VI-RADS score≥3 defined as being positive) and 0.693 and 0.712 (with the VI-RADS score≥4 defined as being positive) in multi-parametric and bi-parametric evaluation, respectively (all P<0.001). The bi-parametric VI-RADS scoring system can achieve a diagnostic efficacy comparable to that of the multi-parametric scoring system, offering an alternative to patients who are unable to undergo contrast-enhanced MRI due to allergic reaction to contrasts.

Integrated microRNA study and pathological analysis provides new insights into the immune response of Ruditapes philippinarum under Vibrio anguillarum challenge

Manila clam (Ruditapes philippenarum) is an important shellfish aquaculture product. The large-scale breeding of clams is often affected by V. anguillarum and causes large-scale death. However, the pathogenesis, immune response and metabolic pathway of V. anguillarum are still unclear. In this study, we found that the bacterial load in the hepatopancreas of R. philippinarum peaked at 48 h after V. anguillarum infection, and then gradually decreased, while the activity of lysozyme reached the peak at 12 h. Tissue section observation reveals that the infected hepatopancreas cells lost normal structure or necrosis. Additionally, six small RNA libraries were constructed using hepatopancreas of clams. A total of 15 differentially expressed (DE) microRNA (miRNA) were identified at 48 h after V. anguillarum infection, including 8 upregulated and 7 downregulated miRNAs. GO and KEGG enrichment results indicated the prediction of 48 known miRNAs and 127 new miRNAs, with functional annotation suggests that endocytosis pathway and bacterial recognition proteins may play key roles in immune response. The sequencing results were basically consistent with the qRT-PCR validation, indicating the accuracy of the data. This study provides a new idea to explore the immune regulation mechanism of shellfish after V. anguillarum infection, which brings important reference significance for modern immunological research.

CCL4 as a potential serum factor in differential diagnosis of central nervous system inflammatory diseases and gliomas.

Computed tomography (CT) scans and magnetic resonance imaging (MRI) are commonly utilized to detect brain gliomas and central nervous system inflammation diseases. However, there are instances where depending solely on medical imaging for a precise diagnosis may result in unsuitable medications or treatments. Pathological analysis is regarded as the definitive method for diagnosing brain gliomas or central nervous system inflammation diseases. To achieve this, a craniotomy or stereotaxic biopsy is necessary to collect brain tissue, which can lead to complications such as cerebral hemorrhage, neurological deficits, cerebrospinal fluid leaks, and cerebral edema. Consequently, the advancement of non-invasive or minimally invasive diagnostic techniques is currently a high priority. This study included samples from four glioma patients and five patients with central nervous system inflammatory diseases, comprising both serum and paired cerebrospinal fluid (CSF). A total of 40 human cytokines were identified in these samples. We utilized a receiver operating characteristic (ROC) analysis to assess the sensitivity and specificity for distinguishing central nervous system inflammation diseases and gliomas. Additionally, we examined the correlation of these factors between serum and CSF in the patients. Ultimately, the identified factors were validated using serum from patients with clinically confirmed gliomas and central nervous system inflammation diseases followed by detection and statistical analysis through ELISA. The levels of serum factors IL-4, IFN-α, IFN-γ, IL-6, TNF-α, CCL4, CCL11, and VEGF were found to be significantly higher in gliomas compared with inflammatory diseases of the central nervous system (p < 0.05). Furthermore, a strong correlation was observed between the levels of CCL4 in serum and CSF, with a correlation coefficient of r = 0.92 (95% CI = 0.20-0.99, p = 0.027). We gathered more clinical samples to provide further validation of the abundance of CCL4 expression. A clinical study analyzing serum samples from 19 glioma patients and 22 patients with central nervous system inflammation diseases revealed that CCL4 levels were notably elevated in the inflammatory group compared with the glioma group (p < 0.001). These results suggest that assessing serum CCL4 levels may be useful in distinguishing those patients for clinical diagnostic purposes.

Fei-yan-qing-hua decoction exerts an anti-inflammatory role during influenza by inhibiting the infiltration of macrophages and neutrophils through NF-κB and p38 MAPK pathways

Ethnopharmacological relevanceFei-Yan-Qing-Hua decoction (FYQHD) is an empirical formula that has shown clinical success in treating community-acquired pneumonia (CAP) for two decades. Influenza viral infection is a significant trigger for severe pneumonia, yet the role of FYQHD in treating influenza remains unclear. Aim of the studyThis study aimed to assess the potential efficacy of FYQHD in treating influenza viral infection and to elucidate its underlying mechanisms. Materials and methodsThe protective effects of FYQHD against influenza were evaluated through survival assessments and pathological analyses. Transcriptomic analysis was performed to identify the genes and pathways influenced by FYQHD in influenza. The anti-inflammatory effects and molecular mechanisms of FYQHD were studied in macrophages stimulated by Toll-like receptor (TLR) 7 ligation in vitro. The key constituents of FYQHD absorbed in mouse sera were identified using untargeted metabolomics, and the anti-inflammatory activity of some of these compounds in macrophages was evaluated using ELISA. ResultsOur findings demonstrate that FYQHD enhances survival and reduces lung damage in PR8-infected mice, primarily through its anti-inflammatory properties. Lung indexes and organ damage were significantly lower in the PR8 + OSV + FYQHD group compared to the PR8 + OSV group, indicating a potential complementary therapeutic effect of FYQHD and OSV in treating influenza. FYQHD effectively reduced chemokine expression, thereby decreasing the chemotaxis and infiltration of inflammatory monocytes/macrophages and neutrophils in the lungs. The anti-inflammatory effects of FYQHD in macrophages were achieved through the inhibition of NF-κB activation and p38 phosphorylation. The key constituents of FYQHD absorbed in mouse sera were identified, with some, such as wogonin, luteolin, kaempferol, and isorhamnetin, showing anti-inflammatory effects in primary macrophages. ConclusionFYQHD demonstrates protective efficacy against influenza and shows promise as an adjuvant therapeutic agent, particularly when used in combination with antiviral drugs like OSV. The potent anti-inflammatory components within FYQHD provide a basis for further exploration in drug research and development aimed at combating influenza.

LiverMap pipeline for 3D imaging of human liver reveals volumetric spatial dysregulation of cirrhotic vasculobiliary architecture.

The liver contains an intricate microstructure that is critical for liver function. Architectural disruption of this spatial structure is pathologic. Unfortunately, 2D histopathology - the gold standard for pathological understanding of many liver diseases - can misrepresent or leave gaps in our understanding of complex 3D structural features. Here, we utilized immunostaining, tissue clearing, microscopy, and computational software to create 3D multilobular reconstructions of both non-fibrotic and cirrhotic human liver tissue. We found that spatial architecture in human cirrhotic liver samples with varying etiologies had sinusoid zonation dysregulation, reduction in glutamine synthetase-expressing pericentral hepatocytes, regression of central vein networks, disruption of hepatic arterial networks, and fragmentation of biliary networks, which together suggest a pro-portalization/decentralization phenotype in cirrhotic tissue. Further implementation of 3D pathological analyses may provide a deeper understanding of cirrhotic pathobiology and inspire novel treatments for liver disease.

Clinical, myopathological, and genetic features of two Chinese families with Andersen-Tawil syndrome.

To explore the clinical, muscle pathological, and pathogenic gene mutation characteristics of Andersen-Tawil Syndrome (ATS) and enhance the understanding of ATS among clinical practitioners. Retrospective analysis of clinical data and muscle pathology of two ATS families, along with genetic testing for probands and some family members. In Family 1, spanning four generations, four individuals were affected, while Family 2 had two affected individuals across four generations. All six patients in both families experienced onset in childhood, presenting with periodic paralysis, arrhythmias, and craniofacial skeletal abnormalities. In Family 1, the proband's periodic paralysis was more triggered by low temperature and exercise, occurring several times a year, lasting 4-7 days. All three adult patients in Family 1 had a history of hypokalemia, and the frequency and severity of attacks were reduced after regular oral potassium supplement therapy. Two adult females in Family 1 experienced limb weakness triggered by stress, exertion, and premenstrual period, with milder symptoms than the proband. In Family 2, the proband's periodic paralysis typically occurred the day after excessive exertion, with a frequency of approximately 2-3 months. Two years prior, the proband developed arrhythmias without palpitations or chest tightness. The proband's brother experienced intermittent limb weakness during adolescence, remained untreated, and had sudden death at age 40. Physical examination revealed characteristic features in Family 1 and both probands: small mandible, wide eye spacing, and fifth-digit clinodactyly. Four adult patients were shorter in stature, while the growth status of a pediatric patient was indeterminate. Supplementary tests showed a history of hypokalemia during muscle weakness episodes in Family 1, while Family 2 patients had normal potassium levels during episodes. The long exercise tests were positive in both probands. Muscle MRI showed no significant abnormalities, but muscle pathology revealed rimmed vacuoles and tubular aggregates. Genetic testing identified KCNJ2 gene mutations in two probands and some of their family members, with c.407C > T (p.S136F) heterozygous mutation in Family 1 and c.652C > T (p.R218W) heterozygous mutation in Family 2. Among the clinical symptoms of the patients with Andersen-Tawil Syndrome in this study, not everyone exhibits the full triad of signs: periodic paralysis is the most common initial symptom, craniofacial and digit skeletal abnormalities are characteristic signs, and ventricular arrhythmias pose the most serious potential risk. Given that these typical symptoms were observed in 5 out of 6 patients, clinicians should pay special attention to these typical symptoms, and patients with these symptoms should be followed up over time. Muscle biopsy May reveal pathological changes such as tubular aggregates, but genetic testing for KCNJ gene mutations remains a crucial diagnostic criterion for this syndrome.