GATA factor TRPS1, a new DNA repair protein, cooperates with reversible PARylation to promote chemoresistance in breast cancer patients.

Resistance to DNA-damaging agents is a major unsolved challenge for breast cancer patients undergoing chemotherapy. Here, we show that elevated expression of transcriptional repressor GATA binding 1 (TRPS1) is associated with lower drug sensitivity, reduced response rate, and poor prognosis in chemotherapy-treated breast cancer patients. Mechanistically, elevated TRPS1 expression promotes hyperactivity of DNA damage repair (DDR) in breast cancer cells. We provide evidence that TRPS1 dynamically localizes to DNA breaks in a Ku70- and Ku80-dependent manner, and that TRPS1 is a new member of the DDR protein family. We also discover that the dynamics of TRPS1 assembly at DNA breaks is regulated by its reversible PARylation in the DDR, and that mutations of the PARylation sites on TRPS1 lead to increased sensitivity to chemotherapeutic drugs. Taken together, our findings provide new mechanistic insights into the DDR and chemoresistance in breast cancer patients and identify TRPS1 as a critical DDR protein. TRPS1 may also be considered as a target to improve chemo-sensitization strategies and, consequently, clinical outcomes for breast cancer patients.

Neuregulin-1 immunoreactivity in peripheral plasma is associated with rs6982890 polymorphism-mediated psychotic symptoms in schizophrenia.

OBJECTIVES: Neuregulin 1 (NRG1) is a risk gene for schizophrenia and involved in neurodevelopment and synaptic plasticity. Polymorphisms in NRG1 may affect psychotic symptoms in schizophrenia. This study investigated the effects of the single nucleotide polymorphism (SNP) rs6982890 on peripheral plasma NRG1 immunoreactivity, clinical symptoms and cognitive functions in schizophrenia patients. MATERIAL AND METHODS: We recruited subjects from the Han population of northern China from 2010 to 2022. We first genotyped and analyzed 6 NRG1 SNPS in 1304 patients with schizophrenia and 871 healthy controls. Then, 91 patients with schizophrenia and 40 healthy controls were selected to detect the peripheral plasma NRG1 immunoreactivity by ELISA. Among them, 84 patients were divided into rs6982890 genotypes to analyze the correlation between NRG1 immunoreactivity and clinical symptoms. RESULTS: Rs6982890 allelic frequencies were statistically significant between patients and controls. Baseline peripheral plasma NRG1 immunoreactivity in patients were significantly lower than controls. NRG1 immunoreactivity in patients were significantly increased after 8 weeks of antipsychotic treatment and significantly correlated with clinical symptoms and cognitive function. Genotyping of patients with SNP rs6982890 indicated NRG1 immunoreactivity in CC genotype increased significantly after treatment, while CT genotype had no significant change. Baseline NRG1 immunoreactivity with the CT genotype were significantly higher than CC genotype. CONCLUSIONS: NRG1 SNP rs6982890 is significantly associated with schizophrenia in the Han population of northern China, and it may affect the effect of antipsychotic drug treatment by regulating the peripheral plasma NRG1 immunoreactivity.

To nap or not? Evidence from a meta-analysis of cohort studies of habitual daytime napping and health outcomes.

Habitual daytime napping is a common behavioral and lifestyle practice in particular countries and is often considered part of a normal daily routine. However, recent evidence suggests that the health effects of habitual daytime napping are controversial. We systematically searched PubMed, Web of Science, Embase, and Cochrane Library databases from inception to March 9, 2024, to synthesize cohort studies of napping and health outcome risk. A total of 44 cohort studies with 1,864,274 subjects aged 20-86 years (mean age 56.4 years) were included. Overall, habitual napping increased the risk of several adverse health outcomes, including all-cause mortality, cardiovascular disease, metabolic disease, and cancer, and decreased the risk of cognitive impairment and sarcopenia. Individuals with a napping duration of 30 min or longer exhibited a higher risk of all-cause mortality, cardiovascular disease, and metabolic disease, whereas those with napping durations less than 30 min had no significant risks. No significant differences in napping and health risks were observed for napping frequency, percentage of nappers, sample size, sex, age, body mass index, follow-up years, or comorbidity status. These findings indicate that individuals with a long napping duration should consider shortening their daily nap duration to 30 min or less.

Elevated plasma matrix metalloproteinase 9 in schizophrenia patients associated with poor antipsychotic treatment response and white matter density deficits.

Oxidative stress and neuroinflammation contribute to schizophrenia (SCZ) pathology and may influence treatment efficacy. Matrix metalloproteinase 9 (MMP9) is a critical molecular node mediating the interaction between oxidative stress and inflammation, and so may influence treatment efficacy. Here we examined the associations of plasma MMP9 concentration with antipsychotic drug responses, clinical symptoms, and brain structure. A total of 129 healthy controls and 124 patients with SCZ were included in this study. Patients were monitored clinically during 8 weeks of antipsychotic treatment and classified as poor responders (n = 49) or good responders (n = 75). We then compared plasma MMP9 concentrations in healthy controls at baseline and both SCZ responder groups at baseline and after the 8-week antipsychotic treatment regimen. Cognitive function was also examined using the MATRICS Consensus Cognitive Battery. In addition, we extracted regional white matter density from magnetic resonance images of patients. Compared to healthy controls, plasma MMP9 levels were significantly elevated in poor responders at baseline and negatively correlated with both white matter density in the right superior temporal gyrus and the change in cognitive symptoms after treatment. Conversely, there was no significant difference in plasma MMP9 between good responders and healthy controls, and no associations of plasma MMP9 with cognitive symptoms or regional white matter density among good responders. Elevated plasma MMP9 is associated with poor antipsychotic drug efficacy and white matter deficits in SCZ patients, and so may be a useful biomarker to guide personalized treatment.

Characterizing and decoding the key odor compounds of Spirulina platensis at different processing stages by sensomics.

Processing is an indispensable technology in the preparation of Spirulina platensis (S. platensis). The key odorants in liquids, muds, and powders from S. platensis (NM and GZ) were characterized. A total of 90 odorants were identified and 41 odorants were sniffed with the flavor dilution (FD) factors ranging from 1 to 729. Among them, nonanal, decanal, d-limonene, ß-cyclocitral, and ß-ionone with FD factors ≥1 were detected in S. platensis during the whole processing stages. In addition, heptanal, (E, E)-2,4-nonadienal, trans-4,5-epoxy-(E)-2-decenal, 1-hepten-3-one, isophorone, 3-ethyl-2,5-dimethylpyrazine, and α-ionone exhibited higher odor activity values in powders; ß-myrcene, methional, and S-methyl methanethiosulphonate were key odorants in muds; while trans-3-penten-2-ol was key odorant in liquids. Besides, the GZ-mud presented stronger earthy and fishy odor than NM-mud. S. platensis powders have the stronger grassy odor, roasted odor, and marine odor than S. platensis muds. Overall, drying process promotes the formation of aldehydes, heterocyclic compounds, and terpenoids.

Etiologies of Persistent Aminotransferase Elevations in Chronic Hepatitis B Patients Treated with Nucleos(t)ide Analogs.

Background/Aims: Recent studies revealed that patients with persistent aminotransferase elevations after antiviral treatment had higher risk of hepatic events; yet its underlying causes remain unclear. Our study aimed to investigate the etiologies of persistent aminotransferase elevations in patients treated with nucleos(t)ide analogs (NAs). Materials and Methods: A retrospective study was conducted on chronic hepatitis B (CHB) patients who had been receiving NA treatment for over a year and had an aminotransferase level greater than 40 IU/mL (more than twice, with a 3-month interval) and subsequently underwent a liver biopsy. Results: The study group included 46 patients (34 males) with a mean age of 44.8 ± 20.3 years (range: 24-71 years).The average dura- tion of NA therapy was 3.7 years (1.1-10.6 years). The etiologies of persistant transaminase elevation were categorized into 4 groups: patients with low hepatitis B virus (HBV) viral load (LVL, n = 11); concurrent non-alcoholic fatty liver disease (NAFLD, n = 12); concurrent other liver diseases (OLD, n = 12); and unknown liver dysfunction (ULD, n = 11). The proportion of G ≥ 2 inflammation was significantly higher in the LVL group (90.9%) compared to NAFLD (33.3%), OLD (50%), and ULD (27.2%) groups (P = .012). The hepatitis B e-antigen (HBeAg)-positive group exhibited a younger age (34.5 ± 10.2 vs. 48.1 ± 9.4 years, P < .001), a lower proportion of fibrosis F ≥ 2 (36.3% vs. 77.1%, P = .012), and a higher prevalence of detectable HBV DNA (54.5% vs.14.2%, P = .00632) compared to the HBeAg-negative group. Conclusion: The etiology of persistent aminotransferase elevations in CHB patients undergoing NAs treatment warrants investigation. Besides the commonly observed NAFLD and low HBV viral load, concurrent presence of other liver diseases requires elucidation.The proportion of G≥2 inflammation was higher in the LVL group.

NtMYB27 acts downstream of NtBES1 to modulate flavonoids accumulation in response to UV-B radiation in tobacco.

UV-B radiation can induce the accumulation of many secondary metabolites, including flavonoids, in plants to protect them from oxidative damage. BRI1-EMS-SUPPRESSOR1 (BES1) has been shown to mediate the biosynthesis of flavonoids in response to UV-B. However, the detailed mechanism by which it acts still needs to be further elucidated. Here, we revealed that UV-B significantly inhibited the transcription of multiple transcription factor genes in tobacco, including NtMYB27, which was subsequently shown to be a repressor of flavonoids synthesis in tobacco. We further demonstrated that NtBES1 directly binds to the E-box motifs present in the promoter of NtMYB27 to mediate its transcriptional repression upon UV-B exposure. The UV-B-repressed NtMYB27 could bind to the ACCT-containing element (ACE) in the promoters of Nt4CL and NtCHS and served as a modulator that promoted the biosynthesis of lignin and chlorogenic acid (CGA) but inhibited the accumulation of flavonoids in tobacco. The expression of NtMYB27 was also significantly repressed by heat stress, suggesting its putative roles in regulating heat-induced flavonoids accumulation. Taken together, our results revealed the role of NtBES1 and NtMYB27 in regulating the synthesis of flavonoids during the plant response to UV-B radiation in tobacco.

A randomized phase 2b study of subcutaneous PD-L1 antibody ASC22 in virally-suppressed, HBeAg negative chronic hepatitis B patients.

BACKGROUND AIMS: Studies have shown that blocking the PD-1/PD-L1 pathway may lead to a potential cure for HBV infections. ASC22 (Envafolimab) is a humanized, single-domain PD-L1 antibody administered subcutaneously. This study aimed to evaluate the efficacy and safety of ASC22 in virally suppressed chronic hepatitis B (CHB) patients on nucleos(t)ide analogs (NAs). APPROACH AND RESULTS: This randomized, single-blind, phase IIb trial enrolled CHB patients in two cohorts for a 24-week treatment with ASC22 or placebo (PBO) once every 2 weeks and 24-week follow-up. In total, 60, 59, and 30 patients were treated with 1.0, 2.5 mg/kg ASC22 and PBO, respectively. The mean HBsAg changes from baseline at week 24 and 24 week follow-up periods were -0.309 (p<0.001) and -0.272 (p<0.023) log10 IU/mL in the 1.0 mg/kg ASC22 group, -0.231 (p=0.007) and -0.205 (p=0.12) log10 IU/mL in the 2.5 mg/kg ASC22 group, and-0.003 and -0.063 log10 IU/mL in the PBO group, respectively (ITT population). Three out of ten patients with baseline HBsAg levels ≤100 IU/mL in the 1.0 mg/kg group obtained on-treatment HBsAg loss. Most AEs were mild (97.9%). There were no study drug-related serious AEs in the 1.0 mg/kg ASC22 group. CONCLUSIONS: Subcutaneous administration of 1.0 mg/kg ASC22 Q2W for 24 weeks was shown to be safe and well tolerated in virally suppressed CHB patients on NAs and can induce HBsAg decline, especially in patients with HBsAg ≤100 IU/mL.

Pharmacovigilance study of GLP-1 receptor agonists for metabolic and nutritional adverse events.

Aims: Glucagon-like peptide-1 receptor agonists (GLP-1 RAs) are employed extensively in the management of type 2 diabetes and obesity. However, there is a paucity of real-world data on their safety and tolerability for metabolic and nutritional adverse events in large sample populations. This study aimed to analyse the metabolic and nutritional safety signatures of different GLP-1 RAs by exploring the Food and Drug Administration (FDA) Adverse Event Reporting System (FAERS). Methods: AEs data were extracted from the FDA Adverse Event Reporting System database for each GLP-1 RA from the time of its launch until the second quarter of 2023. The reported odds ratio (ROR), proportional reporting ratio (PRR), Empirical Bayesian Geometric Mean and Bayesian Confidence Propagation Neural Network were employed to identify AE signals. Results: A system organ class of metabolism and nutrition disorders was employed to filter AE reports, resulting in the identification of 10,450 reports for exenatide, 2,860 reports for liraglutide, 240 reports for albiglutide, 4,847 reports for dulaglutide, 2,905 reports for semaglutide, 1,089 reports for tirzepatide, and 13 reports for lixisenatide. Semaglutide (ROR, 3.34; 95%CI, 3.22), liraglutide (ROR, 2.78; 95%CI, 2.69), and exenatide (ROR, 2.15; 95%CI, 2.11) were associated with metabolism and nutrition disorders. The number of AE signals detected were as follows: albiglutide (n = 1), lixisenatide (n = 2), tirzepatide (n = 11), exenatide (n = 12), liraglutide (n = 16), semaglutide (n = 20), dulaglutide (n = 22). Dehydration was the most frequent AE contributing to serious outcomes for liraglutide (n = 318, 23.93%), dulaglutide (n = 434, 20.90%), semaglutide (n = 370, 25.10%) and tirzepatide (n = 70, 32.86%). The time to onset (TTO) of AE was statistically different between exenatide and the other GLP-1 RAs (p < 0.001), and the Weibull parameters for dehydration for liraglutide, dulaglutide, and semaglutide analyses all showed an early failure-type profile. Conclusion: Our study suggests that exenatide, liraglutide, and semaglutide are more susceptible to metabolic and nutritional AEs than other GLP-1 RAs. Liraglutide, dulaglutide, semaglutide, and tirzepaptide's potential to induce dehydration, necessitates special attention. Despite certain deficiencies, GLP-1 RAs have considerable potential for the treatment of eating disorders.

High accuracy model for HBsAg loss based on longitudinal trajectories of serum qHBsAg throughout long-term antiviral therapy.

OBJECTIVE: Hepatitis B surface antigen (HBsAg) loss is the optimal outcome for patients with chronic hepatitis B (CHB) but this rarely occurs with currently approved therapies. We aimed to develop and validate a prognostic model for HBsAg loss on treatment using longitudinal data from a large, prospectively followed, nationwide cohort. DESIGN: CHB patients receiving nucleos(t)ide analogues as antiviral treatment were enrolled from 50 centres in China. Quantitative HBsAg (qHBsAg) testing was prospectively performed biannually per protocol. Longitudinal discriminant analysis algorithm was used to estimate the incidence of HBsAg loss, by integrating clinical data of each patient collected during follow-up. RESULTS: In total, 6792 CHB patients who had initiated antiviral treatment 41.3 (IQR 7.6-107.6) months before enrolment and had median qHBsAg 2.9 (IQR 2.3-3.3) log10IU/mL at entry were analysed. With a median follow-up of 65.6 (IQR 51.5-84.7) months, the 5-year cumulative incidence of HBsAg loss was 2.4%. A prediction model integrating all qHBsAg values of each patient during follow-up, designated GOLDEN model, was developed and validated. The AUCs of GOLDEN model were 0.981 (95% CI 0.974 to 0.987) and 0.979 (95% CI 0.974 to 0.983) in the training and external validation sets, respectively, and were significantly better than those of a single qHBsAg measurement. GOLDEN model identified 8.5%-10.4% of patients with a high probability of HBsAg loss (5-year cumulative incidence: 17.0%-29.1%) and was able to exclude 89.6%-91.5% of patients whose incidence of HBsAg loss is 0. Moreover, the GOLDEN model consistently showed excellent performance among various subgroups. CONCLUSION: The novel GOLDEN model, based on longitudinal qHBsAg data, accurately predicts HBsAg clearance, provides reliable estimates of functional hepatitis B virus (HBV) cure and may have the potential to stratify different subsets of patients for novel anti-HBV therapies.

Clinical characteristics and natural history of porto-sinusoidal vascular disease: A cohort study of 234 patients in China.

BACKGROUND AND AIMS: Porto-sinusoidal vascular disease (PSVD) is an under-recognized and under-diagnosed disease. The purpose of this study was to investigate the clinical features and prognosis of PSVD. METHODS: The patients who underwent liver biopsies were analyzed retrospectively. The clinical and pathological data were reviewed and screened according to the latest diagnostic criteria of PSVD. RESULTS: A total of 234 patients were diagnosed as PSVD, including 103 patients presented with portal hypertension (PH) and 131 patients without PH. At baseline, the alanine aminotransferase (ALT) and γ-glutamyl transpeptidase (GGT) levels were higher in the no-PH group. The liver stiffness increased in the PH group. In histological review, obliterative portal venopathy, sinusoidal dilatation and architectural disturbance were more common in the PH group, while portal tract abnormalities were more widely distributed in the no-PH group. After a median follow-up of 43.6 months, the survival rate of patients with baseline liver decompensation was 76.0%, and that of patients at a liver compensated stage in the PH group was 98.7%. First variceal bleeding occurred in 13.8% of patients with gastric-oesophageal varices. None of the patients in the no-PH group developed portal hypertension during follow-up. CONCLUSIONS: PSVD can manifest as PH or mild liver enzyme abnormalities. There are significant differences in pathological features among patients with different clinical manifestations. Recurrent ascites are the main cause of death in PSVD patients. However, patients without PH have a slow disease progression, with recurrent elevated GGT levels being their main clinical feature.

Short-term antipsychotic treatment reduces functional connectivity of the striatum in first-episode drug-naïve early-onset schizophrenia.

BACKGROUND: The striatum is thought to play a critical role in the pathophysiology and antipsychotic treatment of schizophrenia. Previous studies have revealed abnormal functional connectivity (FC) of the striatum in early-onset schizophrenia (EOS) patients. However, no prior studies have examined post-treatment changes of striatal FC in EOS patients. METHODS: We recruited 49 first-episode drug-naïve EOS patients to have resting-state functional magnetic resonance imaging scans at baseline and after 8 weeks of treatment with antipsychotics, along with baseline scanning of 34 healthy controls (HCs) for comparison purposes. We examined the FC values between each seed in striatal subregion and the rest of the brain. The Positive and Negative Syndrome Scale (PANSS) was applied to measure psychiatric symptoms in patients. RESULTS: Compared with HCs at baseline, EOS patients exhibited weaker FC of striatal subregions with several brain regions of the salience network and default mode network. Meanwhile, FC between the dorsal caudal putamen (DCP) and left supplementary motor area, as well as between the DCP and right postcentral gyrus, was negatively correlated with PANSS negative scores. Furthermore, after 8 weeks of treatment, EOS patients showed decreased FC between subregions of the putamen and the triangular part of inferior frontal gyrus, middle frontal gyrus, supramarginal gyrus and inferior parietal lobule. CONCLUSIONS: Decreased striatal FC is evident, even in the early stages of schizophrenia, and enhance our understanding of the neurodevelopmental abnormalities in schizophrenia. The findings also demonstrate that reduced striatal FC occurs after antipsychotic therapy, indicating that antipsychotic effects need to be accounted for when considering striatal FC abnormalities in schizophrenia.

Abnormal regional homogeneity as a potential imaging indicator for identifying adolescent-onset schizophrenia: Insights from resting-state functional magnetic resonance imaging.

BACKGROUND: In patients with schizophrenia, there is abnormal regional functional synchrony. However, whether it also in patients with adolescent-onset schizophrenia (AOS) remains unclear. The goal of this study was to analyze the regional homogeneity (ReHo) of resting functional magnetic resonance imaging to explore the functional abnormalities of the brain in patients with AOS. METHODS: The study included 107 drug-naive first-episode AOS patients and 67 healthy, age, sex, and education-matched controls using resting-state functional magnetic resonance imaging scans. The ReHo method was used to analyze the imaging dataset. RESULTS: Compared with the control group, the ReHo values of the right inferior frontal gyrus orbital part, right middle frontal gyrus (MFG.R), left inferior parietal, but supramarginal and angular gyri, and left precentral gyrus (PreCG.L) were significantly increased and the ReHo value of the left posterior cingulate cortex/anterior cuneiform lobe was significantly decreased in schizophrenia patients. ROC analysis showed that the ReHo values of the MFG.R and PreCG.L might be regarded as potential markers in helping to identify patients. Furthermore, the PANSS scores in the patient group and the ReHo values showed a positive correlation between MFG.R ReHo values and general scores. CONCLUSIONS: Our results suggested that AOS patients had ReHo abnormalities. The ReHo values of these abnormal regions may serve as potential imaging biomarkers for the identification of AOS patients.

Mapping Brain Synergy Dysfunction in Schizophrenia: Understanding Individual Differences and Underlying Molecular Mechanisms.

To elucidate the brain-wide information interactions that vary and contribute to individual differences in schizophrenia (SCZ), an information-resolved method is employed to construct individual synergistic and redundant interaction matrices based on regional pairwise BOLD time-series from 538 SCZ and 540 normal controls (NC). This analysis reveals a stable pattern of regionally-specific synergy dysfunction in SCZ. Furthermore, a hierarchical Bayesian model is applied to deconstruct the patterns of whole-brain synergy dysfunction into three latent factors that explain symptom heterogeneity in SCZ. Factor 1 exhibits a significant positive correlation with Positive and Negative Syndrome Scale (PANSS) positive scores, while factor 3 demonstrates significant negative correlations with PANSS negative and general scores. By integrating the neuroimaging data with normative gene expression information, this study identifies that each of these three factors corresponded to a subset of the SCZ risk gene set. Finally, by combining data from NeuroSynth and open molecular imaging sources, along with a spatially heterogeneous mean-field model, this study delineates three SCZ synergy factors corresponding to distinct symptom profiles and implicating unique cognitive, neurodynamic, and neurobiological mechanisms.

MMCA-NET: A Multimodal Cross Attention Transformer Network for Nasopharyngeal Carcinoma Tumor Segmentation Based on a Total-Body PET/CT System.

Nasopharyngeal carcinoma (NPC) is a malignant tumor primarily treated by radiotherapy. Accurate delineation of the target tumor is essential for improving the effectiveness of radiotherapy. However, the segmentation performance of current models is unsatisfactory due to poor boundaries, large-scale tumor volume variation, and the labor-intensive nature of manual delineation for radiotherapy. In this paper, MMCA-Net, a novel segmentation network for NPC using PET/CT images that incorporates an innovative multimodal cross attention transformer (MCA-Transformer) and a modified U-Net architecture, is introduced to enhance modal fusion by leveraging cross-attention mechanisms between CT and PET data. Our method, tested against ten algorithms via fivefold cross-validation on samples from Sun Yat-sen University Cancer Center and the public HECKTOR dataset, consistently topped all four evaluation metrics with average Dice similarity coefficients of 0.815 and 0.7944, respectively. Furthermore, ablation experiments were conducted to demonstrate the superiority of our method over multiple baseline and variant techniques. The proposed method has promising potential for application in other tasks.

Accurate Whole-Brain Image Enhancement for Low-Dose Integrated PET/MR Imaging Through Spatial Brain Transformation.

Positron emission tomography/magnetic resonance imaging (PET/MRI) systems can provide precise anatomical and functional information with exceptional sensitivity and accuracy for neurological disorder detection. Nevertheless, the radiation exposure risks and economic costs of radiopharmaceuticals may pose significant burdens on patients. To mitigate image quality degradation during low-dose PET imaging, we proposed a novel 3D network equipped with a spatial brain transform (SBF) module for low-dose whole-brain PET and MR images to synthesize high-quality PET images. The FreeSurfer toolkit was applied to derive the spatial brain anatomical alignment information, which was then fused with low-dose PET and MR features through the SBF module. Moreover, several deep learning methods were employed as comparison measures to evaluate the model performance, with the peak signal-to-noise ratio (PSNR), structural similarity (SSIM) and Pearson correlation coefficient (PCC) serving as quantitative metrics. Both the visual results and quantitative results illustrated the effectiveness of our approach. The obtained PSNR and SSIM were 41.96 ± 4.91 dB (p < 0.01) and 0.9654 ± 0.0215 (p < 0.01), which achieved a 19% and 20% improvement, respectively, compared to the original low-dose brain PET images. The volume of interest (VOI) analysis of brain regions such as the left thalamus (PCC = 0.959) also showed that the proposed method could achieve a more accurate standardized uptake value (SUV) distribution while preserving the details of brain structures. In future works, we hope to apply our method to other multimodal systems, such as PET/CT, to assist clinical brain disease diagnosis and treatment.

IAIH-PG consensus for histological criteria of AIH: Multicentre validation with focus on chronic liver diseases in China.

BACKGROUND AND AIMS: The International AIH Pathology Group (IAIH-PG) put forward the new histological criteria of autoimmune hepatitis (AIH) in 2022, which have not undergone adequate verification. In this study, we verified the applicability of the new histological criteria in the population of Chinese patients with chronic liver disease, comparing it with the simplified criteria. METHODS: The gold standard for diagnosis in all patients was based on histological findings, combined with clinical manifestations and laboratory tests and determined after a follow-up period of at least 3 years. A total of 640 patients with various chronic liver diseases from multiple centres underwent scoring using the new histological criteria and the simplified criteria, comparing their diagnostic performance. RESULTS: In this study, the new histological criteria showed a sensitivity of 73.6% and 100% for likely and possible AIH, with specificities of 100% and 69.0% respectively. The coincidence rates of possible AIH for the new histological criteria, simplified histological criteria and simplified score were 81.7%, 72.8% and 69.7% respectively. For likely AIH, the rates were 89.2%, 75.9% and 65.6% respectively. Based on the new histological criteria, all patients with AIH were correctly diagnosed. Specifically, 73.6% were diagnosed with likely AIH and 26.4% were possible AIH. Additionally, the simplified histological criteria achieved a diagnosis rate of 98.6% for AIH, while the simplified score could only diagnose 53.8% of AIH. CONCLUSIONS: Compared with the simplified score and simplified histological criteria, the sensitivity and specificity of the new histological criteria for AIH were significantly improved. The results indicate that the new histological criteria exhibit high sensitivity and specificity for diagnosing AIH in China.

Profiling IOP-Responsive Genes in the Trabecular Meshwork and Optic Nerve Head in a Rat Model of Controlled Elevation of Intraocular Pressure.

Purpose: The rat controlled elevation of intraocular pressure (CEI) model allows study of in vivo responses to short-term exposure to defined intraocular pressures (IOP). In this study, we used NanoString technology to investigate in vivo IOP-related gene responses in the trabecular meshwork (TM) and optic nerve head (ONH) simultaneously from the same animals. Methods: Male and female rats (N = 35) were subjected to CEI for 8 hours at pressures simulating mean, daytime normotensive rat IOP (CEI-20), or 2.5× IOP (CEI-50). Naïve animals that received no anesthesia or surgical interventions served as controls. Immediately after CEI, TM and ONH tissues were dissected, RNA was isolated, and samples were analyzed with a NanoString panel containing 770 genes. Postprocessing, raw count data were uploaded to ROSALIND for differential gene expression analyses. Results: For the TM, 45 IOP-related genes were significant in the CEI-50 versus CEI-20 and CEI-50 versus naïve comparisons, with 15 genes common to both comparisons. Bioinformatics analysis identified Notch and transforming growth factor beta (TGFß) pathways to be the most up- and downregulated Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways, respectively. For ONH, 22 significantly differentially regulated genes were identified in the CEI-50 versus naïve comparison. Pathway analysis identified defense response and immune response as two significantly upregulated biological process pathways. Conclusions: This study demonstrated the ability to assay short-term IOP-responsive genes in both TM and ONH tissues simultaneously. In the TM, downregulation of TGFß pathway genes suggests that TM responses may reduce TGFß-induced extracellular matrix synthesis. For ONH, the initial response to short-term elevated IOP may be protective.