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.

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.

Proteome-Wide Multicenter Mendelian Randomization Analysis to Identify Novel Therapeutic Targets for Lung Cancer.

INTRODUCTION: Lung cancer (LC) remains a leading cause of cancer mortality worldwide, underscoring the urgent need for novel therapeutic targets. The integration of Mendelian randomization (MR) with proteomic data presents a novel approach to identifying potential targets for LC treatment. METHODS: This study utilized a proteome-wide MR analysis, leveraging publicly available data from genome-wide association studies (GWAS) and protein quantitative trait loci (pQTL) studies. We analyzed genetic association data for LC from the TRICL-ILCCO Consortium and proteomic data from the Decode cohort. The MR framework was employed to estimate the causal effects of specific proteins on LC risk, supplemented by external validation, co-localization analyses, and exploration of protein-protein interaction (PPI) networks. RESULTS: Our analysis identified five proteins (TFPI, ICAM5, SFTPB, COL6A3, EPHB1) with significant associations to LC risk. External validation confirmed the potential therapeutic relevance of ICAM5 and SFTPB. Co-localization analyses and PPI network exploration provided further insights into the biological pathways involved and their potential mechanistic roles in LC pathogenesis. CONCLUSION: The study highlights the power of integrating genomic and proteomic data through MR analysis to uncover novel therapeutic targets for lung cancer. The identified proteins, particularly ICAM5 and SFTPB, offer promising directions for future research and development of targeted therapies, demonstrating the potential to advance personalized medicine in lung cancer treatment.

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.

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.

Molecular subtypes of neuroendocrine carcinomas: A cross-tissue classification framework based on five transcriptional regulators.

Neuroendocrine carcinomas (NECs) are extremely lethal malignancies that can arise at almost any anatomic site. Characterization of NECs is hindered by their rarity and significant inter- and intra-tissue heterogeneity. Herein, through an integrative analysis of over 1,000 NECs originating from 31 various tissues, we reveal their tissue-independent convergence and further unveil molecular divergence driven by distinct transcriptional regulators. Pan-tissue NECs are therefore categorized into five intrinsic subtypes defined by ASCL1, NEUROD1, HNF4A, POU2F3, and YAP1. A comprehensive portrait of these subtypes is depicted, highlighting subtype-specific transcriptional programs, genomic alterations, evolution trajectories, therapeutic vulnerabilities, and clinicopathological presentations. Notably, the newly discovered HNF4A-dominated subtype-H exhibits a gastrointestinal-like signature, wild-type RB1, unique neuroendocrine differentiation, poor chemotherapeutic response, and prevalent large-cell morphology. The proposal of uniform classification paradigm illuminates transcriptional basis of NEC heterogeneity and bridges the gap across different lineages and cytomorphological variants, in which context-dependent prevalence of subtypes underlies their phenotypic disparities.

Global research trends in CAR-T cell therapy for solid tumors: A comprehensive visualization and bibliometric study (2012-2023).

CAR-T cell therapy has emerged as a significant approach for the management of hematological malignancies. Over the past few years, the utilization of CAR-T cells in the investigation and treatment of solid tumors has gained momentum, thereby establishing itself as a prominent area of research. This descriptive study involved the retrieval of articles about CAR-T cell therapy for solid tumors from the Web of Science Core Collection (WoSCC) database. Subsequently, bibliometric analysis and knowledge map analysis were conducted on these articles. The field under consideration is currently experiencing a period of swift advancement, as evidenced by the escalating number of publications in this domain each year. The United States holds an indisputable position as the foremost leader in this particular field, with the University of Pennsylvania emerging as the most active institution. The authors with the highest citation frequency and co-citation frequency are Carl H. June and Shannon L. Maude, respectively. The research hotspots in this field mainly focus on five aspects. Additionally, 10 emerging themes were identified. This study undertakes a comprehensive, systematic, and objective analysis and exploration of the field of CAR-T cell treatment for solid tumors, utilizing bibliometric methods. The findings of this study are expected to serve as a valuable reference and enlightenment for future research endeavors in this particular domain.

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.

Clinical and immunologic features of co-infection in COVID-19 patients, along with potential traditional Chinese medicine treatments.

Objectives: With the increasing number of people worldwide infected with SARS-CoV-2, the likelihood of co-infection and/or comorbidities is rising. The impact of these co-infections on the patient's immune system remains unclear. This study aims to investigate the immunological characteristics of secondary infections in hospitalized COVID-19 patients, and preliminarily predict potential therapeutic effects of traditional Chinese medicine and their derivatives for the treatment of co-infections. Methods: In this retrospective cohort study, we included 131 hospitalized patients with laboratory-confirmed COVID-19, of whom there were 64 mild and 67 severe cases. We analyzed clinical characteristics and immunologic data, including circulating immune cell numbers, levels of inflammatory factors and viral load, comparing COVID-19 patients with and without co-infection. Results: Among 131 hospitalized COVID-19 patients, 41 (31.3%) were co-infection positive, with 33 (80.5%) having severe disease and 14 (34.1%) of them resulting in fatalities. Co-infected patients exhibited significantly higher severity and mortality rates compared to non-co-infected counterparts. Co-infected patients had significantly lower absolute counts of lymphocytes, total T lymphocytes, CD4+ T cells, CD8+ T cells and B lymphocytes, while levels of hs-CRP, PCT and IL-6 were significantly elevated compared to non-co-infected patients. Additionally, the viral load of co-infected patients was significantly higher than non-co-infected patients. Conclusion: Co-infection emerges as a dangerous factor for COVID-19 patients, elevating the risk of severe pneumonia and mortality. Co-infection suppresses the host's immune response by reducing the number of lymphocytes and increasing inflammation, thereby diminishing the antiviral and anti-infective effects of the immune system, which promotes the severity of the disease. Therefore, it is crucial to implement infection prevention measures to minimize the spread of co-infections among COVID-19 hospitalized patients. Additionally, changes in these biomarkers provide a theoretical basis for the effective treatment of co-infections with traditional Chinese medicine.

Radiological and clinical features of large consolidative-type pulmonary invasive mucinous adenocarcinoma.

BACKGROUND: This study aimed to investigate the radiological, pathological, and prognostic characteristics of large consolidative-type pulmonary invasive mucinous adenocarcinomas (IMA). METHODS: We retrospectively reviewed 738 patients who confirmed IMA between January 2010 and August 2022, and two radiologists reviewed imaging data to determine subtypes. We included 41 patients with pathologically large consolidative-type IMA. We analyzed their radiological, pathological, and prognostic characteristics. The recurrence-free survival (RFS) and overall survival (OS) were determined using the Kaplan-Meier method. RESULTS: Most lesions were located in the lower lobe, with 46.3% patients showing multiple lesions. Halo, angiogram, vacuole, air bronchogram, and dead branch sign were observed in 97.6%, 73.2%, 63.4%, 61.0%, and 61.0% of the cases, respectively. Unevenly low enhancement was observed in 88.89% of patients. T3 and T4 pathological stages were observed in 50.0% and 30.6% of patients, respectively. Lymph node metastasis was observed in 16.7% patients, with no distant metastasis. Spread-through air spaces and intrapulmonary dissemination were observed in 27.8% and 19.4% patients, respectively. Moreover, Kirsten rat sarcoma viral oncogene mutations were found in 68.6% of cases, and no epidermal growth factor receptor mutations were seen. Among all mutation sites, G12V mutation is the most common, accounting for 40%. The average RFS and OS were 19.4 and 66.4 months, respectively, with 3-year RFS and OS rates of 30.0% and 75.0%, respectively. Pleural invasion and lymph node metastasis were independent risk factors for diagnosis. CONCLUSION: Halo, vacuole, angiogram, and dead branch signs were frequently observed in consolidative-type IMA. Kirsten rat sarcoma viral oncogene mutations are common in consolidative-type IMA, especially site G12V, whereas epidermal growth factor receptor mutations were rare; therefore, gene immunotherapy was more difficult. Most patients were in stage T3-T4; however, lymph node metastasis was rare.

Unraveling crop enzymatic browning through integrated omics.

Enzymatic browning reactions, triggered by oxidative stress, significantly compromise the quality of harvested crops during postharvest handling. This has profound implications for the agricultural industry. Recent advances have employed a systematic, multi-omics approach to developing anti-browning treatments, thereby enhancing our understanding of the resistance mechanisms in harvested crops. This review illuminates the current multi-omics strategies, including transcriptomic, proteomic, and metabolomic methods, to elucidate the molecular mechanisms underlying browning. These strategies are pivotal for identifying potential metabolic markers or pathways that could mitigate browning in postharvest systems.

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.

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.

A Janus Gelatin Sponge with a Procoagulant Nanoparticle-Embedded Surface for Coagulopathic Hemostasis.

Apart from the wide and safe application of natural polymer-based hemostatic materials/devices, it is still desirable to develop new types of hemostatic materials that can achieve both potent coagulopathic hemostasis and a facile preparation process. In this work, one Janus gelatin sponge (J-ZGS) is readily constructed for both coagulation-dependent and coagulopathic hemostasis by embedding zein nanoparticles on the surface of a self-prepared gelatin sponge (S-GS): zein nanoparticles were facilely prepared by an antisolvent method to achieve procoagulant blood-material interactions, while S-GS was prepared by freeze-drying a foaming gelatin solution. Due to the distinct secondary structure, the optimal zein nanoparticles possessed a higher in vitro hemostatic property than the pristine zein powder and other nanoparticles, the underlying mechanism of which was revealed as the superior RBC/platelet adhesion property in the presence/absence of plasma proteins. Compared with S-GS and a commercial gelatin sponge, J-ZGS achieved a significantly higher in vitro hemostatic property and similarly good blood compatibility/cytocompatibility. Moreover, in vivo artery-injury models confirmed the outstanding hemostatic performance of J-ZGS under both coagulation-dependent and coagulopathic conditions. Our work offers an appealing approach for developing potent hemostatic sponges from natural polymer-based nanoparticles that could be further extended to versatile hemostatic materials for coagulopathic hemostasis.

Development and validation of a nomogram based on preoperative variables for predicting recurrence-free survival in stage IA lung adenocarcinoma.

BACKGROUND: This study aimed to establish a nomogram for predicting risk of recurrence and provide a model for decision-making between lobectomy and sublobar resection in patients with stage IA lung adenocarcinoma. METHODS: Patients diagnosed with stage IA lung adenocarcinoma (LUAD) between December 2010 and October 2018 from Cancer Hospital Chinese Academy of Medical Sciences were included. Patients were randomly assigned to training and validation cohorts, accounting for 70% and 30% of the total cases, respectively. We collected laboratory variables before surgery. Univariate and multivariate analyses were performed in the training cohort to identify variables significantly associated with recurrence-free survival (RFS) which were subsequently used to construct a nomogram. Validation was conducted in both cohorts. A receiver operating characteristic curve was used to determine the optional cutoff values of the scores calculated from the nomogram. Patients were then divided into low- and high-risk groups. Survival was performed to determine if the nomogram could guide the operation method. RESULTS: A total of 543 patients were included in this study. Gender, albumin level, carcinoembryonic antigen level and cytokeratin-19-fragment level were included in the nomogram. In both cohorts, the nomogram stratified the patients into high- and low-risk groups in terms of RFS. In particular, there was a significant difference in RFS between lobectomy and sublobar resection in the high-risk group. CONCLUSIONS: Gender, albumin level, carcinoembryonic antigen level and cytokeratin-19-fragment level are valuable markers in predicting recurrence and can guide surgical practice in patients with stage IA LUAD.

Breast cancer pre-clinical screening using infrared thermography and artificial intelligence: a prospective, multicentre, diagnostic accuracy cohort study.

BACKGROUND: Given the limited access to breast cancer (BC) screening, the authors developed and validated a mobile phone-artificial intelligence-based infrared thermography (AI-IRT) system for BC screening. MATERIALS AND METHODS: This large prospective clinical trial assessed the diagnostic performance of the AI-IRT system. The authors constructed two datasets and two models, performed internal and external validation, and compared the diagnostic accuracy of the AI models and clinicians. Dataset A included 2100 patients recruited from 19 medical centres in nine regions of China. Dataset B was used for independent external validation and included 102 patients recruited from Langfang People's Hospital. RESULTS: The area under the receiver operating characteristic curve of the binary model for identifying low-risk and intermediate/high-risk patients was 0.9487 (95% CI: 0.9231-0.9744) internally and 0.9120 (95% CI: 0.8460-0.9790) externally. The accuracy of the binary model was higher than that of human readers (0.8627 vs. 0.8088, respectively). In addition, the binary model was better than the multinomial model and used different diagnostic thresholds based on BC risk to achieve specific goals. CONCLUSIONS: The accuracy of AI-IRT was high across populations with different demographic characteristics and less reliant on manual interpretations, demonstrating that this model can improve pre-clinical screening and increase screening rates.

Initial treatment for FIGO 2018 stage IIIC cervical cancer based on histological type: A 14-year multicenter study.

BACKGROUND: To compare the oncological outcomes of radical chemotherapy (R-CT), abdominal radical hysterectomy (ARH), and neoadjuvant chemotherapy and radical surgery (NACT) for International Federation of Gynecology and Obstetrics (FIGO) 2018 stage IIIC cervical cancer, according to histological types: squamous cell carcinoma (SCC) and adenocarcinoma (AC)/adenosquamous cell carcinoma (ASC). METHODS: A comparison of 5-year overall survival (OS) and disease-free survival (DFS) was performed for the SCC and AC/ASC subgroups for the three initial treatments, assessed using Kaplan-Meier and Cox proportional hazards regression analysis and validated using propensity score matching (PSM). RESULTS: The study included 4086 patients: R-CT, n = 1913; ARH, n = 1529; and NACT, n = 644. AC/ASC had a lower survival rate (63.7%) than SCC (73.6%) and a higher recurrence and mortality rate (36.3% and 26.4%, respectively). The 5-year OS and DFS rates were different in the SCC group for R-CT, ARH, and NACT (OS: 69.8% vs. 80.8% vs. 73.0%, p < 0.001; DFS: 66.7% vs. 70.7% vs. 56.4%, p < 0.001), also in the AC/ASC group (OS: 46.1% vs. 70.6% vs. 55.6%, p < 0.001; DFS: 42.7% vs. 64.6% vs. 40.8%, p < 0.001). As for initial treatment, survival outcomes were worse for AC/ASC treated with R-CT and ARH than for SCC (both p < 0.05), with no group differences between the two treated with NACT. CONCLUSION: Initial treatment influences oncological prognosis for patients with FIGO 2018 stage IIIC cervical cancer. ARH is an alternative treatment for stage IIIC cervical SCC and AC/ASC, and NACT needs to be chosen with caution, moreover, R-CT for AC/ASC requires careful selection.