Misdiagnosis of a Drain-site Hernia Containing Fallopian Tube Fimbria on 18F-FDG PET/CT.

In a 55-year-old woman with sigmoid colon cancer, a subcutaneous mass in the left lower abdomen was incidentally found and gradually enlarged. For further diagnosis and staging, an 18F-fluorodeoxyglucose (FDG) positron emission tomography/computed tomography scan was performed, which revealed a subcutaneous mass in the left lower abdomen with mild uptake of 18F-FDG, suggesting the possibility of metastasis. However, post-surgery and pathological confirmation, this mass was diagnosed as a drain-site hernia containing fallopian tube fimbria, which is extremely rare but should be considered in the differential diagnosis of subcutaneous mass in the lower abdomen.

The pathogenic response of cytotoxic T­lymphocytes, a common therapeutic target for cancer, has a direct impact on treatment outcomes (Review).

Cytotoxic T lymphocytes (CTLs), also known as CD8+ T cells, participate in immune function by secreting various cytokines after recognizing specific antigens and class I major histocompatibility complex molecules associated with tumor cells, and thus have a key role in antitumor immunity. However, certain CD8+ T cells show low reactivity and thus cannot effectively remove tumor cells or viral antigens. Due to this heterogeneity, effective biomarkers representing these differences in CD8+ cells are needed. The identification of suitable biomarkers will also enhance the management of cancer treatment. Recent research has improved the understanding of CD8+ T lymphocytes in the tumor microenvironment and circulatory system. Treatment efficacy is impacted directly by the pathogenic response of CTLs, and thus, the use of adjuvant therapies to address these pathological changes, e.g., stimulating the increase in the proportion of reactive T cells or suppressing the proportion of terminally exhausted T cells, would be advantageous.

The potential meat flavoring derived from Maillard reaction products of rice protein isolate hydrolysate-xylose via the regulation of temperature and cysteine.

Maillard reaction products (MRPs) derived from rice protein isolate hydrolysate and D-xylose, with or without L-cysteine, were developed as a potential meat flavoring. The combined impact of temperature (80-140 °C) and cysteine on fundamental physicochemical characteristics, antioxidant activity, and flavor of MRPs were investigated through assessments of pH, color, UV-visible spectra, fluorescence spectra, free amino acids, volatile compounds, E-nose, E-tongue, and sensory evaluation. Results suggested that increasing temperature would reduce pH, deepen color, promote volatile compounds formation, and reduce the overall umami and bitterness. Cysteine addition contributed to the color inhibition, enhancement of DPPH radical-scavenging activity and reducing power, improvement in mouthfulness and continuity, reduction of bitterness, and the formation of sulfur compounds responsible for meaty flavor. Overall, MRPs prepared at 120 °C with cysteine addition could be utilized as a potential meat flavoring with the highest antioxidant activity and relatively high mouthfulness, continuity, umami, meaty aroma, and relatively low bitterness.

Increased secretion of bacterial pyomelanin caused by light accelerates corrosion of low alloy steel.

Microorganisms in the waterline zone can secrete pigments to avoid damage caused by ultraviolet radiation, some of which have corrosive effects. In this work, we found that the secretion of pyomelanin by P3 strain of Pseudoalteromonas lipolytica significantly increases under strong lighting conditions, accelerating the corrosion of the material. Molecular mechanisms indicate that strong light, as a stressful environmental factor, enhances the expression of melanin secretion-related genes to prevent bacteria from being damaged by ultraviolet radiation. Therefore, this work proposes a new corrosion mechanism in the waterline zone, pigment-producing microorganisms are also involved in the waterline corrosion process.

Treatment of Moderate-to-Severe Pain in Hepatocellular Carcinoma with Transcutaneous Electrical Acupoint Stimulation: A Randomized Controlled Trial.

Objective: Moderate-to-severe pain is the most common clinical symptom in patients with hepatocellular carcinoma (HCC).This trial aimed to analyze the clinical efficacy of Transcutaneous electrical acupoint stimulation (TEAS) in patients of HCC with severe pain and provide a reliable reference for optimizing the clinical diagnostic and therapeutic strategies of HCC. Methods: A total of 104 eligible patients were randomly allocated to experimental and control groups in a ratio of 1:1.The treatment was administered for 1 week continuously. Patients in both groups were followed up 1 week after the end of the treatment.The primary outcome measure was the Numerical Rating Scale (NRS) score, whereas the secondary outcome measures included Brief Pain Inventory BPI-Q3, Q4, Q5 scores, analgesic dose, frequency of opioid-induced gastrointestinal side effects, Karnofsky Performance Status (KPS), Quality of Life Scale - Liver Cancer (QOL-LC), and Brief Fatigue Inventory (BFI) scores. Results: The NRS scores of experimental group was significantly lower after treatment and at the follow-up than baseline (average P<0.01), there were also statistical differences between the groups at the above time points (average P<0.01). BPI-Q3, -Q4, and -Q5 scores in the experimental group were decreased after treatment when compared with those before treatment (average P<0.01). Furthermore, there were significant improvements of gastrointestinal side effects, KPS, QOL-LC and BPI in the experimental group after treatment, and the above results were statistically significant compared to the control group. Conclusion: 7-day TEAS treatment can significantly enhance the analgesic effect and maintain for the following week, also reduce the incidence of gastrointestinal side effects caused by opioids, and improve the quality of life of patients with moderate-to-severe HCC-related pain, which has reliable safety and certain clinical promotion value.

Early growth response 1 regulates dual­specificity protein phosphatase 1 and inhibits cell migration and invasion of tongue squamous cell carcinoma.

Oral squamous cell carcinoma (OSCC) is one of the most common malignant tumors in the head and neck, and among the OSCCs, tongue squamous cell carcinoma (TSCC) is one of the most common types. Although therapy strategies have recently advanced, the prognosis of TSCC has not substantially improved. Metastasis is one of the main causes of patient mortality in TSCC; therefore, it is necessary to elucidate the mechanism by which TSCC metastasis is regulated. In the present study, the early growth response 1 (Egr-1) expression in TSCC was analyzed based on GEO datasets and the effect of Egr-1 in TSCC tumor cell migration and invasion was measured using Transwell assay. By overexpressing dual-specificity protein phosphatase 1 (DUSP1) in cells with Egr-1 knockdown using lentivirus infection, the role of DUSP1 in Egr-1-regulated TSCC cell migration and invasion was determined. By using luciferase and ChIP assays, the mechanism behind how DUSP1 is regulated by Egr-1 was detected. In the present study, it was demonstrated that Egr-1 was downregulated in TSCC and the knockdown of Egr-1 increased TSCC cell migration and invasion. The expression of Egr-1 was also correlated with DUSP1. The overexpression of DUSP1 in Egr-1 knockdown cells, reduced the level of cell migration and invasion. Furthermore, it was demonstrated that knockdown of Egr-1 inhibited the promoter activity of DUSP1 and the site through which Egr-1 regulates DUSP1 transcription was identified. In conclusion, the present study demonstrated that Egr-1 regulates TSCC cell migration and invasion through modulating DUSP1, suggesting the potential of Egr-1 and DUSP1 as therapy targets for TSCC.

Unusual presentation of PD-1 inhibitors in people living with HIV with advanced gastric cancer: Case report.

This paper seeks to determine the effect of combination anti-PD-1 and antiretroviral therapy (ART) on people living with HIV (PLWH) with advanced gastric cancer. In our case, a PLWH with recurrent locally advanced gastric cancer was treated with anti-PD-1 inhibitor and ART. A significant reduction in tumor lesions (as demonstrated by contrast-enhanced CT imaging) and a better quality of life were achieved following treatment. There have been limited studies on the treatment of PLWH with advanced gastric cancer. Chemotherapy is most often used, however, with unsatisfactory outcomes. to date, there have been no published reports on the use of PD-1 inhibitors in PLWH with advanced gastric cancer. Our report provides a valuable reference for future management of such patients.

E3 Ubiquitin Ligase NEDD4L Negatively Regulates Skin Tumorigenesis by Inhibiting IL-6/GP130 Signaling Pathway.

IL-6 signaling plays a crucial role in the survival and metastasis of skin cancer. NEDD4L acts as a suppressor of IL-6 signaling by targeting GP130 degradation. However, the effects of the NEDD4L-regulated IL-6/GP130 signaling pathway on skin cancer remain unclear. In this study, protein expression levels of NEDD4L and GP130 were measured in tumor tissues from patients with cutaneous squamous cell carcinoma. Skin tumors were induced in wild-type and Nedd4l-knockout mice, and activation of the IL-6/GP130/signal transducer and activator of transcription 3 signaling pathway was detected. The results indicated a negative correlation between the protein expression levels of NEDD4L and GP130 in cutaneous squamous cell carcinoma tissues from patients. Nedd4l deficiency significantly promoted 7,12-dimethylbenz[a]anthracene/12-O-tetradecanoylphorbol-13-acetate-induced skin tumorigenesis and benign-to-malignant conversion by activating the IL-6/GP130/signal transducer and activator of transcription 3 signaling pathway, which was abrogated by supplementation with the GP130 inhibitor SC144. Furthermore, our findings suggested that NEDD4L can interact with GP130 and promote its ubiquitination in skin tumors. In conclusion, our results indicate that NEDD4L could act as a tumor suppressor in skin cancer, and inhibition of GP130 could be a potential therapeutic method for treating this disease.

Arthroscopic inferior leaf meniscectomy of the involved anterior horn in the lateral meniscus horizontal tear via an accessary extreme far anteromedial portal.

BACKGROUND: An accessory extreme far anteromedial portal can improve visualisation and ease inferior leaf meniscectomy in patients with lateral meniscal anterior horn horizontal tears. However, the therapeutic outcomes of adding an accessory extreme far anteromedial portal remain unclear. This study aimed to evaluate the clinical efficacy of adding an accessory extreme far anteromedial portal for treating lateral meniscal horizontal tears involving the anterior horns. METHODS: This retrospective study included 101 patients with anterior horn involvement in lateral meniscal horizontal tears who underwent arthroscopic unstable inferior leaf meniscectomy between January 2016 and December 2020. The pathologies were diagnosed using physical examinations and magnetic resonance imaging. The anterior horn involved in the lateral meniscal horizontal tears was treated using inferior leaf meniscectomy. The primary endpoints were changes in the visual analogue scale, Lysholm, International Knee Documentation Committee, and Tegner scores at the final follow-up. The secondary endpoint was meniscal cure rate at 3 months postoperatively. The preoperative and postoperative functional scores were compared. The occurrence of complications was recorded. RESULTS: All patients were followed up for an average of 4.9 ± 1.2 years (range 2.3-7.5 years). After 4 months, none of the patients experienced pain, weakness, instability, or tenderness in the lateral joint line, achieving an imaging cure rate of 98%. At the final follow-up, significant postoperative improvements were observed in the average values of the visual analogue scale score (3.5 ± 0.7 vs. 0.7 ± 0.6), Lysholm score (62.7 ± 4.4 vs. 91.8 ± 3.1), International Knee Documentation Committee score (61.9 ± 3.7 vs. 91.7 ± 9.5), and Tegner score (2.0 ± 0.7 vs. 6.1 ± 0.7). Excellent Lysholm scores were obtained in 81 patients, and good outcomes were obtained in 18 patients, with an excellent-to-good rate of 98.0%. CONCLUSIONS: Inferior leaf resection via the accessory far anteromedial portal is a safe treatment option for the involved anterior horn in lateral meniscal horizontal tears. This approach enhances visibility and facilitates surgical procedures, with minimal complications.

Effects of a single subanesthetic dose of esketamine on postoperative subthreshold depressive symptoms in patients undergoing unilateral modified radical mastectomy: a randomised, controlled, double-blind trial.

BACKGROUND: Breast cancer is the most common malignant tumor in females worldwide. During disease development, breast cancer patients suffer anxious and depressed, which may lead to worse quality of life or even higher mortality. Esketamine has been regarded as an antidepressant in breast cancer patients with mild or moderate depression. Here, we wonder whether the administration of esketamine could reduce the postoperative depressive symptom score of breast cancer patients who have no preoperative depression. METHODS: A total of 64 patients treated with unilateral modified radical mastectomy were randomly divided into an experimental group (esketamine group, Group E) and a control group (Group C), with 32 cases in each one. After anesthesia induction, Group C received 0.2 ml/kg of normal saline intravenously and Group E was administered 0.2 mg/kg intravenous esketamine. The primary outcome was the Patient Health Questionnaire-9 (PHQ-9) scores. The secondary outcomes included the Visual Analogue Scale (VAS) scores for pain, inflammatory markers, perioperative-related indicators, and the incidence of postoperative delirium, nausea and vomiting. RESULTS: The PHQ-9 score on postoperative day (POD) 1 in Group E declined from the preoperative level, while the score in Group C was higher than before, and the former was far lower than the latter (P = 0.047). There is no statistically significant difference in PHQ-9 scores between Group E and Group C on POD 3, 7, and 30. Moreover, the postoperative leukocyte level of Group E was higher than that of Group C, and the difference was statistically significant (P = 0.030). CONCLUSIONS: A single subanesthetic dose of esketamine can result in lower postoperative score on subthreshold depressive symptoms compared to the Group C on POD 1, without increasing the occurrence of postoperative adverse reactions. TRIAL REGISTRATION: Registration number: Chinese Clinical Trial Registry ChiCTR2200057028. Date of registration: 26/02/2022.

UHPLC-HRMS based saponins profiling of three morphological regions in American ginseng (Panax quinquefolium L.) and their correlation with the antioxidant activity.

American ginseng (Panax quinquefolium L.) is used as tonic plant and high-grade nourishment. Ultra-high-performance liquid chromatography-high resolution mass spectrometry (UHPLC-HRMS) method was established for identifying the chemical constituent in three morphological regions of American ginseng, including main root (MR), rhizome (RH) and lateral root (LR). The 63 saponins was identified in different morphological regions of 10 American ginseng samples. The chemical maker compounds in corresponding morphological region, while the major compounds of MR (malonyl-ginsenoside Rb1, ginsenoside Rd, Rs2 and pseudo-RC1), LR (stipuleanoside R2, ginsenoside Re and malonyl-ginsenoside Rc), and RH (malonyl-ginsenoside Rd, Rb3, and chikusetsu saponin II) were discovered. Correlation analysis showed that 11 compounds were positively correlated with the antioxidant activity of American ginseng. Supplementary Information: The online version contains supplementary material available at 10.1007/s10068-023-01453-4.

Establishment of cluster of differentiation 20 immobilized cell membrane chromatography for the screening of active antitumor components in traditional Chinese medicine.

Non-Hodgkin lymphoma (NHL) is a heterogeneous group of malignant tumors occurring in B or T lymphocytes, and no small molecule-positive drugs to treat NHL have been marketed. Cluster of differentiation 20 (CD20) is an important molecule regulating signaling for the life and differentiation of B lymphocytes and possesses the characteristics of a drug target for treating NHL. 2-Methoxyestradiol induces apoptosis in lymphoma Raji cells and CD20 protein is highly expressed by Raji lymphoma cells. Therefore, in this study, a CD20-SNAP-tag/CMC model was developed to validate the interaction of 2-methoxyestradiol with CD20. 2-Methoxyestradiol was used as a small molecule control compound, and the system was validated for good applicability. The cell membrane chromatography model was combined with high-performance liquid chromatography ion trap time-of-flight mass spectroscopy (HPLC-IT-TOF-MS) in a two-dimensional system to successfully identify, analyze, and characterize the potential active compounds of Schisandra chinensis (Turcz.) Baill. extract and Lysionotus pauciflorus Maxim. extract, including Schisandrin A, Schizandrol A, Schizandrol B, Schisantherin B, and Nevadensin, which can act on CD20 receptors. The five potential active compounds were analyzed by non-linear chromatography. The thermodynamic and kinetic parameters of their interaction with CD20 were also analyzed, and the mode of interaction was simulated by molecular docking. Their inhibitory effects on lymphoma cell growth were assessed using a Cell Counting Kit-8 (CCK-8). Nevadensin and Schizandrin A were able to induce apoptosis in Raji cells within a certain concentration range. In conclusion, the present experiments provide some bases for improving NHL treatment and developing small molecule lead compounds targeting CD20 with low toxicity and high specificity.

CX3CR1 deficiency promotes resolution of hepatic ischemia-reperfusion injury by regulating homeostatic function of liver infiltrating macrophages.

Hepatic ischemia-reperfusion injury(HIRI) remains to be an unsolved risk factor that contributes to organ failure after liver surgery. Our clinical retrospective study showed that lower donor liver CX3-C chemokine receptor-1(CX3CR1) mRNA expression level were correlated with upregulated pro-resolved macrophage receptor MERTK, as well as promoted restoration efficiency of allograft injury in liver transplant. To further characterize roles of CX3CR1 in regulating resolution of HIRI, we employed murine liver partial warm ischemia-reperfusion model by Wt & Cx3cr1-/- mice and the reperfusion time was prolonged from 6 h to 4-7 days. Kupffer cells(KCs) were depleted by clodronate liposome(CL) in advance to focus on infiltrating macrophages, and repopulation kinetics were determined by FACS, IF and RNA-Seq. CX3CR1 antagonist AZD8797 was injected i.p. to interrogate potential pharmacological therapeutic strategies. In vitro primary bone marrow macrophages(BMMs) culture by LXR agonist DMHCA, as well as molecular and functional studies, were undertaken to dissect roles of CX3CR1 in modulating macrophages cytobiological development and resolutive functions. We observed that deficiency or pharmacological inhibition of CX3CR1 facilitated HIRI resolution via promoted macrophages migration in CCR1/CCR5 manner, as well as enhanced MerTK-mediated efferocytosis. Our study demonstrated the critical roles of CX3CR1 in progression of HIRI and identified it as a potential therapeutic target in clinical liver transplantation.

Association between preoperative frailty and myocardial injury after noncardiac surgery in geriatric patients: study protocol for a prospective, multicentre, real-world observational, cohort trial.

INTRODUCTION: Frailty has become a worldwide health burden that has a large influence on public health and clinical practice. The incidence of frailty is anticipated to increase as the ageing population increases. Myocardial injury after noncardiac surgery (MINS) is associated with short-term and long-term mortality. However, the incidence of MINS in frail geriatric patients is unknown. METHODS AND ANALYSIS: This prospective, multicentre, real-world observational cohort study will be conducted at 18 designated centres in China from January 2023 to December 2024, with an anticipated sample size of 856 patients aged 65 years and older who are scheduled to undergo noncardiac surgery. The primary outcome will be the incidence of MINS. MINS is defined as a fourth-generation plasma cardiac troponin T (cTnT) concentration ≥ 0.03 ng/mL exhibited at least once within 30 days after surgery, with or without symptoms of myocardial ischaemia. All data will be collected via electronic data acquisition. DISCUSSION: This study will explore the incidence of MINS in frail patients. The characteristics, predictive factors and 30-day outcomes of MINS in frail patients will be further investigated to lay the foundation for identifying clinical interventions. CLINICAL TRIAL REGISTRATION: https://beta. CLINICALTRIALS: gov/study/NCT05635877 , NCT05635877.

Inhibition of Gpx4-mediated ferroptosis alleviates cisplatin-induced hearing loss in C57BL/6 mice.

Cisplatin-induced hearing loss is a common side effect of cancer chemotherapy in clinics; however, the mechanism of cisplatin-induced ototoxicity is still not completely clarified. Cisplatin-induced ototoxicity is mainly associated with the production of reactive oxygen species, activation of apoptosis, and accumulation of intracellular lipid peroxidation, which also is involved in ferroptosis induction. In this study, the expression of TfR1, a ferroptosis biomarker, was upregulated in the outer hair cells of cisplatin-treated mice. Moreover, several key ferroptosis regulator genes were altered in cisplatin-damaged cochlear explants based on RNA sequencing, implying the induction of ferroptosis. Ferroptosis-related Gpx4 and Fsp1 knockout mice were established to investigate the specific mechanisms associated with ferroptosis in cochleae. Severe outer hair cell loss and progressive damage of synapses in inner hair cells were observed in Atoh1-Gpx4-/- mice. However, Fsp1-/- mice showed no significant hearing phenotype, demonstrating that Gpx4, but not Fsp1, may play an important role in the functional maintenance of HCs. Moreover, findings showed that FDA-approved luteolin could specifically inhibit ferroptosis and alleviate cisplatin-induced ototoxicity through decreased expression of transferrin and intracellular concentration of ferrous ions. This study indicated that ferroptosis inhibition through the reduction of intracellular ferrous ions might be a potential strategy to prevent cisplatin-induced hearing loss.

Aged AßPPswe/PS1ΔE9 mice as a useful animal model for studying the link between immunological senescence and diseases.

The APPswe/PS1ΔE9 mouse is a double transgenic murine model that harbors two transgenes for Alzheimer's Disease (AD)-related mutant proteins. We previously discovered that this double transgenic animal had a premature immunosenescence phenotype. However, it is unclear how this phenotype progresses to a later stage. This study aimed to elucidate the changes in systemic characteristics aside from those associated with AD between elderly APPswe/PS1ΔE9 mice and littermate control wild-type mice. Tumors in all organs were considerably more frequent in AD mice aged 24 months than in the control wild-type mice. In addition, the survival rate of aged AD mice was considerably lower than that of wild-type control mice. Further, we discovered that the phenotypic difference was mainly caused by severe immunological aging, as evidenced by a high proportion of exhausted T lymphocytes in AD mice compared to wild-type mice of the same age. Based on our findings, the harm produced by normal aging is not as severe as immunological senescence. Addressing immunological aging, as opposed to anti-aging alone, may be a more crucial target for a long life free of cancer.

Mycn ameliorates cardiac hypertrophy-induced heart failure in mice by mediating the USP2/JUP/Akt/ß-catenin cascade.

BACKGROUND: Pathological cardiac hypertrophy is associated with cardiac dysfunction and is a key risk factor for heart failure and even sudden death. This study investigates the function of Mycn in cardiac hypertrophy and explores the interacting molecules. METHODS: A mouse model of cardiac hypertrophy was induced by isoproterenol (ISO). The cardiac dysfunction was assessed by the heart weight-to-body weight ratio (HW/BW), echocardiography assessment, pathological staining, biomarker detection, and cell apoptosis. Transcriptome alteration in cardiac hypertrophy was analyzed by bioinformatics analysis. Gain- or loss-of-function studies of MYCN proto-oncogene (Mycn), ubiquitin specific peptidase 2 (USP2), and junction plakoglobin (JUP) were performed. The biological functions of Mycn were further examined in ISO-treated cardiomyocytes. The molecular interactions were verified by luciferase assay or immunoprecipitation assays. RESULTS: Mycn was poorly expressed in ISO-treated mice, and its upregulation reduced HW/BW, cell surface area, oxidative stress, and inflammation while improving cardiac function of mice. It also reduced apoptosis of cardiomyocytes in mice and those in vitro induced by ISO. Mycn bound to the USP2 promoter to activate its transcription. USP2 overexpression exerted similar myocardial protective functions. It stabilized JUP protein by deubiquitination modification, which blocked the Akt/ß-catenin pathway. Knockdown of JUP restored phosphorylation of Akt and ß-catenin protein level, which negated the protective effects of USP2. CONCLUSION: This study demonstrates that Mycn activates USP2 transcription, which mediates ubiquitination and protein stabilization of JUP, thus inactivating the Akt/ß-catenin axis and alleviating cardiac hypertrophy-induced heart failure.