Pan-cancer characterization of cell-free immune-related miRNA identified as a robust biomarker for cancer diagnosis.

Minimally invasive testing is essential for early cancer detection, impacting patient survival rates significantly. Our study aimed to establish a pioneering cell-free immune-related miRNAs (cf-IRmiRNAs) signature for early cancer detection. We analyzed circulating miRNA profiles from 15,832 participants, including individuals with 13 types of cancer and control. The data was randomly divided into training, validation, and test sets (7:2:1), with an additional external test set of 684 participants. In the discovery phase, we identified 100 differentially expressed cf-IRmiRNAs between the malignant and non-malignant, retaining 39 using the least absolute shrinkage and selection operator (LASSO) method. Five machine learning algorithms were adopted to construct cf-IRmiRNAs signature, and the diagnostic classifies based on XGBoost algorithm showed the excellent performance for cancer detection in the validation set (AUC: 0.984, CI: 0.980-0.989), determined through 5-fold cross-validation and grid search. Further evaluation in the test and external test sets confirmed the reliability and efficacy of the classifier (AUC: 0.980 to 1.000). The classifier successfully detected early-stage cancers, particularly lung, prostate, and gastric cancers. It also distinguished between benign and malignant tumors. This study represents the largest and most comprehensive pan-cancer analysis on cf-IRmiRNAs, offering a promising non-invasive diagnostic biomarker for early cancer detection and potential impact on clinical practice.

The Battle for Accuracy: Identifying the Most Effective Grading System for Lung Invasive Mucinous Adenocarcinoma.

BACKGROUND: The prognostic analysis of lung invasive mucinous adenocarcinoma (IMA) is deficient due to the lack of a universally recommended histological grading system, leading to unregulated treatment approaches. OBJECTIVE: We aimed to examine the clinical trajectory of IMA and assess the viability of utilizing the existing grading system for lung invasive non-mucinous adenocarcinoma in the context of IMA. METHODS: We retrospectively collected clinicopathological data from 265 IMA patients. Each case re-evaluated the tumor grade using the following three classification systems: the 4th Edition of the World Health Organization classification system, the International Association for the Study of Lung Cancer (IASLC) grading system, and a two-tier grading system. We performed a comparative analysis of these grading systems and identified the most effective grading system for IMA. RESULTS: The study comprised a total of 214 patients with pure IMA and 51 patients with mixed IMA. The 5-year overall survival (OS) rates for pure IMA and mixed IMA were 86.7% and 57.8%, respectively. All three grading systems proved to be effective prognostic classifiers for IMA. The value of area under the curve at 1-, 3-, and 5-year OS was highest for the IASLC grading system compared with the other grade systems and the clinical stage. The IASLC classification system was an independent prognostic predictor (p = 0.009, hazard ratio 2.243, 95% confidence interval 1.219-4.127). CONCLUSION: Mixed IMA is more aggressive than pure IMA, with an OS rate on par with that of high-grade pure IMA. The IASLC grading system can better indicate prognosis and is recommended for lung IMA.

Establishment and verification of novel TNM staging system for lung mucinous adenocarcinoma.

BACKGROUND: Lung adenocarcinoma is a high-mortality rate cancer. Within this category, Lung mucinous adenocarcinoma (LMAC) is a rare and distinct subtype of lung adenocarcinoma necessitating further investigation. The study was launched to compare the difference of survival features between LMAC and lung non-mucinous adenocarcinoma (LNMAC) and to investigate the significance and demand for developing a new staging system tailored to LMAC. METHODS: This retrospective study assessed the suitableness of the current staging system for LMAC. It compared the overall survival (OS) between LMAC and LNMAC from 2004 to 2020 (LNMAC: 160,387; LMAC: 6,341) and instituted a novel classification framework for LMAC based on US population. Verification group consisting of patients from two Chinese medical centers from 2010 to 2018 (n = 392) was set to ascertain the applicability of this novel system. The primary endpoint was OS. To minimize the bias, propensity score match (PSM) was employed. Survival analysis and Log-rank test were executed to explore the survival features of LMAC. RESULTS: The results indicated that the existed staging system was not suitable for LMAC. Patients diagnosed with LMAC exhibited a superior OS compared to those with LNMAC in stage IA2 (P < 0.0001), IA3 (P < 0.0001), IB (P = 0.0062), IIA (P = 0.0090), IIB (P = 0.0005). In contrast, a worse OS in stage IVA (P = 0.0103) was found in LMAC patients. The novel classification system proposed for LMAC proved to be highly applicable and demonstrated substantial efficacy, as confirmed by the verification group. CONCLUSION: The newly established classification system was more effective for LMAC, but it necessitates large-scale verification to confirm its applicability and reliability.

LINC00520 promotes colorectal cancer progression through miRNA-195-3p / NAT2 axis.

In this study, we investigated the role of LINC00520 in colorectal cancer (CRC) progression. We analyzed LINC00520 expression in 15 pairs of CRC tissues and adjacent tissues using qRT-PCR, revealing significantly elevated levels in CRC tissues and cell lines. Lentivirus-mediated up/down-regulation of LINC00520 in CRC cell lines demonstrated that increased LINC00520 expression enhanced cell invasiveness, as confirmed by transwell and wound healing assays. Bioinformatics analysis identified a regulatory axis involving LINC00520, microRNA-195-3p, and NAT2. Luciferase assays confirmed direct binding between LINC00520 and microRNA-195-3p, as well as microRNA-195-3p and NAT2. Overexpression of NAT2 reversed the inhibitory effects on invasion and migration induced by LINC00520 silencing. This suggests that LINC00520, highly expressed in CRC tissues, may modulate tumor biological functions through the microRNA-195-3p/NAT2 axis. Our findings provide insights into the mechanism underlying CRC progression, highlighting the potential of LINC00520 as a therapeutic target.

The impact of open access on citations, Pageviews, and downloads: a scientometric analysis in Postgraduate Medical Journal.

PURPOSE: The influence of Open Access (OA) on the citation impact of scholarly articles remains a topic of considerable debate. This study aims to elucidate the relationship between OA publication and citation metrics, as well as article visibility, within the context of the Postgraduate Medical Journal (PMJ). METHODS: We conducted a retrospective analysis of 373 articles published in PMJ between 2020 and 2021. Data on OA status, citations, page views, PDF downloads, and other relevant variables were extracted from Journal Citation Reports and PMJ's official website. Multivariable linear regression and other statistical analyses were used to assess the impact of OA on these metrics. RESULTS: OA articles (n = 78) demonstrated significantly higher citation counts, page views, and PDF downloads compared with subscription-based articles (n = 295). Specifically, OA articles showed a significant increase in citation frequency with a ß coefficient of 25.08 and a 95% CI of 17.168-32.992 (P < .001). Similarly, OA status was independently associated with increases in page views [ß = 288.636, 95%CI: 177.749-399.524, P < .001] and PDF downloads [ß = 118.966, 95%CI: 86.357-151.575, P < .001]. Strong correlations among total citations, page views, and PDF downloads were observed in both OA and subscription articles. CONCLUSION: The study highlights a significant and independent association of OA publishing with increased citation counts, page views, and PDF downloads in PMJ, suggesting that OA articles have broader reach and greater visibility. Further research, including randomized controlled studies across various journals, is needed to confirm these findings and explore the full impact of OA publishing.

Short-and long-term outcomes of one-stage versus two-stage gastrectomy for perforated gastric cancer: a multicenter retrospective propensity score-matched study.

OBJECTIVE: There is no scientific consensus about the treatment of perforated gastric cancer (PGC). Therefore, the aim of this study was to investigate which is the better treatment option for PGC between the single-stage and two-stage strategies. METHODS: All 81 PGC patients from 13 medical institutions were retrospectively enrolled in this study. The PGC patients who underwent R0 gastrectomy were divided into one-stage surgery and two-stage surgery groups. The clinicopathological characteristics of the two groups were compared, and 415 regular gastric cancer patients without perforation were randomly selected as a control. The propensity score matching (PSM) method was used to find matched regular GC patients with similar clinicopathological parameters. The OS (overall survival) and the number harvested lymph nodes from PGC patients and regular GC patients were compared. RESULTS: Compared with PGC patients who underwent one-stage surgery, those who underwent two-stage surgery harvested significantly more lymph nodes [31(27, 38) vs 17 (12, 24), P < 0.001], required less blood transfusion [0 (0, 100) vs 200 (0, 800), P = 0.034], had a shorter ICU stay [0 (0, 1.5) vs 3 (0, 3), P = 0.009], and had a significantly better OS (Median OS: 45 months vs 11 months, P = 0.007). Compared with propensity score-matched regular GC patients without perforation, PGC patients who underwent one-stage gastrectomy had a poorer quality of lymphadenectomy [17 (12, 24) vs 29 (21, 37), P < 0.001] and suffered a worse OS (Median OS: 18 months vs 30 months, P = 0.024). Conversely, two-stage gastrectomy can achieve a comparable quality of lymphadenectomy (P = 0.506) and a similar OS (P = 0.096) compared to propensity score-matched regular GC patients. CONCLUSIONS: For PGC patients in poor condition, two-stage treatment is a better option when D2 radical gastrectomy cannot be achieved in emergency surgery, based on our findings that two-stage gastrectomy could provide PGC patients with a better quality of lymphadenectomy and a better OS.

Navigating Challenges and Seizing Opportunities in China's Era of Online Health Education.

The rapid growth of internet users in China presents opportunities for advancing the "Healthy China 2030" initiative through online health education. Platforms like "Shanghai Health Cloud" and "National Health Information Platform" improve health literacy and management, enhancing overall public health. However, challenges such as the digital divide and the spread of unverified health information hinder progress. Addressing these issues requires enhancing digital infrastructure, employing advanced technologies for information validation, and setting high standards for online health services. Integrated efforts from various sectors are essential to maximize the benefits of online health education in China.

Costimulatory molecule expression profile as a biomarker to predict prognosis and chemotherapy response for patients with small cell lung cancer.

Owing to the paucity of specimens, progress in identifying prognostic and therapeutic biomarkers for small cell lung cancer (SCLC) has been stagnant for decades. Considering that the costimulatory molecules are essential elements in modulating immune responses and determining therapeutic response, we systematically revealed the expression landscape and identified a costimulatory molecule-based signature (CMS) to predict prognosis and chemotherapy response for SCLCs for the first time. We found T cell activation was restrained in SCLCs, and costimulatory molecules exhibited widespread abnormal genetic alterations and expression. Using a LASSO Cox regression model, the CMS was built with a training cohort of 77 cases, which successfully divided patients into high- or low-risk groups with significantly different prognosis and chemotherapy benefit (both P < 0.001). The CMS was well validated in an independent cohort containing 131 samples with qPCR data. ROC and C-index analysis confirmed the superior predictive performance of the CMS in comparison with other clinicopathological parameters from different cohorts. Importantly, the CMS was confirmed as a significantly independent prognosticator for clinical outcomes and chemotherapy response in SCLCs through multivariate Cox analysis. Further analysis revealed that low-risk patients were characteristic by an activated immune phenotype with distinct expression of immune checkpoints. In summary, we firstly uncovered the expression heterogeneity of costimulatory molecules in SCLC and successfully constructed a novel predictive CMS. The identified signature contributed to more accurate patient stratification and provided robust prognostic value in estimating survival and the clinical response to chemotherapy, allowing optimization of treatment and prognosis management for patients with SCLC.

Optimal velocity loss threshold for inducing post activation potentiation in track and field athletes.

The aim of this study was to determine the optimal velocity loss (VL) threshold that maximises the post activation potentiation (PAP) stimulus for achieving larger and more consistent performance gains in track and field athletes. Twenty-two athletes from athletics participated in four back squat PAP tests with four different VL threshold (5%, 10%, 15% and 20% VL) at an intensity of 85%1RM. Countermovement jump (CMJ) height, power, and momentum were assessed before, and 10 s, 4, 8, 12, 16 minutes after the PAP condition. Repetitions of the squat in all the PAP conditions were also recorded. Only the 5% VL condition produced significant improvements in height (ES = 0.73, P = 0.038), peak power output (ES = 0.73, P = 0.038) and momentum (ES = 0.72, P = 0.041) of CMJ, and these changes appeared 8 minutes after the condition. The total number of repetitions during the 5% VL condition was significantly lower than that observed in the 15% (P = 0.003) and 20% VL (P < 0.001) trials. The results from this study indicate that 5%VL during the 2 sets preconditioning squat at 85%1RM was optimal for eliciting PAP in a CMJ exercise, and resulted in significant increases at the 8-min recovery period. The same squat condition also had the least number of repetitions. However, considering the efficiency in practice, athletes can also choose the rest time of 4-min, which can also achieve similar results.

Comprehensive analyses of N6 -methyladenosine-related long noncoding RNA profiles with prognosis, chemotherapy response, and immune landscape in small cell lung cancer.

Small cell lung cancer (SCLC) is the most devastating subtype of lung cancer with no clinically available prognostic biomarkers. N6 -methyladenosine (m6 A) and noncoding RNAs play critical roles in cancer development and treatment response. However, little is known about m6 A-related long noncoding RNAs (lncRNAs) in SCLC. We used 206 limited-stage SCLC (LS-SCLC) samples from two cohorts to undertake the first and most comprehensive exploration of the m6 A-related lncRNA profile in SCLC and constructed a relevant prognostic signature. In total, 289 m6 A-related lncRNAs were screened out. We then built a seven-lncRNA-based signature in the training cohort with 48 RNA sequencing data using univariate and multivariate Cox regression models. The signature was well validated in an independent cohort containing 158 cases with quantitative PCR data. In both cohorts, the signature divided patients into high- and low-risk groups with significantly different survival rates (both p < 0.001). Our signature predicted chemotherapy survival benefit in patients with LS-SCLC. Receiver operating characteristic and C-index analyses indicated that the signature was better at predicting prognosis and chemotherapy benefit than other clinicopathologic features. Moreover, the signature was identified as an independent predictor of prognosis and chemotherapy response in different cohorts. Furthermore, functional analysis showed that multiple activated immune-related pathways were enriched in the low-risk group. Additionally, the signature was also closely related to various immune checkpoints and inflammatory responses. We generated the first clinically available m6 A-related lncRNA signature to predict prognosis and chemotherapy benefit in patients with LS-SCLC. Our findings could help optimize the clinical management of patients with LS-SCLC and inform future therapeutic targets for SCLC.