Deoxycholic acid inducing chronic atrophic gastritis with colonic mucosal lesion correlated to mucosal immune dysfunction in rats.

The present study aimed to explore the underlying mechanism of bile reflux-inducing chronic atrophic gastritis (CAG) with colonic mucosal lesion. The rat model of CAG with colonic mucosal lesion was induced by free-drinking 20 mmol/L sodium deoxycholate to simulate bile reflux and 2% cold sodium salicylate for 12 weeks. In comparison to the control group, the model rats had increased abundances of Bacteroidetes and Firmicutes but had decreased abundances of Proteobacteria and Fusobacterium. Several gut bacteria with bile acids transformation ability were enriched in the model group, such as Blautia, Phascolarctobacter, and Enterococcus. The cytotoxic deoxycholic acid and lithocholic acid were significantly increased in the model group. Transcriptome analysis of colonic tissues presented that the down-regulated genes enriched in T cell receptor signaling pathway, antigen processing and presentation, Th17 cell differentiation, Th1 and Th2 cell differentiation, and intestinal immune network for IgA production in the model group. These results suggest that bile reflux-inducing CAG with colonic mucosal lesion accompanied by gut dysbacteriosis, mucosal immunocompromise, and increased gene expressions related to repair of intestinal mucosal injury.

Multiparametric mri-based radiomics nomogram for predicting lymph-vascular space invasion in cervical cancer.

PURPOSE: To develop and validate a multiparametric magnetic resonance imaging (mpMRI)-based radiomics model for predicting lymph-vascular space invasion (LVSI) of cervical cancer (CC). METHODS: The data of 177 CC patients were retrospectively collected and randomly divided into the training cohort (n=123) and testing cohort (n = 54). All patients received preoperative MRI. Feature selection and radiomics model construction were performed using max-relevance and min-redundancy (mRMR) and the least absolute shrinkage and selection operator (LASSO) on the training cohort. The models were established based on the extracted features. The optimal model was selected and combined with clinical independent risk factors to establish the radiomics fusion model and the nomogram. The diagnostic performance of the model was assessed by the area under the curve. RESULTS: Feature selection extracted the thirteen most important features for model construction. These radiomics features and one clinical characteristic were selected showed favorable discrimination between LVSI and non-LVSI groups. The AUCs of the radiomics nomogram and the mpMRI radiomics model were 0.838 and 0.835 in the training cohort, and 0.837 and 0.817 in the testing cohort. CONCLUSION: The nomogram model based on mpMRI radiomics has high diagnostic performance for preoperative prediction of LVSI in patients with CC.

The clinical and predictive value of 18F-FDG PET/CT metabolic patterns in a clinical Chinese cohort with autoimmune encephalitis.

AIMS: To investigate the diagnostic and predictive role of 18F-FDG PET/CT in patients with autoimmune encephalitis (AE) as a whole group. METHODS: Thrty-five patients (20 females and 15 males) with AE were recruited. A voxel-to-voxel semi-quantitative analysis based on SPM12 was used to analyze 18F-FDG PET/CT imaging data compared to healthy controls. Further comparison was made in different prognostic groups categorized by modified Rankin Scale (mRS). RESULTS: In total, 24 patients (68.6%) were tested positive neuronal antibodies in serum and/or CSF. Psychiatric symptoms and seizure attacks were major clinical symptoms. In the acute stage, 13 patients (37.1%) demonstrated abnormal brain MRI results, while 33 (94.3%) presented abnormal metabolism patterns. 18F-FDG PET/CT was more sensitive than MRI (p < 0.05). Patients with AE mainly presented mixed metabolism patterns compared to the matched controls, demonstrating hypermetabolism mainly in the cerebellum, BG, MTL, brainstem, insula, middle frontal gyrus, and relatively hypometabolism in the frontal cortex, occipital cortex, temporal gyrus, right parietal gyrus, left cingulate gyrus (p < 0.05, FWE corrected). After a median follow-up of 26 months, the multivariable analysis identified a decreased level of consciousness as an independent risk factor associated with poor outcome of AE (HR = 3.591, p = 0.016). Meanwhile, decreased metabolism of right superior frontal gyrus along with increased metabolism of the middle and upper brainstem was more evident in patients with poor outcome (p < 0.001, uncorrected). CONCLUSION: 18F-FDG PET/CT was more sensitive than MRI to detect neuroimaging abnormalities of AE. A mixed metabolic pattern, characterized by large areas of cortical hypometabolism with focal hypermetabolism was a general metabolic pattern. Decreased metabolism of right superior frontal gyrus with increased metabolism of the middle and upper brainstem may predict poor long-term prognosis of AE.

[68Ga]Ga­PSMA­617 PET-based radiomics model to identify candidates for active surveillance amongst patients with GGG 1-2 prostate cancer at biopsy.

PURPOSE: To develop a radiomics-based model using [68Ga]Ga-PSMA PET/CT to predict postoperative adverse pathology (AP) in patients with biopsy Gleason Grade Group (GGG) 1-2 prostate cancer (PCa), assisting in the selection of patients for active surveillance (AS). METHODS: A total of 75 men with biopsy GGG 1-2 PCa who underwent radical prostatectomy (RP) were enrolled. The patients were randomly divided into a training group (70%) and a testing group (30%). Radiomics features of entire prostate were extracted from the [68Ga]Ga-PSMA PET scans and selected using the minimum redundancy maximum relevance algorithm and the least absolute shrinkage and selection operator regression model. Logistic regression analyses were conducted to construct the prediction models. Receiver operating characteristic (ROC) curve, decision curve analysis (DCA), and calibration curve were employed to evaluate the diagnostic value, clinical utility, and predictive accuracy of the models, respectively. RESULTS: Among the 75 patients, 30 had AP confirmed by RP. The clinical model showed an area under the curve (AUC) of 0.821 (0.695-0.947) in the training set and 0.795 (0.603-0.987) in the testing set. The radiomics model achieved AUC values of 0.830 (0.720-0.941) in the training set and 0.829 (0.624-1.000) in the testing set. The combined model, which incorporated the Radiomics score (Radscore) and free prostate-specific antigen (FPSA)/total prostate-specific antigen (TPSA), demonstrated higher diagnostic efficacy than both the clinical and radiomics models, with AUC values of 0.875 (0.780-0.970) in the training set and 0.872 (0.678-1.000) in the testing set. DCA showed that the net benefits of the combined model and radiomics model exceeded those of the clinical model. CONCLUSION: The combined model shows potential in stratifying men with biopsy GGG 1-2 PCa based on the presence of AP at final pathology and outperforms models based solely on clinical or radiomics features. It may be expected to aid urologists in better selecting suitable patients for AS.

Translocator protein (18 kDa) positron emission tomography imaging as a biomarker of neuroinflammation in epilepsy.

Increasing evidence indicate that neuroinflammation triggered by glial cells plays a significant role in epileptogenesis. To this effect, the overexpression of translocator protein 18 kDa (TSPO) in activated microglia and astrocytes has been identified as an inflammatory biomarker in epilepsy. It is now possible to quantify neuroinflammation using non-invasive positron emission tomography (PET) imaging of TSPO. With the advancement of radiotracers, TSPO PET has become an innovative tool in elucidating the "neuroinflammatory machinery" of drug-resistant epilepsy. Furthermore, TSPO PET has demonstrated potential in detecting MRI-negative epileptogenic zones (EZ) and provided an innovative perspective in epileptic medical treatment. This manuscript presents a comprehensive exploration of the neuroinflammatory mechanisms of epilepsy, alongside a thorough review of TSPO PET studies conducted in clinical and preclinical settings. The primary objective is to deepen our understanding of epilepsy progression and to establish TSPO PET as an effective monitoring tool for treatment efficacy.

Evaluation of gastrin-releasing peptide receptor, prostate-specific membrane antigen, and neurotensin receptor 1 as potential biomarkers for accurate prostate cancer stratified diagnosis.

BACKGROUND: Studies on single-target PET imaging of gastrin-releasing peptide receptor (GRPR), prostate-specific membrane antigen (PSMA), or neurotensin receptor 1(NTR1) have been reported. However, the performance of these three targets in the progression of PCa remains unclear. Our study aims to compare the expression of GRPR, PSMA, and NTR1 in patients with prostatic intraepithelial neoplasia (PIN), prostate cancer (PCa), and lymph node metastasis. We synthesized molecular probes targeting the markers to achieve a non-invasive precise detection of PCa patients with PET/CT imaging. METHODS: In this study, the expression of GRPR, PSMA, and NTR1 was evaluated by immunohistochemistry in 34 PIN, 171 PCa, and 22 lymph node metastasis tissues of patients. The correlation between their expression and the clinicopathological parameters of PCa patients was assessed. Sixteen PCa patients with different Gleason scores (GS) underwent dual-tracer (68Ga-NOTA-RM26 and 68Ga-NOTA-PSMA617) PET/CT. RESULTS: In the PIN stage, the expression of GRPR was significantly higher than that of PSMA and NTR1 (P < 0.001), while NTR1 expression was significantly higher than PSMA and GRPR expression in primary PCa (P = 0.001). High PSMA expression in PCa patients was associated with shorter progression-free survival (P = 0.037) and overall survival (P = 0.035). PCa patients with high GS had higher tumor uptake of 68Ga-NOTA-PSMA617 than those with low GS (P = 0.001), while PCa patients with low GS had higher tumor uptake of 68Ga-NOTA-RM26 than those with high GS (P = 0.001). CONCLUSIONS: This study presents three novel biomarkers (PSMA, GRPR, and NTR1) as imaging agents for PET/CT, and may offer a promising approach for non-invasive precise detection and Gleason grade prediction of PCa patients.

Aggregation-Induced Emission CN-Based Nanoparticles to Alleviate Hypoxic Liver Fibrosis via Triggering HSC Ferroptosis and Enhancing Photodynamic Therapy.

Hypoxia can lead to liver fibrosis and severely limits the efficacy of photodynamic therapy (PDT). Herein, carbon nitride (CN)-based hybrid nanoparticles (NPs) VPSGCNs@TSI for light-driven water splitting were utilized to solve this problem. CNs were doped with selenide glucose (Se-glu) to enhance their red/NIR region absorption. Then, vitamin A-poly(ethylene glycol) (VA-PEG) fragments and aggregation-induced emission (AIE) photosensitizers TSI were introduced into Se-glu-doped CN NPs (VPSGCNs) to construct VPSGCNs@TSI NPs. The introduction of VA-PEG fragments enhanced the targeting of the NPs to activated hepatic stellate cells (HSCs) and reduced their toxicity to ordinary liver cells. VPSGCN units could trigger water splitting to generate O2 under 660 nm laser irradiation, improve the hypoxic environment of the fibrosis site, downregulate HIF-1α expression, and activate HSC ferroptosis via the HIF-1α/SLC7A11 pathway. In addition, generated O2 could also increase the reactive oxygen species (ROS) production of TSI units in a hypoxic environment, thereby completely reversing hypoxia-triggered PDT resistance to enhance the PDT effect. The combination of water-splitting materials and photodynamic materials showed a 1 + 1 > 2 effect in increasing oxygen levels in liver fibrosis, promoting ferroptosis of activated HSCs and reversing PDT resistance caused by hypoxia.

Lower synaptic density and its association with cognitive dysfunction in patients with obsessive-compulsive disorder.

Background: Understanding synaptic alteration in obsessive-compulsive disorder (OCD) is crucial for elucidating its pathological mechanisms, but in vivo research on this topic remains limited. Aims: This study aimed to identify the synaptic density indicators in OCD and explore the relationship between cognitive dysfunction and synaptic density changes in OCD. Methods: This study enrolled 28 drug-naive adults with OCD aged 18-40 years and 16 healthy controls (HCs). Three-dimensional T1-weighted structural magnetic resonance imaging and 18F-SynVesT-1 positron emission tomography were conducted. Cognitive function was assessed using the Wisconsin Cart Sorting Test (WCST) in patients with OCD and HCs. Correlative analysis was performed to examine the association between synaptic density reduction and cognitive dysfunction. Results: Compared with HCs, patients with OCD showed reduced synaptic density in regions of the cortico-striato-thalamo-cortical circuit such as the bilateral putamen, left caudate, left parahippocampal gyrus, left insula, left parahippocampal gyrus and left middle occipital lobe (voxel p<0.001, uncorrected, with cluster level above 50 contiguous voxels). The per cent conceptual-level responses of WCST were positively associated with the synaptic density reduction in the left middle occipital gyrus (R2=0.1690, p=0.030), left parahippocampal gyrus (R2=0.1464, p=0.045) and left putamen (R2=0.1967, p=0.018) in patients with OCD. Conclusions: Adults with OCD demonstrated lower 18F-labelled difluoro analogue of 18F-SynVesT-1 compared with HCs, indicating potentially lower synaptic density. This is the first study to explore the synaptic density in patients with OCD and provides insights into potential biological targets for cognitive dysfunctions in OCD.

Glial growth factor 2 treatment alleviates ischemia and reperfusion-damaged integrity of the blood-brain barrier through decreasing Mfsd2a/caveolin-1-mediated transcellular and Pdlim5/YAP/TAZ-mediated paracellular permeability.

The impairment of blood-brain barrier (BBB) integrity is the pathological basis of hemorrhage transformation and vasogenic edema following thrombolysis and endovascular therapy. There is no approved drug in the clinic to reduce BBB damage after acute ischemic stroke (AIS). Glial growth factor 2 (GGF2), a recombinant version of neuregulin-1ß that can stimulates glial cell proliferation and differentiation, has been shown to alleviate free radical release from activated microglial cells. We previously found that activated microglia and proinflammatory factors could disrupt BBB after AIS. In this study we investigated the effects of GGF2 on AIS-induced BBB damage as well as the underlying mechanisms. Mouse middle cerebral artery occlusion model was established: mice received a 90-min ischemia and 22.5 h reperfusion (I/R), and were treated with GGF2 (2.5, 12.5, 50 ng/kg, i.v.) before the reperfusion. We showed that GGF2 treatment dose-dependently decreased I/R-induced BBB damage detected by Evans blue (EB) and immunoglobulin G (IgG) leakage, and tight junction protein occludin degradation. In addition, we found that GGF2 dose-dependently reversed AIS-induced upregulation of vesicular transcytosis increase, caveolin-1 (Cav-1) as well as downregulation of major facilitator superfamily domain containing 2a (Mfsd2a). Moreover, GGF2 decreased I/R-induced upregulation of PDZ and LIM domain protein 5 (Pdlim5), an adaptor protein that played an important role in BBB damage after AIS. In addition, GGF2 significantly alleviated I/R-induced reduction of YAP and TAZ, microglial cell activation and upregulation of inflammatory factors. Together, these results demonstrate that GGF2 treatment alleviates the I/R-compromised integrity of BBB by inhibiting Mfsd2a/Cav-1-mediated transcellular permeability and Pdlim5/YAP/TAZ-mediated paracellular permeability.

[Impact of Mild SARS-CoV-2 Infection on Hematological Parameters and Suitability of Apheresis Platelets Donation in Blood Donors].

OBJECTIVE: To investigate the effects of mild SARS-CoV-2 infection on hematological parameters of adult blood donors and the suitability of apheresis platelet donation, the changes of the hematological parameters in blood donors with mild infection of the SARS-CoV-2 Omicron variant strain were evaluated. METHODS: Seventy-two blood donors with mild COVID-19 symptoms who donated consecutive apheresis platelets for 3 times from December 2022 to January 2023, 42 cases among which were included in the infection-positive group, and 30 cases in the suspected infection group. Forty-two donors un-vaccinated against SARS-CoV-2, un-infected, and donated three consecutive apheresis platelets from October to November 2022 were included in the control group. The changes of blood routine testing in the positive group and the suspected infection group were retrospectively compared before (Time1) and after (Time2 and Time3) the onset of symptoms, three consecutive times (Time1, Time2, Time3) in the control group by repeated measures analysis of variance. The Bayesian discriminant method was used to establish a discriminant equation to determine whether the recent infection of SARS-CoV-2 occurred or not. RESULTS: Simple effect of the number times of tests in the positive and suspected infection groups was significant（ Finfection-positive group=6.98, P < 0.001, partial η2=0.79, Fsuspected infection group=4.31, P < 0.001, partial η2=0.70）. The positive group and the suspected infection group had lower RBC, HCT, and HGB, and higher PLT and PCT at Time2 compared to Time1 and Time3(P < 0.05). The positive group and the suspected infection group showes RDW-CV and RDW-SD at Time3 higher than Time1 and Time2 (P < 0.001). The simple effect of the number times of tests in the control group was not significant ( F=0.96, P =0.55, partial η2=0.34). The difference of the whole blood count parameters in the control group for three times was not statistically significant (P >0.05). We established a discriminant equation to determine whether the recent infection of SARS-CoV-2 occurred or not. The equation had an eigenvalue of 0.22, a canonical correlation of 0.43 (χ2=27.81, P < 0.001), and an analysis accuracy of 72.9%. CONCLUSION: The hematological indicators of RBC, HCT, HGB, PLT, PCT, RDW-CV and RDW-SD in blood donors who had infected with mild COVID-19 showed dynamic changes. The discriminant equation for whether they are infected recently with COVID-19 has a high accuracy rate.

Effect of Implementing an Informatization Case Management Model on the Management of Chronic Respiratory Diseases in a General Hospital: Retrospective Controlled Study.

Background: The use of chronic disease information systems in hospitals and communities plays a significant role in disease prevention, control, and monitoring. However, there are several limitations to these systems, including that the platforms are generally isolated, the patient health information and medical resources are not effectively integrated, and the "Internet Plus Healthcare" technology model is not implemented throughout the patient consultation process. Objective: The aim of this study was to evaluate the efficiency of the application of a hospital case management information system in a general hospital in the context of chronic respiratory diseases as a model case. Methods: A chronic disease management information system was developed for use in general hospitals based on internet technology, a chronic disease case management model, and an overall quality management model. Using this system, the case managers provided sophisticated inpatient, outpatient, and home medical services for patients with chronic respiratory diseases. Chronic respiratory disease case management quality indicators (number of managed cases, number of patients accepting routine follow-up services, follow-up visit rate, pulmonary function test rate, admission rate for acute exacerbations, chronic respiratory diseases knowledge awareness rate, and patient satisfaction) were evaluated before (2019-2020) and after (2021-2022) implementation of the chronic disease management information system. Results: Before implementation of the chronic disease management information system, 1808 cases were managed in the general hospital, and an average of 603 (SD 137) people were provided with routine follow-up services. After use of the information system, 5868 cases were managed and 2056 (SD 211) patients were routinely followed-up, representing a significant increase of 3.2 and 3.4 times the respective values before use (U=342.779; P<.001). With respect to the quality of case management, compared to the indicators measured before use, the achievement rate of follow-up examination increased by 50.2%, the achievement rate of the pulmonary function test increased by 26.2%, the awareness rate of chronic respiratory disease knowledge increased by 20.1%, the retention rate increased by 16.3%, and the patient satisfaction rate increased by 9.6% (all P<.001), while the admission rate of acute exacerbation decreased by 42.4% (P<.001) after use of the chronic disease management information system. Conclusions: Use of a chronic disease management information system improves the quality of chronic respiratory disease case management and reduces the admission rate of patients owing to acute exacerbations of their diseases.

Nano-Proteolysis Targeting Chimeras (Nano-PROTACs) in Cancer Therapy.

Proteolysis-targeting chimeras (PROTACs) are heterobifunctional molecules that have the capability to induce specific protein degradation. While playing a revolutionary role in effectively degrading the protein of interest (POI), PROTACs encounter certain limitations that impede their clinical translation. These limitations encompass off-target effects, inadequate cell membrane permeability, and the hook effect. The advent of nanotechnology presents a promising avenue to surmount the challenges associated with conventional PROTACs. The utilization of nano-proteolysis targeting chimeras (nano-PROTACs) holds the potential to enhance specific tissue accumulation, augment membrane permeability, and enable controlled release. Consequently, this approach has the capacity to significantly enhance the controllable degradation of target proteins. Additionally, they enable a synergistic effect by combining with other therapeutic strategies. This review comprehensively summarizes the structural basis, advantages, and limitations of PROTACs. Furthermore, it highlights the latest advancements in nanosystems engineered for delivering PROTACs, as well as the development of nano-sized PROTACs employing nanocarriers as linkers. Moreover, it delves into the underlying principles of nanotechnology tailored specifically for PROTACs, alongside the current prospects of clinical research. In conclusion, the integration of nanotechnology into PROTACs harbors vast potential in enhancing the anti-tumor treatment response and expediting clinical translation.

Comparative pharmacognosy and secondary metabolite analysis of Balanophorae herbs from different sources.

The Balanophorae are not only traditional Chinese herbal medicines but also functional foods with diverse sources. This study aimed to distinguish pharmacognostic characteristics and secondary metabolites among different species of Balanophorae. Eight species of Balanophorae herbs were harvested, including 21 batches with 209 samples. Ultra-high-performance liquid chromatography-quadrupole time-of-flight mass spectrometry was used to analyze secondary metabolites of Balanophorae from 21 sources. Targeted metabolomic analysis was performed to compare differences among the groups. Rhopalocnemis phalloide and B. indica can be identified by their pharmacognostic characteristics. Then, 41 secondary metabolites were identified or characterized in the mixed extracts of the 209 samples, mainly phenolic acids, flavonoids, and their derivatives. The distribution of these secondary metabolites revealed apparent differences among different species. In addition, targeted metabolomic analysis suggested that the secondary metabolite profiles of seven species of Balanophorae showed noticeable differences, and differences were also observed among different growing regions. Finally, five important metabolic markers were screened to successfully distinguish B. laxiflora, B. harlandii, and B. polyandra, including three phenolic acids and two flavonoids. This is the first study to systematically compare both the morphology and secondary metabolites among different sources of Balanophorae, which could provide effective information for identifying diverse species.

Overexpression of PavHIPP16 from Prunus avium enhances cold stress tolerance in transgenic tobacco.

BACKGROUND: The heavy metal-associated isoprenylated plant protein (HIPP) is an important regulatory element in response to abiotic stresses, especially playing a key role in low-temperature response. RESULTS: This study investigated the potential function of PavHIPP16 up-regulated in sweet cherry under cold stress by heterologous overexpression in tobacco. The results showed that the overexpression (OE) lines' growth state was better than wild type (WT), and the germination rate, root length, and fresh weight of OE lines were significantly higher than those of WT. In addition, the relative conductivity and malondialdehyde (MDA) content of the OE of tobacco under low-temperature treatment were substantially lower than those of WT. In contrast, peroxidase (POD), superoxide dismutase (SOD), catalase (CAT) activities, hydrogen peroxide (H2O2), proline, soluble protein, and soluble sugar contents were significantly higher than those of WT. Yeast two-hybrid assay (Y2H) and luciferase complementation assay verified the interactions between PavbHLH106 and PavHIPP16, suggesting that these two proteins co-regulated the cold tolerance mechanism in plants. The research results indicated that the transgenic lines could perform better under low-temperature stress by increasing the antioxidant enzyme activity and osmoregulatory substance content of the transgenic plants. CONCLUSIONS: This study provides genetic resources for analyzing the biological functions of PavHIPPs, which is important for elucidating the mechanisms of cold resistance in sweet cherry.

Transcriptional, post-transcriptional, and post-translational regulation of polyunsaturated fatty acid synthase genes in Aurantiochytrium limacinum strain BL10: Responses to nitrogen starvation.

Under nitrogen deficient conditions, the Aurantiochytrium limacinum strain BL10 greatly increases the production of docosahexaenoic acid (DHA) and n-6 docosapentaenoic acid. Researchers have yet to elucidate the mechanism by which BL10 promotes the activity of polyunsaturated fatty acid synthase (Pfa), which plays a key role in the synthesis of polyunsaturated fatty acid (PUFA). Analysis in the current study revealed that in nitrogen-depleted environments, BL10 boosts the transcription and synthesis of proteins by facilitating the expression of pfa genes via transcriptional regulation. It was also determined that BL10 adjusts the lengths of the 5'- and 3'-untranslated regions (suggesting post-transcriptional regulation) and modifies the ratio of two Pfa1 isoforms to favor PUFA production via post-translational regulation (ubiquitination). These findings clarify the exceptional DHA production of BL10 and provide additional insights into the regulatory mechanisms of PUFA biosynthesis in Aurantiochytrium.

Haplotype analysis on association between C-reactive protein gene and susceptibility to type 2 diabetes mellitus in Chinese Han population : CRP gene and type 2 diabetes mellitus.

AIMS: We aimed to evaluate the impact of C-reactive protein (CRP) gene polymorphism, additional gene-gene interaction, and haplotypes on susceptibility to type 2 diabetes mellitus (T2DM). METHODS: SNPstats online software ( https://www.snpstats.net/start.htm ) was employed to evaluate the association between CRP gene and T2DM risk. High-order interactions among SNPs was tested using generalized multifactor dimensionality reduction, and the testing balanced accuracy, training balanced accuracy and cross-validation consistency were calculated. The SHEsisPlus ( http://shesisplus.bio-x.cn/SHEsis.html ) online software was used for haplotype analysis. RESULTS: A total of 730 T2DM patients and 765 controls were enrolled. The T allele of rs1205 is associated with increased susceptibility to T2DM, OR (95% CI) were 1.51 (1.13-2.01), 1.44 (1.10-1.89) and 1.25 (1.01-1.54) for codominant, dominant and over-dominant models, respectively. We also found that minor allele of rs2794521 is associated with decreased susceptibility to T2DM under codominant and recessive models, OR (95%CI) were 0.38 (0.18-0.79) and 0.37 (0.16-0.80) for codominant and recessive models, respectively. No significant gene-gene interaction existed among CRP gene SNPs, all interaction p- values were more than 0.05. Haplotype analyses suggested the CGCA haplotype containing rs1205-C, rs1130864-G, rs2794521- C and rs3093059- A allele was associated with decreased risk of T2DM, OR (95% CI) = 0.83 (0.68-0.98), P = 0.047. CONCLUSIONS: Minor allele of rs1205 was associated with increased T2DM risk. Minor allele of rs2794521 and the CGCA haplotype were associated with decreased T2DM risk.

Multi-omics Analysis Reveals Key Gut Microbiota and Metabolites Closely Associated with Huntington's Disease.

Dysbiosis of the gut microbiota is closely associated with neurodegenerative diseases, including Huntington's disease (HD). Gut microbiome-derived metabolites are key factors in host-microbiome interactions. This study aimed to investigate the crucial gut microbiome and metabolites in HD and their correlations. Fecal and serum samples from 11 to 26 patients with HD, respectively, and 16 and 23 healthy controls, respectively, were collected. The fecal samples were used for shotgun metagenomics while the serum samples for metabolomics analysis. Integrated analysis of the metagenomics and metabolomics data was also conducted. Firmicutes, Bacteroidota, Proteobacteria, Uroviricota, Actinobacteria, and Verrucomicrobia were the dominant phyla. At the genus level, the presence of Bacteroides, Faecalibacterium, Parabacteroides, Alistipes, Dialister, and Christensenella was higher in HD patients, while the abundance of Lachnospira, Roseburia, Clostridium, Ruminococcus, Blautia, Butyricicoccus, Agathobaculum, Phocaeicola, Coprococcus, and Fusicatenibacter decreased. A total of 244 differential metabolites were identified and found to be enriched in the glycerophospholipid, nucleotide, biotin, galactose, and alpha-linolenic acid metabolic pathways. The AUC value from the integrated analysis (1) was higher than that from the analysis of the gut microbiota (0.8632). No significant differences were found in the ACE, Simpson, Shannon, Sobs, and Chao indexes between HD patients and controls. Our study determined crucial functional gut microbiota and potential biomarkers associated with HD pathogenesis, providing new insights into the role of the gut microbiota-brain axis in HD occurrence and development.

Sex differences of neural connectivity in internet gaming disorder and its association with sleep quality: an exploratory fMRI study.

Objectives: Sex-specific differences in internet gaming disorder (IGD) neurophysiology remain underexplored. Here we investigated sex-related variability in regional homogeneity (ReHo) and functional connectivity (FC) in IGD and their correlations with sleep quality. Methods: Resting-state functional magnetic resonance imaging (fMRI) scans were performed on 52 subjects with IGD and 50 healthy controls (HCs). Two-way ANOVA was used to examine sex and diagnosis interactions in ReHo and FC, followed by post-hoc analyses to explore FC biomarkers for different sexes. Results: In ReHo analysis, the four groups showed significant sex and diagnosis interactions in the right middle frontal gyrus (rMFG). FC analysis with rMFG as the seed region revealed a significant sex and diagnosis interaction effect in FC of the rMFG with the bilateral postcentral gyrus (PoCG). In male IGD group, FC between the rMFG and the bilateral PoCG correlates strongly with daytime dysfunction score and the Pittsburgh sleep quality inventory (PSQI) total score. Conclusion: These findings emphasize the importance of considering sexual dimorphism in the neurobiology of IGD, which might influence subsequent treatment strategies.

Bilirubin influences the predictive effect of body mass index on hospital mortality in critically ill patients.

Introduction: Body mass index (BMI) can predict mortality in critically ill patients. Moreover, mortality is related to increased bilirubin levels. Thus, herein, we aimed to investigate the effect of bilirubin levels on the usefulness of BMI in predicting mortality in critically ill patients. Methods: Data were extracted from the Medical Information Mart for Intensive Care (MIMIC IV) database. Patients were divided into two groups according to their total bilirubin levels within 24 h. Cox proportional hazard regression models were applied to obtain adjusted hazard ratios and 95 % confidence intervals for the correlation between BMI categories and hospital mortality. The dose-response relationship was flexibly modeled using a restricted cubic spline (RCS) with three knots. Results: Of the 14376 patients included, 3.4 % were underweight, 29.3 % were of normal body weight, 32.2 % were overweight, and 35.1 % were obese. For patients with total bilirubin levels <2 mg/dL, hospital mortality was significantly lower in patients with obesity than in normal body weight patients (p < 0.05). However, the opposite results were observed for patients with total bilirubin levels ≥2 mg/dL. The Cox proportional hazard regression models suggested that the risk of death was lower in patients with overweightness and obesity than in normal body weight patients when the total bilirubin levels were <2 mg/dL, but not in the other case (total bilirubin levels ≥2 mg/dL). RCS analyses showed that, for patients with total bilirubin levels <2 mg/dL, the risk of death gradually decreased with increasing BMI. Conversely, for patients with total bilirubin levels ≥2 mg/dL, this risk did not decrease with increasing BMI until reaching obesity, after which it increased rapidly. Conclusion: BMI predicted the risk of death differently in critically ill patients with different bilirubin levels.