A small molecule MST1/2 inhibitor accelerates murine liver regeneration with improved survival in models of steatohepatitis.

Dysfunctional liver regeneration following surgical resection remains a major cause of postoperative mortality and has no therapeutic options. Without targeted therapies, the current treatment paradigm relies on supportive therapy until homeostasis can be achieved. Pharmacologic acceleration of regeneration represents an alternative therapeutic avenue. Therefore, we aimed to generate a small molecule inhibitor that could accelerate liver regeneration with an emphasis on diseased models, which represent a significant portion of patients who require surgical resection and are often not studied. Utilizing a clinically approved small molecule inhibitor as a parent compound, standard medicinal chemistry approaches were utilized to generate a small molecule inhibitor targeting serine/threonine kinase 4/3 (MST1/2) with reduced off-target effects. This compound, mCLC846, was then applied to preclinical models of murine partial hepatectomy, which included models of diet-induced metabolic dysfunction-associated steatohepatitis (MASH). mCLC846 demonstrated on target inhibition of MST1/2 and reduced epidermal growth factor receptor inhibition. The inhibitory effects resulted in restored pancreatic beta-cell function and survival under diabetogenic conditions. Liver-specific cell-line exposure resulted in Yes-associated protein activation. Oral delivery of mCLC846 perioperatively resulted in accelerated murine liver regeneration and improved survival in diet-induced MASH models. Bulk transcriptional analysis of regenerating liver remnants suggested that mCLC846 enhanced the normal regenerative pathways and induced them following liver resection. Overall, pharmacological acceleration of liver regeneration with mCLC846 was feasible, had an acceptable therapeutic index, and provided a survival benefit in models of diet-induced MASH.

STAMENLESS1 activates SUPERWOMAN 1 and FLORAL ORGAN NUMBER 1 to control floral organ identities and meristem fate in rice.

Floral patterns are unique to rice and contribute significantly to its reproductive success. SL1 encodes a C2H2 transcription factor that plays a critical role in flower development in rice, but the molecular mechanism regulated by it remains poorly understood. Here, we describe interactions of the SL1 with floral homeotic genes, SPW1, and DL in specifying floral organ identities and floral meristem fate. First, the sl1 spw1 double mutant exhibited a stamen-to-pistil transition similar to that of sl1, spw1, suggesting that SL1 and SPW1 may located in the same pathway regulating stamen development. Expression analysis revealed that SL1 is located upstream of SPW1 to maintain its high level of expression and that SPW1, in turn, activates the B-class genes OsMADS2 and OsMADS4 to suppress DL expression indirectly. Secondly, sl1 dl displayed a severe loss of floral meristem determinacy and produced amorphous tissues in the third/fourth whorl. Expression analysis revealed that the meristem identity gene OSH1 was ectopically expressed in sl1 dl in the fourth whorl, suggesting that SL1 and DL synergistically terminate the floral meristem fate. Another meristem identity gene, FON1, was significantly decreased in expression in sl1 background mutants, suggesting that SL1 may directly activate its expression to regulate floral meristem fate. Finally, molecular evidence supported the direct genomic binding of SL1 to SPW1 and FON1 and the subsequent activation of their expression. In conclusion, we present a model to illustrate the roles of SL1, SPW1, and DL in floral organ specification and regulation of floral meristem fate in rice.

Effective substances and molecular mechanisms guided by network pharmacology: An example study of Scrophulariae Radix treatment of hyperthyroidism and thyroid hormone-induced liver and kidney injuries.

ETHNOPHARMACOLOGICAL RELEVANCE: Scrophulariae Radix (Xuanshen [XS]) has been used for several years to treat hyperthyroidism. However, its effective substances and pharmacological mechanisms in the treatment of hyperthyroidism and thyroid hormone-induced liver and kidney injuries have not yet been elucidated. AIM OF THE STUDY: This study aimed to explore the pharmacological material basis and potential mechanism of XS therapy for hyperthyroidism and thyroid hormone-induced liver and kidney injuries based on network pharmacology prediction and experimental validation. MATERIALS AND METHODS: Based on 31 in vivo XS compounds identified using ultra-performance liquid chromatography tandem quadruple exactive orbitrap high-resolution accurate-mass spectrometry (UPLC-QE-HRMS), a network pharmacology approach was used for mechanism prediction. Systematic networks were constructed to identify the potential molecular targets, biological processes (BP), and signaling pathways. A component-target-pathway network was established. Mice were administered levothyroxine sodium through gavage for 30 d and then treated with different doses of XS extract with or without propylthiouracil (PTU) for 30 d. Blood, liver, and kidney samples were analyzed using an enzyme-linked immunosorbent assay (ELISA) and western blotting. RESULTS: A total of 31 prototypes, 60 Phase I metabolites, and 23 Phase II metabolites were tentatively identified in the plasma of rats following the oral administration of XS extract. Ninety-six potential common targets between the 31 in vivo compounds and the diseases were identified. Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis revealed that Bcl-2, BAD, JNK, p38, and ERK1/2 were the top targets. XS extract with or without PTU had the following effects: inhibition of T3/T4/fT3/fT4 caused by levothyroxine; increase of TSH levels in serum; restoration of thyroid structure; improvement of liver and kidney structure and function by elevating the activities of anti-oxidant enzymes catalase (CAT),superoxide dismutase (SOD), and glutathione peroxidase (GSH-Px); activation anti-apoptotic proteins Bcl-2; inhibition the apoptotic protein p-BAD; downregulation inflammation-related proteins p-ERK1/2, p-JNK, and p-p38; and inhibition of the aggregation of pro-inflammatory cytokines TNF-α, IL-1ß, and IL-6, as well as immune cells in the liver. CONCLUSION: XS can be used to treat hyperthyroidism and liver and kidney injuries caused by thyroid hormones through its anti-oxidant, anti-inflammatory, and anti-apoptotic properties. In addition, serum pharmacochemical analysis revealed that five active compounds, namely 4-methylcatechol, sugiol, eugenol, acetovanillone, and oleic acid, have diverse metabolic pathways in vivo and exhibit potential as effective therapeutic agents.

Health-related quality of life and its influencing factors among lung cancer patients receiving immune checkpoint inhibitors: A cross-sectional study.

PURPOSE: The aim of this study was to examine the level of health-related quality of life (HRQOL) of lung cancer patients receiving immune checkpoint inhibitors (ICIs) and analyze its influencing factors. METHOD: A cross-sectional study was conducted. From April 2022 to March 2023, 560 lung cancer patients receiving ICIs at three medical bases in Guangzhou, China were recruited using a convenient sampling method. A general information questionnaire, the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire Core 30 (EORTC QLQ-C30), the Social Support Rating Scale (SSRS) and the Medical Coping Modes Questionnaire (MCMQ) were used for collecting data on sociodemographic and clinical characteristics, HRQOL, social support and medical coping mode. A descriptive analysis was conducted to describe HRQOL. Multiple regression analysis was applied to determine the factors influencing HRQOL. RESULTS: For lung cancer patients receiving ICIs, the mean score of HRQOL was 59.21 ± 19.86. Multivariate analysis indicated that acceptance-resignation coping mode (ß = -0.37, P < 0.01), Eastern Cooperative Oncology Group (ECOG) score (ß = -0.35, P < 0.01), combination of chemotherapy and/or bevacizumab (ß = -0.14, P < 0.01), and subjective support (ß = 0.07, P = 0.04) all contributed to 42.7% of the variance in HRQOL of the patients receiving ICIs. CONCLUSIONS: It is imperative to address and resolve the HRQOL issue for lung cancer patients receiving ICIs. The findings suggest nurse practitioners should be aware of a variety of factors that influence HRQOL and provide tailored inventions to patients as early as possible to help them achieve better HRQOL.

Application of diffusional kurtosis imaging for insights into structurally aberrant topology in Parkinson's disease.

BACKGROUND: Parkinson's disease (PD) has been regarded as a disconnection syndrome with functional and structural disturbances. However, as the anatomic determinants, the structural disconnections in PD have yet to be fully elucidated. PURPOSE: To non-invasively construct structural networks based on microstructural complexity and to further investigate their potential topological abnormalities in PD given the technical superiority of diffusion kurtosis imaging (DKI) to the quantification of microstructure. MATERIAL AND METHODS: The microstructural data of gray matter in both the PD group and the healthy control (HC) group were acquired using DKI. The structural networks were constructed at the group level by a covariation approach, followed by the calculation of topological properties based on graph theory and statistical comparisons between groups. RESULTS: A total of 51 patients with PD and 50 HCs were enrolled. Individuals were matched between groups with respect to demographic characteristics (P >0.05). The constructed structural networks in both the PD and HC groups featured small-world properties. In comparison with the HC group, the PD group exhibited significantly altered global properties, with higher normalized characteristic path lengths, clustering coefficients, local efficiency values, and characteristic path lengths and lower global efficiency values (P <0.05). In terms of nodal centralities, extensive nodal disruptions were observed in patients with PD (P <0.05); these disruptions were mainly distributed in the sensorimotor network, default mode network, frontal-parietal network, visual network, and subcortical network. CONCLUSION: These findings contribute to the technical application of DKI and the elucidation of disconnection syndrome in PD.

The study of variant s antigen expression revealing a novel c.160C>T (p.Arg54Cys) variant on GYPB*s allele associated with partial s phenotype.

BACKGROUND: Little s antigen is mainly defined by a single nucleotide polymorphism at c.143C (p.Thr48) on the GYPB gene. Several variants on GYPB can alter the expression of s antigen. The aim of this study was to investigate the molecular basis of variant s antigen expression in the Chinese population. STUDY DESIGN AND METHODS: A total of 4983 whole blood samples were collected to screen the individuals with discrepant s typing results using two different monoclonal anti-s. Then, the sequence of GYPB exon 4 was analyzed by Sanger sequencing. Flow cytometry analysis was performed to quantify s antigen expression on red blood cells (RBCs). In vitro expression study was performed to verify the effect of the GYPB variants identified on the expression of s antigen. RESULTS: Four donors were identified to have discrepant s typing results. Sanger sequencing showed that three donors carried the c.173C > G variant (p.Pro58Arg) specific for sD antigen, the other one carried a novel GYPB (c.160C > T, p.Arg54Cys) variant. Flow cytometry identified a partial and weak expression of s antigen on the RBCs of the four donors. Furthermore, in vitro expression study confirmed the effect of the two variants on the s antigen expression. CONCLUSION: The results demonstrated that in addition to p.Thr48, the two extra amino acids p.Arg54 and p.Pro58 are also important for full expression of s antigen. Since the individuals with partial s antigen are at risk for the development of alloanti-s, it is important to select at least two different monoclonal anti-s for correct s typing.

MR-Transformer: Multiresolution Transformer for Multivariate Time Series Prediction.

Multivariate time series (MTS) prediction has been studied broadly, which is widely applied in real-world applications. Recently, transformer-based methods have shown the potential in this task for their strong sequence modeling ability. Despite progress, these methods pay little attention to extracting short-term information in the context, while short-term patterns play an essential role in reflecting local temporal dynamics. Moreover, we argue that there are both consistent and specific characteristics among multiple variables, which should be fully considered for MTS modeling. To this end, we propose a multiresolution transformer (MR-Transformer) for MTS prediction, modeling MTS from both the temporal and the variable resolution. Specifically, for the temporal resolution, we design a long short-term transformer. We first split the sequence into nonoverlapping segments in an adaptive way and then extract short-term patterns within segments, while long-term patterns are captured by the inherent attention mechanism. Both of them are aggregated together to capture the temporal dependencies. For the variable resolution, besides the variable-consistent features learned by long short-term transformer, we also design a temporal convolution module to capture the specific features of each variable individually. MR-Transformer enhances the MTS modeling ability by combining multiresolution features between both time steps and variables. Extensive experiments conducted on real-world time series datasets show that MR-Transformer significantly outperforms the state-of-the-art MTS prediction models. The visualization analysis also demonstrates the effectiveness of the proposed model.

Human umbilical cord mesenchymal stem cells-derived exosomes exert anti-inflammatory effects on osteoarthritis chondrocytes.

Inflammation of chondrocytes plays a critical role in the occurrence and development of osteoarthritis (OA). Recent evidence indicated exosomes derived from mesenchymal stem cells (MSCs-Exos) exhibit excellent anti-inflammatory ability in many troublesome inflammatory diseases including OA. In the present study, we aimed to explore the role of human umbilical cord-derived MSCs-Exos (hUC-MSCs-Exos) in treating the inflammation of chondrocytes and its related mechanisms. Ultracentrifugation was applied to isolate hUC-MSCs-Exos from the culture supernatant of hUC-MSCs. Two OA-like in vitro inflammation models of human articular chondrocytes induced with interleukin 1ß (IL-1ß) and co-incubation with macrophage utilizing transwell cell culture inserts were both used to evaluate the anti-inflammatory effects of hUC-MSCs-Exos. The mRNA sequencing of chondrocytes after treatment and microRNA (miRNA) sequencing of hUC-MSCs-Exos were detected and analyzed for possible mechanism analysis. The results of the study confirmed that hUC-MSCs-Exos had a reversed effect of IL-1ß on chondrocytes in the expression of collagen type II alpha 1 (COL2A1) and matrix metalloproteinase 13 (MMP13). The addition of hUC-MSCs-Exos to M1 macrophages in the upper chamber showed down-regulation of IL-1ß and tumor necrosis factor α (TNF-α), up-regulation of IL-10 and arginase1 (ARG1), and reversed the gene and protein expression of COL2A1 and MMP13 of the chondrocytes seeded in the lower chamber. The results of this study confirmed the anti-inflammatory effects of hUC-MSCs-Exos in the human articular chondrocytes inflammation model. hUC-MSCs-Exos may be used as a potential cell-free treatment strategy for chondrocyte inflammation in OA.

Epidemiology of and factors associated with overall survival for patients with head and neck adenoid cystic carcinoma.

BACKGROUND: Updated epidemiologic and survival data of head and neck adenoid cystic carcinoma (HNACC) are lacking. This retrospective study aimed to clarify the incidence, prevalence, and overall survival (OS) of patients with HNACC and establish relevant nomogram. METHODS: Trends in incidence, limited-duration prevalence, and relative survival (RS) rates were evaluated using data from the Surveillance, Epidemiology, and End Results (SEER) database, and annual percent change (APC) in rates was calculated using joinpoint regression. Data on age, sex, site, stage, and surgery were used in construction and validation of the nomogram. RESULTS: The study included 6474 patients; 57.7% were female and 78.6% were white. The age-adjusted incidence rates of HNACC decreased significantly from 0.41 to 0.25 per 100,000 [1975-2018; average annual percent change (AAPC): - 1.37, P < 0.001], which was dominated by the localized stage. The 20-year limited duration prevalence increased from 0.00028% to 0.00262%. The 5- and 10-year RS rates of all HNACC patients were 80.0% and 65.5%, respectively. RS rates in HNACC showed a slight increase over time, with APC values of 0.03 for 5-year (P < 0.05) and 0.13 for 10-year (P < 0.05) RS. A prognostic model was constructed. The C-indices for the training and testing sets were both 0.734. The nomogram's discrimination efficiency was evaluated using the receiver operating characteristic curve and had moderate predictive power. CONCLUSIONS: Over the past 40 years, the incidence of HNACC decreased accompanied by slightly improved survival rates. Nomogram was capable of predicting the 5- and 10-year OS rates with moderate accuracy.

Effect of 3-Dimensional Imaging Device on Polyp and Adenoma Detection During Colonoscopy: A Randomized Controlled Trial.

INTRODUCTION: To evaluate the effect of 3-dimensional (3D) imaging device on polyp and adenoma detection during colonoscopy. METHODS: In a single-blind, randomized controlled trial, participants aged 18-70 years who underwent diagnostic or screening colonoscopy were consecutively enrolled between August 2019 and May 2022. Each participant was randomized in a 1:1 ratio to undergo either 2-dimensional (2D-3D) colonoscopy or 3D-2D colonoscopy through computer-generated random numbers. Primary outcome included polyp detection rate (PDR) and adenoma detection rate (ADR), defined as the proportion of individuals with at least 1 polyp or adenoma detected during colonoscopy. The primary analysis was intention-to-treat. RESULTS: Of 1,196 participants recruited, 571 in 2D-3D group and 583 in 3D-2D group were finally included after excluding those who met the exclusion criteria. The PDR between 2D and 3D groups was separately 39.6% and 40.5% during phase 1 (odds ratio [OR] = 0.96, 95% confidence interval [CI]: 0.76-1.22, P = 0.801), whereas PDR was significantly higher in 3D group (27.7%) than that of 2D group (19.9%) during phase 2, with a 1.54-fold increase (1.17-2.02, P = 0.002). Similarly, the ADR during phase 1 between 2D (24.7%) and 3D (23.8%) groups was not significant (OR = 1.05, 0.80-1.37, P = 0.788), while ADR was significantly higher in 3D group (13.8%) than that of 2D group (9.9%) during phase 2, with a 1.45-fold increase (1.01-2.08, P = 0.041). Further subgroup analysis confirmed significantly higher PDR and ADR of 3D group during phase 2, particularly in midlevel and junior endoscopists. DISCUSSION: The 3D imaging device could improve overall PDR and ADR during colonoscopy, particularly in midlevel and junior endoscopists. Trial number: ChiCTR1900025000.

DNA repair pathways-targeted cyclovirobuxine inhibits castration-resistant prostate cancer growth by promoting cell apoptosis and cycle arrest.

BACKGROUND: Castration-resistant prostate cancer (CRPC) is a deadly malignancy without effective therapeutics. Cyclovirobuxine (CVB) can play an anticancer role by inhibiting mitochondrial function, regulating tumor cell apoptosis, dysregulating autophagy, and other mechanisms. This study aimed to examine the function and mechanism of CVB in CRPC to provide new insights into CRPC treatment. METHODS: The effect of CVB on PC3 and C4-2 cell viability was determined using a CCK8 assay. Core therapeutic targets of CVB in CRPC cells were identified using RNA sequencing, online database, and PPI network analyses. Western blotting, RT-qPCR and molecular docking were performed to evaluate the regulation of core targets by CVB. Utilizing GO and KEGG enrichment analyses, the probable anti-CRPC mechanism of CVB was investigated. Immunofluorescence, flow cytometry and colony formation assays were used to verify the potential phenotypic regulatory role of CVB in CRPC. RESULTS: CVB inhibited CRPC cell activity in a concentration-dependent manner. Mechanistically, it primarily regulated BRCA1-, POLD1-, BLM-, MSH2-, MSH6- and PCNA-mediated mismatch repair, homologous recombination repair, base excision repair, Fanconi anemia repair, and nucleotide excision repair pathways. Immunofluorescence, Western blot, flow cytometry and colony formation experiments showed that CVB induced DNA damage accumulation, cell apoptosis, and cell cycle arrest and inhibited CRPC cell proliferation. CONCLUSION: CVB can induce DNA damage accumulation in CRPC cells by targeting DNA repair pathways and then induce cell apoptosis and cell cycle arrest, eventually leading to inhibition of the long-term proliferation of CRPC cells.

CDK2 and CDK4 targeted liensinine inhibits the growth of bladder cancer T24 cells.

Bladder cancer (BCa) is a urinary tumor with limited treatment options and high mortality. Liensinine (LIEN), a natural bisbenzylisoquinoline alkaloid, has shown excellent anti-tumor effects in numerous preclinical studies. However, the anti-BCa effect of LIEN remains unclear. To the best of our knowledge, this is the first study to investigate the molecular mechanism of LIEN in the management of BCa. First, we identified the treatment-related targets of BCa; those that repeatedly occur in more than two databases, including GeneCards, Online Mendelian Inheritance in Man, DisGeNET, Therapeutic Target Database, and Drugbank. The SwissTarget database was used to screen LIEN-related targets, and those with a probability >0 were possible LIEN targets. The prospective targets of LIEN in the treatment of BCa were then determined using a Venn diagram. Second, we discovered that the PI3K/AKT pathway and senescence mediated the anti-BCa action of LIEN by using GO and KEGG enrichment analysis to explore the function of LIEN therapeutic targets. A protein-protein interaction network was created using the String website, and six algorithms of the CytoHubba plug-in were then used in Cytoscape to assess the core targets of LIEN for the therapy of BCa. The outcomes of molecular docking and dynamics simulation demonstrated that CDK2 and CDK4 proteins were the direct targets of LIEN in the management of BCa, among which CDK2 was more stable in binding to LIEN than CDK4. Finally, in vitro experiments showed that LIEN inhibited the activity and proliferation of T24 cells. The expression of p-/AKT, CDK2, and CDK4 proteins progressively decreased, while the expression and fluorescence intensity of the senescence-related protein, γH2AX, gradually increased with increasing LIEN concentration in T24 cells. Therefore, our data suggest that LIEN may promote senescence and inhibit proliferation by inhibiting the CDK2/4 and PI3K/AKT pathways in BCa.

Heat shock protein 70 is involved in polaprezinc driven cell protection against Helicobacter pylori-induced injury.

Polaprezinc (PZ) plays a role in the protection of gastric mucosa and inhibiting Helicobacter pylori (H. pylori) growth in vitro. The objective of this study was to determine the protective effects of PZ on human gastric epithelial cells (GES-1) against H. pylori-induced damage, while also examining heat shock protein 70 (HSP70) as a potential underlying factor in this protection. Our findings revealed that PZ exerted bactericidal effects against H. pylori strains. We also observed that PZ mitigated the H. pylori-induced damage to GES-1 cells by increasing cell viability, reducing LDH release, and decreasing the secretion of pro-inflammatory factors such as MCP-1 and IL-6. Co-culturing PZ with GES-1 cells significantly up-regulated the GES-1 HSP70 expression in both a time and dose-dependent manner. Pre-incubating (for 12 h) or co-culturing (for 24 h) GES-1 cells with PZ reversed the down-regulation of HSP70 in GES-1 cells caused by H. pylori infection. However, when quercetin was used to inhibit the up-regulation of HSP70 in GES-1 cells, the protective effect of PZ on GES-1 cells was significantly reduced. Based on the results of this study, PZ exhibits a protective role on GES-1 cells against H. pylori injury, as well as a direct bactericidal effect on H. pylori. HSP70 is involved in the PZ-driven host cell protection against H. pylori injury. These findings provide insight into alternative strategies for H. pylori treatment.

Association between radiotherapy for surgically treated oral cavity cancer and secondary lung cancer.

Background: There is limited research on the incidence of secondary lung cancer (SLC) after radiotherapy (RT) for oral cavity cancer (OCC). Therefore, we investigated the association between RT for OCC and the risk of SLC and the overall survival of these patients. Methods: Patients diagnosed with OCC between 1975 and 2015 were selected from the Surveillance, Epidemiology, and End Results database. The cumulative incidence of SLC, relative risk (RR) of RT vs. no RT (NRT), standardized incidence ratios (SIR), and survival outcomes were assessed. Results: A total of 10,936 patients with OCC were included. Of these, 429 (3.92%) patients developed SLC, where 136 (5.02%) received RT and 293 (3.56%) did not. The cumulative incidence of SLC during follow-up was 6.89% and 4.84% in the RT and NRT patients, respectively. RT was associated with a higher risk of SLC. In the subset analysis, the results showed that a higher risk of developing SLC among patients with index OCC in most subgroups. Dynamic RR and SIR revealed a decreased risk of SLC with increasing latency time. No difference was observed in the 10-year survival rates for patients with SLC who received RT or not or compared with primary lung cancer. Conclusion: RT was associated with a higher risk of SLC, and patients diagnosed with OCC could be followed for 5-10 years after diagnosis.

Quantitative Methylation of Lignin Monomers Using Tetrabutylammonium Hydroxide and MeI and Applications in Organic Synthesis.

Efficient O-alkylation of phenols and carboxylic acids has essential applications in organic synthesis. A mild alkylation method for phenolic and carboxylic OH groups is developed using alkyl halides as alkylation reagents and tetrabutylammonium hydroxide as a base, and lignin monomers can be fully methylated in quantitative yields. Additionally, phenolic and carboxylic OH groups can be alkylated by different alkyl halides in one pot in different solvent systems.

The usefulness of fecal hemoglobin and calprotectin tests in diagnosing significant bowel diseases: a prospective study.

OBJECTIVES: Although colonoscopy remains the gold standard for determining bowel diseases, it's invasive and expensive. New non-invasive diagnostic methods are urgently needed as an initial screening modality. We aimed to investigate the value of fecal calprotectin (FC) and fecal immunochemical test (FIT) in differentiation of significant and non- significant bowel diseases. METHODS: In this prospective study, consecutive individuals were included if they underwent colonoscopy for symptoms of lower gastrointestinal (GI) tract, positive fecal occult blood test, surveillance for IBD or colorectal cancer (CRC) screening. Diagnostic value of FC and FIT in discriminating significant bowel diseases (advanced neoplasia, active inflammatory bowel diseases or bowel inflammation due to other causes) and non-significant bowel diseases (normal, asymptomatic diverticulum, non-adenomatous polyp, or non-advanced neoplasia) were evaluated. RESULTS: Among 201 individuals included, 107 patients had significant bowel diseases. FC and FIT had an area under the curve (AUC) of 0.722 (95% confidence interval [CI] 0.653-0.792) and 0.797 (95%CI 0.734-0.860), respectively, for determining significant bowel diseases. Combination of FC and FIT predicted significant bowel diseases with an AUC, sensitivity, specificity, and accuracy of 0.832 (95% CI 0.775-0.890), 77.6%, 74.5%, and 76.1%, respectively. Moreover, combination of FC and FIT was more sensitive among patients with lower GI symptoms than asymptomatic individuals (80.8% vs. 74.1%) to identify significant bowel diseases. CONCLUSIONS: A single measurement of FC or FIT is not sufficiently accurate to identify patients with significant bowel disease. However, combination of FC and FIT can help increase the sensitivity, especially in patients with lower GI symptoms.

Topological disruption of high-order functional networks in cognitively preserved Parkinson's disease.

AIMS: This study aimed to characterize the topological alterations and classification performance of high-order functional connectivity (HOFC) networks in cognitively preserved patients with Parkinson's disease (PD), relative to low-order FC (LOFC) networks. METHODS: The topological metrics of the constructed networks (LOFC and HOFC) obtained from fifty-one cognitively normal patients with PD and 60 matched healthy control subjects were analyzed. The discriminative abilities were evaluated using machine learning approach. RESULTS: The HOFC networks in the PD group showed decreased segregation and integration. The normalized clustering coefficient and small-worldness in the HOFC networks were correlated to motor performance. The altered nodal centralities (distributed in the precuneus, putamen, lingual gyrus, supramarginal gyrus, motor area, postcentral gyrus and inferior occipital gyrus) and intermodular FC (frontoparietal and visual networks, sensorimotor and subcortical networks) were specific to HOFC networks. Several highly connected nodes (thalamus, paracentral lobule, calcarine fissure and precuneus) and improved classification performance were found based on HOFC profiles. CONCLUSION: This study identified disrupted topology of functional interactions at a high level with extensive alterations in topological properties and improved differentiation ability in patients with PD prior to clinical symptoms of cognitive impairment, providing complementary insights into complex neurodegeneration in PD.

Triglyceride glucose index and Atherogenic index of plasma for predicting colorectal neoplasms in patients without cardiovascular diseases.

Background and aims: Colorectal neoplasms (CRN) include colorectal cancer (CRC) and colorectal adenoma (CRA). The relationship between CRN and triglyceride-glucose (TyG) index or between CRN and atherogenic index of plasma (AIP) is unclear. This study aims to investigate the roles of TyG index and AIP in predicting CRN in people without cardiovascular disease (CVD). Methods: 2409 patients without CVD underwent colonoscopy were enrolled. Clinical information and relevant laboratory test results of these patients were collected and recorded. According to endoscopic and pathological results, all participants were divided into a neoplasms group and a non-neoplasms group. The TyG index was calculated as ln (TGs×FPG/2), while AIP was calculated as log (TGs/HDL-C). We used uni- and multivariate logistic regression and restricted cubic spline (RCS) to analyze the association between the TyG inedx, AIP and CRN, develop predictive models and construct the nomograms. Receiver operating characteristic (ROC) curves were utilized to evaluate the predictive value for CRN. Results: Participants in the neoplasms group were more likely to be older, have higher TyG index, higher AIP and higher rates of fecal occult blood test positivity, and were more likely to be male, smokers and those with the family history of CRC (P < 0.05). The higher TyG index was related to the higher risk of CRN [OR (95% CI): 1.23 (1.08 - 1.41), P = 0.003]. The higher AIP was related to the higher risk of CRN [OR (95% CI): 1.55 (1.16 - 2.06), P = 0.003]. These two indicators are better for predicting CRN in women than men. The combined use of the TyG index and other independent risk factors (age, sex, smoking status, family history and FOBT) to distinguish CRN was effective, with a sensitivity of 61.0%, a specificity of 65.1% and an AUC of 0.669 (95%CI, 0.639 - 0.698). Likewise, the combined use of the AIP and other independent risk factors to distinguish CRN was also effective, the model had an overall 56.3% sensitivity and 68.7% specificity with an AUC of 0.667 (95%CI, 0.638 - 0.697). Conclusion: This study showed that the TyG index and the AIP might be biomarkers that could be used to predict the risk of CRN in patients without CVD.