Quantification of MicroRNA in a Single Living Cell via Ionic Current Rectification-Based Nanopore for Triple Negative Breast Cancer Diagnosis.

Accurate analysis of microRNAs (miRNAs) at the single-cell level is extremely important for deeply understanding their multiple and intricate biological functions. Despite some advancements in analyzing single-cell miRNAs, challenges such as intracellular interferences and insufficient detection limits still remain. In this work, an ultrasensitive nanopore sensor for quantitative single-cell miRNA-155 detection is constructed based on ionic current rectification (ICR) coupled with enzyme-free catalytic hairpin assembly (CHA). Benefiting from the enzyme-free CHA amplification strategy, the detection limit of the nanopore sensor for miRNA-155 reaches 10 fM and the nanopore sensor is more adaptable to complex intracellular environments. With the nanopore sensor, the concentration of miRNA-155 in living single cells is quantified to realize the early diagnosis of triple-negative breast cancer (TNBC). Furthermore, the nanopore sensor can be applied in screening anticancer drugs by tracking the expression level of miRNA-155. This work provides an adaptive and universal method for quantitatively analyzing intracellular miRNAs, which will greatly improve our understanding of cell heterogeneity and provide a more reliable scientific basis for exploring major diseases at the single-cell level.

Training in cognitive reappraisal normalizes whole-brain indices of emotion regulation in borderline personality disorder.

BACKGROUND: Borderline personality disorder is the prototypical disorder of emotion dysregulation. We have previously shown that borderline personality disorder patients are impaired in their capacity to engage cognitive reappraisal, a frequently-employed adaptive emotion regulation strategy. METHODS: Here we report on the efficacy of longitudinal training in cognitive reappraisal to enhance emotion regulation in borderline patients. Specifically, the training targeted psychological distancing, a reappraisal tactic whereby negative stimuli are viewed dispassionately as though experienced by an objective, impartial observer. At each of 5 sessions over 2 weeks, 22 borderline (14 Female) and 22 healthy control (13 Female) participants received training in psychological distancing and then completed a widely-used picture-based reappraisal task. Self-reported negative affect ratings and functional magnetic resonance imaging (fMRI) data were acquired at the first and fifth sessions. In addition to behavioral analyses, we performed whole-brain pattern expression analyses using independently-defined patterns for negative affect and cognitive reappraisal implementation for each session. RESULTS: Borderline patients showed a decrease in negative affect pattern expression following reappraisal training, reflecting a normalization in neural activity. They did not, however, show significant change in behavioral self-reports. CONCLUSIONS: To our knowledge, this study represents the first longitudinal fMRI examination of task-based cognitive reappraisal training. Using a brief, proof-of-concept design, the results suggest a potential role for reappraisal training in the treatment of borderline patients.

Study of the antivirus function mediated by STING in Micropterus salmoides.

Stimulator of interferon genes (STING) has been demonstrated as a critical mediator in the innate immune response to cytosolic DNA and RNA derived from different pathogens. While the role of Micropterus salmoides STING (MsSTING) in largemouth bass virus is still unknown. In this study, RT-qPCR assay and Western-blot assay showed that the expression levels of MsSTING and its downstream genes were up-regulated after LMBV infection. Pull down experiment proved that a small peptide called Fusion peptide (FP) that previously reported to target to marine and human STING as a selective inhibitor also interacted with MsSTING in vitro. Comparing with the RNA-seq of Largemouth bass infected with LMBV singly, 326 genes were significantly up-regulated and 379 genes were significantly down-regulated in the FP plus LMBV group in which Largemouth bass was treatment with FP before LMBV-challenged. KEGG analysis indicated that the differentially expressed genes (DEGs) were mainly related to signaling transduction, infectious disease viral, immune system and endocrine system. Besides, the survival rate of LMBV-infected largemouth bass was highly decreased following FP treatment. Taken together, our study showed that MsSTING played an important role in immune response against LMBV infection.

Engineering Phage Nanocarriers Integrated with Bio-Intelligent Plasmids for Personalized and Tunable Enzyme Delivery to Enhance Chemodynamic Therapy.

Customizable and number-tunable enzyme delivery nanocarriers will be useful in tumor therapy. Herein, a phage vehicle, T4-Lox-DNA-Fe (TLDF), which adeptly modulates enzyme numbers using phage display technology to remodel the tumor microenvironment (TME) is presented. Regarding the demand for lactic acid in tumors, each phage is engineered to display 720 lactate oxidase (Lox), contributing to the depletion of lactic acid to restructure the tumor's energy metabolism. The phage vehicle incorporated dextran iron (Fe) with Fenton reaction capabilities. H2O2 is generated through the Lox catalytic reaction, amplifying the H2O2 supply for dextran iron-based chemodynamic therapy (CDT). Drawing inspiration from the erythropoietin (EPO) biosynthetic process, an EPO enhancer is constructed to impart the EPO-Keap1 plasmid (DNA) with tumor hypoxia-activated functionality, disrupting the redox homeostasis of the TME. Lox consumes local oxygen, and positive feedback between the Lox and the plasmid promotes the expression of kelch ECH Associated Protein 1 (Keap1). Consequently, the downregulation of the antioxidant transcription factor Nrf2, in synergy with CDT, amplifies the oxidative killing effect, leading to tumor suppression of up to 78%. This study seamlessly integrates adaptable T4 phage vehicles with bio-intelligent plasmids, presenting a promising approach for tumor therapy.

Bacterial Biohybrids for Invasion of Tumor Cells Promote Antigen Cross-Presentation Through Gap Junction.

Due to inherent differences in cellular composition and metabolic behavior with host cells, tumor-harbored bacteria can discriminatorily affect tumor immune landscape. However, the mechanisms by which intracellular bacteria affect antigen presentation process between tumor cells and antigen-presenting cells (APCs) are largely unknown. The invasion behavior of attenuated Salmonella VNP20009 (VNP) into tumor cells is investigated and an attempt is made to modulate this behavior by modifying positively charged polymers on the surface of VNP. It is found that non-toxic chitosan oligosaccharide (COS) modified VNP (VNP@COS) bolsters the formation of gap junction between tumor cells and APCs by enhancing the ability of VNP to infect tumor cells. On this basis, a bacterial biohybrid is designed to promote in situ antigen cross-presentation through intracellular bacteria induced gap junction. This bacterial biohybrid also enhances the expression of major histocompatibility complex class I molecules on the surface of tumor cells through the incorporation of Mdivi-1 coupled with VNP@COS. This strategic integration serves to heighten the immunogenic exposure of tumor antigens; while, preserving the cytotoxic potency of T cells. A strategy is proposed to precisely controlling the function and local effects of microorganisms within tumors.

First report of Fusarium commune Causing Bulb Rot on Lily (Lilium brownii var. Viridulum Baker) in Hunan Province of China.

Lily (Lilium brownii var. Viridulum Baker) is a well-known edible plant with large, white and sweet bulb scales that has important medicinal value (Zhou et al. 2021) and is grown mainly in the Hebei, Shanxi and Henan provinces of China. In May 2021, a case of bulb rot was discovered in a 3.33 hm2 plantation in Huaihua, Hunan Province, affecting 20% of the area (27°59'30″N, 110°32'20″E). The disease is most severe during the rainy season in May and June. In the early stage, irregular brown spots appeared on the lily scales, the necrosis was depressed and gradually enlarges, and in the later stage, the scales were scattered from the base of the disc and slough off. Ten samples were taken randomly from different plants in the plantation area to isolate the pathogens. After washing with sterile water, they were cut into small pieces and sterilised with 3% hydrogen peroxide for 30 s, 75% ethanol for 90 s, rinsed three times with sterile water and dried on sterile filter paper, then placed on a water agar plate and incubated in the dark in a constant temperature incubator at 28℃ for 3 to 5 days. After 2 days, the mycelium at the edge of the colony was transferred to a PDA plate and incubated for 3-5 days at 28°C in the dark to obtain pure fungal isolates. Eighteen purified fungal isolates were obtained, of which sixteen looked like Fusarium (88.9% isolation rate) and three representative isolates (BHBR2, BHBR3 and BHBR5) were selected for further study. The surface of this fungus was white with dense aerial mycelium. Some had an orange centre in the medium. Microconidia were oval in shape and appeared either straight or slightly curved. These microconidia were colourless, had 0-1 septa and measured 3.334 to 14.724 × 2.216 to 5.385 µm (n=100). Macroconidia were predominantly three-septate, crescent-shaped structures that were thin-walled and slightly curved. Cells at the apex and base were similarly curved. Macroconidia measured 17.956 to 32.150 × 2.788 to 4.492 µm (n=100). The mitochondrial small subunit (mtSSU) and translation elongation factor 1-α (TEF1) genes were amplified and sequenced using the NMS1/NMS2 and TEF-R/TEF-F primers to verify the identity of the pathogens (Stewart et al. 2006). The sequences were submitted to GenBank (BHBR2: mtSSU, PP273435; TEF, OR900976; BHBR3: mtSSU, PP277729; TEF, OR900977; BHBR5: mtSSU, PP277728; TEF, OR900978). A concatenated phylogenetic tree of the two genes was constructed and analysis showed that BHBR2, BHBR3 and BHBR5 were significantly clustered with Fusarium commune. Based on the results of morphological identification and phylogenetic tree analysis, the three isolates were identified as Fusarium commune. We carried out pathogenicity tests using two methods, one in which 6 × 6 mm fungal blocks were inoculated on lily (L. brownie var. viridulum Baker) scales and controls inoculated with sterile blocks, and the other in which strain BHBR2 was selected to carry out pathogenicity tests on bulbs of live plants soaked with 50 ml of a 1 × 106 conidial suspension and bulbs of control plants soaked with sterile water, all in three replicates. They were placed in a growth chamber at 28°C and 80% relative humidity, and the scales were moistened with moistened sterile filter paper. After 3 days of rearing treated scales, lesions appeared on lily scales inoculated with mycelial blocks and expanded with time, whereas no lesions appeared on lily scales inoculated with sterile blocks. One month later, whole plants soaked in the spore suspension wilted, while the control plants grew well. The pathogens re-isolated from the diseased tissues had the same morphological characteristics as representative isolates. This confirms Koch's hypothesis. Fusarium commune has been shown to be the most important pathogenic fungus causing root rot in Alfalfa (Medicago sativa) (Yang et al. 2022) and blueberry (Vaccinium uliginosum L.) (Li et al. 2023) in China. To our knowledge, this is the first report of Fusarium commune causing lily bulb rot in the world, which will lay the foundation for future control of lily bulb rot.

The mechanism governing the formation of intermolecular charge transfer bands: a series of polyoxomolybdates as a case study.

A series of proof-of-concept models of polyoxomolybdates with different protonated disubstituted aniline counterions and the same ß-Mo8O26 polyanion were synthesized to study the mechanism governing the formation of the intermolecular charge transfer (inter-CT) band.

Self-Delivery Nanoplatform Based on Amphiphilic Apoptosis Peptide for Precise Mitochondria-Targeting Photothermal Therapy.

Mitochondria-targeting photothermal therapy could significantly enhance the tumor cell killing effect. However, since therapeutic reagents need to overcome a series of physiological obstacles to arrive at mitochondria accurately, precise mitochondria-targeting photothermal therapy still faces great challenges. In this study, we developed a self-delivery nanoplatform that specifically targeted the mitochondria of tumor cells for precise photothermal therapy. Photothermal agent IR780 was encapsulated by amphiphilic apoptotic peptide KLA with mitochondria-targeting ability to form nanomicelle KI by self-assembly through hydrophilic and hydrophobic interactions. Subsequently, negatively charged tumor-targeting polymer HA was coated on the surface of KI through electrostatic interactions, to obtain tumor mitochondria-targeting self-delivery nanoplatform HKI. Through CD44 receptor-mediated recognition, HKI was internalizated by tumor cells and then disassembled in an acidic environment with hyaluronidase in endosomes, resulting in the release of apoptotic peptide KLA and photothermal agent IR780 with mitochondria anchoring capacity, which achieved precise mitochondria guidance and destruction. This tumor mitochondria-targeting self-delivery nanoplatform was able to effectively deliver photothermal agents and apoptotic peptides to tumor cell mitochondria, resulting in precise destruction to mitochondria and enhancing tumor cell inhibition at the subcellular organelle level.

Asymptomatic low-grade appendiceal mucinous neoplasm: A case report.

BACKGROUND: Low-grade appendiceal neoplasms (LAMN) are characterized by low incidence and atypical clinical presentations, often leading to misdiagnosis as acute or chronic appendicitis before surgery. The primary diagnostic tool for LAMN is abdominal computed tomography (CT) imaging. Surgical resection remains the cornerstone of LAMN management, necessitating en bloc tumor excision to minimize the risk of iatrogenic rupture. Laparoscopy, known for its minimal invasiveness, reduced postoperative discomfort, and expedited recovery, is a safe and reliable approach for LAMN treatment. Despite the possibility of pseudomyxoma peritonei development, appendectomy and partial appendectomy generally result in negative tumor margins and favorable outcomes, which can be attributed to the disease's slow growth and lower malignancy. CASE SUMMARY: A 71-year-old male patient was admitted to our hospital with a pelvic space-occupying lesion detected 1 mo prior. Physical examination showed a soft abdomen without tenderness or rebound and no palpable masses. No shifting dullness was noted, and digital rectal examination revealed no palpable mass. Enteroscopy revealed a raised, smooth-surfaced mass measuring 3.0 cm in the cecum. Abdominal contrast-enhanced CT showed a markedly thickened and dilated appendix with visible cystic shadows. Laparoscopic surgery was performed and revealed a significantly dilated appendix, leading to laparoscopic resection of the appendix and part of the cecum. Post-surgical pathologic analysis confirmed LAMN. The patient received symptomatic and supportive post-operative care and was discharged on postoperative day 4 without complications such as abdominal bleeding, intestinal obstruction, or incision infection. No tumor recurrence was observed during a 7-mo follow-up period. CONCLUSION: LAMN is a rare disease that lacks specific clinical manifestations. Abdominal CT plays a crucial role in diagnosing LAMN, and laparoscopic surgery is a safe and effective diagnostic and therapeutic approach.

Neural specialization with generalizable representations underlies children's cognitive development of attention.

From childhood to adulthood, the human brain develops highly specialized yet interacting neural modules that give rise to nuanced attention and other cognitive functions. Each module can specialize over development to support specific functions, yet also coexist in multiple neurobiological modes to support distinct processes. Advances in cognitive neuroscience have conceptualized human attention as a set of cognitive processes anchored in highly specialized yet interacting neural systems. The underlying mechanisms of how these systems interplay to support children's cognitive development of multiple attention processes remain unknown. Leveraging developmental functional magnetic resonance imaging with attention network test paradigm, we demonstrate differential neurocognitive development of three core attentional processes from childhood to adulthood, with alerting reaching adult-like level earlier, followed by orienting and executive attention with more protracted development throughout middle and late childhood. Relative to adults, young children exhibit immature specialization with less pronounced dissociation of neural systems specific to each attentional process. Children manifest adult-like distributed representations in the ventral attention and cingulo-opercular networks, but less stable and weaker generalizable representations across multiple processes in the dorsal attention network. Our findings provide insights into the functional specialization and generalization of neural representations scaffolding cognitive development of core attentional processes from childhood to adulthood. (PsycInfo Database Record (c) 2024 APA, all rights reserved).

Impact of Ganoderma lucidum fermentation on the nutritional composition, structural characterization, metabolites, and antioxidant activity of Soybean, sweet potato and Zanthoxylum pericarpium residues.

One of the major issues in the food sector is the lack of resource utilization and the contamination of the environment caused by by-products. This study aimed to investigate the effects of Ganoderma lucidum (GL) fermentation on the nutritional components, structural characterization, metabolites, and antioxidant activity of soybean residue (SR), sweet potato residue (SPR), and zanthoxylum pericarpium residue (ZPR). The results showed that the nutrient contents of SR, SPR and ZPR increased. The active substances, amino acids (umami, aromatic and basic), metabolites and antioxidant activity (DPPH, ABTS, FRAP) (SR and SPR increased by 11.43, 32.64, 40.19 µmol Trolox/100 g and 19.29, 17.7, 32.35 µmol Trolox/100 g, respectively) of SR and SPR were increased. However, the results of ZPR showed a decrease in the content of bioactive substances, amino acids, and antioxidant activity. The results show that using GL fermentation can provide novel ideas and theoretical basis for improving SR and SPR to obtain new raw materials for antioxidant products.

Carbon dioxide production index (VCO2i) predicts hyperlactatemia during cardiopulmonary bypass in pediatric carDiac surGery (pGDP- VCO2i): Study protocol for a nested case-control trial.

BACKGROUND: Hyperlactatemia (HL) during cardiopulmonary bypass (CPB) is relatively frequent in infants and associates with increased morbidity and mortality. Studies on adults have shown that carbon dioxide production index (VCO2i) during CPB is linked to the occurrence of HL, with 'critical thresholds' for VCO2i reported to be 60 mL/min/m2. However, considering infants have a higher metabolic rate and lower tolerance to hypoxia, the critical threshold of VCO2i in infants cannot be replied to the existing adults' standards. The objective of this study is to investigate the association of VCO2i during CPB and HL, and explore the critical VCO2i threshold during CPB in infants. METHODS: VCO2i predicts hyperlactatemia during cardiopulmonary bypass in pediatric cardiac surgery (pGDP-VCO2i) is a nested case-control study. A cohort of consecutive pediatric patients of less than 3 years of age, undergoing congenital cardiac surgeries between May 2021 and December 2023 in West China Hospital will be enrolled. The VCO2i levels of each patient will be recorded every 5 min during CPB. The primary outcome is the rate of HL. The infants will be divided into two groups based on the presence or not of HL. Pre- and intraoperative factors will be tested for independent association with HL. Then, we will make an analysis, and the critical value of VCO2i will be obtained. The postoperative outcome of patients with or without HL will be compared. DISCUSSION: This will be the first trial to investigate the association of VCO2i during CPB and HL, and explore the critical VCO2i threshold during CPB in pediatrics. The results of this study are expected to lay a foundation for clinical application of goal-directed perfusion (GDP) management strategy, and optimize the perfusion strategy and improve the prognosis of pediatric patients undergoing cardiac surgery. TRIAL REGISTRATION: Chictr.org.cn, ChiCTR2100044296 on 16 March 2021.

Advances of Photothermal Agents with Fluorescence Imaging/Enhancement Ability in the Field of Photothermal Therapy and Diagnosis.

Photothermal therapy (PTT) is an effective cancer treatment method. Due to its easy focusing and tunability of the irradiation light, direct and accurate local treatment can be performed in a noninvasive manner by PTT. This treatment strategy requires the use of photothermal agents to convert light energy into heat energy, thereby achieving local heating and triggering biochemical processes to kill tumor cells. As a key factor in PTT, the photothermal conversion ability of photothermal agents directly determines the efficacy of PTT. In addition, photothermal agents generally have photothermal imaging (PTI) and photoacoustic imaging (PAI) functions, which can not only guide the optimization of irradiation conditions but also achieve the integration of disease diagnosis. If the photothermal agents have function of fluorescence imaging (FLI) or fluorescence enhancement, they can not only further improve the accuracy in disease diagnosis but also accurately determine the tumor location through multimodal imaging for corresponding treatment. In this paper, we summarize recent advances in photothermal agents with FLI or fluorescence enhancement functions for PTT and tumor diagnosis. According to the different recognition sites, the application of specific targeting photothermal agents is introduced. Finally, limitations and challenges of photothermal agents with fluorescence imaging/enhancement in the field of PTT and tumor diagnosis are prospected.

RGDAN: A random graph diffusion attention network for traffic prediction.

Traffic Prediction based on graph structures is a challenging task given that road networks are typically complex structures and the data to be analyzed contains variable temporal features. Further, the quality of the spatial feature extraction is highly dependent on the weight settings of the graph structures. In the transportation field, the weights of these graph structures are currently calculated based on factors like the distance between roads. However, these methods do not take into account the characteristics of the road itself or the correlations between different traffic flows. Existing approaches usually pay more attention to local spatial dependencies extraction while global spatial dependencies are ignored. Another major problem is how to extract sufficient information at limited depth of graph structures. To address these challenges, we propose a Random Graph Diffusion Attention Network (RGDAN) for traffic prediction. RGDAN comprises a graph diffusion attention module and a temporal attention module. The graph diffusion attention module can adjust its weights by learning from data like a CNN to capture more realistic spatial dependencies. The temporal attention module captures the temporal correlations. Experiments on three large-scale public datasets demonstrate that RGDAN produces predictions with 2%-5% more precision than state-of-the-art methods.

Efficacy and Safety of Ketamine to Treat Cancer Pain in Adult Patients: A Systematic Review.

CONTEXT: Ketamine is a well-characterized anesthetic agent, and subanesthetic ketamine possesses analgesic effects in both acute and chronic pain. OBJECTIVES: A systematic review was performed to ascertain the efficacy and safety of ketamine in treating pain for cancer patients. METHODS: Eight databases were searched from the inception to March 20th, 2023 to obtain randomized controlled trials (RCTs) on ketamine for treating pain in cancer patients. Two reviewers independently screened studies, extracted the data and assessed the risk of bias of included studies; then, meta-analysis was performed by using Revman 5.3 software and Stata 14.0 software. RESULTS: Thirty-five studies were included, involving 2279 patients with cancer pain. The results of meta-analysis showed that ketamine could significantly reduce pain intensity. Subgroup analysis revealed that, when compared with control group, ketamine decreased markedly visual analogue scale (VAS) scores in two days after the end of treatment with ketamine, and ketamine administrated by patient controlled epidural analgesia (PCEA) was effective. Meanwhile, ketamine could significantly reduce the number of patient-controlled analgesia (PCA) compressions within 24 hours and morphine dosage. Ketamine could not decrease Ramsay sedation score. Additionally, the adverse events significantly decreased in the ketamine group, including nausea and vomiting, constipation, pruritus, lethargy, uroschesis, hallucination, and respiratory depression. In addition, compared with the control group, ketamine could reduce Hamilton depression scale (HAMD) score and relieve depressive symptoms. CONCLUSION: Ketamine may be used as an effective therapy to relieve cancer pain. However, more rigorously designed RCTs with larger sample sizes are required to verify the above conclusions.

Ultrasmall Bi/Cu Coordination Polymer Combined with Glucose Oxidase for Tumor Enhanced Chemodynamic Therapy by Starvation and Photothermal Treatment.

Multi-modal combination therapy for tumor is expected to have superior therapeutic effect compared with monotherapy. In this study, a super-small bismuth/copper-gallic acid coordination polymer nanoparticle (BCN) protected by polyvinylpyrrolidone is designed, which is co-encapsulated with glucose oxidase (GOX) by phospholipid to obtain nanoprobe BCGN@L. It shows that BCN has an average size of 1.8 ± 0.7 nm, and photothermal conversion of BCGN@L is 31.35% for photothermal imaging and photothermal therapy (PTT). During the treatment process of 4T1 tumor-bearing nude mice, GOX catalyzes glucose in the tumor to generate gluconic acid and hydrogen peroxide (H2 O2 ), which reacts with copper ions (Cu2+ ) to produce toxic hydroxyl radicals (•OH) for chemodynamic therapy (CDT) and new fresh oxygen (O2 ) to supply to GOX for further catalysis, preventing tumor hypoxia. These reactions increase glucose depletion for starvation therapy , decrease heat shock protein expression, and enhance tumor sensitivity to low-temperature PTT. The in vitro and in vivo results demonstrate that the combination of CDT with other treatments produces excellent tumor growth inhibition. Blood biochemistry and histology analysis suggests that the nanoprobe has negligible toxicity. All the positive results reveal that the nanoprobe can be a promising approach for incorporation into multi-modal anticancer therapy.

UGT1A1 genotype-guided irinotecan dosing during neoadjuvant chemoradiotherapy for locally advanced rectal cancer: A prospective analysis of SN-38 concentration.

Irinotecan plays a crucial role in the neoadjuvant chemoradiotherapy (nCRT) of rectal cancer, but its optimal dosing is still unclear. In this study, we included 101 eligible patients with the UGT1A1*28 genotype of UGT1A1*1*1 (74.3%) and UGT1A1*1*28 (25.7%) and UGT1A1*6 genotypes of GG (63.4%), GA (32.7%), and AA (3.9%). All patients received preoperative radiotherapy (50 Gy/25 fractions) with concurrent irinotecan (UGT1A1*1*1: 80 mg/m2 ; UGT1A1*1*28: 65 mg/m2 ) and capecitabine (CapIri). SN-38 concentrations were measured at 1.5, 24, and 49 h post-administration. Patients were divided into four groups (Q1-Q4) based on the SN-38 concentration. The complete-response (CR) rate was the primary endpoint. The analysis demonstrated that the 49 h SN-38 concentration was relatively optimal for predicting efficacy and toxicity. The Q4 group had a significantly higher CR rate than the Q1 group (p = .019), but also higher rates of adverse events (p = .009). We screened the recommended 49 h SN-38, with a 0.5-1.0 ng/mL concentration range. We also validated the correlation between UGT1A1*6 polymorphism and SN-38 concentration, along with the clinical efficacy of irinotecan. In conclusion, our study identified the relatively optimal timepoint and concentration range for monitoring SN38 concentrations and revealed the clinical significance of UGT1A1*6 and UGT1A1*28 polymorphisms in guiding irinotecan administration, offering meaningful insights for personalised irinotecan dosing.

Association between inflammatory bowel disease and risk of stroke: a systematic review and meta-analysis of cohort studies.

Background/objectives: Recently, four meta-analyses have explored the association between inflammatory bowel disease (IBD) and the risk of stroke. These studies have demonstrated that people with IBD may be at an increased risk of stroke. However, some limitations such as high heterogeneity and the lack of uniformity in the types of research, especially the reuse of some sample sizes, cannot be neglected. These factors reduce the credibility of their research conclusions. Therefore, we conducted a meta-analysis to explore this possible association. Methods: PubMed, Embase, and Web of Science were searched from inception to 30 June 2023. A random effects model with the generic inverse variance method was used in this meta-analysis. The Review Manager software was used to obtain all relative risks (RRs) and their 95% confidence intervals (CIs). Publication bias was tested, and sensitivity and subgroup analyses were conducted to explore possible heterogeneities. Results: This meta-analysis included 12 cohort studies (involving 4,495,055 individuals). Meta-analysis of these data has shown that IBD was associated with an increased risk of stroke (RR = 1.19, 95%CI:1.14-1.24, p < 0.00001). Our results were stable and robust in subgroup and sensitivity analyses. Conclusions: Our results suggest that IBD is associated with an increased risk of stroke. To reduce the incidence of stroke, patients with IBD are encouraged to undergo stroke risk assessments, especially for young female patients; assessing the risk of ischemic stroke is of particular importance. Prospective studies considering stroke subtypes, IBD severity and treatments, regions, and other confounding factors are needed to further explore the nature of each association. Systematic review registration: https://www.crd.york.ac.uk/PROSPERO/, identifier CRD42022373656.

A pyroptosis-related signature in colorectal cancer: exploring its prognostic value and immunological characteristics.

Background: The heterogeneity of colorectal cancer (CRC) is the main cause of the disparity of drug sensitivity and the variability of prognosis. Pyroptosis is closely associated with the development and prognosis of various tumors, including CRC. Dividing CRC into distinct subgroups based on pyroptosis is a worthwhile topic for improving the precision treatment and prognosis prediction of CRC. Methods: We classified patients into two clusters using the consensus clustering based on the pyroptosis-related genes (PRGs). Next, the prognostic signature was developed with LASSO regression analysis using the screened genes from differentially expressed genes (DEGs) by univariate and multivariate Cox analyses. According to the pyroptosis-related score (PR score) calculated with the signature, patients belonged to two groups with distinct prognosis. Moreover, we assessed the immune profile to explore the relationship between the signature and immunological characteristics. Two single cell sequencing databases were adopted for further exploration of tumor immune microenvironment (TME). In addition, we applied our own cohort and Drugbank to explore the correlation of the signature and clinical therapies. We also studied the expression of key genes by immunohistochemistry. Results: The signature performed well in predicting the prognosis of CRC as the high area under curve (AUC) value demonstrated. Patients with a higher PR score had poorer prognosis and higher expression of immune checkpoints but more abundant infiltration of immune cells. Combining with the indicator of therapeutic analysis, they might benefit more from immune checkpoint blockade (ICB) and neo-adjuvant chemoradiotherapy (nCRT). Conclusion: In conclusion, our study is based on genomics and transcriptomics to investigate the role of PRGs in CRC. We have established a prognostic signature and integrated single-cell data to study the relationship between the signature with the TME in CRC. Its clinical application in reliable prediction of prognosis and personalized treatment was validated by public and own sequencing cohort. It provided a new insight for the personalized treatment of CRC.