An axis of genetic heterogeneity in autism is indexed by age at diagnosis and is associated with varying developmental and mental health profiles.

There is growing recognition that earliest signs of autism need not clearly manifest in the first three years of life. To what extent is this variation in developmental trajectories associated with age at autism diagnosis? Does the genetic profile of autism vary with age at autism diagnosis? Using longitudinal data from four birth cohorts, we demonstrate that two different trajectories of socio-emotional behaviours are associated with age at diagnosis. We further demonstrate that the age at autism diagnosis is partly heritable (h2 SNP = 0.12, s.e.m = 0.01), and is associated with two moderately correlated (rg = 0.38, s.e.m = 0.07) autism polygenic factors. One of these factors is associated with earlier diagnosis of autism, lower social and communication abilities in early childhood. The second factor is associated with later autism diagnosis, increased socio-emotional difficulties in adolescence, and has moderate to high positive genetic correlations with Attention-Deficit/Hyperactivity Disorder, mental health conditions, and trauma. Overall, our research identifies an axis of heterogeneity in autism, indexed by age at diagnosis, which partly explains heterogeneity in autism and the profiles of co-occurring neurodevelopmental and mental health profiles. Our findings have important implications for how we conceptualise autism and provide one model to explain some of the diversity within autism.

Classification of Suicide Attempt Risk Using Environmental and Lifestyle Factors in 3 Large Youth Cohorts.

Importance: Suicide is the third-leading cause of death among US adolescents. Environmental and lifestyle factors influence suicidal behavior and can inform risk classification, yet quantifying and incorporating them in risk assessment presents a significant challenge for reproducibility and clinical translation. Objective: To quantify the aggregate contribution of environmental and lifestyle factors to youth suicide attempt risk classification. Design, Setting, and Participants: This was a cohort study in 3 youth samples: 2 national longitudinal cohorts from the US and the UK and 1 clinical cohort from a tertiary pediatric US hospital. An exposome-wide association study (ExWAS) approach was used to identify risk and protective factors and compute aggregate exposomic scores. Logistic regression models were applied to test associations and model fit of exposomic scores with suicide attempts in independent data. Youth from the Adolescent Brain Cognitive Development (ABCD) study, the UK Millennium Cohort Study (MCS), and the Children's Hospital of Philadelphia emergency department (CHOP-ED) were included in the study. Exposures: A single-weighted exposomic score that sums significant risk and protective environmental/lifestyle factors. Main Outcome and Measure: Self-reported suicide attempt. Results: A total of 40 364 youth were included in this analysis: 11 564 from the ABCD study (3 waves of assessment; mean [SD] age, 12.0 [0.7] years; 6034 male [52.2%]; 344 attempted suicide [3.0%]; 1154 environmental/lifestyle factors were included in the ABCD study), 9000 from the MCS cohort (mean [SD] age, 17.2 [0.3] years; 4593 female [51.0%]; 661 attempted suicide [7.3%]; 2864 environmental/lifestyle factors were included in the MCS cohort), and 19 800 from the CHOP-ED cohort (mean [SD] age, 15.3 [1.5] years; 12 937 female [65.3%]; 2051 attempted suicide [10.4%]; 36 environmental/lifestyle factors were included in the CHOP-ED cohort). In the ABCD discovery subsample, ExWAS identified 99 risk and protective exposures significantly associated with suicide attempt. A single weighted exposomic score that sums significant risk and protective exposures was associated with suicide attempt in an independent ABCD testing subsample (odds ratio [OR], 2.2; 95% CI, 2.0-2.6; P < .001) and explained 17.6% of the variance (based on regression pseudo-R2) in suicide attempt over and above that explained by age, sex, race, and ethnicity (2.8%) and by family history of suicide (6.3%). Findings were consistent in the MCS and CHOP-ED cohorts (explaining 22.6% and 19.3% of the variance in suicide attempt, respectively) despite clinical, demographic, and exposure differences. In all cohorts, compared with youth at the median quintile of the exposomic score, youth at the top fifth quintile were substantially more likely to have made a suicide attempt (OR, 4.3; 95% CI, 2.6-7.2 in the ABCD study; OR, 3.8; 95% CI, 2.7-5.3 in the MCS cohort; OR, 5.8; 95% CI, 4.7-7.1 in the CHOP-ED cohort). Conclusions and Relevance: Results suggest that exposomic scores of suicide attempt provided a generalizable method for risk classification that can be applied in diverse samples from clinical or population settings.

Low expression of selenoprotein S induces oxidative damage in cartilages.

Low levels of the indispensable trace element selenium (Se) can cause oxidative stress and disrupt environmental homeostasis in humans and animals. Selenoprotein S (Selenos), of which Se is a key component, is a member of the selenoprotein family involved in various biological processes. This study aimed to investigate whether low-level SELENOS gene expression can induce oxidative stress and decrease the antioxidative capacity of chondrocytes. Compared with control cells, SELENOS-knockdown ATDC5 cells showed substantially higher dihydroethidium, reactive oxygen species and malondialdehyde levels, and lower superoxide dismutase (SOD) expression. Knockout of the gene in C57BL/6 mice increased the 8-hydroxy-2-deoxyguanosine level considerably and decreased SOD expression in cartilages relative to the levels in wild-type mice. The results showed that the increased nuclear factor erythroid 2-related factor 2/heme oxygenase-1 signaling mediated by low-level SELENOS expression was involved in oxidative damage. The proliferative zone of the cartilage growth plate of SELENOS-knockout mice was shortened, suggesting cartilage differentiation dysfunction. In conclusion, this study confirmed that low-level Selenos expression plays a role in oxidative stress in cartilages.

Causal role of immune cells in hypertension: a bidirectional Mendelian randomization study.

Background: Although Hypertension (HTN) is considered to be a cardiovascular disease caused by multiple factors, the cause of it is still unknown. In this study, we aim to find out whether circulating immune cell characteristics have an impact on susceptibility to HTN. Methods: This study employed a comprehensive two-sample Mendelian randomization (MR) analysis to investigate the causal association between immune cell characteristics and HTN. Utilizing publicly accessible genetic data, we examined the causal relationship between HTN and the susceptibility to 731 immune cell signatures. To ensure the reliability and validity of the findings, a comprehensive sensitivity analysis was conducted to assess heterogeneity, confirm the robustness of the results and evaluate the presence of horizontal pleiotropy. Results: After FDR correction, immune phenotype had an effect on HTN. In our study, one immunophenotype was identified as being positively associated with HTN risk significance: HLA DR on CD33- HLA DR+. In addition, we examined 8 immune phenotype with no statistically significant effect of HTN, but it is worth mentioning that they had an unadjusted low P-value phenotype. Conclusions: Our MR study by genetic means demonstrated the close relationship between HTN and immune cells, thus providing guidance for future clinical prediction and subsequent treatment of HTN.

Brain topology improved spiking neural network for efficient reinforcement learning of continuous control.

The brain topology highly reflects the complex cognitive functions of the biological brain after million-years of evolution. Learning from these biological topologies is a smarter and easier way to achieve brain-like intelligence with features of efficiency, robustness, and flexibility. Here we proposed a brain topology-improved spiking neural network (BT-SNN) for efficient reinforcement learning. First, hundreds of biological topologies are generated and selected as subsets of the Allen mouse brain topology with the help of the Tanimoto hierarchical clustering algorithm, which has been widely used in analyzing key features of the brain connectome. Second, a few biological constraints are used to filter out three key topology candidates, including but not limited to the proportion of node functions (e.g., sensation, memory, and motor types) and network sparsity. Third, the network topology is integrated with the hybrid numerical solver-improved leaky-integrated and fire neurons. Fourth, the algorithm is then tuned with an evolutionary algorithm named adaptive random search instead of backpropagation to guide synaptic modifications without affecting raw key features of the topology. Fifth, under the test of four animal-survival-like RL tasks (i.e., dynamic controlling in Mujoco), the BT-SNN can achieve higher scores than not only counterpart SNN using random topology but also some classical ANNs (i.e., long-short-term memory and multi-layer perception). This result indicates that the research effort of incorporating biological topology and evolutionary learning rules has much in store for the future.

Cyborg islets: implanted flexible electronics reveal principles of human islet electrical maturation.

Flexible electronics implanted during tissue formation enable chronic studies of tissue-wide electrophysiology. Here, we integrate tissue-like stretchable electronics during organogenesis of human stem cell-derived pancreatic islets, stably tracing single-cell extracellular spike bursting dynamics over months of functional maturation. Adapting spike sorting methods from neural studies reveals maturation-dependent electrical patterns of α and ß-like (SC-α and ß) cells, and their stimulus-coupled dynamics. We identified two major electrical states for both SC-α and ß cells, distinguished by their glucose threshold for action potential firing. We find that improved hormone stimulation capacity during extended culture reflects increasing numbers of SC-α/ß cells in low basal firing states, linked to energy and hormone metabolism gene upregulation. Continuous recording during further maturation by entrainment to daily feeding cycles reveals that circadian islet-level hormone secretion rhythms reflect sustained and coordinate oscillation of cell-level SC-α and ß electrical activities. We find that this correlates with cell-cell communication and exocytic network induction, indicating a role for circadian rhythms in coordinating system-level stimulus-coupled responses. Cyborg islets thus reveal principles of electrical maturation that will be useful to build fully functional in vitro islets for research and therapeutic applications.

Success of susceptibility-guided eradication of Helicobacter pylori in a region with high secondary clarithromycin and levofloxacin resistance rates.

BACKGROUND: Resistance to clarithromycin (CLA) and levofloxacin (LFX) of Helicobacter pylori (H. pylori) is increasing in severity, and successful eradication is essential. Presently, the eradication success rate has greatly declined, leaving a large number of patients with previous treatment histories. AIM: To investigate secondary resistance rates, explore risk factors for antibiotic resistance, and assess the efficacy of susceptibility-guided therapy. METHODS: We recruited 154 subjects positive for Urea Breath Test who attended The First Affiliated Hospital of China Medical University between July 2022 and April 2023. Participants underwent a string test after an overnight fast. The gastric juice was obtained and transferred to vials containing storage solution. Subsequently, DNA extraction and the specific DNA amplification were performed using quantitative polymerase chain reaction (qPCR). Demographic information was also analyzed as part of the study. Based on these results, the participants were administered susceptibility-guided treatment. Efficacy was compared with that of the empiric treatment group. RESULTS: A total of 132 individuals tested positive for the H. pylori ureA gene by qPCR technique. CLA resistance rate reached a high level of 82.6% (n = 109), LFX resistance rate was 69.7% (n = 92) and dual resistance was 62.1% (n = 82). Gastric symptoms [odds ratio (OR) = 2.782; 95% confidence interval (95%CI): 1.076-7.194; P = 0.035] and rural residence (OR = 5.152; 95%CI: 1.407-18.861; P = 0.013) were independent risk factors for secondary resistance to CLA and LFX, respectively. A total of 102 and 100 individuals received susceptibility-guided therapies and empiric treatment, respectively. The antibiotic susceptibility-guided treatment and empiric treatment groups achieved successful eradication rates of 75.5% (77/102) and 59.0% (59/411) by the intention-to-treat (ITT) analysis and 90.6% (77/85) and 70.2% (59/84) by the per-protocol (PP) analysis, respectively. The eradication rates of these two treatment strategies were significantly different in both ITT (P = 0.001) and PP (P = 0.012) analyses. CONCLUSION: H. pylori presented high secondary resistance rates to CLA and LFX. For patients with previous treatment failures, treatments should be guided by antibiotic susceptibility tests or regional antibiotic resistance profile.

Direct 3D Printing of Recycled PET/PP Granules by Shear Screw Extrusion.

This article introduces a one-step extrusion-based fused deposition modeling (FDM) approach for the challenging separation of polypropylene (PP) and polyethylene terephthalate (PET) during recycling. A shear screw printer (SSP) with shear elements was designed, and it was compared to a conventional single-screw printer (CSP) to investigate the differences in print stability, degradation levels, tensile performance, molecular orientation, and crystallization when preparing recycled PP and recycled PET blends. Although the retention effect of the SSP screw slightly increases the degradation of the blended rPP/rPET, the strong shear (2.6 × 104 s-1) applied near the extrusion exit improves the blending efficiency. The SSP also enhances molecular orientation, modulus of the parts, and reduces performance fluctuations. Additionally, the SSP has the potential to simplify the recycling process, enabling the transformation of blended recycled materials into products with just one melt process.

Five-week of solution-focused group counseling successfully reduces internet addiction among college students: A pilot study.

Background and Aims: In the digital age, Internet addiction (IA) was deemed an epidemic and few treatments had been effectively developed for it. Here, we proposed a solution-focused group counseling (SFGC) as a potentially solution to reduce Internet addiction among college students. The present study examined the short- and long-term effect of a five-week solution-focused group counseling intervention on Internet addiction. Methods: Thirty-two participants were recruited and randomly assigned to either the experimental or control group, and twenty-six participants completed the whole intervention. The experimental group (n = 14) received the intervention, while control group (n = 12) did not. The revised version of the Chinese Internet Addiction Scale (CIAS-R), the Future Time Perspective, and resting-state EEG were administered pre-intervention, post-intervention, and at two follow-up tests (one month and six months after intervention). Results: The results showed that the scores of the CIAS-R in the experimental group were significantly decreased after intervention, and these effects could be sustained for one month and six months follow-ups. Additionally, the intervention conducted an increase in future time perspective. EEG results further suggested that the alpha, beta, and gamma absolute power decreased after the intervention. Conclusion: These results from the pilot-study primarily suggested that solution-focused group counseling could be an effective intervention for Internet addiction.

Clinical features and relapse risks factors of IgG4 related disease: a single-center retrospective study.

OBJECTIVE: The aim of this study was to observe the demographic and clinical characteristics of immunoglobulin (Ig) G4-related disease (IgG4-RD). We aimed to compare different treatment methods and to identify the risk factors for non-response and relapse after treatment. METHODS: We performed a retrospective study of 201 IgG4-RD patients initially diagnosed and treated at the First Affiliated Hospital of China Medical University from January 2016 to December 2020. Patients' sex, age, clinical manifestations, baseline biochemical values, the number of organs involved, and the type of organ involvement were recorded. All patients received glucocorticoid (GC) monotherapy or GC + immunosuppressant combination therapy. The serum IgG4 concentration as well as the details of clinical response, relapse, and side effects were recorded at 1, 3, 6, and 12 months after treatment. RESULTS: The incidence of IgG4-RD was primarily centered in the age group of 50-70 years old, and the proportion of affected male patients increased with age. The most common clinical symptom was swollen glands or eyes (42.79%). The rates of single- and double-organ involvement were 34.83% and 46.27%, respectively. The pancreas (45.77%) was the most frequently involved organ in cases of single-organ involvement, and the pancreas and biliary tract (45.12%) was the most common organ combination in cases of double-organ involvement. Correlation analysis showed that the number of organs involved was positively related to the serum IgG4 concentration (r = 0.161). The effective rate of GC monotherapy was 91.82%, the recurrence rate was 31.46%, and the incidence of adverse reactions was 36.77%. Meanwhile, the effective rate of GC + immunosuppressant combination therapy was 88.52%, the recurrence rate was 19.61%, and the adverse reaction rate was 41.00%. There were no statistically significant differences in response, recurrence, and adverse reactions. The overall response rate within 12 months was 90.64%. Age (< 50 years old) and aorta involvement were significantly associated with non-response. The overall recurrence rate within 12 months was 26.90%. Age (< 50 years old), low serum C4 concentration, a high number of involved organs, and lymph node involvement were significantly associated with recurrence. CONCLUSION: The clinical features vary among different age groups and according to gender. The number of organs involved in IgG4-RD is related to the serum IgG4 concentration. Age (< 50 years old), low serum C4 concentration, a high number of involved organs, and lymph node involvement are risk factors for recurrence.

Spontaneous brain microstates correlate with impaired inhibitory control in internet addiction disorder.

The prevalence of the Internet addiction disorder (IAD) has been on the rise, making it increasingly imperative to explore the neurophysiological markers of it. Using the whole-brain imaging approach of EEG microstate analysis, which treats multichannel EEG recordings as a series of quasi-steady states, similar as the resting-state networks found by fMRI, the present study aimed to investigate the specificity of the IAD in class C of the four canonical microstates. The existing EEG data of 40 participants (N = 20 for each group) was used, and correlation between the time parameters of microstate C and the performance of the Go/NoGo task was analyzed. Results suggested that the duration and coverage of class C were significantly reduced in the IAD group as compared to the healthy control (HC) group. Furthermore, the duration of class C had a significant inverse correlation with Go RTs in the IAD group. These results implied that class C might serve as a neurophysiological marker of IAD, helping to understand the underlying neural mechanism of inhibitory control in IAD.

HMGA2 knockdown alleviates the progression of nonalcoholic fatty liver disease (NAFLD) by downregulating SNAI2 expression.

Non-alcoholic fatty liver disease (NAFLD) is a complex disease that is considered as the next major health epidemic with alarmingly increasing global prevalence. To explore the pathogenesis of NAFLD, data from GSE118892 were analyzed. High mobility group AT-hook 2 (HMGA2), a member of the high mobility group family, is declined in liver tissues of NAFLD rats. However, its role in NAFLD remains unknown. This study attempted to identify the multiple roles of HMGA2 in NAFLD process. NAFLD was induced in rats using a high-fat diet (HFD). In vivo, HMGA2 knockdown using adenovirus system attenuated liver injury and liver lipid deposition, accompanied by decreased NAFLD score, increased liver function, and decreased CD36 and FAS, indicating the deceleration of NAFLD progression. Moreover, HMGA2 knockdown restrained liver inflammation by decreasing the expression of related inflammatory factors. Importantly, HMGA2 knockdown attenuated liver fibrosis via downregulating the expression of fibrous proteins, and inhibiting the activation of TGF-ß1/SMAD signaling pathway. In vitro, HMGA2 knockdown relieved palmitic acid (PA)-induced hepatocyte injury and attenuated TGF-ß1-induced liver fibrosis, consistent with in vivo findings. Strikingly, HMGA2 activated the transcription of SNAI2, which was evidenced by the dual luciferase assays. Moreover, HMGA2 knockdown largely downregulated SNAI2 levels. Indeed, SNAI2 overexpression effectively blocked the inhibitory effect of HMGA2 knockdown on NAFLD. Totally, our findings reveal that HMGA2 knockdown alleviates the progression of NAFLD by directly regulating the transcription of SNAI2. HMGA2 inhibition may emerge as a potential therapeutic target for NAFLD.

Explainable multi-task learning for multi-modality biological data analysis.

Current biotechnologies can simultaneously measure multiple high-dimensional modalities (e.g., RNA, DNA accessibility, and protein) from the same cells. A combination of different analytical tasks (e.g., multi-modal integration and cross-modal analysis) is required to comprehensively understand such data, inferring how gene regulation drives biological diversity and functions. However, current analytical methods are designed to perform a single task, only providing a partial picture of the multi-modal data. Here, we present UnitedNet, an explainable multi-task deep neural network capable of integrating different tasks to analyze single-cell multi-modality data. Applied to various multi-modality datasets (e.g., Patch-seq, multiome ATAC + gene expression, and spatial transcriptomics), UnitedNet demonstrates similar or better accuracy in multi-modal integration and cross-modal prediction compared with state-of-the-art methods. Moreover, by dissecting the trained UnitedNet with the explainable machine learning algorithm, we can directly quantify the relationship between gene expression and other modalities with cell-type specificity. UnitedNet is a comprehensive end-to-end framework that could be broadly applicable to single-cell multi-modality biology. This framework has the potential to facilitate the discovery of cell-type-specific regulation kinetics across transcriptomics and other modalities.

Ulcerative colitis complicated by primary sclerosing cholangitis and autoimmune hepatitis overlap syndrome: a case report and literature review.

Primary sclerosing cholangitis (PSC), autoimmune hepatitis (AIH), and ulcerative colitis (UC) are immune diseases of the digestive system. Some patients develop overlap syndrome, the presentation of two or more of the clinical, biochemical, immunological, and histological features of these conditions simultaneously or sequentially. The incidence of UC in PSC-AIH overlap syndrome is as high as 50%. In contrast, PSC-AIH overlap syndrome is rare in UC patients. However, because it has a low prevalence and has been studied in less detail, PSC is often misdiagnosed as primary biliary cholangitis (PBC) in its early stage. Herein, we reported a case of a 38-year-old male patient who presented to a clinician in 2014 with irregular bowel habits. A colonoscopy suggested UC. In 2016, the patient was found to have abnormal liver function and was diagnosed with PBC by pathology. He was treated with ursodeoxycholic acid (UDCA) but this had no effect on his liver function. Additional liver biopsies in 2018 indicated PBC-AIH overlap syndrome. The patient refused hormone therapy for personal reasons. Following UDCA monotherapy, his liver function remained abnormal. The patient was reexamined after repeated abnormal liver function tests and bowel symptoms. Systematic laboratory testing, imaging diagnosis, colonoscopy, liver biopsy, and various pathological examinations conducted in 2021 were used to diagnose the patient with PSC-AIH-UC overlap syndrome. He was treated with various drugs, including UDCA, methylprednisolone, mycophenolate mofetil, and mesalazine. His liver function improved significantly after treatment and follow-up is ongoing. Our case report highlights the need to raise awareness about rare and difficult-to-diagnose clinical disorders.

Brain structural and functional alterations in individuals with combined overweight/obesity and mood disorders: A systematic review of neuroimaging studies.

Growing evidence suggests there is a bidirectional relationship between depression and obesity, which are associated with structural and functional brain abnormalities. However, the underlying neurobiological mechanisms subserving the foregoing associations have yet to be characterized. It is necessary to summarize the neuroplastic brain changes in relation to depression and obesity. We systematically searched articles from 1990 to November 2022 on databases including MEDLINE/PubMed, Web of Science, PsycINFO. Only neuroimaging studies within the scope of potential differences in brain function and structure in individuals with depression and obesity/ BMI changes were included. Twenty-four eligible studies were included in the review herein, consisting of 17 studies reporting changes in brain structure, 4 studies reporting abnormal brain function, and 3 studies reporting both changes in brain structure and function. Results indicated an interaction between depression and obesity on brain functions, and their influence on brain structure is both extensive and specific. Overall, reduced whole brain, intracranial, and gray matter volume (e.g. frontal, temporal gyri, thalamic, and hippocampal) and impaired white matter integrity was observed in persons with depression and obesity comorbidity. Additional evidence on resting state fMRI reveals select brain regions associated with cognitive control, emotion regulation, and reward functions. Due to the diversity of tasks in task fMRI, the distinct neural activation patterns are revealed separately. The bidirectional relationship between depression and obesity reflects different characteristics in brain structure and function. Longitudinal designs should be reinforced in follow-up studies.

Hepatitis B virus pathogenesis relevant immunosignals uncovering amino acids utilization related risk factors guide artificial intelligence-based precision medicine.

Background: Although immune microenvironment-related chemokines, extracellular matrix (ECM), and intrahepatic immune cells are reported to be highly involved in hepatitis B virus (HBV)-related diseases, their roles in diagnosis, prognosis, and drug sensitivity evaluation remain unclear. Here, we aimed to study their clinical use to provide a basis for precision medicine in hepatocellular carcinoma (HCC) via the amalgamation of artificial intelligence. Methods: High-throughput liver transcriptomes from Gene Expression Omnibus (GEO), NODE (https://www.bio.sino.org/node), the Cancer Genome Atlas (TCGA), and our in-house hepatocellular carcinoma patients were collected in this study. Core immunosignals that participated in the entire diseases course of hepatitis B were explored using the "Gene set variation analysis" R package. Using ROC curve analysis, the impact of core immunosignals and amino acid utilization related gene on hepatocellular carcinoma patient's clinical outcome were calculated. The utility of core immunosignals as a classifier for hepatocellular carcinoma tumor tissue was evaluated using explainable machine-learning methods. A novel deep residual neural network model based on immunosignals was constructed for the long-term overall survival (LS) analysis. In vivo drug sensitivity was calculated by the "oncoPredict" R package. Results: We identified nine genes comprising chemokines and ECM related to hepatitis B virus-induced inflammation and fibrosis as CLST signals. Moreover, CLST was co-enriched with activated CD4+ T cells bearing harmful factors (aCD4) during all stages of hepatitis B virus pathogenesis, which was also verified by our hepatocellular carcinoma data. Unexpectedly, we found that hepatitis B virus-hepatocellular carcinoma patients in the CLSThighaCD4high subgroup had the shortest overall survival (OS) and were characterized by a risk gene signature associated with amino acids utilization. Importantly, characteristic genes specific to CLST/aCD4 showed promising clinical relevance in identifying patients with early-stage hepatocellular carcinoma via explainable machine learning. In addition, the 5-year long-term overall survival of hepatocellular carcinoma patients can be effectively classified by CLST/aCD4 based GeneSet-ResNet model. Subgroups defined by CLST and aCD4 were significantly involved in the sensitivity of hepatitis B virus-hepatocellular carcinoma patients to chemotherapy treatments. Conclusion: CLST and aCD4 are hepatitis B virus pathogenesis-relevant immunosignals that are highly involved in hepatitis B virus-induced inflammation, fibrosis, and hepatocellular carcinoma. Gene set variation analysis derived immunogenomic signatures enabled efficient diagnostic and prognostic model construction. The clinical application of CLST and aCD4 as indicators would be beneficial for the precision management of hepatocellular carcinoma.

Tuberous Sclerosis Complex With Multiple Organ Tumors: Case Report and Literature Review.

Pancreatic neuroendocrine neoplasms (PNEN) are tumors that originate from neuroendocrine cells. Only about 1% patients are related to mutation of tuberous sclerosis complex gene. Here, we reported a rare case with involvement of multiple organs and space-occupying lesions. Initially, the patient was thought to have metastasis of a pancreatic tumor. However, the patient was diagnosed as pancreatic neuroendocrine tumors, liver perivascular epithelioid tumors, splenic hamartoma, and renal angiomyolipoma by pathological examination after surgery. We performed genetic mutation detection to identify that tuberous sclerosis complex 2 gene presented with a heterozygous variant. Tuberous sclerosis often presents with widespread tumors, but it is less common to present with pancreatic neuroendocrine tumors and liver perivascular tumors as highlighted in the case. So we analyzed the relationship between TSC gene mutations and related tumors. And we also reviewed the current molecular mechanisms and treatments for tuberous sclerosis complex.

Genetic correlates of phenotypic heterogeneity in autism.

The substantial phenotypic heterogeneity in autism limits our understanding of its genetic etiology. To address this gap, here we investigated genetic differences between autistic individuals (nmax = 12,893) based on core and associated features of autism, co-occurring developmental disabilities and sex. We conducted a comprehensive factor analysis of core autism features in autistic individuals and identified six factors. Common genetic variants were associated with the core factors, but de novo variants were not. We found that higher autism polygenic scores (PGS) were associated with lower likelihood of co-occurring developmental disabilities in autistic individuals. Furthermore, in autistic individuals without co-occurring intellectual disability (ID), autism PGS are overinherited by autistic females compared to males. Finally, we observed higher SNP heritability for autistic males and for autistic individuals without ID. Deeper phenotypic characterization will be critical in determining how the complex underlying genetics shape cognition, behavior and co-occurring conditions in autism.

Prevalence and Risk Factors of Gallbladder Stones and Polyps in Liaoning, China.

Objective: To investigate the incidence and risk factors of gallbladder stones and polyps in individuals undergoing physical examinations in Liaoning province, China. Methods: This is a retrospective study of adults who underwent routine health examinations at Xikang Medical Center in Liaoning Province (Shenyang, Dandong, and Dalian) from 01/2016 to 12/2020. The routine health examination included anthropometry, blood tests, and liver ultrasound. Based on liver ultrasound results, patients were grouped into those with gallbladder stones, those with gallbladder polyps, those with both stones and polyps, and those with neither. Results: Of the 284,129 included subjects, 6,537 (2.30%) were diagnosed with gallbladder stones, and 18,873 (6.64%) were diagnosed with gallbladder polyps. The overall prevalence in Liaoning province increased each year, peaking in 2020. The prevalence of gallbladder stones was higher among females than males (2.39% vs. 2.23%, respectively), while the prevalence of gallbladder polyps was higher among males. The gallbladder polyp group had higher BMI, FBG, SBP, DBP, TG, TC, LDL-C, HDL-C, AST, ALP, GGT, BUN, Scr, SUA. Except for HDL-C, all factors were also higher in the gallbladder stone group. Patients with fatty liver had a higher prevalence of gallbladder stones and polyps than participants without fatty liver. Conclusion: The prevalence of gallbladder stones and polyps in Liaoning varies by sex, economic status of the city of residence, BMI, and metabolic indicators.

IgG4-Related Disease With Gastrointestinal Involvement: Case Reports and Literature Review.

IgG4-related disease is an immune-mediated chronic, systemic, and autoinflammatory disease that can affect various organs throughout the body. The most commonly affected areas are the pancreas and biliary system. Due to the diverse clinical manifestations of the disease, it affects widely distributed organs. Thus, it is often easy to misdiagnose or miss. The digestive tract is a rarely affected system, and most IgG4-related gastric diseases manifest as tumors detected by endoscopy. This article reports two special cases with IgG4-related disease involving atrophic gastritis and intestinal polyps to provide a more empirical and theoretical basis for clinical diagnosis and treatment.