Extracellular vesicles in endometriosis: role and potential.

Endometriosis is a chronic inflammatory gynecological disease, which profoundly jeopardizes women's quality of life and places a significant medical burden on society. The pathogenesis of endometriosis remains unclear, posing major clinical challenges in diagnosis and treatment. There is an urgent demand for the development of innovative non-invasive diagnostic techniques and the identification of therapeutic targets. Extracellular vesicles, recognized for transporting a diverse array of signaling molecules, have garnered extensive attention as a novel mode of intercellular communication. A burgeoning body of research indicates that extracellular vesicles play a pivotal role in the pathogenesis of endometriosis, which may provide possibility and prospect for both diagnosis and treatment. In light of this context, this article focuses on the involvement of extracellular vesicles in the pathogenesis of endometriosis, which deliver information among endometrial stromal cells, macrophages, mesenchymal stem cells, and other cells, and explores their potential applications in the diagnosis and treatment, conducing to the emergence of new strategies for clinical diagnosis and treatment.

CDK-independent role of D-type cyclins in regulating DNA mismatch repair.

Although mismatch repair (MMR) is essential for correcting DNA replication errors, it can also recognize other lesions, such as oxidized bases. In G0 and G1, MMR is kept in check through unknown mechanisms as it is error-prone during these cell cycle phases. We show that in mammalian cells, D-type cyclins are recruited to sites of oxidative DNA damage in a PCNA- and p21-dependent manner. D-type cyclins inhibit the proteasomal degradation of p21, which competes with MMR proteins for binding to PCNA, thereby inhibiting MMR. The ability of D-type cyclins to limit MMR is CDK4- and CDK6-independent and is conserved in G0 and G1. At the G1/S transition, the timely, cullin-RING ubiquitin ligase (CRL)-dependent degradation of D-type cyclins and p21 enables MMR activity to efficiently repair DNA replication errors. Persistent expression of D-type cyclins during S-phase inhibits the binding of MMR proteins to PCNA, increases the mutational burden, and promotes microsatellite instability.

D-type cyclins regulate DNA mismatch repair in the G1 and S phases of the cell cycle, maintaining genome stability.

The large majority of oxidative DNA lesions occurring in the G1 phase of the cell cycle are repaired by base excision repair (BER) rather than mismatch repair (MMR) to avoid long resections that can lead to genomic instability and cell death. However, the molecular mechanisms dictating pathway choice between MMR and BER have remained unknown. Here, we show that, during G1, D-type cyclins are recruited to sites of oxidative DNA damage in a PCNA- and p21-dependent manner. D-type cyclins shield p21 from its two ubiquitin ligases CRL1SKP2 and CRL4CDT2 in a CDK4/6-independent manner. In turn, p21 competes through its PCNA-interacting protein degron with MMR components for their binding to PCNA. This inhibits MMR while not affecting BER. At the G1/S transition, the CRL4AMBRA1-dependent degradation of D-type cyclins renders p21 susceptible to proteolysis. These timely degradation events allow the proper binding of MMR proteins to PCNA, enabling the repair of DNA replication errors. Persistent expression of cyclin D1 during S-phase increases the mutational burden and promotes microsatellite instability. Thus, the expression of D-type cyclins inhibits MMR in G1, whereas their degradation is necessary for proper MMR function in S.

Coronary computed tomography angiography analysis using artificial intelligence for stenosis quantification and stent segmentation: a multicenter study.

Background: Accurate interpretation of coronary computed tomography angiography (CCTA) is a labor-intensive and expertise-driven endeavor, as inexperienced readers may inadvertently overestimate stenosis severity. Recent artificial intelligence (AI) advances in medical imaging present compelling prospects for auxiliary diagnostic tools in CCTA. This study aimed to externally validate an AI-assisted analysis system capable of rapidly evaluating stenosis severity, exploring its potential integration into routine clinical workflows. Methods: This multicenter study consisted of an internal and external cohort of patients who underwent CCTA scans between April 2017 and February 2023. CCTA scans were evaluated using Coronary Artery Disease Reporting and Data System (CAD-RADS) scores to determine stenosis severity, while ground-truth stents were manually annotated by expert readers. The InferRead CT Heart (version 1.6; Infervision Medical Technology Co., Ltd., Beijing, China), which incorporates AI-assisted coronary artery stenosis quantification and automatic stent segmentation, was employed for CCTA scan analysis. AI-based stenosis assessment performance was determined using sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV), while the AI-based stent segmentation overlap was assessed using the Dice similarity coefficient (DSC). Results: For ≥50% stenosis diagnoses, the AI system attained per-patient sensitivity, specificity, PPV, and NPV surpassing 90.0% for the internal dataset; for the external dataset, the per-patient values were 88.0% [95% confidence interval (CI): 81.0-94.4%], 94.5% (95% CI: 90.7-97.6%), 90.0% (95% CI: 83.3-95.6%), and 93.4% (95% CI: 89.2-96.8%), respectively. For ≥70% stenosis diagnoses, the per-patient values on the internal dataset were 94.2% (95% CI: 89.2-98.1%), 95.8% (95% CI: 94.1-97.4%), 80.8% (95% CI: 73.5-87.7%), and 98.9% (95% CI: 97.9-99.6%), respectively; for the external dataset, the per-patient values were 91.9% (95% CI: 82.6-100.0%), 97.3% (95% CI: 94.9-99.1%), 85.0% (95% CI: 72.5-94.6%), and 98.6% (95% CI: 96.8-100.0%), respectively. Regarding CAD-RADS categorization, the Cohen kappa was 0.75 and 0.81 for the internal per-patient and per-vessel basis, respectively, and 0.72 and 0.76 for the external per-patient and per-vessel basis, respectively. The DSC for stent segmentation was 0.96±0.06. Conclusions: The AI-assisted analysis system for CCTA interpretation exhibited exceptional proficiency in stenosis quantification and stent segmentation, indicating that AI holds considerable potential in advancing CCTA postprocessing techniques.

Current status and influencing factors of participating satisfaction during surgical treatment decision-making among breast cancer patients with immediate breast reconstruction.

OBJECTIVE: Breast reconstruction (BR) is a positive contribution to aesthetic effect among breast cancer patients. Identification of influenced factors for participating satisfaction may provide insights on the decision-making theory to promote patient's autonomy in surgical choice. The purpose of this study was to examine the level of participating satisfaction with surgical treatment decision-making and its predictors among breast cancer patients with immediate BR. METHODS: A cross-sectional study was conducted including 163 breast cancer patients with immediate BR in Mainland China. Data was collected using patients' participation satisfaction in medical decision-making scale (PSMDS), Big five Short-Form (BFI) Scale, Patient Participation Competence Scale(PPCS) and Patients' Preference (MPP) scale. Descriptive, bivariate, and multivariate regression analyses were used. RESULTS: Scores of PSMD were 86.38 ± 15.74. Multiple regression analyses indicated autonomous decision-making, marital statue, information acquisition competence, agreeableness, and decision-making preferences as indicators, explaining 29.6% of the response variation (P < 0.05). CONCLUSIONS: The level of PSMD in breast cancer patients with immediate BR need to be improved. Patients with greater autonomous decision-making, married, higher information acquisition competence, agreeableness, and collaborative role are more likely to have an preferable PSMD. A comprehensive assessment and effective decision-making support are needed initially for BC patients to promote positive participation when making surgical decision.

The effects of supplementation of noni (Morinda citrifolia L.) fruit polysaccharides-rich extract on antioxidant status and immune function in cashmere goats.

This experiment was designed to examine the effects of a dietary supplementation of polysaccharides-rich noni (Morinda citrifolia L.) fruit extract (NFP) on the anti-oxidant enzyme activities, cytokines level, and expression of corresponding genes in blood of cashmere goats. Twelve castrated, 2-yr-old male cashmere goats (45.44 ± 3.30 kg of BW ± SD) were used in a 2 × 2 crossover design: the basal diet with or without (CON) supplementation of NFP at 4 g per kg DM (0.4%). Each period lasted for 29 d, including 1 wk for diet transition, 20 d for adaptation, and the last 2 d for sampling. The results showed that NFP supplementation increased (P < 0.05) the levels of nitric oxide, interleukin-6 (IL-6) and tumor necrosis factor-alpha (TNF-α), and the activities of catalase (CAT), glutathione peroxidase (GPx), thioredoxin reductase (TrxR), and total superoxide dismutase (T-SOD) in serum. The expressions of CAT, GPx4, TrxR, SOD1, IL-6, and TNF-α genes were upregulated (P < 0.05), whereas the levels of malondialdehyde (P = 0.015) and reactive oxygen species (P = 0.051) in serum were reduced. The body weight gain of goats was increased (P = 0.006) with a nonsignificant increase of feed intake with NFP supplementation. In conclusion, dietary NFP supplementation enhanced the antioxidant status and immune function in blood of cashmere goats.

Due to the limited pasture supply and the seasonal imbalance of nutrients in grazed pastures in China, cashmere goats are commonly raised in a confined yard-feeding system, which may result in oxidative stress from a lack of green pastures. Noni (Morinda citrifolia L.) fruit polysaccharides contain various biological compounds that function as anti-inflammatory, antitumor, and to enhance immune responses, hence likely to relieve oxidative stress in animals. Previous researches in our laboratory have shown that polysaccharides-rich extract from noni fruit (NFP) enhanced rumen fermentation in cashmere goats. This experiment was designed to evaluate the effect of NFP supplementation on serum antioxidant status and immune function in cashmere goats. The results showed that dietary supplementation of 0.40% NFP enhanced the immune signaling molecule levels and antioxidant enzyme activities by upregulating the expression of related genes in blood and reduced the levels of lipid peroxides and free radicals in serum, while mature goats improved body weight. Therefore, NFP could be a viable source of antioxidants for cashmere goats.

Downregulation of GTSE1 leads to the inhibition of proliferation, migration, and Warburg effect in cervical cancer by blocking LHDA expression.

AIM: G2 and S phase-expressed-1 (GTSE1) has been identified to play a vital role in several kinds of cancers, but its role in cervical cancer development remains unknown. Herein, we aimed to reveal the role and underlying mechanism of GTSE1 in cervical cancer cell growth, migration, and aerobic glycolysis. METHODS: GTSE1 expression levels in cervical cancer tissues and normal cervical tissues were determined by real time PCR and immunohistochemistry. Human short hairpin RNA was used to downregulate GTSE1 level in cervical cancer cells SiHa and HeLa cells. Colony formation, cell counting kit-8, and wound-healing assays were used for cell function evaluation. Lactate production, lactate dehydrogenase activity, and glucose concentration were tested to assess the Warburg effect. RESULTS: GTSE1 expressions at both mRNA and protein levels were significantly elevated in cervical cancer tissues compared with normal tissues. Downregulation of GTSE1 induced significant repressions in cell colony formation, viability and migration, and Warburg effect, as well as reduced expression of lactate dehydrogenase isoform A (LDHA) at mRNA and protein levels. Additionally, downregulation of GTSE1 weakened the tumorigenesis of HeLa and SiHa cells in vivo. CONCLUSION: This study demonstrated that downregulation of GTSE1 led to significant inhibitions in cell proliferation, migration, tumorigenesis, and Warburg effect in cervical cancer by blocking the expression of LHDA.

Clinical significance of serum markers reflecting gastric function and H. pylori infection in colorectal cancer.

Purpose: The study was conducted to investigate the relationship of serum pepsinogens PGI, PGII, gastrin-17, and Hp-IgG with colorectal cancer (CRC), aiming to explore the clinical significance of serum markers reflecting gastric function and H. pylori infection in CRC. Methods: A total of 569 CRC cases and 569 age and sex-matched controls were enrolled in this study between June 2012 and April 2016 from The First Hospital of China Medical University. The serum markers reflecting gastric function and H. pylori infection were detected using ELISA, including PGI, PGII, PGI/II ratio, G-17 and Hp-IgG. Information of clinicopathological parameters and tumor biomarkers was collected from the medical records of inpatients, including CEA, CA199, CA125, CA153 and AFP. Results: Serum PGII, G-17 levels and Hp-IgG were increased in CRC, while PGI and PGI/II ratio appeared no significant difference between CRC and controls. In subgroup analysis, PGII was more significant in males (P=0.014). Hp-IgG was demonstrated higher in age<60y (P=0.001). With respect to the association with serum tumor biomarkers, G-17 level was associated with the rise of CA125 (P=0.005, OR (95%CI): 4.89 (1.90-12.57)), Hp-IgG increasing was associated with the rise of CA125 (P=0.024, OR (95%CI): 4.10 (1.54-10.93)). Conclusions: Serum PGII, G-17 and Hp-IgG were associated with CRC risk. The serum levels of G-17 and Hp-IgG were associated with the rise of CA125 in patients with CRC.

Impact of the preoperative prognostic nutritional index on postoperative and survival outcomes in colorectal cancer patients who underwent primary tumor resection: a systematic review and meta-analysis.

PURPOSE: We aimed to explore whether the preoperative prognostic nutritional index (PNI) could be an indicator of prognostic outcomes in colorectal cancer (CRC) patients. METHODS: A systematic review and meta-analysis was conducted using the PubMed, Embase, and Web of Science databases. All original comparative studies published in English that were related to a high PNI versus a low PNI in CRC patients were included. RESULTS: A total of 10 studies involving 6372 patients were included in our meta-analysis. Our overall analysis indicated that the low-PNI group had a significantly reduced overall survival (OS) (HR = 1.87, 95% CI = 1.45-2.42, P < 0.01), cancer-specific survival (HR = 1.53, 95% CI = 1.07-2.19, P = 0.02), and disease-free survival (HR = 1.67, 95% CI = 1.23-2.26, P < 0.01) compared with the high-PNI group. Furthermore, our subgroup results indicated that a high PNI could be a significant indicator of improved OS in TNM stage II (HR = 1.93, 95% CI = 1.29-2.90, P < 0.01) and III (HR = 1.71, 95% CI = 1.25-2.34, P < 0.01), and a similar trend in TNM stage I or IV could also be observed though without statistical significance. Regarding postoperative complications, our pooled results indicated that the low-PNI group had a significantly increased incidence of total and severe postoperative complications. CONCLUSIONS: Our findings indicated that CRC patients with a preoperative high PNI had a significantly improved OS. However, almost only Asian CRC patients were included based on current issue.

Identification of differentially expressed genes and biological characteristics of colorectal cancer by integrated bioinformatics analysis.

Colorectal cancer (CRC) ranks as one of the most common malignant tumors worldwide. Its mortality rate has remained high in recent years. Therefore, the aim of this study was to identify significant differentially expressed genes (DEGs) involved in its pathogenesis, which may be used as novel biomarkers or potential therapeutic targets for CRC. The gene expression profiles of GSE21510, GSE32323, GSE89076, and GSE113513 were downloaded from the Gene Expression Omnibus (GEO) database. After screening DEGs in each GEO data set, we further used the robust rank aggregation method to identify 494 significant DEGs including 212 upregulated and 282 downregulated genes. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses were performed by DAVID and the KOBAS online database, respectively. These DEGs were shown to be significantly enriched in different cancer-related functions and pathways. Then, the STRING database was used to construct the protein-protein interaction network. The module analysis was performed by the MCODE plug-in of Cytoscape based on the whole network. We finally filtered out seven hub genes by the cytoHubba plug-in, including PPBP, CCL28, CXCL12, INSL5, CXCL3, CXCL10, and CXCL11. The expression validation and survival analysis of these hub genes were analyzed based on The Cancer Genome Atlas database. In conclusion, the robust DEGs associated with the carcinogenesis of CRC were screened through the GEO database, and integrated bioinformatics analysis was conducted. Our study provides reliable molecular biomarkers for screening and diagnosis, prognosis as well as novel therapeutic targets for CRC.

Identification of a five-gene signature with prognostic value in colorectal cancer.

Colorectal cancer (CRC) ranks as one of the most commonly diagnosed malignancies worldwide. Although mortality rates have been decreasing, the prognosis of CRC patients is still highly dependent on the individual. Therefore, identifying and understanding novel biomarkers for CRC prognosis remains crucial. The gene expression profiles of five-gene expression omnibus (GEO) data sets of CRC were first downloaded. A total of 352 consistent differentially expressed genes (DEGs) were identified for CRC and paired with normal tissues. Functional analysis including gene ontology and Kyoto encyclopedia of genes and genomes pathway enrichment revealed that these DEGs were related to metabolic pathways, tight junctions, and the cell cycle. Ten hub DEGs were identified based on the search tool for the retrieval of interacting genes database and protein-protein interaction networks. By using univariate Cox proportional hazard regression analysis, we found 11 survival-related genes among these DEGs. We finally established a five-gene signature (kinesin family member 15, N-acetyltransferase 2, glutathione peroxidase 3, secretogranin II, and chloride channel accessory 1) with prognostic value in CRC by step multivariate Cox regression analysis. Based on this risk scoring system, patients in the high-risk group had significantly poorer survival results compared with those in the low-risk group (log-rank test, p < 0.0001). Finally, we validated our gene signature scoring system in two independent GEO cohorts (GSE17536 and GSE33113). We found all five of the signature genes to be DEGs in The Cancer Genome Atlas database. In conclusion, our findings suggest that our five DEG-based signature can provide a novel biomarker with useful applications in CRC prognosis.

Psychosocial Predictors of Adjustment to Disability Among Patients With Breast Cancer: A Cross-Sectional Descriptive Study.

BACKGROUND: Acceptance of disability relates to the process of adaptation, which reflects how the values of a patient change over time to accept herself or himself as an intrinsically worthy person. Acceptance of disability (AOD) plays an important role in the adjustment of persons with physical disability to their environment. However, no studies on the level of AOD in patients with breast cancer are available in the literature. PURPOSE: The aim of this study was to explore the significant factors that influence disability acceptance in Chinese women with breast cancer. METHODS: A cross-sectional study was conducted on 292 patients with breast cancer between January and April 2017. Participants were assessed using the Acceptance of Disability Scale-Revised, Medical Coping Modes Questionnaire, Sense of Coherence Scale, Social Relational Quality Scale, and general information questionnaire. Multiple regression analysis was used to determine the factors associated with the level of disability acceptance. RESULTS: The mean score for AOD was 79.14 and ranged from 32 to 128. Multiple regression analysis indicated that family intimacy, friendships, confrontation, manageability, family commitment, marital status, surgery, and acceptance-resignation significantly affected disability acceptance, explaining 49.1% of the total variance in disability acceptance. CONCLUSIONS/IMPLICATIONS FOR PRACTICE: The participants had a moderate level of disability acceptance. Disability acceptance is an important factor in the psychosocial adaptation to cancer. Healthcare staff should pay special attention to low scores for this factor and explore the potential of psychological interventions to effectively reduce the posttraumatic stress response, encourage the adoption of positive coping strategies, and hasten disability acceptance and return to society.

Can sarcopenia be a predictor of prognosis for patients with non-metastatic colorectal cancer? A systematic review and meta-analysis.

PURPOSE: We aimed to explore whether sarcopenia diagnosed with the third lumbar vertebra skeletal muscle index (L3 SMI) can be a predictor of prognosis for colorectal cancer (CRC) patients. METHODS: A systematic review and meta-analysis was conducted using PubMed, Embase, and the Web of Science databases. All original comparative studies published in English that were related to sarcopenia versus non-sarcopenia in non-metastatic CRC patients based on postoperative and survival outcomes were included. Data synthesis and statistical analysis were carried out using Stata software. RESULTS: A total of 12 studies including 5337 patients were included in our meta-analysis. In our overall analyses of postoperative outcomes, we indicated that CRC patients with sarcopenia would have longer hospital stays, higher incidence of total postoperative morbidity (OR = 1.70, 95% CI = 1.07-2.70, P < 0.01), mortality (OR = 3.45, 95% CI = 1.69-7.02, P < 0.01), and infection (OR = 2.21, 95% CI = 1.50-3.25, P < 0.01) but not anastomosis leakage or intestinal obstruction when compared to non-sarcopenia patients. Regarding survival outcomes, our results showed that sarcopenia predicted a decreased overall survival (HR = 1.63, 95% CI = 1.24-2.14, P < 0.01), disease-free survival, and cancer-specific survival for non-metastatic CRC patients. Moreover, our subgroup analyses showed similar tendency with our overall analyzed results. CONCLUSIONS: Sarcopenia diagnosed with L3 SMI can be a negative predictor of postoperative and survival outcomes for non-metastatic CRC patients. Prospective studies with a uniform definition of sarcopenia are needed to update our findings.

The diagnostic, prediction of postoperative recurrence and prognostic value of HE4 in epithelial ovarian cancer.

PURPOSE: To explore the clinical value of the level of human epididymis protein 4 (HE4) in serum in the diagnosis, prediction of postoperative recurrence and prognosis of epithelial ovarian cancer (EOC). METHODS: A total of 103 EOC patients and 121 individuals with benign ovarian lesions were selected. All of them were admitted to our hospital between January 2013 and January 2014 as group A (EOC, n=103) and group B (benign ovarian lesions, n=121), respectively. Additionally, 106 serum samples collected from healthy people who underwent physical examination were selected as group C. The serum levels of HE4 were assessed one day before and one day after the operation to reveal differences among the three groups. In addition, we analyzed the clinical value of HE4 in the diagnosis, prediction of recurrence and progression-free survival (PFS) of EOC patients. RESULTS: In group A, the level of HE4 was significantly higher than in groups B and C (p<0.05), while comparison between the group B and C revealed no statistically significant difference (p>0.05). The sensitivity, specificity, positive predictive value and negative predictive value of HE4 in the diagnosis of EOC were 82.52, 84.46, 83.47 and 92.34%, respectively. In the prediction of recurrence of EOC, the sensitivity and specificity of HE4 alone were 87.57 and 92.45%, respectively, while the sensitivity and specificity of HE4 combined with CA-125 were 93.45 and 94.24%, respectively. In addition, the level of HE4 showed a significant negative effect on PFS (p<0.05). CONCLUSIONS: Detection of HE4 is conducive to the diagnosis and prediction of recurrence of EOC, and HE4 in high concentration suggests poor prognosis.