Amide proton transfer-weighted and arterial spin labeling imaging may improve differentiation between high-grade glioma recurrence and radiation-induced brain injury.

Rationale and objectives: The management of tumor recurrence (TR) and radiation-induced brain injury (RIBI) poses significant challenges, necessitating the development of effective differentiation strategies. In this study, we investigated the potential of amide proton transfer-weighted (APTw) and arterial spin labeling (ASL) imaging for discriminating between TR and RIBI in patients with high-grade glioma (HGG). Methods: A total of 64 HGG patients receiving standard treatment were enrolled in this study. The patients were categorized based on secondary pathology or MRI follow-up results, and the demographic characteristics of each group were presented. The APTw, rAPTw, cerebral blood flow (CBF) and rCBF values were quantified. The differences in various parameters between TR and RIBI were assessed using the independent-samples t-test. The discriminative performance of these MRI parameters in distinguishing between the two conditions was assessed using receiver operating characteristic (ROC) curve analysis. Additionally, the Delong test was employed to further evaluate their discriminatory ability. Results: The APTw and CBF values of TR were significantly higher compared to RIBI (P < 0.05). APTw MRI demonstrated superior diagnostic efficiency in distinguishing TR from RIBI (area under the curve [AUC]: 0.864; sensitivity: 75.0 %; specificity: 81.8 %) when compared to ASL imaging. The combined utilization of APTw and CBF value further enhanced the AUC to 0.922. The Delong test demonstrated that the combination of APTw and ASL exhibited superior performance in the identification of TR and RIBI, compared to ASL alone (P = 0.048). Conclusion: APTw exhibited superior diagnostic efficacy compared to ASL in the evaluation of TR and RIBI. Furthermore, the combination of APTw and ASL exhibits greater discriminatory capability and diagnostic performance.

Interleukin-1ß stimulated macrophage derived exosomes improve myocardial injury in sepsis via regulation of mitochondrial homeostasis: Experimental research.

BACKGROUND: The purpose of this study was to investigate the effects of interleukin-1ß (IL-1ß) stimulation on the protection of macrophage derived exosomes miR-146a (M-IL-exo-146a) on sepsis induced myocardial injury (SMI) in vitro and in vivo. METHODS: Macrophage derived exosomes (M-exo) and IL-1ß stimulated macrophage exosomes (M-IL-exo) were isolated from macrophages of sepsis with or without IL-1ß. The expressions of miR-146a in M-exo and M- IL-exo were detected by fluorescence quantitative PCR. Related molecular biology technologies were used to evaluate the role and mechanism of M-exo-146a and M-IL-exo-146a on SMI and the enhancing effect of IL-1ß. RESULTS: Compared with M-exo, the expression of miR-146a in M-IL-exo was significantly increased. M-IL-exo-146a significantly alleviated SMI by decreasing the level of serum myocardial enzymes, serum and myocardial oxidative stress and cytokines, and improved myocardial mitochondrial imbalance. The mechanism responsible for IL-1ß enhancing the production of IL-M-exo miR-146a was via JNK-1/2 signal pathway. The mechanism responsible for M-exo-IL-miR-146a protecting SMI was related to miR-146a inhibiting inflammatory response and mitochondrial function via MAPK4/Drp1 signal pathway. CONCLUSIONS: This study provides a new strategy for the treatment of SMI by delivering IL-1ß stimulated macrophage derived exosomes.

Molecular mechanisms, targets and clinical potential of berberine in regulating metabolism: a review focussing on databases and molecular docking studies.

Background: Metabolic imbalance is the common basis of many diseases. As natural isoquinoline alkaloid, berberine (BBR) has shown great promise in regulating glucose and lipids metabolism and treating metabolic disorders. However, the related mechanism still lacks systematic research. Aim: To discuss the role of BBR in the whole body's systemic metabolic regulation and further explore its therapeutic potential and targets. Method: Based on animal and cell experiments, the mechanism of BBR regulating systemic metabolic processes is reviewed. Potential metabolism-related targets were summarized using Therapeutic Target Database (TTD), DrugBank, GeneCards, and cutting-edge literature. Molecular modeling was applied to explore BBR binding to the potential targets. Results: BBR regulates the whole-body metabolic response including digestive, circulatory, immune, endocrine, and motor systems through adenosine 5'-monophosphate (AMP)-activated protein kinase (AMPK)/mammalian target of rapamycin (mTOR), sirtuin (SIRT)1/forkhead box O (FOXO)1/sterol regulatory element-binding protein (SREBP)2, nuclear factor erythroid 2-related factor (Nrf) 2/heme oxygenase (HO)-1, and other signaling pathways. Through these reactions, BBR exerts hypoglycemic, lipid-regulating, anti-inflammatory, anti-oxidation, and immune regulation. Molecular docking results showed that BBR could regulate metabolism targeting FOXO3, Nrf2, NAD(P)H quinone oxidoreductase 1 (NQO1), glutathione peroxidase (Gpx) 4 and phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha (PIK3CA). Evaluating the target clinical effects, we found that BBR has the therapeutic potential of anti-aging, anti-cancer, relieving kidney disease, regulating the nervous system, and alleviating other chronic diseases. Conclusion: This review elucidates the interaction between potential targets and small molecular metabolites by exploring the mechanism of BBR regulating metabolism. That will help pharmacologists to identify new promising metabolites interacting with these targets.

AQP5 promotes epithelial-mesenchymal transition and tumor growth through activating the Wnt/ß-catenin pathway in triple-negative breast cancer.

BACKGROUND: Emerging data identifies aquaporin 5 (AQP5) as a vital player in many kinds of cancers. Over expression of AQP5 was associated with increased metastasis and poor prognosis, suggesting that AQP5 may facilitate cancer cell proliferation and migration. Our previous studies also showed that AQP3 and AQP5 were highly expressed in triple-negative breast cancer (TNBC) and the expression of AQP3 and AQP5 in TNBC tissue was positive correlated with advanced clinical stage. OBJECTIVE: We aim to investigate the role of AQP5 in TNBC oncogenesis and development. METHODS: MDA-MB-231 cells were transfected with siRNA-AQP5 and AQP5 overexpression vector to establish a differential expression system for AQP5. Cell proliferation and apoptosis of MDA-MB-231 cells were detected by CCK-8 (Cell Counting Kit-8) and FCM (flow cytometry), respectively. Cell migration and invasion abilities were evaluated by wound healing assay and transwell assay. The qRT-PCR and western blot assays were used to study the effect of AQP5 expression level on the expression of epithelial-to-mesenchymal transition (EMT) related molecules. The effects of ICG-001, a Wnt/ß-catenin signaling pathway inhibitor, on the invasive and migratory capabilities of overexpressed AQP5 cells and downstream molecules were measured. RESULTS: 1. The expression of AQP5 in the MDA-MB-231 cells was significantly higher than that in the MCF-10A cells. 2. Up-regulation of AQP5 significantly promoted the proliferation, migration and invasion of TNBC cells, while inhibited the cell apoptosis; in addition, up-regulation of AQP5 increased the expression of Bcl-2 and decreased the expression of Caspase-3. However, knockdown of AQP5 presented the adverse effects of AQP5 overexpression. 3. Overexpressed AQP5 induced the overexpression of EMT-related factors, which further promoted the migration and invasion of cells. 4. Overexpression of AQP5 could up-regulate the expression of ß-catenin in the nucleus followed by increasing the expression levels of downstream genes in Wnt/ß-catenin signaling pathway. Moreover, ICG-001, the inhibitor of Wnt/ß-catenin signaling pathway, could significantly attenuate the effect of overexpression of AQP5 on cells, further confirming that AQP5 may promote the proliferation, migration and invasion of TNBC cells by activating Wnt/ß-catenin signaling pathway. CONCLUSIONS: In the TNBC cells, AQP5 modulates the expression levels of EMT-related proteins through activation of Wnt/ß-catenin signaling pathway, thus enhancing the cell proliferation, migration and invasion while inhibiting the cell apoptosis.

RNF149 Destabilizes IFNGR1 in Macrophages to Favor Post-Infarction Cardiac Repair.

BACKGROUND: Macrophage-driven inflammation critically involves in cardiac injury and repair following myocardial infarction (MI). However, the intrinsic mechanisms that halt the immune response of macrophages, which is critical to preserve homeostasis and effective infarct repair, remain to be fully defined. Here, we aimed to determine the ubiquitination-mediated regulatory effects on averting exaggerated inflammatory responses in cardiac macrophages. METHODS: We used transcriptome analysis of mouse cardiac macrophages and bone marrow-derived macrophages to identify the E3 ubiquitin ligase RNF149 (RING finger protein 149) as a modulator of macrophage response to MI. Employing loss-of-function methodologies, bone marrow transplantation approaches, and adenovirus-mediated RNF149 overexpression in macrophages, we elucidated the functional role of RNF149 in MI. We explored the underlying mechanisms through flow cytometry, transcriptome analysis, immunoprecipitation/mass spectrometry analysis, and functional experiments. RNF149 expression was measured in the cardiac tissues of patients with acute MI and healthy controls. RESULTS: RNF149 was highly expressed in murine and human cardiac macrophages at the early phase of MI. Knockout of RNF149, transplantation of Rnf149-/- bone marrow, and bone marrow macrophage-specific RNF149-knockdown markedly exacerbated cardiac dysfunction in murine MI models. Conversely, overexpression of RNF149 in macrophages attenuated the ischemia-induced decline in cardiac contractile function. RNF149 deletion increased infiltration of proinflammatory monocytes/macrophages, accompanied by a hastened decline in reparative subsets, leading to aggravation of myocardial apoptosis and impairment of infarct healing. Our data revealed that RNF149 in infiltrated macrophages restricted inflammation by promoting ubiquitylation-dependent proteasomal degradation of IFNGR1 (interferon gamma receptor 1). Loss of IFNGR1 rescued deleterious effects of RNF149 deficiency on MI. We further demonstrated that STAT1 activation induced Rnf149 transcription, which, in turn, destabilized the IFNGR1 protein to counteract type-II IFN (interferon) signaling, creating a feedback control mechanism to fine-tune macrophage-driven inflammation. CONCLUSIONS: These findings highlight the significance of RNF149 as a molecular brake on macrophage response to MI and uncover a macrophage-intrinsic posttranslational mechanism essential for maintaining immune homeostasis and facilitating cardiac repair following MI.

Current Progress of Ferroptosis Study in Hepatocellular Carcinoma.

Ferroptosis, an emerging type of programmed cell death, is initiated by iron-dependent and excessive ROS-mediated lipid peroxidation, which eventually leads to plasma membrane rupture and cell death. Many canonical signalling pathways and biological processes are involved in ferroptosis. Furthermore, cancer cells are more susceptible to ferroptosis due to the high load of ROS and unique metabolic characteristics, including iron requirements. Recent investigations have revealed that ferroptosis plays a crucial role in the progression of tumours, especially HCC. Specifically, the induction of ferroptosis can not only inhibit the growth of hepatoma cells, thereby reversing tumorigenesis, but also improves the efficacy of immunotherapy and enhances the antitumour immune response. Therefore, triggering ferroptosis has become a new therapeutic strategy for cancer therapy. In this review, we summarize the characteristics of ferroptosis based on its underlying mechanism and role in HCC and provide possible therapeutic applications.

Groundwater health risk assessment and its temporal and spatial evolution based on trapezoidal fuzzy number-Monte Carlo stochastic simulation: A case study in western Jilin province.

The United States Environmental Protection Agency (USEPA) Four-step-Method (FSM) is a straightforward and extensively utilized tool for evaluating regional health risks, However, the complex and heterogeneous groundwater environment system causes great uncertainty in the assessment process. Triangular stochastic simulation (TSS) possesses certain advantages in solving uncertainty problems, but its inadequacy with discrete data reveals limitations in this aspect. To solve the above problems, this study proposes to construct trapezoidal fuzzy number-Monte Carlo stochastic simulation (TFN-MCSS) to compensate for the shortcomings of the first two methods. This method adopted trapezoidal fuzzy number (TFN) analysis to comprehensively consider the characteristics of a large dispersion of water quality monitoring data and the uncertainty of the human health risk assessment (HHRA) process. Concurrently, to overcome the subjectivity and uncertainty of artificially determining the interval of TFN in traditional methods, the slope was used to select the most probable interval value (TMPIV) of TFN combined with the α-truncated set technique (α-TST) and MCSS. Based on these, a TFN-MCSS was constructed and applied to groundwater HHRA in western Jilin Province. First, the groundwater chemical characteristic determination and water quality evaluation in western Jilin were performed to identify the main pollution indicators, and the health risk effects of pollutants in groundwater of different aquifers at different time periods on adults and children were evaluated using the TFN-MCSS. The uncertainty and sensitivity were analyzed, and the primary risk control indicators were identified and compared to FSM and TSS. The results reveal that TFN-MCSS was more sensitive to data and could reduce the uncertainty of assessment process. It indicated that over a 10-year period, the health risks associated with unconfined groundwater (UW) and confined water (CW) decreased by greater than 52 %. However, the highest total non-carcinogenic risk index (THI) was 1.3-fold higher than the safety threshold, and this posed a health risk.

Minimally Invasive versus Traditional Surgery: Efficacy of PELD and PLIF in Treating Pyogenic Spondylodiscitis.

BACKGROUND Pyogenic spondylodiscitis is infection of the intervertebral disc or discs and the adjacent vertebrae. This retrospective study aimed to compare the effectiveness of percutaneous endoscopic lumbar debridement (PELD) versus posterior lumbar interbody fusion (PLIF) in 40 patients with pyogenic spondylodiscitis (PSD). MATERIAL AND METHODS Medical records of patients who underwent PELD (n=18) or PLIF (n=22) for PSD between 2018 and 2023 were reviewed. The recorded outcomes encompassed surgical duration, intraoperative blood loss, Oswestry Disability Index (ODI) measurements, Visual Analog Scale (VAS) assessments, C-reactive protein (CRP) levels, duration of hospitalization, erythrocyte sedimentation rate (ESR), American Spinal Injury Association (ASIA) grading, lumbar sagittal parameters, and the incidence of complications. RESULTS The PELD group had shorter surgical duration, less intraoperative blood loss, and shorter length of hospital stay compared to the PLIF group (P<0.01). At the last follow-up, both groups had significant improvement in ESR, CRP levels, and ASIA classification (P<0.001), but there was no significant difference between the 2 groups (P>0.05). The PELD group had lower ODI and VAS ratings at 1 month and 3 months, respectively (P<0.01). The PLIF group had significant improvements in intervertebral space height and lumbar lordosis angle (P<0.01). CONCLUSIONS Both PLIF and PELD surgical approaches demonstrate adequate clinical efficacy in the treatment of monosegmental PSD. PLIF can better ensure more spinal stability than PELD, but PELD offers advantages such as reduced minimal surgical trauma, shorter operative duration, and faster recovery after surgery.

[Corrigendum] T7 peptide inhibits angiogenesis via downregulation of angiopoietin­2 and autophagy.

Following the publication of this article, an interested reader drew to the authors' attention that two pairs of protein bands featured in the western blots in Fig. 3A and 5D on p. 679 and 681 respectively appeared to be strikingly similar. After having re­examined their original data, the authors realized that Fig. 5D had been assembled incorrectly. The revised version of Fig. 5, now including the correct data for Fig. 5D, is shown on the next page. Note that the errors made in terms of assembling the data in Fig. 5 did not greatly affect either the results or the conclusions reported in this paper, and all the authors agree to the publication of this corrigendum. The authors regret that these errors went unnoticed prior to the publication of their article, are grateful to the Editor of Oncology Reports for allowing them this opportunity to publish this corrigendum. They also apologize to the readership for any inconvenience caused. [Oncology Reports  33: 675­684, 2015; DOI: 10.3892/or.2014.3653].

Huangqin Tang Alleviates Colitis-associated Colorectal Cancer via Amino Acids Homeostasisand PI3K/AKT/mTOR Pathway Modulation.

ETHNOPHARMACOLOGICAL RELEVANCE: Huangqin Tang (HQT), a traditional Chinese medicine formula, is commonly used in clinical practice for the treatment of inflammatory bowel diseases. It has been reported that HQT exerts antitumor effects on colitis-associated colorectal cancer (CAC). However, the mechanism by which HQT interferes with the inflammation-to-cancer transformation remains unclear. AIMS OF THE STUDY: The purpose of this study was to dynamically evaluate the efficacy of HQT in alleviating or delaying CAC and to reveal the underlying mechanism. METHODS: We established a mouse model of CAC using azoxymethane combined with 1.5% dextran sodium sulphate. The efficacy of HQT was evaluated based on pathological sections and serum biochemical indices. Subsequently, amino acids (AAs) metabolism analyses were performed using ultra-performance liquid chromatography-tandem mass spectrometry, and the phosphatidylinositol 3 kinase/protein kinase B/mechanistic target of rapamycin (PI3K/AKT/mTOR) pathway was detected by western blotting. RESULTS: The data demonstrated that HQT could alleviate the development of CAC in the animal model. HQT effectively reduced the inflammatory response, particularly interleukin-6 (IL-6), in the inflammation induction stage, as well as in the stages of proliferation initiation and tumorigenesis. During the proliferation initiation and tumorigenesis stages, immunohistochemistry staining showed that the expression of the proliferation marker Ki67 was reduced, while apoptosis was increased in the HQT group. Accordingly, HQT substantially decreased the levels of specific AAs in the colon with CAC, including glutamic acid, glutamine, arginine, and isoleucine. Furthermore, HQT significantly inhibited the activated PI3K/AKT/mTOR pathway, which may contribute to suppression of cell proliferation and enhancement of apoptosis. CONCLUSION: HQT is effective in alleviating and delaying the colon "inflammation-to-cancer". The mechanism of action may involve HQT maintained AAs metabolism homeostasis and regulated PI3K/AKT/mTOR pathway, so as to maintain the balance between proliferation and apoptosis, and then interfere in the occurrence and development of CAC.

Prior to ABOi liver transplant with PD-1 inhibitor in patients with hepatocellular carcinoma: A case report.

BACKGROUND: Liver transplantation (LT) is a unique and effective method for treating end-stage liver diseases and acute liver failure, bringing hope to many patients with liver cancer. LT is currently widely used in the treatment of liver diseases. However, there have been no patients with liver cancer who have undergone ABO-incompatible (ABOi) LT after treatment with the programmed cell death protein 1 (PD-1) inhibitor reported in the literature. CASE PRESENTATION: A patient with liver cancer who received sintilimab injection, an anti-PD1 therapy, before LT was admitted in the transplantation centre. This patient underwent ABOi LT. The perioperative treatment strategy of this patient was reported. A desensitisation protocol was conducted urgently for the patient before operation, and the immunosuppression programme of LT was adjusted. After operation, isoagglutinin titer and liver function indicators were strictly monitored. The patient recovered well after operation, and no sign of rejection reaction was observed. CONCLUSION: We reported a patient with hepatocellular carcinoma (HCC) who received PD-1 inhibitor treatment before operation and successfully underwent ABOi LT. The present case report provides novel insights into the perioperative management of utilizing PD-1 inhibitors prior to ABOi LT in patients diagnosed with hepatocellular carcinoma (HCC).

Application of predictive model based on CT radiomics and machine learning in diagnosis for occult locally advanced esophageal squamous cell carcinoma before treatment: A two-center study.

PURPOSE: Development and validation of a radiomics model for predicting occult locally advanced esophageal squamous cell carcinoma (LA-ESCC) on computed tomography (CT) radiomic features before implementation of treatment. METHODS: The study retrospectively collected 574 patients with esophageal squamous cell carcinoma (ESCC) from two medical centers, which were divided into three cohorts for training, internal and external validation. After delineating volume of interest (VOI), radiomics features were extracted and subjected to feature selection using three robust methods. Subsequently, 10 machine learning models were constructed, among which the optimal model was utilized to establish a radiomics signature. Furthermore, a predictive nomogram incorporating both clinical and radiomics signatures was developed. The performance of these models was evaluated through receiver operating characteristic curves, calibration curves, decision curve analysis as well as measures including accuracy, sensitivity, and specificity. RESULTS: A total of 19 radiomics features were selected. The multilayer perceptron (MLP), which was found to be optimal, achieved an AUC of 0.919, 0.864 and 0.882 in the training, internal and external validation cohorts, respectively. Similarly, MLP showed good accuracy in distinguish occult LA-ESCC in subgroup of cT1-2N0M0 diagnosed by clinicians with 0.803 and 0.789 in two validation cohorts respectively. By incorporating the radiomics signature with clinical signature, a predictive nomogram demonstrated superior prediction performance with an AUC of 0.877 and accuracy of 0.85 in external validation cohort. CONCLUSION: The radiomics and machine learning model can offers improved accuracy in prediction of occult LA-ESCC, providing valuable assistance to clinicians when choosing treatment plans.

Comprehensive insights on genetic alterations and immunotherapy prognosis in Chinese melanoma patients.

Immune checkpoint inhibitors (ICI) have emerged as a promising therapeutic option for melanoma, which demonstrating improved clinical outcomes in melanoma patients regardless of specific genetic mutations. However, the identification of reliable biomarkers for predicting immunotherapy response and prognosis remains a challenge. In this study, we performed genetic profiling of the melanoma patients with different subtypes and evaluated the efficacy of ICI treatment. A total of 221 melanoma patients were included in our cohort, consisting primarily of acral lentiginous melanoma (ALM), cutaneous malignant melanoma (CMM), and mucosal malignant melanoma (MMM). Genetic analysis revealed BRAF mutations was predominant in CMM and NRAS mutations was prevalent in ALM. Copy number variants (CNVs) and structural variants (SV) were also detected, with CCND1 and CDK4 being the most affected genes in CNV and BRAF, ALK and RAF1 being the druggable targets in SV. Furthermore, NRAS mutations were associated with a poor prognosis in ALM, while TERT mutations were linked to unfavorable outcomes in CMM after receiving PD-1 therapy. Additionally, ALK expression exhibited improved outcomes in both ALM and CMM subtypes. Our study provides a comprehensive genomic and pathological profiling of Chinese melanoma patients, shedding light on the molecular landscape of the disease. Furthermore, numbers of gene mutations and ALK expression were identified as prognostic indicators. These findings contribute to the understanding of melanoma genetics in the Chinese population and have implications for personalized treatment approaches.

Prognostic value of sarcopenia and inflammatory indices synergy in patients with esophageal squamous cell carcinoma undergoing chemoradiotherapy.

BACKGROUND AND PURPOSE: Sarcopenia has been demonstrated to be adversely correlated with the prognosis of various cancers. Our study aimed to estimate the prognostic value of sarcopenia in conjunction with inflammatory indices [neutrophil-to-lymphocyte ratio (NLR)] for evaluating the prognosis of patients with esophageal squamous cell carcinoma (ESCC) undergoing chemoradiotherapy. MATERIALS AND METHODS: This study retrospectively analyzed 255 patients with ESCC who received chemoradiotherapy from January 2012 to December 2018. Multivariate Cox regression analysis was employed to identify prognostic values of assessed factors following a novel prognostic scoring system (SMI-NLR), covering sarcopenia and NLR during different treatment courses. RESULTS: Kaplan-Meier analysis revealed significantly greater overall survival (OS) rates in the nonsarcopenia group than in the sarcopenia group (P = 0.011). The low NLR group (< 4.84) demonstrated significantly higher OS rates than the high NLR group (≥ 4.84) (P < 0.001). The SMI-NLR prognostic model was established through multivariate analysis, revealing that Karnofsky performance status [hazard ratio (HR) = 0.285; 95% confidence interval (CI) = 0.117-0.699; P = 0.006], clinical staging (HR = 5.223; 95% CI = 1.879-14.514; P = 0.002), and preSMI-NLR (HR = 0.544; 95% CI = 0.330-0.898; P = 0.017) were independent factors affecting the prognosis of patients with ESCC. Nomograms were constructed based on these data providing more accurate 1-, 3-, and 5-year survival rates for patients with ESCC. CONCLUSION: Our study indicates the effectiveness of the combined sarcopenia and NLR prognostic model for the prognostic evaluation of patients with ESCC having undergone chemoradiotherapy.

The associations between the Geriatric Nutritional Risk Index and all-cause, cancer-specific, and cardiovascular mortality in the U.S. population: a large-scale pooled survey.

BACKGROUND: Previous studies have reported a close association between the Geriatric Nutritional Risk Index (GNRI) and various conditions. However, the association between the GNRI and mortality remains unclear. To examine the correlation between the GNRI and all-cause, cancer-specific, and cardiovascular mortality, this study was performed. METHODS: We analyzed elderly participants in the National Health and Nutrition Examination Survey from 2005 to 2016. The GNRI was calculated using body mass index and serum albumin. Kaplan-Meier survival curves were drawn to compare the survival probability between the normal and decreased GNRI groups. Weighted multivariate Cox regression and restricted cubic spline (RCS) models were employed to determine the linear and non-linear associations of the GNRI with all-cause, cancer-specific, and cardiovascular mortality. RESULTS: A total of 3,276 participants were included in the analysis. The Kaplan-Meier survival curve showed that the decreased GNRI group had a lower survival probability for all-cause mortality and cancer-specific mortality (P < 0.001) but not for cardiovascular mortality (P > 0.05). In the full regression models, the decreased group had a higher risk of all-cause mortality (HR = 1.67, 95% CI = 1.21-2.30, P = 0.002), and cancer-specific mortality (HR = 2.20, 95% CI = 1.32-3.67, P = 0.003) than the normal group. For cardiovascular mortality, no significant association with GNRI (HR = 1.39, 95% CI = 0.60-3.22, P = 0.436) was detected. Notably, the RCS analysis identified a linear downward trend between the GNRI and all-cause, alongside cancer-specific mortalities (all P for overall < 0.05). The time-dependent Receiver Operating Characteristic (ROC) analysis unveiled the predictive power of the GNRI for 5-year all-cause mortality, cancer mortality, and cardiovascular mortality was 0.754, 0.757, and 0.836, respectively, after adjusting for covariates. CONCLUSIONS: Individuals with a decreased GNRI had increased risks of all-cause, and cancer-specific mortality. There were linear associations of the GNRI with all-cause, and cancer-specific mortality. Nutritional status should be carefully monitored, which may improve the overall prognosis for the general population.

Prognostic significance of serum Chemerin and neutrophils levels in patients with oral squamous cell carcinoma.

Objectives: Chemerin, as a novel multifunctional adipokine, is proposed to be involved in high cancer risk and mortality. The present study was aimed to evaluate the prognostic value of serum Chemerin and neutrophils in patients with oral squamous cell carcinoma (OSCC). Materials and methods: 120 patients with OSCC were included in this prospective cohort study. The levels of serum Chemerin were measured by enzyme-linked immunosorbent assay (ELISA). We also explored the possible effects of Chemerin on neutrophils' chemokines in OSCC using a real-time PCR, western blotting. Results: Levels of serum Chemerin, neutrophils and NLR were significantly higher among non-survivors compared to survivors of OSCC (both P < 0.05). Higher serum Chemerin levels were associated with advanced TNM stage, lymph node metastasis, differentiation and tumor recurrence (both P < 0.05). Serum Chemerin levels correlated with neutrophils and NLR levels (r = 0.708, r = 0.578, both P < 0.05). Based on ROC analysis, Chemerin + NLR predicted OSCC patient mortality with 81.54 % sensitivity and 87.27 % specificity, with an AUC of 0.8898. In a Kaplan-Meier analysis, high serum Chemerin levels, high neutrophil levels and high NLR levels were associated with shorter overall and disease-free survival (both P < 0.05). A univariate and multivariate Cox regression analysis showed that serum Chemerin and neutrophils were independent risk factors for OSCC. (both P < 0.05). QRT-PCR and western blotting results showed that Chemerin upregulated the expression of chemokines IL-17 and CXCL-5 in neutrophils (both P < 0.05). Conclusions: Our study suggests that measurement of serum Chemerin and neutrophils might be a useful diagnostic and prognostic biomarker for OSCC patients. Chemerin may promote neutrophils infiltration in OSCC through upregulation of chemokines IL17 and CXCL-5.

Effect of oral glucose tolerance test-based insulin resistance on embryo quality in women with/without polycystic ovary syndrome.

Objective: To explore the effects of insulin resistance (IR) on embryo quality and pregnancy outcomes in women with or without polycystic ovary syndrome (PCOS) undergoing in vitro fertilization (IVF)/intracytoplasmic sperm injection (ICSI). Methods: A retrospective cohort study concerning patients with/without PCOS who received gonadotropin-releasing hormone (GnRH)-antagonist protocol for IVF/ICSI from January 2019 to July 2022 was conducted. All the patients included underwent oral glucose tolerance test plus the assessment of insulin release within 6 months before the controlled ovarian stimulation. The Matsuda Index was calculated to diagnose IR. Two populations (PCOS and non-PCOS) were included and each was divided into IR and non-IR groups and analyzed respectively. The primary outcome was the high-quality day 3 embryo rate. Results: A total of 895 patients were included (751 with PCOS and 144 without PCOS). For patients with PCOS, the IR group had a lower high-quality day 3 embryo rate (36.8% vs. 39.7%, p=0.005) and available day 3 embryo rate (67.2% vs. 70.6%, p<0.001). For patients without PCOS, there was no significant difference between the IR and non-IR groups in high-quality day 3 embryo rate (p=0.414) and available day 3 embryo rate (p=0.560). There was no significant difference in blastocyst outcomes and pregnancy outcomes for both populations. Conclusion: Based on the diagnosis by the Matsuda Index, IR may adversely affect the day 3 embryo quality in patients with PCOS but not pregnancy outcomes. In women without PCOS, IR alone seems to have less significant adverse effects on embryo quality than in patients with PCOS. Better-designed studies are still needed to compare the differences statistically between PCOS and non-PCOS populations.

Expression levels of KATP channel subunits and morphological changes in the mouse liver after exposure to radiation.

BACKGROUND: ATP sensitive K+ (KATP) channels are ubiquitously distributed in various of cells and tissues, including the liver. They play a role in the pathogenesis of myocardial and liver ischemia. AIM: To evaluate the radiation-induced changes in the expression of KATP channel subunits in the mouse liver to understand the potential role of KATP channels in radiation injury. METHODS: Adult C57BL/6 mice were randomly exposed to γ-rays at 0 Gy (control, n = 2), 0.2 Gy (n = 6), 1 Gy (n = 6), or 5 Gy (n = 6). The livers were removed 3 and 24 h after radiation exposure. Hematoxylin and eosin staining was used for morphological observation; immunohistochemical staining was applied to determine the expression of KATP channel subunits in the liver tissue. RESULTS: Compared with the control group, the livers exposed to 0.2 Gy γ-ray showed an initial increase in the expression of Kir6.1 at 3 h, followed by recovery at 24 h after exposure. Exposure to a high dose of 5.0 Gy resulted in decreased expression of Kir6.1 and increased expression of SUR2B at 24 h. However, the expression of Kir6.2, SUR1, or SUR2A had no remarkable changes at 3 and 24 h after exposure to any of these doses. CONCLUSION: The expression levels of Kir6.1 and SUR2B in mouse liver changed differently in response to different radiation doses, suggesting a potential role for them in radiation-induced liver injury.

Bone Marrow Stimulation Does Not Lead to Lower Retear Rates, Better Functional Outcomes, or Higher Complication Rates at Short-Term Follow-Up for Arthroscopic Rotator Cuff Repair: A Meta-analysis of Randomized Controlled Trials.

PURPOSE: To determine the effect of bone marrow stimulation (BMS) on retear rates, functional outcomes, and complication rates in patients who underwent arthroscopic rotator cuff repair (RCR) through a meta-analysis of randomized controlled trials. METHODS: PubMed, EMBASE, Web of Science, and The Cochrane Library were searched on March 25, 2023. Two evaluators independently screened the literature, extracted data, and assessed the methodologic quality of the enrolled studies. Meta-analysis was conducted using RevMan software, version 5.4. RESULTS: A total of 7 randomized controlled trials with 638 patients were included. The evaluation of rotator cuff tendon integrity was conducted using distinct imaging modalities. Specifically, 259 patients underwent magnetic resonance imaging whereas 208 patients underwent ultrasound. Additionally, a subset of 95 patients underwent either of these modalities; however, the precise distribution between these 2 modalities was not explicitly delineated. Compared with RCR alone, RCR combined with BMS provided similar retear rates (P = .51, I2 = 46%), Constant-Murley scores (P = .14, I2 = 0%), American Shoulder and Elbow Surgeons (standardized shoulder assessment form) scores (P = .56, I2 = 0%), Western Ontario Rotator Cuff Index scores (P = .20, I2 = 0%), visual analog scale scores (P = .19, I2 = 0%), forward flexion (P = .18, I2 = 0%), external rotation (P = .62, I2 = 0%), severe complication rates (P = .56, I2 = 0%), and mild complication rates (P = .10, I2 = 0%). CONCLUSIONS: Compared with the outcomes observed after isolated arthroscopic RCR, arthroscopic RCR with BMS showed comparable results in terms of retear rate, functional outcomes, and incidence of complications. LEVEL OF EVIDENCE: Level II, meta-analysis of Level I and II studies.