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BACKGROUND: The objective of this study was to investigate the value of mismatch negativity (MMN) and P300 event-related potentials for discriminating the consciousness state and predicting improvement of consciousness at 6 months in patients with coma and other disorders of consciousness (DOC). METHODS: We performed MMN and P300 on 42 patients with DOC with a mean onset time of 40.21 ± 19.43 days. These patients with DOC were categorized into coma, unresponsive wakefulness syndrome (UWS), minimal consciousness minus (MCS-), and minimal consciousness plus (MCS +) groups according to neurobehavioral assessment and the Coma Recovery Scale-Revised score. The primary outcome was the improvement of consciousness at 6 months in patients with DOC. We assessed the efficacy of MMN and P300 in quantitatively predicting the prognosis at 6 months and the capability of MMN and P300 parameters to differentiate between DOC. RESULTS: At least one significant difference in either MMN or P300 parameters was displayed among the DOC groups, but not between the MCS- and MCS+ groups (significance level: 0.05). Both MMN and P300 amplitudes showed desirable predictive accuracy at 6 months, with areas under the curve (AUCs) of 0.859 and 0.856, respectively. The optimal thresholds for MMN and P300 amplitudes were 2.044 and 1.095 µV. However, the combined MMN-P300 amplitude showed better 6-month predictive accuracy (AUC 0.934, 95% confidence interval 0.860-1.000), with a sensitivity of 85% and a specificity of 90.9%. CONCLUSIONS: MMN and P300 may help discriminate among coma, UWS, and MCS, but not between patients with MCS- and patients with MCS+ . The MMN amplitude, P300 amplitude, and especially combined MMN-P300 amplitude at 6 months may be interesting predictors of consciousness improvement at 6 months in patients with DOC. TRIAL REGISTRATION: Chinese Clinical Trial Registry identifier ChiCTR2400083798.
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BACKGROUND: Shizao decoction (SZD) consisted of Euphorbia kansui (EK), Euphorbia pekinensis (EP), Daphne genkwa (DG), and Fructus Jujubae (FJ) is a classic Chinese herbal medicine formula for treating malignant ascites, which is closely related to the modulation of gut microbiota by our previous study. For water-expelling members (WEM) including EK, EP, and DG may have side effects on the intestine, FJ is employed for detoxification and effectivity enhancement of WEM. However, the underlying mechanism for the compatibility of WEM and FJ is still unknown. PURPOSE: To investigate the effect of the compatibility of WEM with FJ in SZD on malignant ascites and elucidate the potential mechanism from the perspective of the modulation of gut microbiota and related metabolic function. METHODS: Qualitative and quantitative evaluation of main components was conducted for comprehensive characterization of SZD and WEM. The effect of WEM and SZD was compared on malignant ascites effusion (MAE) rats. The intestinal injury was evaluated by HE staining and oxidative damage. Ascites weight, urine amount, fecal water content, the expression of aquaporins, and cytokines in ascites (IL-6, VEGF, and TNF-α) were measured to estimate the water-expelling activity. The intestinal flora was detected by 16S rDNA sequencing and the content of fecal short-chain fatty acids (SCFAs) was analyzed using gas chromatography-mass spectrometry. Pseudo-germ-free (PGF) and fecal bacteria transplantation animal experiments were subsequently employed to validate this finding. The fecal metabolomics and correlation analysis were finally conducted to explore the related metabolic changes. RESULTS: 51 and 33 components were identified in SZD and WEM, respectively. Compared to WEM alone, the compatibility with FJ remarkably reduced intestinal oxidative damage in MAE rats. Ascites was also relieved by downregulating the expression of AQP3 in the colon and decreasing the levels of IL-6, TNF-α and VEGF in ascites. The diversity of gut microbiota was reversed with an increase in Lactobacillus and Clostridia_UCG-014 while a decrease in Colidextribacter. Under the PGF condition, compatibility of WEM with FJ failed to reduce intestinal injury and alleviate MA significantly, but this effect was further enhanced after FMT. 23 potential fecal metabolites were finally identified. Correlation analysis further showed that Lactobacillus and Clostridia_UCG-014 were positively correlated with SCFAs and l-tryptophan. Colidextribacter was negatively correlated with thymidine but positively correlated with ursodeoxycholic acid and deoxycholic acid. CONCLUSION: FJ cooperated with WEM reduced intestinal injury and alleviated malignant ascites by modulating gut microbiota, short-chain fatty and tryptophan metabolism. These findings provide a scientific basis for the clinical application of FJ from SZD and the safe usage of SZD.
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On-chip integration of 2D materials with unique structures and properties endow integrated devices with new functionalities and improved performance. With high flexibility in ways to modify its properties and compatibility with integrated platforms, graphene oxide (GO) is an exceptionally attractive 2D material for hybrid integrated photonic chips. Here, by harnessing unique property changes induced by photothermal effects in 2D GO films, novel functionalities beyond the capability of photonic integrated circuits are demonstrated. These include all-optical control and tuning, optical power limiting, and nonreciprocal light transmission. The 2D layered GO films are integrated onto photonic chips with precise control of their thickness and size. Benefitting from the broadband optical response of 2D GO films, all three functionalities feature a very wide operational optical bandwidth. By fitting the experimental results with theory, the changes in GO film properties induced by the photothermal effects are analyzed, revealing interesting insights about the physics of 2D GO films. These results highlight the versatility of 2D GO films in implementing new functions for integrated photonic devices for a wide range of applications.
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The effect of low-FODMAPs diet on irritable bowel syndrome (IBS) in Western China has not been reported. We aimed to investigate the effect of low-FODMAPs diet on IBS patients in the area and whether low-FODMAPs diet-induced alterations of microbiota could be improved through probiotics. IBS patients were randomized to the control group, low-FODMAPs diet group, probiotics group, or combined group. IBS Symptom Severity Score questionnaire (IBS-SSS) and IBS Quality of Life Score questionnaire (IBS-QOL) were completed at baseline, 2 and 4 weeks to evaluate the severity of symptoms. Fresh feces were collected for analyses of gut microbiota and short-chain fatty acids at baseline and 4 weeks after intervention. Seventy-three patients were included in the per protocol analysis. After intervention, there was significant improvement in IBS-SSS in the low-FODMAPs group (37.5%, 44.2%), probiotics group (51.4%, 62.0%), and combined group (34.1%, 40.4%) at both 2 weeks and 4 weeks, compared with the baseline (p < .05). In the low-FODMAPs group, the abundance of several microbiota (Lachnoclostridium, Enterococcus, etc.) was significantly decreased. Furthermore, after the supplementation of probiotics in the combined group, the abundance of Genus_Ruminococcus, Coprococcus, Acidaminococcus, Ruminiclostridium, Akkermansia, Eggerthella, and Oxalobacter was significantly increased, which was associated with the improvements of symptoms score in the Pearson correlation analysis. Our study confirmed the effectiveness and safety of short-term low-FODMAPs diet in IBS symptoms based on the Chinese diet in Western China. The combination of low-FODMAPs and probiotics plays a beneficial role in gut microbiota in IBS.
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Transient electric fields across cell bilayer membranes can lead to electroporation and cell fusion, effects crucial to cell viability whose biological implications have been extensively studied. However, little is known about these behaviours in a materials context. Here we find that transmembrane electric fields can lead to a massive, reversible modulation of the sliding friction between surfaces coated with lipid-bilayer membranes-a 200-fold variation, up to two orders of magnitude greater than that achieved to date. Atomistic simulations reveal that the transverse fields, resembling those at cell membranes, lead to fully reversible electroporation of the confined bilayers and the formation of inter-bilayer bridges analogous to the stalks preceding intermembrane fusion. These increase the interfacial dissipation through reduced hydration at the slip plane, forcing it to revert in part from the low-dissipation, hydrated lipid-headgroup plane to the intra-bilayer, high-dissipation acyl tail interface. Our results demonstrate that lipid bilayers under transmembrane electric fields can have striking materials modification properties.
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BACKGROUND: It's necessary to reassess the patients' short-term and long-term postoperative outcome in the post-COVID-19 era. This study aims to provide more comprehensive evidence regarding the timing of surgery after COVID-19 infection among the vaccinated population upon Omicron variant, considering the duration after acute COVID-19 infection, severity of COVID-19, patients' comorbidities, and the full course quality of postoperative recovery. MATERIALS AND METHODS: This is a single-center cohort study. Patients diagnosed with preoperative COVID-19 infection were consecutively included before surgery. Patients' demographics, surgical characteristics, and COVID-19 related factors were documented. Exposure was the time interval from COVID-19 infection to surgery. The primary outcome was postoperative complications within 30 days. The secondary outcomes included postoperative mortality within 30 days, functional disability at 6 and 12 months after surgery. RESULTS: A total of 4953 patients were included, and postoperative complications occurred in 353 patients (7.1%) within 30 days after surgery. Time interval from COVID-19 infection to surgery was associated with postoperative complications within 30 days after surgery (adjusted odds ratio [aOR] per day: 0.99; 95% CI, 0.99-1.00; P<0.01), as well as postoperative 6- and 12-month functional disability ([aOR]: 1.00; 95% CI, 0.99-1.00; P<0.01; and [aOR] 0.99; 95% CI, 0.98-1.00; P=0.01, respectively). Delaying surgery beyond a time interval of 2 weeks was associated with reduced postoperative 30-day complications ([aOR]: 0.63; 95% CI, 0.43-0.91; P=0.01) and mortality ([aOR]: 0.07; 95% CI, 0.01-0.38; P<0.01). Meanwhile, delaying surgery beyond a time interval of 7 weeks was associated with reduced functional disability at both 6-month ([aOR]: 0.67; 95% CI, 0.58-0.79; P<0.01) and 12-month postoperatively ([aOR]: 0.71; 95% CI, 0.53-0.95; P=0.02). CONCLUSION: A 2 weeks delay after COVID-19 infection is necessary for decreasing short-term postoperative risks, and a longer waiting period could be beneficial for long-term functional recovery.
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Acute myeloid leukemia (AML) is a malignant clonal hematopoietic disease with a poor prognosis. Understanding the interaction between leukemic cells and the tumor microenvironment (TME) can help predict the prognosis of leukemia and guide its treatment. Re-analyzing the scRNA-seq data from the CSC and G20 cohorts, using a Python-based pipeline including machine-learning-based scVI-tools, recapitulated the distinct hierarchical structure within the samples of AML patients. Weighted correlation network analysis (WGCNA) was conducted to construct a weighted gene co-expression network and to identify gene modules primarily focusing on hematopoietic stem cells (HSCs), multipotent progenitors (MPPs), and natural killer (NK) cells. The analysis revealed significant deregulation in gene modules associated with aerobic respiration and ribosomal/cytoplasmic translation. Cell-cell communications were elucidated by the CellChat package, revealing an imbalance of activating and inhibitory immune signaling pathways. Interception of genes upregulated in leukemic HSCs & MPPs as well as in NKG2A-high NK cells was used to construct prognostic models. Normal Cox and artificial neural network models based on 10 genes were developed. The study reveals the deregulation of mitochondrial and ribosomal genes in AML patients and suggests the co-occurrence of stimulatory and inhibitory factors in the AML TME.
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Leucemia Mieloide Aguda , Microambiente Tumoral , Humanos , Leucemia Mieloide Aguda/genética , Leucemia Mieloide Aguda/patología , Microambiente Tumoral/genética , Microambiente Tumoral/inmunología , Pronóstico , Ribosomas/metabolismo , Ribosomas/genética , Mitocondrias/genética , Mitocondrias/metabolismo , Redes Reguladoras de Genes , Perfilación de la Expresión Génica/métodos , Genes MitocondrialesRESUMEN
INTRODUCTION: Sulfur-fumigation of Paeoniae Radix Alba (PRA) could induce the chemical transformation of its bioactive component paeoniflorin into a sulfur-containing derivative paeoniflorin sulfite, and thus alter the quality, bioactivities, pharmacokinetics, and toxicities of PRA. However, how sulfur-fumigated PRA (S-PRA) affects the quality of PRA-containing complex preparations has not been intensively evaluated. OBJECTIVES: We intend to evaluate the influence of S-PRA on the overall quality of three kinds of Si-Wu-Tang (SWT) formulations, i.e., decoction (SWT-D), granule (SWT-G), and mixture (SWT-M). MATERIAL AND METHODS: An UPLC-DAD multi-components quantification method was used to compare the transfer rates of paeoniflorin sulfite and other 10 bioactive components between S-PRA-containing and NS-PRA-containing SWT formulations. An UPLC-QTOF-MS/MS-based target metabolomics approach was applied to explore the differential sulfur-containing derivatives in S-PRA-containing SWT formulations. RESULTS: The transfer rates of paeoniflorin sulfite in three S-PRA-containing SWT formulations were all higher than 100%. Moreover, S-PRA also increased the transfer rate of 5-hydroxymethylfurfural, 1,2,3,4,6-O-pentagalloylglucose, whereas decreased that of paeoniflorin, albiflorin, and ferulic acid in three SWT formulations. Six pinane monoterpene glucoside sulfites originally identified in S-PRA, were also detectable in three S-PRA-containing SWT formulations. In addition, seven phenolic acid sulfites including (3Z)-6-sulfite-ligustilide, (3E)-6-sulfite-ligustilide, 6,8-disulfite-ligustilide, ferulic acid sulfite, neochlorogenic acid sulfite, chlorogenic acid sulfite, and angelicide sulfite (or isomer) were newly identified in these three S-PRA-containing formulations. CONCLUSION: S-PRA could differentially affect the transfer rate of paeoniflorin sulfite and other bioactive components during the preparation of three SWT formulations and subsequently the overall quality thereof.
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Medicamentos Herbarios Chinos , Fumigación , Paeonia , Azufre , Espectrometría de Masas en Tándem , Paeonia/química , Medicamentos Herbarios Chinos/química , Cromatografía Líquida de Alta Presión/métodos , Espectrometría de Masas en Tándem/métodos , Azufre/química , Fumigación/métodos , Glucósidos/química , Monoterpenos/química , Metabolómica/métodosRESUMEN
Zinc (Zn) is a vital micronutrient that strengthens the immune system, aids cellular activities, and treats infectious diseases. A deficiency in Zn can lead to an imbalance in the immune system. This imbalance is particularly evident in severe deficiency cases, where there is a high susceptibility to various viral infections, including COVID-19 caused by SARS-CoV-2. This review article examines the nutritional roles of Zn in human health, the maintenance of Zn concentration, and Zn uptake. As Zn is an essential trace element that plays a critical role in the immune system and is necessary for immune cell function and cell signaling, the roles of Zn in the human immune system, immune cells, interleukins, and its role in SARS-CoV-2 infection are further discussed. In summary, this review paper encapsulates the nutritional role of Zn in the human immune system, with the hope of providing specific insights into Zn research.
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The purpose of this study is to evaluate loose suture-related inflammation and activation of conjunctiva-associated lymphoid tissue (CALT) in patients after keratoplasty. The patients who were treated with keratoplasty at the First Affiliated Hospital of Harbin Medical University between 2015 and 2022 were recruited into the study. We evaluated the time and location of loose suture development in patients after keratoplasty. In addition, in vivo confocal microscopy was used to evaluate the activation of CALT and the accumulation of inflammatory cells around loose sutures. Meso Scale Discovery assay detection kits were used to evaluate the inflammatory cytokines in the tears of patients before and after the loose suture was removed. In this study, we collected the information from 212 cases (212 eyes) who had PK (126 eyes) and DALK-treated (86 eyes) for corneal transplantation, including 124 males and 88 females, aged 14-84 years old. The average age was 50.65 ± 16.81 years old. Corneal sutures were more prone to loose at 3 months and 6 months after keratoplasty, and the frequent sites were at 5 and 6 o'clock. An increased number of inflammatory cells could be observed around the loose sutures than normal sutures (P < 0.001). In CALT, the density of diffuse lymphocytes (P < 0.001), follicles (P < 0.001), and parafollicular lymphocytes (P < 0.001) were higher and the central reflection of the follicles (P < 0.001) was stronger when suture loosening happened. The levels of inflammatory cytokines such as IL-1ß (P = 0.003), IL-8 (P = 0.012), and TNF-α (P < 0.001) were higher in the tears of the patients with loose sutures. The activation of CALT was partly settled after removing the loose sutures. In conclusion, loose sutures after corneal transplantation can lead to increased infiltration of inflammatory cells, activation of CALT, and increased secretion of inflammatory cytokines in the tears of patients. Regular follow-up to identify and solve the problem in time can avoid suture-related complications.
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Conjuntiva , Trasplante de Córnea , Tejido Linfoide , Suturas , Humanos , Femenino , Masculino , Persona de Mediana Edad , Adulto , Anciano , Conjuntiva/metabolismo , Conjuntiva/patología , Conjuntiva/cirugía , Anciano de 80 o más Años , Trasplante de Córnea/efectos adversos , Adolescente , Suturas/efectos adversos , Adulto Joven , Tejido Linfoide/metabolismo , Tejido Linfoide/patología , Citocinas/metabolismo , Inflamación/metabolismo , Inflamación/patología , Inflamación/etiología , Lágrimas/metabolismoRESUMEN
The ferric trichloride (FeCl3)-intercalated graphite intercalation compound (GIC) has high reversible capacity and bulk density, making it a promising anode material for lithium ion batteries. However, its practical application has been limited by the poor cycle performance due to chloride dissolution and shuttling issues. Herein, FeCl3-GIC is used as the precursor material to synthesize a nano-Fe3O4-modified intercalation material by a solvothermal method. The Fe3O4 moiety at the edge of FeCl3-GIC provides a robust chemical anchoring effect on the chlorides. Together with the two-dimensional graphite layer, it forms a confinement space, which effectively immobilizes soluble chlorides. Attributed to the distinctive structural design, the Fe3O4-FeCl3/GIC 25% C electrode offers a high reversible capacity of 691.4 mA h g-1 at 1000 mA g-1 after 400 cycles. At 2000 and 5000 mA g-1, the reversible specific capacity of the Fe3O4-FeCl3/GIC 25% C electrode is 345.6 and 218.3 mA h g-1, respectively. This work presents an innovative method to improve the lifespan of GIC.
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Ginseng is a most popular health-promoting food with ginsenosides as its main bioactive ingredients. Illegal sulfur-fumigation causes ginsenosides convert to toxic sulfur-containing derivatives, and reduced the efficacy/safety of ginseng. 24-sulfo-25-ene ginsenoside Rg1 (25-ene SRg1), one of the sulfur-containing derivatives, is a potential quality control marker of fumigated ginseng, but with low accessibility owing to its unknown generation mechanism. In this study, metals/bisulfite system involved generation mechanism was investigated and verified. The generation of 25-ene SRg1 in sulfur-fumigated ginseng is that SO2, formed during sulfur-fumigation, reacted with water and ionized into HSO3-. On the one hand, under the metals/bisulfite system, HSO3- generates HSO5- and free radicals which converted ginsenoside Rg1 to 24,25-epoxide Rg1; on the other hand, as a nucleophilic group, HSO3- reacted with 24,25-epoxide Rg1 and further dehydrated to 25-ene SRg1. This study provided a technical support for the promotion of 25-ene SRg1 as the characteristic quality control marker of sulfur-fumigated ginseng.
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Fumigación , Ginsenósidos , Panax , Control de Calidad , Azufre , Ginsenósidos/química , Ginsenósidos/análisis , Panax/química , Azufre/química , Sulfitos/química , Sulfitos/análisis , Metales/química , Metales/análisis , Extractos Vegetales/químicaRESUMEN
BACKGROUND: Although hepatitis B virus (HBV) infection is a major risk factor for hepatic cancer, the majority of HBV carriers do not develop this lethal disease. Additional molecular alterations are thus implicated in the process of liver tumorigenesis. Since phosphatase and tensin homolog (PTEN) is decreased in approximately half of liver cancers, we investigated the significance of PTEN deficiency in HBV-related hepatocarcinogenesis. METHODS: HBV-positive human liver cancer tissues were checked for PTEN expression. Transgenic HBV, Alb-Cre and Ptenfl/fl mice were inter-crossed to generate WT, HBV, Pten-/- and HBV; Pten-/- mice. Immunoblotting, histological analysis and qRT-PCR were used to study these livers. Gp73-/- mice were then mated with HBV; Pten-/- mice to illustrate the role of hepatic tumor biomarker golgi membrane protein 73 (GP73)/ golgi membrane protein 1 (GOLM1) in hepatic oncogenesis. RESULTS: Pten deletion and HBV transgene synergistically aggravated liver injury, inflammation, fibrosis and development of mixed hepatocellular carcinoma (HCC) and intrahepatic cholangiocarcinoma (ICC). GP73 was augmented in HBV; Pten-/- livers. Knockout of GP73 blunted the synergistic effect of deficient Pten and transgenic HBV on liver injury, inflammation, fibrosis and cancer development. CONCLUSIONS: This mixed HCC-ICC mouse model mimics liver cancer patients harboring HBV infection and PTEN/AKT signaling pathway alteration. Targeting GP73 is a promising therapeutic strategy for cancer patients with HBV infection and PTEN alteration.
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Carcinoma Hepatocelular , Hepatitis B , Neoplasias Hepáticas , Fosfohidrolasa PTEN , Animales , Humanos , Ratones , Carcinoma Hepatocelular/patología , Fibrosis , Hepatitis B/complicaciones , Virus de la Hepatitis B , Inflamación/patología , Hígado/patología , Neoplasias Hepáticas/patología , Proteínas de la Membrana/metabolismo , Ratones Noqueados , Fosfohidrolasa PTEN/metabolismoRESUMEN
Dasatinib-related resistance frequently occurs and may lead to the failure of chemotherapy; thus, dose interruptions are necessary. Cannabidiol (CBD) has potential for integration with orthodox cancer care. In this study, we explored the combination effect of CBD and dasatinib on A549 cells. CBD in combination with dasatinib could induce significant synergistic apoptosis in vitro (ZIP > 10) and in vivo. The combination of CBD and low-dose dasatinib exhibited antiproliferative and proapoptotic effects through up-regulation of caspase-3 and Bax, and down-regulation of Bcl-2 in A549 cells. The xenograft mouse model suggested that the combination was more efficient and safer. In short, CBD and low-dose dasatinib exhibited a synergistic effect on anticancer by targeting the SRC/PI3K/AKT signaling pathway, suggesting a potential therapeutic option for the treatment of lung cancer.
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Cannabidiol , Neoplasias Pulmonares , Humanos , Animales , Ratones , Dasatinib/farmacología , Dasatinib/uso terapéutico , Neoplasias Pulmonares/tratamiento farmacológico , Neoplasias Pulmonares/metabolismo , Proteínas Proto-Oncogénicas c-akt/metabolismo , Fosfatidilinositol 3-Quinasas/metabolismo , Cannabidiol/farmacología , Cannabidiol/uso terapéutico , Transducción de Señal , Línea Celular Tumoral , Apoptosis , Proliferación Celular , Inhibidores de Proteínas Quinasas/farmacologíaRESUMEN
This study aims to conduct a cost-effectiveness analysis of three different anesthesia strategies, namely chatting while under local anesthesia (Chat-LA), total intravenous anesthesia (TIVA), and general anesthesia with laryngeal mask airway (GA-LMA), employed in transperineal magnetic resonance imaging (MRI)/ultrasound (US) fusion prostate biopsy (TP-MUF-PB). A retrospective study was conducted involving 1202 patients who underwent TP-MUF-PB from June 2016 to April 2023 at The First Affiliated Hospital of Soochow University (Suzhou, China). Clinical data and outcomes, including total costs, complications, and quality-adjusted life years (QALYs), were compared. Probability sensitivity and subgroup analyses were also performed. Chat-LA was found to be the most cost-effective option, outperforming both TIVA and GA-LMA. However, subgroup analyses revealed that in younger patients (under 65 years old) and those with smaller prostate volumes (<40 ml), TIVA emerged as a more cost-effective strategy. While Chat-LA may generally be the most cost-effective and safer anesthesia method for TP-MUF-PB, personalization of anesthesia strategies is crucial, considering specific patient demographics such as age and prostate volume.
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Análisis Costo-Beneficio , Biopsia Guiada por Imagen , Próstata , Neoplasias de la Próstata , Humanos , Masculino , Persona de Mediana Edad , Anciano , Estudios Retrospectivos , Próstata/patología , Próstata/diagnóstico por imagen , Biopsia Guiada por Imagen/métodos , Biopsia Guiada por Imagen/economía , Neoplasias de la Próstata/patología , Neoplasias de la Próstata/diagnóstico por imagen , Imagen por Resonancia Magnética/economía , Imagen por Resonancia Magnética/métodos , Anestesia Local/economía , Anestesia Local/métodos , Años de Vida Ajustados por Calidad de Vida , Anestesia General/economía , Análisis de Costo-EfectividadRESUMEN
AIMS: RNA-binding proteins (RBPs) play pivotal roles in carcinogenesis and immunotherapy. Leucine-rich pentapeptide repeat-containing protein (LRPPRC) is crucial for RNA polyadenylation, transport, and stability. Although recent studies have suggested LRPPRC's potential role in tumor progression, its significance in tumor prognosis, diagnosis, and immunology remains unclear. MAIN METHODS: We comprehensively analyzed LRPPRC expression in tumors using various databases, including Human Transcriptome Cell Atlas (HTCA), University of California Santa Cruz (UCSC), Human Protein Atlas (HPA), Sangerbox, TISIDB, GeneMANIA, GSCALite, and CellMiner. We examined the correlation between LRPPRC expression level and prognosis, immune infiltration, immunotherapy, methylation, biological function, and drug sensitivity. Single-cell analysis was performed using Tumor Immune Single Cell Hub (TISCH) and CancerSEA software. Patients with acute myeloid leukemia (AML) were categorized based on LRPPRC levels for functional and immune infiltration analyses. The role of LRPPRC in cancer was validated using in vitro experiments. KEY FINDINGS: Our findings revealed that LRPPRC was highly expressed in almost all cancer types, indicating its significant prognostic and diagnostic potential. Notably, LRPPRC was associated with diverse immune features, such as immune cell infiltration, immune checkpoint genes, tumor mutational burden, and microsatellite instability, suggesting its value in guiding immunotherapy strategies. Within AML, the high-expression group had lower levels of immune cells, including CD8+ T cells. In vitro experiments confirmed the inhibitory effects of LRPPRC knockdown on AML cell proliferation. SIGNIFICANCE: This study highlights LRPPRC as a reliable pan-cancer prognostic and immune biomarker, particularly in AML. It lays the groundwork for future research on LRPPRC-targeted cancer therapies.
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Biomarcadores de Tumor , Carcinogénesis , Leucemia Mieloide Aguda , Humanos , Linfocitos T CD8-positivos , Proteínas de Neoplasias , PronósticoRESUMEN
BACKGROUND: A substantial number of patients with bladder cancer fail to benefit from immune checkpoint inhibitors (ICIs). We aim to investigate whether the addition of other therapeutic modalities into immunotherapy may augment the immune reactivity, thereby improving the overall response rate. METHODS: We conducted a comprehensive assessment of the immunological changes following immunotherapy and chemotherapy, employing both single-cell RNA sequencing and bulk RNA sequencing analyses. RESULTS: The bladder cancer patient treated with ICIs exhibited a higher abundance of B cells and T follicular helper cells compared to the treatment-naïve patient. Analysis of public datasets and the in-house RJBLC-I2N003 cohort revealed the induction of tertiary lymphoid structure (TLS) neogenesis and maturation by immunotherapy. The IMvigor 210 study suggested that TLS could serve as a predictor of immunotherapy response and patient prognosis. In addition, genome-wide transcriptome data unveiled a shift towards the immune-enriched subtype over the desert subtype in patients receiving neoadjuvant chemotherapy. Notably, the proportions of CD20 + B cells, T follicular helper cells, and TLSs were significantly increased. In patients treated with a combination of neoadjuvant chemotherapy and ICIs, TLS positivity and maturity were improved compared to the baseline. Furthermore, neoadjuvant chemoimmunotherapy resulted in a higher rate of pathological complete response compared to monotherapies. CONCLUSIONS: This work pinpointed the individual effect of immunotherapy and chemotherapy in fostering TLS development, and underscored the superior effectiveness of combined modalities in enhancing TLS maturation and response rates.
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Estructuras Linfoides Terciarias , Neoplasias de la Vejiga Urinaria , Humanos , Inmunoterapia , Neoplasias de la Vejiga Urinaria/tratamiento farmacológico , Vejiga Urinaria , Linfocitos B , Microambiente Tumoral , PronósticoRESUMEN
INTRODUCTION: Zishui-Qinggan decoction (ZQD) is a classical traditional Chinese medicine formula (TCMF) for alleviating menopausal symptoms (MPS) induced by endocrine therapy in breast cancer patients. In the production of TCMF modern preparations, ethanol precipitation (EP) is a commonly but not fully verified refining process. OBJECTIVES: Chemical profiling/serum pharmacochemistry and network pharmacology approaches were integrated for exploring the rationality of the EP process in the production of ZQD modern preparations. MATERIAL AND METHODS: Ultra-performance liquid chromatography-quadrupole time-of-flight tandem mass spectrometry (UPLC-QTOF-MS/MS) was applied to identify the chemical profiles and absorbed components of ZQD. Network pharmacology was used to identify targets and pathways related to MPS-relieving efficacy. RESULTS: The chemicals of ZQDs without/with EP process (referred to as ZQD-W and ZQD-W-P, respectively) were qualitatively similar with 89 and 87 components identified, respectively, but their relative contents were different; 51 components were detectable in the serum of rats orally administered with ZQD-W, whereas only 19 were detected in that administered with ZQD-W-P. Key targets, such as AKT1, and pathways, such as the PI3K-Akt signalling pathway, affected by ZQD-W and ZQD-W-P were similar, while the neuroactive ligand-receptor interaction pathway among others and the MAPK signalling pathway among others were specific pathways affected by ZQD-W and ZQD-W-P, respectively. The specifically absorbed components of ZQD-W could combine its specific key targets. CONCLUSION: The EP process quantitatively altered the chemical profiles of ZQD, subsequently affected the absorbed components of ZQD, and then affected the key targets and pathways of ZQD for relieving MPS. The EP process might result in variation of the MPS-relieving efficacy of ZQD, which deserves further in vivo verification.
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Medicamentos Herbarios Chinos , Etanol , Farmacología en Red , Espectrometría de Masas en Tándem , Medicamentos Herbarios Chinos/química , Espectrometría de Masas en Tándem/métodos , Cromatografía Líquida de Alta Presión/métodos , Animales , Etanol/química , Ratas Sprague-Dawley , Ratas , Precipitación Química , Medicina Tradicional ChinaRESUMEN
Adenocarcinoma of the bladder is a rare urinary bladder carcinoma with limited therapy options due to lack of molecular characterization. Here, we aimed to reveal the mutational and transcriptomic landscapes of adenocarcinoma of the bladder and assess any relationship with prognosis. Between February 2015 and June 2021, a total of 23 patients with adenocarcinoma of the bladder were enrolled. These included 16 patients with primary bladder adenocarcinomas and seven patients with urachal adenocarcinoma. Whole exome sequencing (16 patients), whole genome sequencing (16 patients), bulk RNA sequencing (RNA-seq) (19 patients), and single-cell RNA-seq (5 patients) were conducted for the specimens. Correlation analysis, survival analysis, and t-tests were also performed. Prevalent T>A substitutions were observed among somatic mutations, and major trinucleotide contexts included 5'-CTC-3' and 5'-CTG-3'. This pattern was mainly contributed by COSMIC signature 22 related to chemical carcinogen exposure (probably aristolochic acid), which has not been reported in bladder adenocarcinoma. Moreover, genes with copy number changes were also enriched in the KEGG term 'chemical carcinogenesis'. Transcriptomic analysis suggested high immune cell infiltration and luminal-like features in the majority of samples. Interestingly, a small fraction of samples with an APOBEC-derived mutational signature exhibited a higher risk of disease progression compared with samples with only a chemical carcinogen-related signature, confirming the molecular and prognostic heterogeneity of bladder adenocarcinoma. This study presents mutational and transcriptomic landscapes of bladder adenocarcinoma, and indicates that a chemical carcinogen-related mutational signature may be related to a better prognosis compared with an APOBEC signature in adenocarcinoma of the bladder. © 2024 The Pathological Society of Great Britain and Ireland.