Downstream-of-gene (DoG) transcripts contribute to an imbalance in the cancer cell transcriptome.

Downstream-of-gene (DoG) transcripts are an emerging class of noncoding RNAs. However, it remains largely unknown how DoG RNA production is regulated and whether alterations in DoG RNA signatures exist in major cancers. Here, through transcriptomic analyses of matched tumors and nonneoplastic tissues and cancer cell lines, we reveal a comprehensive catalog of DoG RNA signatures. Through separate lines of evidence, we support the biological importance of DoG RNAs in carcinogenesis. First, we show tissue-specific and stage-specific differential expression of DoG RNAs in tumors versus paired normal tissues with their respective host genes involved in tumor-promoting versus tumor-suppressor pathways. Second, we identify that differential DoG RNA expression is associated with poor patient survival. Third, we identify that DoG RNA induction is a consequence of treating colon cancer cells with the topoisomerase I (TOP1) poison camptothecin and following TOP1 depletion. Our results underlie the significance of DoG RNAs and TOP1-dependent regulation of DoG RNAs in diversifying and modulating the cancer transcriptome.

Mining the interpretable prognostic features from pathological image of intrahepatic cholangiocarcinoma using multi-modal deep learning.

BACKGROUND: The advances in deep learning-based pathological image analysis have invoked tremendous insights into cancer prognostication. Still, lack of interpretability remains a significant barrier to clinical application. METHODS: We established an integrative prognostic neural network for intrahepatic cholangiocarcinoma (iCCA), towards a comprehensive evaluation of both architectural and fine-grained information from whole-slide images. Then, leveraging on multi-modal data, we conducted extensive interrogative approaches to the models, to extract and visualize the morphological features that most correlated with clinical outcome and underlying molecular alterations. RESULTS: The models were developed and optimized on 373 iCCA patients from our center and demonstrated consistent accuracy and robustness on both internal (n = 213) and external (n = 168) cohorts. The occlusion sensitivity map revealed that the distribution of tertiary lymphoid structures, the geometric traits of the invasive margin, the relative composition of tumor parenchyma and stroma, the extent of necrosis, the presence of the disseminated foci, and the tumor-adjacent micro-vessels were the determining architectural features that impacted on prognosis. Quantifiable morphological vector extracted by CellProfiler demonstrated that tumor nuclei from high-risk patients exhibited significant larger size, more distorted shape, with less prominent nuclear envelope and textural contrast. The multi-omics data (n = 187) further revealed key molecular alterations left morphological imprints that could be attended by the network, including glycolysis, hypoxia, apical junction, mTORC1 signaling, and immune infiltration. CONCLUSIONS: We proposed an interpretable deep-learning framework to gain insights into the biological behavior of iCCA. Most of the significant morphological prognosticators perceived by the network are comprehensible to human minds.

An Endocellulase-Triggered NO Targeted-Release Enzyme-Prodrug Therapy System and Its Application in Ischemia Injury.

Nitric oxide (NO) is a crucial gaseous signaling molecules in regulating cardiovascular, immune, and nervous systems. Controlled and targeted NO delivery is imperative for treating cancer, inflammation, and cardiovascular diseases. Despite various enzyme-prodrug therapy (EPT) systems facilitating controlled NO release, their clinical utility is hindered by nonspecific NO release and undesired metabolic consequence. In this study, a novel EPT system is presented utilizing a cellobioside-diazeniumdiolate (Cel2-NO) prodrug, activated by an endocellulase (Cel5A-h38) derived from the rumen uncultured bacterium of Hu sheep. This system demonstrates nearly complete orthogonality, wherein Cel2-NO prodrug maintains excellent stability under endogenous enzymes. Importantly, Cel5A-h38 efficiently processes the prodrug without recognizing endogenous glycosides. The targeted drug release capability of the system is vividly illustrated through an in vivo near-infrared imaging assay. The precise NO release by this EPT system exhibits significant therapeutic potential in a mouse hindlimb ischemia model, showcasing reductions in ischemic damage, ambulatory impairment, and modulation of inflammatory responses. Concurrently, the system enhances tissue repair and promotes function recovery efficacy. The novel EPT system holds broad applicability for the controlled and targeted delivery of essential drug molecules, providing a potent tool for treating cardiovascular diseases, tumors, and inflammation-related disorders.

NFκB signalling in colorectal cancer: Examining the central dogma of IKKα and IKKß signalling.

The NFκB pathway, known as the central regulator of inflammation, has a well-established role in colorectal cancer (CRC) initiation, progression, and therapy resistance. Due to the pathway's overarching roles in CRC, there have been efforts to characterise NFκB family members and target the pathway for therapeutic intervention. Initial research illustrated that the canonical NFκB pathway, driven by central kinase IKKß, was a promising target for drug intervention. However, dose limiting toxicities and specificity concerns have resulted in failure of IKKß inhibitors in clinical trials. The field has turned to look at targeting the less dominant kinase, IKKα, which along with NFκB inducing kinase (NIK), drives the lesser researched non-canonical NFκB pathway. However prognostic studies of the non-canonical pathway have produced conflicting results. There is emerging evidence that IKKα is involved in other signalling pathways, which lie outside of canonical and non-canonical NFκB signalling. Evidence suggests that some of these alternative pathways involve a truncated form of IKKα, and this may drive poor cancer-specific survival in CRC. This review aims to explore the multiple components of NFκB signalling, highlighting that NIK may be the central kinase for non-canonical NFκB signalling, and that IKKα is involved in novel pathways which promote CRC.

[Responses of radial growth of Fraxinus mandshurica from different provenances to climate at Maoershan in Northeast China]. / 东北地区帽儿山种源实验林区不同种源水曲柳径向生长对气候的响应.

To understand the responses of radial growth of Fraxinus mandshurica from different provenances to climatic factors, we used the dendrochronological method to establish the standard chronologies of F. mandshurica from 20 provenances in Maoershan provenance test forest, and analyzed the differences in radial growth and their correlation with climate factors. The results showed that the overall trend of F. mandshurica chronologies from 20 provenances was generally similar. There were differences in growth amplitude, with the average radial growth of F. mandshurica from Dailing, Lushuihe and Sanchazi being the highest. The radial growth of F. mandshurica from 20 provenances was significantly positively correlated with the highest temperature in July and the average temperature in July except for Huinan. The radial growth of F. mandshurica from 14 provenances was significantly positively correlated with the precipitation in August. The radial growth of F. mandshurica was constrained by temperature and precipitation during the growing season. There was difference in radial growth among F. mandshurica from different provenances under drought stress. F. mandshurica from Wangqing, Dailing, and Hailin had stronger resistance to drought, while that from Wandianzi, Zhanhe, and Xinglong had better recovery ability after drought.

Screening of active components of Ganoderma lucidum and decipher its molecular mechanism to improve learning and memory disorders.

Learning and memory impairment (LMI), a common degenerative central nervous system disease. Recently, more and more studies have shown that Ganoderma lucidum (GL) can improve the symptoms of LMI. The active ingredients in GL and their corresponding targets were screened through TCMSP (Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform) and BATMAN-TCM (Bioinformatics Analysis Tool for Molecular Mechanism of Traditional Chinese Medicine) databases, and the potential LMI targets were searched for through GeneCard (GeneCards Human Gene Database) and DrugBank. Then, we construct a "main active ingredient-target" network and a protein-protein interaction (PPI) network diagram.The GO (Gene Ontology) functional enrichment analysis and KEGG (Kyoto Encyclopedia of Genes and Genomes) pathway annotation analysis were performed on the common targets through DAVID (Database for Annotation Visualization and Integrated Discovery) to clarify the potential molecular mechanism of action of active ingredients in GL. The TNF protein was verified by western blot;Twenty one active ingredients in GL and 142 corresponding targets  were screened out, including 59 targets shared with LMI. The 448 biological processes shown by the GO functional annotation results and 55 signal pathways shown by KEGG enrichment analysis were related to the improvement of LMI by GL, among which the correlation of Alzheimer disease pathway is the highest, and TNF was the most important protein; TNF can improve LMI.GL can improve LMI mainly by 10 active ingredients in it, and they may play a role by regulating Alzheimer disease pathway and TNF protein.

Clinical comprehensive treatment protocol for managing diabetic foot ulcers: A retrospective cohort study.

BACKGROUND: Diabetic foot ulcers (DFUs) are a common complication of diabetes, often leading to severe infections, amputations, and reduced quality of life. The current standard treatment protocols for DFUs have limitations in promoting efficient wound healing and preventing complications. A comprehensive treatment approach targeting multiple aspects of wound care may offer improved outcomes for patients with DFUs. The hypothesis of this study is that a comprehensive treatment protocol for DFUs will result in faster wound healing, reduced amputation rates, and improved overall patient outcomes compared to standard treatment protocols. AIM: To compare the efficacy and safety of a comprehensive treatment protocol for DFUs with those of the standard treatment protocol. METHODS: This retrospective study included 62 patients with DFUs, enrolled between January 2022 and January 2024, randomly assigned to the experimental (n = 32) or control (n = 30) group. The experimental group received a comprehensive treatment comprising blood circulation improvement, debridement, vacuum sealing drainage, recombinant human epidermal growth factor and anti-inflammatory dressing, and skin grafting. The control group received standard treatment, which included wound cleaning and dressing, antibiotics administration, and surgical debridement or amputation, if necessary. Time taken to reduce the white blood cell count, number of dressing changes, wound healing rate and time, and amputation rate were assessed. RESULTS: The experimental group exhibited significantly better outcomes than those of the control group in terms of the wound healing rate, wound healing time, and amputation rate. Additionally, the comprehensive treatment protocol was safe and well tolerated by the patients. CONCLUSION: Comprehensive treatment for DFUs is more effective than standard treatment, promoting granulation tissue growth, shortening hospitalization time, reducing pain and amputation rate, improving wound healing, and enhancing quality of life.

Disrupting Smad3 potentiates immunostimulatory function of NK cells against lung carcinoma by promoting GM-CSF production.

Through Smad3-dependent signalings, transforming growth factor-ß (TGF-ß) suppresses the development, maturation, cytokine productions and cytolytic functions of NK cells in cancer. Silencing Smad3 remarkably restores the cytotoxicity of NK-92 against cancer in TGF-ß-rich microenvironment, but its effects on the immunoregulatory functions of NK cells remain obscure. In this study, we identified Smad3 functioned as a transcriptional repressor for CSF2 (GM-CSF) in NK cells. Therefore, disrupting Smad3 largely mitigated TGF-ß-mediated suppression on GM-CSF production by NK cells. Furthermore, silencing GM-CSF in Smad3 knockout NK cells substantially impaired their anti-lung carcinoma effects. In-depth study demonstrated that NK-derived GM-CSF strengthened T cell immune responses by stimulating dendritic cell differentiation and M1 macrophage polarization. Meanwhile, NK-derived GM-CSF promoted the survival of neutrophils, which in turn facilitated the terminal maturation of NK cells, and subsequently boosted NK-cell mediated cytotoxicity against lung carcinoma. Thus, Smad3-silenced NK-92 (NK-92-S3KD) may serve as a promising immunoadjuvant therapy with clinical translational value given its robust cytotoxicity against malignant cells and immunostimulatory functions to reinforce the therapeutic effects of other immunotherapies.

Differences between long- and short-wavelength light-induced retinal damage and the role of PARP-1 in retinal injury induced by blue light.

Photobiomodulation (PBM) therapy uses light of different wavelengths to treat various retinal degeneration diseases, but the potential damage to the retina caused by long-term light irradiation is still unclear. This study were designed to detect the difference between long- and short-wavelength light (650-nm red light and 450-nm blue light, 2.55 mW/cm2, reference intensity in PBM)-induced injury. In addition, a comparative study was conducted to investigate the differences in retinal light damage induced by different irradiation protocols (short periods of repeated irradiation and a long period of constant irradiation). Furthermore, the protective role of PARP-1 inhibition on the molecular mechanism of blue light-induced injury was confirmed by a gene knockdown technique or a specific inhibitor through in vitro and in vivo experiments. The results showed that the susceptibility to retinal damage caused by irradiation with long- and short-wavelength light is different. Shorter wavelength lights, such as blue light, induce more severe retinal damage, while the retina exhibits better resistance to longer wavelength lights, such as red light. In addition, repeated irradiation for short periods induces less retinal damage than constant exposure over a long period. PARP-1 plays a critical role in the molecular mechanism of blue light-induced damage in photoreceptors and retina, and inhibiting PARP-1 can significantly protect the retina against blue light damage. This study lays an experimental foundation for assessing the safety of phototherapy products and for developing target drugs to protect the retina from light damage.

Elemental diet preventative effects for adverse events during chemotherapy in patients with esophageal cancer - A systematic review and meta-analysis.

Introduction: The effectiveness of an elemental diet (ED) for preventing adverse events (AEs) during chemotherapy for patients with esophageal cancer (EC) remains unclear. The aim of this meta-analysis was to comprehensively assess the efficacy of ED for preventing AE in EC patients during chemotherapy. Medline (via PubMed), Embase, the Cochrane Library, and Web of Science were searched to retrieve prospective and randomized studies published before April 12, 2023. The odds ratio (OR) of each AE was calculated using Review Manger 5.4.1. The risk of bias was assessed, and a random effect model-based meta-analysis was used to analyze the available data. Four prospective and randomized studies involving 237 patients were identified after a systematic search. Regarding gastrointestinal toxicities, the findings indicated a trend toward a decrease in the risk of mucositis (OM) (OR = 0.54, 95 % CI: 0.25-1.14), constipation (OR = 0.87, 95 % CI: 0.49-1.53), and anorexia (OR = 0.99, 95 % CI: 0.32-3.05), as well as an increasing trend in the risk of diarrhea (OR = 1.48, 95 % CI: 0.79-2.79), among patients treated with ED. However, none of these reached statistical significance. For hematological toxicities, the risk of all-grade neutropenia (OR = 0.28, 95 % CI: 0.14-0.57), grade ≥ 2 leucopenia (OR = 0.43, 95 % CI: 0.22-0.84), grade ≥ 2 neutropenia (OR = 0.34, 95 % CI: 0.17-0.67), and grade ≥ 3 neutropenia (OR = 0.28, 95 % CI: 0.12-0.63) was significantly decreased. There is no firm evidence confirming the preventive effect of an ED against OM or diarrhea. However, an ED may potentially be helpful in preventing neutropenia and leucopenia.

Introducción: La efectividad de una dieta elemental (DE) para prevenir eventos adversos (EA) durante la quimioterapia en pacientes con cáncer de esófago (CE) sigue sin estar clara. Este metaanálisis evalúa la eficacia de DE para prevenir EA en pacientes con CE durante quimioterapia. Se realizaron búsquedas en Medline (con PubMed), Embase, Biblioteca Cochrane y Web of Science para recuperar estudios prospectivos y aleatorios publicados antes del 12/04/2023. La razón de probabilidad (RP) de cada EA se calculó usando Review Manger 5.4.1. Se evaluó el riesgo de sesgo y se utilizó un metaanálisis basado en modelo de efectos aleatorios para analizar los datos disponibles. Después de una búsqueda sistemática, se identificaron cuatro estudios prospectivos y aleatorios con 237 pacientes. En cuanto a las toxicidades gastrointestinales, los hallazgos indicaron una tendencia hacia una disminución en el riesgo de mucositis (OM) (OR = 0,54, IC 95 %: 0,25-1,14), estreñimiento (OR = 0,87, IC 95 %: 0,49-1,53) y anorexia (OR = 0,99, IC 95 %: 0,32-3,05) y una tendencia creciente en el riesgo de diarrea (OR = 1,48, IC 95 %: 0,79-2,79) entre los pacientes tratados con DE. Sin embargo, no hubo muestras estadísticas significativas. Para toxicidades hematológicas, el riesgo de neutropenia de todos los grados (RP = 0,28; IC del 95 %: 0,14-0,57), leucopenia grado ≥ 2 (RP = 0,43; IC del 95 %: 0,22-0,84), neutropenia grado ≥ 2 (RP = 0,34; IC del 95 %: 0,17-0,67) y neutropenia grado ≥ 3 (RP = 0,28; IC del 95 %: 0,12-0,63) disminuyó significativamente. Ninguna evidencia firme confirmó el efecto preventivo de DE frente a OM o la diarrea. Una DE sería útil previniendo neutropenia y leucopenia.

Efficacy of taurine-enhanced enteral nutrition in improving the outcomes of critically ill patients: A systematic review and meta-analysis.

BACKGROUND: Taurine is considered an immunomodulatory agent. From current reports on clinical studies, we conducted a systematic review and meta-analysis to investigate the effects of taurine-enhanced enteral nutrition (EN) on the outcomes of critically ill patients to resolve conflicting evidence in literature. METHODS: Literature from PubMed, EMBASE, Web of Science, Cochrane Library, CNKI, SINOMED, and WanFang databases were retrieved, and randomized controlled trials (RCTs) were identified. The time range spanned from January 1, 2000, to January 31, 2024. The Cochrane Collaboration Tool was used to evaluate the risk of bias. We used the GRADE approach to rate the quality of evidence and the I2 test to assess the statistical heterogeneity of the results. Risk ratio (RR), mean difference (MD), and 95% confidence interval (95% CI) were used to analyze measurement data. RESULTS: Four trials involving 236 patients were finally included. The meta-analysis results indicated that taurine-enhanced EN did not reduce mortality (RR = 0.70, p = 0.45, 95% CI [0.28, 1.80], two trials, 176 participants, low quality). There was also no significant difference in length of stay in the intensive care unit (ICU) between the taurine-enhanced EN and control groups. Taurine-enhanced EN may reduce pro-inflammatory factor interleukin-6 (IL-6) levels in critically ill patients（the result about IL-6 cannot be pooled）. However, taurine-enhanced EN had no significant impact on high-sensitivity-C-reactive protein levels (MD = -0.41, p = 0.40, 95% CI [-1.35, 0.54], two trials, 60 participants, low quality). DISCUSSION: Taurine-enhanced EN may reduce IL-6 levels and is not associated with improved clinical outcomes in critically ill patients, which may have potential immunoregulatory effects in critically ill patients. Given that published studies have small samples, the above conclusions need to be verified by more rigorously designed large-sample clinical trials.

Characterising the challenges of managing difficult red blood cell alloantibodies in liver transplant recipients.

AIMS: Formation of red blood cell alloantibodies (RBCAs) complicates transfusion support in liver transplantation (LT). Difficult RBCAs (DAs, >3 antibodies or antibodies for which <25% donors are antigen negative) further challenge care. This study characterises DA outcomes relative to non-difficult RBCAs (NDAs). METHODS: Single-centre, retrospective analysis of LT patients (2002-2021). RBCAs were defined as clinically significant antibodies. DAs were compared with NDAs. RESULTS: 89 patients had clinically significant RBCAs (DA=50, NDA=39). More DAs were anti-Jka, anti-M; fewer were anti-E, anti-K (all p<0.05). DA patients often had multiple antibodies (44% vs 12.8% NDA, p=0.0022). Probability of finding antigen-negative blood was lower for DAs (17.4% vs 68.1% NDA, p<0.0001) as was RBCs received (9.4 vs 14.7 units in NDA, p=0.0036). Although survival was similar, patients with DAs had more adverse reactions (8% vs 0%, p=0.128). Some antibodies appeared to occur with specific liver diseases (such as primary sclerosing cholangitis, alcoholic steatohepatitis and recurrent disease); however, due to low sample size, definitive conclusions cannot be made. CONCLUSIONS: DA LT recipients contain >1 RBCA, have a lower probability of finding antigen negative blood and may experience more adverse transfusion event (ATE). Despite this, the incidence of ATEs was still quite low.

Clinical and molecular correlates of the Index of Severity for Eosinophilic Esophagitis.

BACKGROUND: The Index of Severity for Eosinophilic Esophagitis (I-SEE) is a new expert-defined clinical tool that classifies disease severity of eosinophilic esophagitis (EoE). OBJECTIVE: We aimed to determine whether I-SEE is associated with patient characteristics, molecular features of EoE, or both. METHODS: We analyzed a prospective cohort of patients with EoE from the Consortium of Eosinophilic Gastrointestinal Disease Researchers (CEGIR). Associations between I-SEE and clinical and molecular features (assessed by an EoE diagnostic panel [EDP]) were assessed. RESULTS: In 318 patients with chronic EoE (209 adults, 109 children), median total I-SEE score was 7.0, with a higher symptoms and complications score in children than adults (4.0 vs 1.0; P < .001) and higher inflammatory and fibrostenotic features scores in adults than children (3.0 vs 1.0 and 3.0 vs 0, respectively; both P < .001). Total I-SEE score had a bimodal distribution with the inactive to moderate categories and severe category. EDP score correlated with total I-SEE score (r = -0.352, P < .001) and both inflammatory and fibrostenotic features scores (r = -0.665, P < .001; r = -0.446, P < .001, respectively), but not with symptoms and complications scores (r = 0.047, P = .408). Molecular severity increased from inactive to mild and moderate, but not severe, categories. Longitudinal changes of modified I-SEE scores and inflammatory and fibrostenotic features scores reflected histologic and molecular activity. CONCLUSIONS: I-SEE score is associated with select clinical features across severity categories and with EoE molecular features for nonsevere categories, warranting further validation.

Nonepithelial Gene Expression Correlates With Symptom Severity in Adults With Eosinophilic Esophagitis.

BACKGROUND: The mechanistic basis of the variable symptomatology seen in eosinophilic esophagitis (EoE) remains poorly understood. OBJECTIVE: We examined the correlation of a validated, patient-reported outcome metric with a broad spectrum of esophageal transcripts to uncover potential symptom pathogenesis. METHODS: We extracted data from 146 adults with EoE through the Consortium of Eosinophilic Gastrointestinal Disease Researchers. Patients were subgrouped by esophageal dilation history. We compared a validated patient-reported outcome metric, the EoE Activity Index (EEsAI), with a set of transcripts expressed in the esophagus of patients with EoE, the EoE Diagnostic Panel (EDP). We used single-cell RNA sequencing data to identify the cellular source of EEsAI-related EDP genes and further analyzed patients with mild and severe symptoms. RESULTS: The EEsAI correlated with the EDP total score, especially in patients without recent esophageal dilation (r = -0.31; P = .003). We identified 14 EDP genes that correlated with EEsAI scores (r ≥ 0.3; P < .05). Of these, 11 were expressed in nonepithelial cells and three in epithelial cells. During histologic remission, only four of 11 nonepithelial genes (36%) versus all three epithelial genes (100%) had decreased expression to less than 50% of that in active EoE. Fibroblasts expressed five of 11 nonepithelial EEsAI-associated EDP genes (45%). A subset of nonepithelial genes (eight of 11; 73%), but not EoE-representative genes (none of four; 0%; CCL26, CAPN14, DSG1, and SPINK7), was upregulated in patients with EoE with the highest versus lowest symptom burden. CONCLUSION: The correlation of symptoms and nonepithelial esophageal gene expression substantiates that nonepithelial cells (eg, fibroblasts) likely contribute to symptom severity.

Prognostic model incorporating immune checkpoint genes to predict the immunotherapy efficacy for lung adenocarcinoma: a cohort study integrating machine learning algorithms.

This study aimed to develop and validate a nomogram based on immune checkpoint genes (ICGs) for predicting prognosis and immune checkpoint blockade (ICB) efficacy in lung adenocarcinoma (LUAD) patients. A total of 385 LUAD patients from the TCGA database and 269 LUAD patients in the combined dataset (GSE41272 + GSE50081) were divided into training and validation cohorts, respectively. Three different machine learning algorithms including random forest (RF), least absolute shrinkage and selection operator (LASSO) logistic regression analysis, and support vector machine (SVM) were employed to select the predictive markers from 82 ICGs to construct the prognostic nomogram. The X-tile software was used to stratify patients into high- and low-risk subgroups based on the nomogram-derived risk scores. Differences in functional enrichment and immune infiltration between the two subgroups were assessed using gene set variation analysis (GSVA) and various algorithms. Additionally, three lung cancer cohorts receiving ICB therapy were utilized to evaluate the ability of the model to predict ICB efficacy in the real world. Five ICGs were identified as predictive markers across all three machine learning algorithms, leading to the construction of a nomogram with strong potential for prognosis prediction in both the training and validation cohorts (all AUC values close to 0.800). The patients were divided into high- (risk score ≥ 185.0) and low-risk subgroups (risk score < 185.0). Compared to the high-risk subgroup, the low-risk subgroup exhibited enrichment in immune activation pathways and increased infiltration of activated immune cells, such as CD8 + T cells and M1 macrophages (P < 0.05). Furthermore, the low-risk subgroup had a greater likelihood of benefiting from ICB therapy and longer progression-free survival (PFS) than did the high-risk subgroup (P < 0.05) in the two cohorts receiving ICB therapy. A nomogram based on ICGs was constructed and validated to aid in predicting prognosis and ICB treatment efficacy in LUAD patients.

Solitary bone plasmacytoma: Long-term clinical outcomes in a single center.

BACKGROUND: A solitary plasmacytoma is classified into a solitary plasmacytoma of the bone (SBP) and a solitary extramedullary (soft tissue mass) plasmacytoma, based on the site of the lesion. Despite the high local control rate with radiotherapy, approximately half of patients' conditions progress to multiple myeloma (MM) within 3-5 years after diagnosis, with SBP having a worse prognosis. PATIENTS AND METHODS: We retrospectively assessed the treatment and outcomes of patients with SBP in a hospital in China from 2008 to 2021. Twenty-four patients treated over 13 years with SBP were enrolled in this retrospective study. RESULTS: The most common sites for SBP were the axial skeleton and femur. The M protein was detected in 11 patients (46 %), of which 8 (33 %) had light chains, 2 (8 %) had immunoglobulin G kappa and 1 (4 %) had immunoglobulin D kappa. Flow cytometry revealed that 5 patients (21 %) had minimal bone marrow involvement. The treatment included chemotherapy, surgery, and radiotherapy in 18 (75 %), 12 (50 %), and 9 (38 %) patients, respectively, of whom 13 (54 %) received combined treatment. Over a median follow-up period of 67.2 months, 9 patients (38 %) developed MM in a median time of 101.5 months. The 5- and 10-year progression-free survival rates were 67.3 % and 37.4 %, respectively. One patient died due to pneumonia without progression and the other died due to relapse. CONCLUSION: This study confirmed the high rate of progression of SBP to MM, indicating a need for adjunct chemotherapy for the management of SBP.

Analysis of quality evaluation and optimal harvest period of Aurantii Fructus from different sources using UHPLC-Q-TOF-MS/MS.

INTRODUCTION: The active constituents in Aurantii Fructus sourced from different regions within Hunan Province exhibit variations, with certain samples demonstrating substandard quality. OBJECTIVES: The aim of this study is to conduct a comparative analysis of the chemical composition and quality of Aurantii Fructus from various sources, establish a robust methodology for quality evaluation, and determine the optimal harvesting period. MATERIALS AND METHODS: The components of Aurantii Fructus were qualitatively analyzed using a non-targeted metabolomics approach. Multivariate statistical analyses were conducted to identify potential markers, enabling qualitative and quantitative evaluation of the quality and optimal harvest period of Aurantii Fructus. RESULTS: Overall, 155 compounds were identified in Aurantii Fructus, with Huangpi exhibiting the highest number of components. Eleven potential markers were selected to assess the quality of Aurantii Fructus. The average content of Huangpi was the highest, indicating a high level of similarity. The samples' overall scores were ordered as follows: Huangpi > Xiangcheng > Choucheng > Daidai. Anren and Changde's Huangpi exhibited high contents, being rich in chemical components, resulting in favorable scores. Similarly, Changde's Xiangcheng displayed significant medicinal value. As the harvest time was delayed, there was an increase in fruit size, accompanied by thinner peels and a continuous decrease in the contents of potential markers. The best harvest period of Aurantii Fructus was within 1 week before and after the Lesser Heat. CONCLUSION: The present study establishes a precise and efficient method for evaluating the quality of Aurantii Fructus, thereby providing more comprehensive insights into its composition. This research lays the foundation for subsequent development and utilization of Aurantii Fructus.

Shared genetic basis and causality between schizophrenia and inflammatory bowel disease: evidence from a comprehensive genetic analysis.

BACKGROUND: The comorbidity between schizophrenia (SCZ) and inflammatory bowel disease (IBD) observed in epidemiological studies is partially attributed to genetic overlap, but the magnitude of shared genetic components and the causality relationship between them remains unclear. METHODS: By leveraging large-scale genome-wide association study (GWAS) summary statistics for SCZ, IBD, ulcerative colitis (UC), and Crohn's disease (CD), we conducted a comprehensive genetic pleiotropic analysis to uncover shared loci, genes, or biological processes between SCZ and each of IBD, UC, and CD, independently. Univariable and multivariable Mendelian randomization (MR) analyses were applied to assess the causality across these two disorders. RESULTS: SCZ genetically correlated with IBD (rg = 0.14, p = 3.65 × 10−9), UC (rg = 0.15, p = 4.88 × 10−8), and CD (rg = 0.12, p = 2.27 × 10−6), all surpassed the Bonferroni correction. Cross-trait meta-analysis identified 64, 52, and 66 significantly independent loci associated with SCZ and IBD, UC, and CD, respectively. Follow-up gene-based analysis found 11 novel pleiotropic genes (KAT5, RABEP1, ELP5, CSNK1G1, etc) in all joint phenotypes. Co-expression and pathway enrichment analysis illustrated those novel genes were mainly involved in core immune-related signal transduction and cerebral disorder-related pathways. In univariable MR, genetic predisposition to SCZ was associated with an increased risk of IBD (OR 1.11, 95% CI 1.07­1.15, p = 1.85 × 10−6). Multivariable MR indicated a causal effect of genetic liability to SCZ on IBD risk independent of Actinobacteria (OR 1.11, 95% CI 1.06­1.16, p = 1.34 × 10−6) or BMI (OR 1.11, 95% CI 1.04­1.18, p = 1.84 × 10−3). CONCLUSIONS: We confirmed a shared genetic basis, pleiotropic loci/genes, and causal relationship between SCZ and IBD, providing novel insights into the biological mechanism and therapeutic targets underlying these two disorders.

Four sulfur-containing compounds with anti-colon cancer effect from marine-derived fungus Aspergillus terreus.

Sulfur-containing natural products possess a variety of biological functions including antitumor, antibacterial, anti-inflammatory and antiviral activities. In this study, four previously undescribed sulfur-containing compounds asperteretals L and M, terreins A and B, together with 17 known compounds were obtained from a culture of marine fungus A. terreus supplemented with inorganic sulfur source Na2SO4. Their planar structures and absolute configurations were elucidated by NMR, HRESIMS, and ECD experiments. The in vitro cytotoxicities of compounds 1-21 against HCT-116 and Caco-2 were evaluated by SRB assay. Asperteretal M (2) exhibited activity against HCT-116 with the IC50 value at 30µM. The antiproliferative effect of asperteretal M was confirmed by colony formation assay and cell death staining. Furthermore, the preliminary study on the anti-colon cancer mechanism of asperteretal M was performed by RNA-seq analysis. Western blotting validated that asperteretal M significantly decreased the expression of cell-cycle regulatory proteins CDK1, CDK4, and PCNA in a concentration-dependent manner.

[Progress of intraosseous basivertebral nerve ablation for symptomatic Modic alterations].

Chronic lumbar and back pain caused by degenerative vertebral endplates presents a challenging issue for patients and clinicians. As a new minimally invasive spinal treatment method, radiofrequency ablation of vertebral basal nerve in bone can denature the corresponding vertebral basal nerve through radiofrequency ablation of degenerative vertebral endplate. It blocks the nociceptive signal transmission of the vertebral base nerve, thereby alleviating the symptoms of low back pain caused by the degenerative vertebral endplate. At present, many foreign articles have reported the operation principle, operation method, clinical efficacy and related complications of radiofrequency ablation of the vertebral basal nerve. The main purpose of this paper is to conduct a comprehensive analysis of the current relevant research, and provide a reference for the follow-up clinical research.