Pan-cancer analysis of CDKN2A alterations identifies a subset of gastric cancer with a cold tumor immune microenvironment.

BACKGROUND: Although CDKN2A alteration has been explored as a favorable factor for tumorigenesis in pan-cancers, the association between CDKN2A point mutation (MUT) and intragenic deletion (DEL) and response to immune checkpoint inhibitors (ICIs) is still disputed. This study aims to determine the associations of CDKN2A MUT and DEL with overall survival (OS) and response to immune checkpoint inhibitors treatment (ICIs) among pan-cancers and the clinical features of CDKN2A-altered gastric cancer. METHODS: This study included 45,000 tumor patients that underwent tumor sequencing across 33 cancer types from four cohorts, the MSK-MetTropism, MSK-IMPACT, OrigiMed2020 and TCGA cohorts. Clinical outcomes and genomic factors associated with response to ICIs, including tumor mutational burden, copy number alteration, neoantigen load, microsatellite instability, tumor immune microenvironment and immune-related gene signatures, were collected in pan-cancer. Clinicopathologic features and outcomes were assessed in gastric cancer. Patients were grouped based on the presence of CDKN2A wild type (WT), CDKN2A MUT, CDKN2A DEL and CDKN2A other alteration (ALT). RESULTS: Our research showed that CDKN2A-MUT patients had shorter survival times than CDKN2A-WT patients in the MSK MetTropism and TCGA cohorts, but longer OS in the MSK-IMPACT cohort with ICIs treatment, particularly in patients having metastatic disease. Similar results were observed among pan-cancer patients with CDKN2A DEL and other ALT. Notably, CDKN2A ALT frequency was positively related to tumor-specific objective response rates to ICIs in MSK MetTropism and OrigiMed 2020. Additionally, individuals with esophageal carcinoma or stomach adenocarcinoma who had CDKN2A MUT had poorer OS than patients from the MSK-IMPACT group, but not those with adenocarcinoma. We also found reduced levels of activated NK cells, T cells CD8 and M2 macrophages in tumor tissue from CDKN2A-MUT or DEL pan-cancer patients compared to CDKN2A-WT patients in TCGA cohort. Gastric cancer scRNA-seq data also showed that CDKN2A-ALT cancer contained less CD8 T cells but more exhausted T cells than CDKN2A-WT cancer. A crucial finding of the pathway analysis was the inhibition of three immune-related pathways in the CDKN2A ALT gastric cancer patients, including the interferon alpha response, inflammatory response, and interferon gamma response. CONCLUSIONS: This study illustrates the CDKN2A MUT and DEL were associated with a poor outcome across cancers. CDKN2A ALT, on the other hand, have the potential to be used as a biomarker for choosing patients for ICI treatment, notably in esophageal carcinoma and stomach adenocarcinoma.

miR-92b-3p Protects against Myocardial Ischemia-Reperfusion Injury by Inhibiting MAP3K2 in a Mouse Model.

OBJECTIVE: MicroRNAs are well-known RNA regulators modulating biological functions in complex signaling networks. This work aims to explore the impact of microRNA-92b-3p (miR-92b-3p) on myocardial ischemia-reperfusion (I/R) injury. MATERIALS AND METHODS: The I/R model was established by left anterior descending coronary artery ligation in mice. The hemodynamic parameters were detected through a multichannel physiological recorder. Myocardial injury markers: serum cardiac troponin I, myocardial kinase isoenzyme (creatine kinase-MB), and serum inflammatory factors (tumor necrosis factor-α, interleukin [IL]-1ß, and IL-6) were evaluated by enzyme-linked immunosorbent assay. Cardiac tissue oxidative stress-related factors (malondialdehyde, glutathione peroxidase, total antioxidation capability, and superoxide dismutase) were assessed by colorimetry, myocardial pathology was observed by hematoxylin-eosin staining, and cardiomyocyte apoptosis was measured by triphosphate nick end-labeling staining, as well as the expression of miR-92b-3p and mitogen-activated protein kinase kinase kinase 2 (MAP3K2) in cardiac tissues were determined by reverse transcription quantitative polymerase chain reaction or western blot assay. The targeting relationship between miR-92b-3p and MAP3K2 was verified by bioinformatics, RNA immunoprecipitation, and luciferase reporter assays. RESULTS: miR-92b-3p was lowly expressed and MAP3K2 was highly expressed in myocardial I/R injury mice. Upregulation of miR-92b-3p improved hemodynamic indices, decreased serum levels of myocardial injury biomarkers, inhibited serum inflammatory response, alleviated cardiac tissue oxidative stress, relieved myocardial pathology, and reduced cardiomyocyte apoptosis during the myocardial I/R injury in mice. MAP3K2 was a direct target gene of miR-92b-3p. CONCLUSION: This research suggests that miR-92b-3p protects against myocardial I/R injury by inhibiting MAP3K2, which may provide novel candidates for treatment of myocardial I/R injury.

Conjoint Tendon Lengthening Improves Internal Rotation Following Reverse Total Shoulder Arthroplasty: A Cadaveric Study.

INTRODUCTION: Reverse Shoulder Arthroplasty (RSA) is a common procedure for treating a variety of shoulder pathologies. However, many patients struggle with postoperative internal rotation deficits, which often hinder their activities of daily living. The conjoint tendon provides an anatomic barrier that can impede the postoperative internal rotation of the shoulder, and this study aims to evaluate the effect of a conjoint tendon lengthening on the glenohumeral range of motion following RSA. METHODS: This study used ten fresh-frozen cadaver specimens of the upper extremity. An RSA was implanted using a standard deltopectoral approach, and the range of motion was assessed post-implantation. Following this, the conjoint tendon was identified and lengthened using a tendon sheath z-plasty, and the range of motion was re-recorded. Statistical significance for the range of motion gains after conjoint tendon lengthening was determined with a significance level of p < 0.05. RESULTS: Following the lengthening of the conjoint tendon, there were statistically significant improvements in all ranges of motion (p < 0.05). Subjects demonstrated a notable gain in internal rotation to the back by 10.3 cm (p < 0.01), and all ranges of motion increased by at least 10°, except for forward flexion, which increased by 6° (p < 0.001). CONCLUSIONS: This study suggests that lengthening the conjoint tendon improves postoperative range of motion of the glenohumeral joint after RSA, offering a potential solution to a considerable internal rotation deficits that are commonly encountered post-RSA. Subsequent clinical and biomechanical studies should assess the stability of the shoulder joint following conjoint tendon lengthening.

Multi-instance learning based artificial intelligence model to assist vocal fold leukoplakia diagnosis: A multicentre diagnostic study.

OBJECTIVE: To develop a multi-instance learning (MIL) based artificial intelligence (AI)-assisted diagnosis models by using laryngoscopic images to differentiate benign and malignant vocal fold leukoplakia (VFL). METHODS: The AI system was developed, trained and validated on 5362 images of 551 patients from three hospitals. Automated regions of interest (ROI) segmentation algorithm was utilized to construct image-level features. MIL was used to fusion image level results to patient level features, then the extracted features were modeled by seven machine learning algorithms. Finally, we evaluated the image level and patient level results. Additionally, 50 videos of VFL were prospectively gathered to assess the system's real-time diagnostic capabilities. A human-machine comparison database was also constructed to compare the diagnostic performance of otolaryngologists with and without AI assistance. RESULTS: In internal and external validation sets, the maximum area under the curve (AUC) for image level segmentation models was 0.775 (95 % CI 0.740-0.811) and 0.720 (95 % CI 0.684-0.756), respectively. Utilizing a MIL-based fusion strategy, the AUC at the patient level increased to 0.869 (95 % CI 0.798-0.940) and 0.851 (95 % CI 0.756-0.945). For real-time video diagnosis, the maximum AUC at the patient level reached 0.850 (95 % CI, 0.743-0.957). With AI assistance, the AUC improved from 0.720 (95 % CI 0.682-0.755) to 0.808 (95 % CI 0.775-0.839) for senior otolaryngologists and from 0.647 (95 % CI 0.608-0.686) to 0.807 (95 % CI 0.773-0.837) for junior otolaryngologists. CONCLUSIONS: The MIL based AI-assisted diagnosis system can significantly improve the diagnostic performance of otolaryngologists for VFL and help to make proper clinical decisions.

One-stop detection of anterior cruciate ligament injuries on magnetic resonance imaging using deep learning with multicenter validation.

Background: Anterior cruciate ligament (ACL) injuries are closely associated with knee osteoarthritis (OA). However, diagnosing ACL injuries based on knee magnetic resonance imaging (MRI) has been subjective and time-consuming for clinical doctors. Therefore, we aimed to devise a deep learning (DL) model leveraging MRI to enable a comprehensive and automated approach for the detection of ACL injuries. Methods: A retrospective study was performed extracting data from the Osteoarthritis Initiative (OAI). A total of 1,589 knees (comprising 1,443 intact, 90 with partial tears, and 56 with full tears) were enrolled to construct the classification model. This one-stop detection pipeline was developed using a tailored YOLOv5m architecture and a ResNet-18 convolutional neural network (CNN) to facilitate tasks based on sagittal 2-dimensional (2D) intermediate-weighted fast spin-echo sequence at 3.0T. To ensure the reliability and robustness of the classification system, it was subjected to external validation across 3 distinct datasets. The accuracy, sensitivity, specificity, and the mean average precision (mAP) were utilized as the evaluation metric for the model performance by employing a 5-fold cross-validation approach. The radiologist's interpretations were employed as the reference for conducting the evaluation. Results: The localization model demonstrated an accuracy of 0.89 and a sensitivity of 0.93, achieving a mAP score of 0.96. The classification model demonstrated strong performance in detecting intact, partial tears, and full tears at the optimal threshold on the internal dataset, with sensitivities of 0.941, 0.833, and 0.929, specificities of 0.925, 0.947, and 0.991, and accuracies of 0.940, 0.941, and 0.989, respectively. In comparison, on a subset consisting of 171 randomly selected knees from the OAI, the radiologists demonstrated a sensitivity ranging between 0.660 and 1.000, specificity ranging between 0.691 and 1.000, and accuracy ranging between 0.689 and 1.000. On a subset consisting of 170 randomly selected knees from the Chinese dataset, the radiologists exhibited a sensitivity ranging between 0.711 and 0.948, specificity ranging between 0.768 and 0.977, and accuracy ranging between 0.683 and 0.917. After retraining, the model achieved sensitivities ranging between 0.630 and 0.961, specificities ranging between 0.860 and 0.961, and accuracies ranging between 0.832 and 0.951, respectively, on the external validation dataset. Conclusions: The proposed model utilizing knee MRI showcases robust performance in the domains of ACL localization and classification.

Revealing molecular and cellular heterogeneity in hypopharyngeal carcinogenesis through single-cell RNA and TCR/BCR sequencing.

Introduction: Hypopharyngeal squamous cell carcinoma (HSCC) is one of the malignant tumors with the worst prognosis in head and neck cancers. The transformation from normal tissue through low-grade and high-grade intraepithelial neoplasia to cancerous tissue in HSCC is typically viewed as a progressive pathological sequence typical of tumorigenesis. Nonetheless, the alterations in diverse cell clusters within the tissue microenvironment (TME) throughout tumorigenesis and their impact on the development of HSCC are yet to be fully understood. Methods: We employed single-cell RNA sequencing and TCR/BCR sequencing to sequence 60,854 cells from nine tissue samples representing different stages during the progression of HSCC. This allowed us to construct dynamic transcriptomic maps of cells in diverse TME across various disease stages, and experimentally validated the key molecules within it. Results: We delineated the heterogeneity among tumor cells, immune cells (including T cells, B cells, and myeloid cells), and stromal cells (such as fibroblasts and endothelial cells) during the tumorigenesis of HSCC. We uncovered the alterations in function and state of distinct cell clusters at different stages of tumor development and identified specific clusters closely associated with the tumorigenesis of HSCC. Consequently, we discovered molecules like MAGEA3 and MMP3, pivotal for the diagnosis and treatment of HSCC. Discussion: Our research sheds light on the dynamic alterations within the TME during the tumorigenesis of HSCC, which will help to understand its mechanism of canceration, identify early diagnostic markers, and discover new therapeutic targets.

Helicid Alleviates Neuronal Apoptosis of Rats with Depression-Like Behaviors by Downregulating lncRNA-NONRATT030918.2.

Helicid (HEL) has been found to possess antidepressant pharmacological activity. The paper was to testify to the precise molecular mechanism through which HEL regulates lncRNA-NONRATT030918.2 to exert an antidepressant impression in depression models. A depression model stimulated using chronic unpredictable mild stress (CUMS) was created in rats, and the depressive state of the rats was assessed through behavioral experiments. Additionally, an in vitro model of PC12 cells induced by corticosterone (CORT) was established, and cytoactive was tested using the CCK8. The subcellular localization of the NONRATT030918.2 molecule was confirmed through a fluorescence in situ hybridization experiment. The relationship between NONRATT030918.2, miRNA-128-3p, and Prim1 was analyzed using dual-luciferase reporter gene assay, RNA Binding Protein Immunoprecipitation assay, and RNA pull-down assay. The levels of NONRATT030918.2, miRNA-128-3p, and Prim1 were tested using Q-PCR. Furthermore, the levels of Prim1, Bax, Bcl-2, and caspase3 were checked through Western blot. The HEL can alleviate the depression-like behavior of CUMS rats (P < 0.05), and reduce the mortality of hippocampal via downregulating the level of NONRATT030918.2 (P < 0.05). In CORT-induced PC12 cells, intervention with HEL led to decreased expression of NONRATT030918.2 and Prim1 (P < 0.05), as well as increased expression of miRNA-128-3p (P < 0.05). This suggests that HEL regulates the expression of NONRATT030918.2 to upregulate miRNA-128-3p (P < 0.05), which in turn inhibits CORT-induced apoptosis in PC12 cells by targeting Prim1 (P < 0.05). The NONRATT030918.2/miRNA-128-3p/Prim1 axis could potentially serve as a crucial regulatory network for HEL to exert its neuroprotective effects.

Telephone follow-up based on empowerment theory to improve resilience and quality of life among patients after coronary artery stent implantation: a randomized controlled trial.

Background: Coronary heart disease has a high incidence rate, a high mortality rate, a high recurrence rate, and a high medical cost. In addition, some patients need to undergo percutaneous coronary artery stent implantation (CASI), which is a kind of traumatic treatment. Patients can easily experience negative emotions such as anxiety and depression after surgery, which seriously affects quality of life. Objectives: The aim of this study was to evaluate the effectiveness of an empowerment-based telephone follow-up intervention on resilience and quality of life in patients who underwent CASI. Design: The design of the study is a randomized controlled trial. Methods: A total of 92 patients were recruited after CASI from the Internal Medicine Cardiovascular Department of a Grade A tertiary hospital in Xi'an, China. The patients were randomly divided into a control group and an intervention group. The control group performed routine care, whereas the intervention group developed a telephone follow-up program based on empowerment theory while carrying out routine care. Patients were investigated using the coronary heart disease-related knowledge questionnaire, the Connor-Davidson Resilience Scale (CD-RISC), and the 36-Item Short-Form Health Survey (SF-36) to compare the effects of the intervention before and after 1 month of intervention. Results: After a 1-month telephone follow-up intervention based on the empowerment theory for patients after CASI, the variations in knowledge related to coronary heart disease and all of its subscale scores were greater in the intervention group than in the control group. Except for the three dimensions of risk factor, induction factor, and rehabilitation-related knowledge, the variations in knowledge related to coronary heart disease and the other subscale scores were significantly different between the two groups (p < 0.05). The variations in resilience and scores on the three subscales in the intervention group were greater than those in the control group, and the difference between the two groups was statistically significant (p < 0.05). The variations in the quality of life and overall health, emotional functions, and social functions were significantly greater in the intervention group than in the control group (p < 0.05). Conclusions: A telephone follow-up intervention based on the empowerment theory can effectively improve the resilience and quality of life of patients after CASI. This follow-up approach can provide a theoretical basis and practical reference for hospitals and communities to carry out targeted continuing nursing for patients after CASI. The long-term effects of the intervention and its underlying mechanisms require further study. Clinical trial registration: http://www.chictr.org.cn/showproj.aspx?proj=173682, identifier ChiCTR2200064950.

GC/MS-based untargeted metabolomics reveals the differential metabolites for discriminating vintage of Chenxiang-type baijiu.

The "outstanding and unique aged aroma" of Chinese Chenxiang-type baijiu (CXB)-Daoguang 25 (DG25) mainly originates from a "extraordinary storage technology" of Mujiuhai (a wooden container), so it is mysterious and interesting. In this study, an untargeted GC/MS-based metabolomics was used to reveals the volatile differential metabolites for discriminating six different vintages of DG25 combing with chemometrics. A total of 100 volatile metabolites (including unknowns) were extracted and identified, including esters (41%), alcohols (10%) and acids (7%) so on. Finally, 33 differential metabolites were identified as aging-markers. Among them, 25 aging-markers showed a downtrend, including 17 esters such as ethyl acetate, ethyl hexanoate and ethyl palmitate so on. Moreover, it was interesting and to further study that furans showed a significant downtrend. Statistically speaking, ethyl benzoate played an important role in discriminating vintage of 1Y and 3Y, and the other 24 differential metabolites with downtrend discriminating the unstored (0Y-aged) DG25. Eight differential metabolites, such as ethyl octanoate, benzaldehyde, 3-methylbutanol and 1,1-diethoxyaccetal so on increased during aging of DG25, and they played a statistical role in discriminating the 5Y-, 10Y- and 20Y-aged DG25. This study provides a theoretical basis way for the formation mechanism of aging aroma for CXB.

Graph-Regularized Non-Negative Matrix Factorization for Single-Cell Clustering in scRNA-Seq Data.

The advent of single-cell RNA sequencing (scRNA-seq) has brought forth fresh perspectives on intricate biological processes, revealing the nuances and divergences present among distinct cells. Accurate single-cell analysis is a crucial prerequisite for in-depth investigation into the underlying mechanisms of heterogeneity. Due to various technical noises, like the impact of dropout values, scRNA-seq data remains challenging to interpret. In this work, we propose an unsupervised learning framework for scRNA-seq data analysis (aka Sc-GNNMF). Based on the non-negativity and sparsity of scRNA-seq data, we propose employing graph-regularized non-negative matrix factorization (GNNMF) algorithm for the analysis of scRNA-seq data, which involves estimating cell-cell similarity and gene-gene similarity through Laplacian kernels and p-nearest neighbor graphs ( p-NNG). By assuming intrinsic geometric local invariance, we use a weighted p-nearest known neighbors ( p-NKN) of cell-cell interactions to guide the matrix decomposition process, promoting the closeness of cells with similar types in cell-gene data space and determining a more suitable embedding space for clustering. Sc-GNNMF demonstrates superior performance compared to other methods and maintains satisfactory compatibility and robustness, as evidenced by experiments on 11 real scRNA-seq datasets. Furthermore, Sc-GNNMF yields excellent results in clustering tasks, extracting useful gene markers, and pseudo-temporal analysis.

The Effects of Antofine on the Morphological and Physiological Characteristics of Phytophthora capsici.

Phytophthora capsici is an important plant pathogenic oomycete that causes great losses to vegetable production around the world. Antofine is an important alkaloid isolated from Cynanchum komarovii Al. Iljinski and exhibits significant antifungal activity. In this study, the effect of antofine on the mycelial growth, morphology, and physiological characteristics of P. capsici was investigated using colorimetry. Meanwhile, the activity of mitochondrial respiratory chain complexes of P. capsici was evaluated following treatment with a 30% effective concentration (EC30), as well as EC50 and EC70, of antofine for 0, 12, 24, and 48 h. The results showed that antofine had a significant inhibitory effect against P. capsici, with an EC50 of 5.0795 µg/mL. After treatment with antofine at EC50 and EC70, the mycelia were rough, less full, and had obvious depression; they had an irregular protrusion structure; and they had serious wrinkles. In P. capsici, oxalic acid and exopolysaccharide contents decreased significantly, while cell membrane permeability and glycerol content increased when treated with antofine. Reactive oxygen species (ROS) entered a burst state in P. capsici after incubation with antofine for 3 h, and fluorescence intensity was 2.43 times higher than that of the control. The activities of the mitochondrial respiratory chain complex II, III, I + III, II + III, V, and citrate synthase in P. capsici were significantly inhibited following treatment with antofine (EC50 and EC70) for 48 h compared to the control. This study revealed that antofine is likely to affect the pathways related to the energy metabolism of P. capsici and thus affect the activity of respiratory chain complexes. These results increase our understanding of the action mechanism of antofine against P. capsici.

A Novel Tetramethylpyrazine Chalcone Hybrid- HCTMPPK, as a Potential Anti-Lung Cancer Agent by Downregulating MELK.

Purpose: Lung adenocarcinoma currently ranks the leading causes of cancer-related mortality worldwide. Many anti-inflammation herbs, like tetramethylpyrazine, have shown their anti-tumor potentials. Here, we evaluated the role of a novel chalcone derivative of tetramethylpyrazine ((E) -1- (E) -1- (2-hydroxy-5-chlorophenyl) -3- (3,5,6-trimethylpyrazin-2-yl) -2-propen-1, HCTMPPK) in lung adenocarcinoma. Methods: The effects of HCTMPPK on cell proliferation, apoptosis, and invasion were investigated by in-vitro assays, including CCK-8, colony formation assay, flow cytometry, transwell assay, and wound-healing assay. The therapeutic potential of HCTMPPK in vivo was evaluated in xenograft mice. To figure out the target molecules of HCTMPPK, a network pharmacology approach and molecular docking studies were employed, and subsequent experiments were conducted to confirm these candidate molecules. Results: HCTMPPK effectively suppressed the proliferative activity and migration, as well as enhanced the apoptosis of A549 cells in a concentration-dependent manner. Consistent with this, tumor growth was inhibited by HCTMPPK significantly in vivo. Regarding the mechanisms, HCTMPPK down-regulated Bcl-2 and MMP-9 and up-regulating Bax and cleaved-caspase-3. Subsequently, we identified 601 overlapping DEGs from LUAD patients in TCGA and GEO database. Then, 15 hub genes were identified by PPI network and CytoHubba. Finally, MELK was verified to be the HCTMPPK targeted site, through the molecular docking studies and validation experiments. Conclusion: Overall, our study indicates HCTMPPK as a potential MELK inhibitor and may be a promising candidate for the therapy of lung cancer.

Minnelide exhibits antileukemic activity by targeting the Ars2/miR-190a-3p axis.

BACKGROUND: The identification of a novel and effective strategy for the clinical treatment of acute leukemia (AL) is a long-term goal. Minnelide, a water-soluble prodrug of triptolide, has recently been evaluated in phase I and II clinical trials in patients with multiple cancers and has shown promise as an antileukemic agent. However, the molecular mechanism underlying minnelide's antileukemic activity remains unclear. PURPOSE: To explore the molecular mechanisms by which minnelide exhibits antileukemic activity. METHODS: AL cells, primary human leukemia cells, and a xenograft mouse model were treated with triptolide and minnelide. The molecular mechanism was elucidated using western blotting, immunoprecipitation, flow cytometry, GSEA and liquid chromatography-mass spectrometry analysis. RESULTS: Minnelide was highly effective in inhibiting leukemogenesis and improving survival in two complementary AL mouse models. Triptolide, an active form of minnelide, causes cell cycle arrest in G1 phase and induces apoptosis in both human AL cell lines and primary AL cells. Mechanistically, we identified Ars2 as a new chemotherapeutic target of minnelide for AL treatment. We found that triptolide directly targeted Ars2, resulting in the downregulation of miR-190a-3p, which led to the disturbance of PTEN/Akt signaling and culminated in G1 cell cycle arrest and apoptosis. CONCLUSIONS: Our findings demonstrate that targeting Ars2/miR-190a-3p signaling using minnelide could represent a novel chemotherapeutic strategy for AL treatment and support the evaluation of minnelide for the treatment of AL in clinical trials.

A novel model combining genes associated with disulfidptosis and glycolysis to predict breast cancer prognosis, molecular subtypes, and treatment response.

Breast cancer (BC) is a heterogeneous malignancy with a dismal prognosis. Disulfidptosis is a novel type of regulated cell death that happens in the presence of glucose deficiency and is linked to the metabolic process of glycolysis. However, the mechanism of action of disulfidptosis and glycolysis-related genes (DGRG) in BC, as well as their prognostic value in BC patients, remain unknown. After identifying the differentially expressed DGRG in normal and BC tissues, a number of machine learning algorithms were utilized to select essential prognostic genes to develop a model, including SLC7A11, CACNA1H, SDC1, CHST1, and TFF3. The expression characteristics of these genes were then examined using single-cell RNA sequencing, and BC was classified into three clusters using "ConsensusClusterPlus" based on these genes. The DGRG model's median risk score can categorize BC patients into high-risk and low-risk groups. Furthermore, we investigated variations in clinical landscape, immunoinvasion analysis, tumor immune dysfunction and rejection (TIDE), and medication sensitivity in patients in the DGRG model's high- and low-risk groups. Patients in the low-risk group performed better on immunological and chemotherapeutic therapies and had lower TIDE scores. In conclusion, the DGRG model we developed has significant clinical application potential because it can accurately predict the prognosis of BC, TME, and pharmacological treatment responses.

An unusually high prevalence of allergic rhinitis at high altitudes in 6-7 year old children - An epidemiological study.

Objectives: To compare the epidemiology and disease patterns of allergic rhinitis (AR) at 2 different altitudes in children aged 6-7 years, and subsequently to compare with and augment data from international studies. Materials and methods: This is a multistage, clustered and stratified random sample study. The study area comprises 2 distinct areas within Yunnan Province, China. Low altitude was represented by Xishuangbanna Prefecture (XB), while high altitude was represented by Diqing Prefecture (DiQ). Each study area was subdivided into 3 sub-areas, and children aged 6-7 years were randomly sampled based on proportion-weighted sampling. The area studied includes the well-known area of Shangri-La city. Questionnaires were distributed and jointly completed by study participants and their parents or guardians, under the guidance of professional medical staff. Results: 2796 valid questionnaires out of 2933 distributed were obtained (survey response rate 95.3%). The prevalence of AR is statistically significantly higher at high altitude (DiQ, 36.0%, 95%CI 33.2-38.8) as compared to low altitude (XB, 19.7%, 95%CI 17.8-21.6) (p < 0.001). Both areas studied had a greater prevalence of AR compared to international data. In both XB and DiQ, male gender, history of early antibiotic use, urban place of birth and place of residence, presence of smokers within the same household, family history of allergic diseases (such as atopic dermatitis), as well as higher parental educational level were all associated with a higher prevalence of AR (p < 0.05). In DiQ, the prevalence of AR in Han ethnicity was greater than that of ethnic minorities (p < 0.05). In XB, being a single child was associated with an increased prevalence of AR compared to those who had siblings (p < 0.05). Conclusion: Our study found that the prevalence of AR is relatively greater at higher altitudes. Genetic and environmental factors both play an important role in the pathogenesis of AR. While altitude may be an important environmental factor, confounding factors may include humidity, temperature and distribution pattern of common aeroallergens.

Apple-arbuscular mycorrhizal symbiosis confers resistance to Fusarium solani by inducing defense response and elevating nitrogen absorption.

Fusarium solani exerts detrimental effects on plant growth, which is one of the reasons for the incidence of apple replant disease. Arbuscular mycorrhizal fungi (AMF) enhance plant resistance to Fusarium wilt; however, the mechanism remains poorly understood. Therefore, the present study investigated the symbiosis between apple and AMF and explored the physiology, especially nitrate metabolism, antioxidant defense, and photosynthetic performance, when infected by F. solani. The experiment was carried out with four treatments, namely -AMF - F. solani, -AMF + F. solani, -AMF + F. solani, and + AMF + F. solani. In this study, the -AMF + F. solani treatment increased the activity of enzymes associated with nitrogen metabolism, such as the nitrate and nitrite reductases, in the apple root system. The +AMF + F. solani treatment showed higher antioxidant enzyme activities than the -AMF + F. solani by F. solani infection. The apple seedlings of the +AMF + F. solani treatment decreased reactive oxygen accumulation and reduced the oxidative damages triggered by F. solani infection. The improvement in antioxidant capacity due to the +AMF + F. solani treatment was closely associated with the upregulation of genes related to the antioxidant system. The F. solani infection greatly damaged the photosynthetic process, while the +AMF + F. solani treatment significantly improved it compared to the -AMF + F. solani treatment. In conclusion, the study demonstrated that the apple-AMF symbiosis plays an active role in regulating the resistance against F. solani infection by enhancing defense response and nitrogen metabolism.

Magnetic resonance imaging-based lymph node radiomics for predicting the metastasis of evaluable lymph nodes in rectal cancer.

BACKGROUND: Lymph node (LN) staging in rectal cancer (RC) affects treatment decisions and patient prognosis. For radiologists, the traditional preoperative assessment of LN metastasis (LNM) using magnetic resonance imaging (MRI) poses a challenge. AIM: To explore the value of a nomogram model that combines Conventional MRI and radiomics features from the LNs of RC in assessing the preoperative metastasis of evaluable LNs. METHODS: In this retrospective study, 270 LNs (158 nonmetastatic, 112 metastatic) were randomly split into training (n = 189) and validation sets (n = 81). LNs were classified based on pathology-MRI matching. Conventional MRI features [size, shape, margin, T2-weighted imaging (T2WI) appearance, and CE-T1-weighted imaging (T1WI) enhancement] were evaluated. Three radiomics models used 3D features from T1WI and T2WI images. Additionally, a nomogram model combining conventional MRI and radiomics features was developed. The model used univariate analysis and multivariable logistic regression. Evaluation employed the receiver operating characteristic curve, with DeLong test for comparing diagnostic performance. Nomogram performance was assessed using calibration and decision curve analysis. RESULTS: The nomogram model outperformed conventional MRI and single radiomics models in evaluating LNM. In the training set, the nomogram model achieved an area under the curve (AUC) of 0.92, which was significantly higher than the AUCs of 0.82 (P < 0.001) and 0.89 (P < 0.001) of the conventional MRI and radiomics models, respectively. In the validation set, the nomogram model achieved an AUC of 0.91, significantly surpassing 0.80 (P < 0.001) and 0.86 (P < 0.001), respectively. CONCLUSION: The nomogram model showed the best performance in predicting metastasis of evaluable LNs.

SERPINB3/B4 is Increased in Psoriasis and Rosacea Lesions and has Pro-inflammatory Effects in Mouse Models of these Diseases.

Psoriasis and rosacea are both chronic inflammatory skin disorders resulted from aberrant keratinocyte-immune cell crosstalk, but the common molecular foundations for these two conditions are poorly understood. Here, we reveal that both psoriasis and rosacea patients, as well as their mice models, have significantly elevated expressions of SERPINB3/B4 (members of serine protease inhibitor) in the lesional skin. Skin inflammation in mice that resembles both psoriasis and rosacea is prevented by SERPINB3/B4 deficiency. Mechanistically, we demonstrate that SERPINB3/B4 positively induces NF-κB signaling activation, thereby stimulating disease-characteristic inflammatory chemokines and cytokines production in keratinocytes, and promoting the chemotaxis of CD4+ T cells. Our results suggest that, in keratinocytes, SERPINB3/B4 may be involved in the pathogenesis of both psoriasis and rosacea by stimulating NF-κB signaling, and they indicate a possible treatment overlap between these two diseases.

Multi-Instance Learning for Vocal Fold Leukoplakia Diagnosis Using White Light and Narrow-Band Imaging: A Multicenter Study.

OBJECTIVES: Vocal fold leukoplakia (VFL) is a precancerous lesion of laryngeal cancer, and its endoscopic diagnosis poses challenges. We aim to develop an artificial intelligence (AI) model using white light imaging (WLI) and narrow-band imaging (NBI) to distinguish benign from malignant VFL. METHODS: A total of 7057 images from 426 patients were used for model development and internal validation. Additionally, 1617 images from two other hospitals were used for model external validation. Modeling learning based on WLI and NBI modalities was conducted using deep learning combined with a multi-instance learning approach (MIL). Furthermore, 50 prospectively collected videos were used to evaluate real-time model performance. A human-machine comparison involving 100 patients and 12 laryngologists assessed the real-world effectiveness of the model. RESULTS: The model achieved the highest area under the receiver operating characteristic curve (AUC) values of 0.868 and 0.884 in the internal and external validation sets, respectively. AUC in the video validation set was 0.825 (95% CI: 0.704-0.946). In the human-machine comparison, AI significantly improved AUC and accuracy for all laryngologists (p < 0.05). With the assistance of AI, the diagnostic abilities and consistency of all laryngologists improved. CONCLUSIONS: Our multicenter study developed an effective AI model using MIL and fusion of WLI and NBI images for VFL diagnosis, particularly aiding junior laryngologists. However, further optimization and validation are necessary to fully assess its potential impact in clinical settings. LEVEL OF EVIDENCE: 3 Laryngoscope, 2024.

Assessing family function: older adults vs. care nurses: a cross-sectional comparative study.

BACKGROUND: This study aimed to assess family function in home care for older adults. Understanding family dynamics is essential for providing quality care to older adults choosing to age in place. METHODS: In a cross-sectional study, 53 patients aged 65 or older receiving home care were evaluated, along with four home care nurses. The General Function of Family Assessment Device (FAD-GF) was used for self-assessment to examine family resources. RESULTS: Only 5.7% of older adults reported good family function. Strong correlations were found between assessments by nurses and older adults. Among the six aspects of family function, "problem solving," "communication," "affective responsiveness," and the overall results showed no disparities between the evaluations of older adults and nurses. CONCLUSIONS: Home care nurses can effectively assess family function using the FAD-GF, particularly after six months of care. This assessment can help identify family issues and enhance home care quality through nurse training in FAD-GF application.