Microglia-containing human brain organoids for the study of brain development and pathology.

Microglia are resident immune cells in the central nervous system, playing critical roles in brain development and homeostasis. Increasing evidence has implicated microglia dysfunction in the pathogenesis of various brain disorders ranging from psychiatric disorders to neurodegenerative diseases. Using a human cell-based model to illuminate the functional mechanisms of microglia will promote pathological studies and drug development. The recently developed microglia-containing human brain organoids (MC-HBOs), in-vitro three-dimensional cell cultures that recapitulate key features of the human brain, have provided a new avenue to model brain development and pathology. However, MC-HBOs generated from different methods differ in the origin, proportion, and fidelity of microglia within the organoids, and may have produced inconsistent results. To help researchers to develop a robust and reproducible model that recapitulates in-vivo signatures of human microglia to study brain development and pathology, this review summarized the current methods used to generate MC-HBOs and provided opinions on the use of MC-HBOs for disease modeling and functional studies.

Risk estimation for postoperative nausea and vomiting: development and validation of a nomogram based on point-of-care gastric ultrasound.

BACKGROUND: We aimed to develop a nomogram that can be combined with point-of-care gastric ultrasound and utilised to predict postoperative nausea and vomiting (PONV) in adult patients after emergency surgery. METHODS: Imaging and clinical data of 236 adult patients undergoing emergency surgery in a university hospital between April 2022 and February 2023 were prospectively collected. Patients were divided into a training cohort (n = 177) and a verification cohort (n = 59) in a ratio of 3:1, according to a random number table. After univariate analysis and multivariate logistic regression analysis of the training cohort, independent risk factors for PONV were screened to develop the nomogram model. The receiver operating characteristic curve, calibration curve, decision curve analysis (DCA) and clinical impact curve (CIC) were used to evaluate the prediction efficiency, accuracy, and clinical practicability of the model. RESULTS: Univariate analysis and multivariate logistic regression analysis showed that female sex, history of PONV, history of migraine and gastric cross-sectional area were independent risk factors for PONV. These four independent risk factors were utilised to construct the nomogram model, which achieved significant concordance indices of 0.832 (95% confidence interval [CI], 0.771-0.893) and 0.827 (95% CI, 0.722-0.932) for predicting PONV in the training and validation cohorts, respectively. The nomogram also had well-fitted calibration curves. DCA and CIC indicated that the nomogram had great clinical practicability. CONCLUSIONS: This study demonstrated the prediction efficacy, differentiation, and clinical practicability of a nomogram for predicting PONV. This nomogram may serve as an intuitive and visual guide for rapid risk assessment in patients with PONV before emergency surgery.

Shear Wave Elastography for Detecting Calf Muscle Stiffness: An Effective Tool for Assessing Sarcopenia.

OBJECTIVES: To explore the feasibility of shear wave elastography for evaluating sarcopenia. METHODS: The shear wave velocities (SWV) of the tibialis anterior, medial gastrocnemius, and soleus were measured in 130 subjects in the Second Affiliated Hospital of Fujian Medical University from January 2021 to June 2022. Consistency was evaluated in 20 cases using the intraclass correlation coefficient. According to the 2019 Asian Working Group for Sarcopenia（AWGS） diagnostic criteria, the patients were divided into a healthy and a sarcopenia group. The differences in SWV between the two groups were compared, and their correlation between calf muscles and muscle mass, grip strength, and pace were analyzed. The diagnostic cutoff value of calf muscle SWV for sarcopenia was obtained using receiver operating characteristic (ROC) curves, and the diagnostic efficacy of different ROC curves was compared. RESULTS: The SWV inter-group and intra-group correlation coefficients of the three lower limbs muscles were all greater than 0.85. Moreover, the corresponding SWV in the sarcopenia group were significantly smaller than those in the healthy control group (P < .05). Further, SWV were positively correlated with the appendicular skeletal muscle mass index (ASMI), grip strength, and gait speed. Finally, the SWV of the anterior tibialis and medial gastrocnemius muscles were 3.02 and 2.26 m/s, respectively, and their diagnostic efficacy for sarcopenia did not differ significantly (Z = 0.190, P = .8497). CONCLUSION: SWE can be used to detect the hardness of the anterior tibialis and medial gastrocnemius, calculate their muscle mass as an effective tool to evaluate sarcopenia.

Efficacy and Safety of Ultrasound-Guided Percutaneous Ablation for Adrenal Metastases: A Meta-Analysis.

OBJECTIVES: To assess the efficacy and safety of ultrasound-guided percutaneous ablation (US-PA) for adrenal metastases (AMs) using a meta-analysis. METHODS: A systematic search of PubMed, Cochrane, Web of Science, and Embase electronic databases was performed to identify studies on US-PA for AM. Seven studies published between January 2000 and August 2022 were analyzed, which resulted in a sample size of 140 patients. Both random effects and common effects meta-analysis models were used to analyze the following efficacy and safety outcomes: the first and secondary technical success rate, 1-year overall survival rates, 1-year local tumor control rate, incidence rate of intraoperative hypertensive crises, and major complications. The subgroup analysis was performed to explore the origin of heterogeneity. RESULTS: Among 140 patients from 7 studies included in this meta-analysis: 51 (36.43%) underwent radiofrequency ablation (RFA), and 89 (63.57%) underwent microwave ablation (MWA). Pooled data analysis revealed that the first and secondary technical success rates were 85% (95% confidence interval [CI], 73-96) and 99% (95% CI, 96-100), the 1-year overall survival rate was 83% (95% CI, 71-93), the 1-year local tumor control rate was 83% (95% CI, 75-90), and the incidence rate of intraoperative hypertensive crises was 14% (95% CI, 8-20). The overall rate of major complications was 3.6%. In the subgroup analysis, lower heterogeneity was indicated to be associated with mean tumor size and ablation type. CONCLUSIONS: This meta-analysis showed that US-PA can be both effective and safe for AM in terms of overall survival, technical success rate, and local control for AM.

Reference range of fetal thorax using two-dimensional and three-dimensional ultrasound VOCAL technique and application in fetal thoracic malformations.

BACKGROUND: To establish the normal reference range of fetal thorax by two-dimensional (2D) and three-dimensional (3D) ultrasound VOCAL technique and evaluate the application in diagnosing fetal thoracic malformations. METHODS: A prospective cross-sectional study was undertaken involving 1077 women who have a normal singleton pregnancy at 13-40 weeks gestational age (GA). 2D ultrasound and 3D ultrasound VOCAL technique were utilized to assess fetal thoracic transverse diameter, thoracic anteroposterior diameter, thoracic circumference, thoracic area, lung volume, thoracic volume and lung-to-thoracic volume ratio. The nomograms of 2D and 3D fetal thoracic measurements were created to GA. 50 cases were randomly selected to calculate intra- and inter-observer reliability and agreement. In addition, the case groups including congenital skeletal dysplasia (SD) (15), congenital diaphragmatic hernia (CDH) (30), pulmonary sequestration (PS) (25) and congenital cystic adenomatoid malformation (CCAM) (36) were assessed by the nomograms and followed up subsequently. RESULTS: Both 2D and 3D fetal thoracic parameters increased with GA using a quadratic regression equation. The intra- and inter-observer reliability and agreement of each thoracic parameter were excellent. 2D fetal thoracic parameters could initially evaluate the fetal thoracic development and diagnose the skeletal thoracic deformity, and lung volume, thoracic volume and lung-to-thorax volume ratio were practical to diagnose and differentiate CDH, PS and CCAM. CONCLUSION: We have established the normal fetal thoracic reference range at 13-40 weeks, which has a high value in diagnosing congenital thoracic malformations.

Evaluating Skin Involvement in Systemic Sclerosis Using High-Frequency Ultrasound and Virtual Touch Tissue Imaging.

OBJECTIVE: This study aimed to explore the diagnostic significance of high-frequency ultrasound combined with visual touch tissue imaging quantification (VTIQ) in the diagnosis and management of systemic sclerosis (SSc). METHODS: Patients diagnosed with SSc and normal volunteers were recruited and divided into an experimental group and a control group, with 30 cases in each group, respectively. The skin thickness at six sites was assessed using high-frequency ultrasound, and the shear wave velocity (SWV) was determined using the VTIQ method. The differences in skin thickness and SWV between the experimental group and the control group were compared and a receiver operating characteristic (ROC) curve was plotted. The value of high-frequency ultrasound, VTIQ, and high-frequency ultrasound combined with VTIQ for evaluating skin involvement in SSc was determined. RESULTS: The difference in SWV sum at six sites and the thickness sum was statistically significant (all p = 0.000 < 0.05) from that of the control group, and there was a strong association between the SWV sum, thickness sum, and Rodnan skin score at the six sites in the experimental group (p = 0.000, r = 0.726; p = 0.000, r = 0.679). Based on the ROC curve, the area under the curve (AUC) for high-frequency ultrasound examination was 0.789. The AUC for VTIQ examination was 0.893, while the AUC for high-frequency ultrasound combined with VTIQ examination was 0.923. The combined examination method showed the highest AUC, indicating the best diagnostic performance. CONCLUSION: The integration of high-frequency ultrasound and VTIQ provides a quantitative approach for assessing the extent of skin involvement in SSc patients, offering valuable insights for clinical diagnosis and treatment purposes.

Establishment and Validation of a Predictive Model for Sarcopenia Based on 2-D Ultrasound and Shear Wave Elastography in the Medial Gastrocnemius Muscle.

OBJECTIVE: To develop and validate a predictive model for sarcopenia. METHODS: A total of 240 subjects who visited our hospital between August 2021 and May 2023 were randomly divided by time of entry into a training set containing 2/3 of patients and a validation set containing 1/3 of patients. The muscle thickness (MT), echo intensity (EI), and shear wave velocity (SWV) of the medial gastrocnemius muscle were measured. Indicators that were meaningful in the univariate analysis in the training set were included in a binary logistic regression to derive a regression model, and the model was evaluated using a consistency index, calibration plot, and clinical validity curve. Diagnostic efficacy and clinical applicability were compared between the model and unifactorial indicators. RESULTS: Four meaningful variables, age, body mass index (BMI), MT, and SWV, were screened into the predictive model. The model was Logit Y = 21.292 + 0.065 × Age - 0.411 × BMI - 0.524 × MT - 3.072 × SWV. The model was well differentiated with an internally validated C-index of 0.924 and an external validation C-index of 0.914. The calibration plot predicted probabilities against actual probabilities showed excellent agreement. The specificity, sensitivity, and Youden's index of the model were 73.80%, 97.40%, and 71.20%, respectively, when using the diagnostic cut-off value of >0.279 for sarcopenia. The logistic model had higher diagnostic efficacy (p < 0.001) and higher net clinical benefit (p < 0.001) over the same threshold range compared to indicators. CONCLUSION: The logistic model of sarcopenia has been justified to have good discriminatory, calibrated, and clinical validity, and has higher diagnostic value than indicators.

The association between Parkinson's disease and autoimmune diseases: A systematic review and meta-analysis.

Parkinson's disease (PD) is a neurodegenerative disorder that frequently occurs in the older population. Previous epidemiological studies have suggested an association between PD and autoimmune diseases (AIDs). However, some studies have shown conflicting results. This study aimed to summarize existing epidemiological studies on the association between PD with AIDs and to conduct a meta-analysis of combinable results. Four electronic databases (PubMed, Embase, Web of Science Core Collection, and MEDLINE) were searched from each database's inception date until December 12, 2022. All studies that explored the relationship between PD and AIDs were included for quantitative analysis and qualitative review. The pooled relative risk with 95% confidence intervals (CIs) was calculated using a random or fixed effects model. A total of 46 observational studies involving 873,643 patients and 13,402,821 controls were included; ultimately, 38 studies were included in the meta-analysis. The risk of PD combined with AIDs was significantly higher (odds ratio [OR]=1.55, 95% CI: 1.33-1.81), and subgroup analysis found no significant differences in risk by study type, gender, age, and race. Regarding the AID types, the results showed an increased risk of PD combined with bullous pemphigoid (OR=2.67, 95% CI: 2.15-3.31), inflammatory bowel disease (OR=1.30, 95% CI: 1.18-1.45), Crohn's disease (OR=1.30, 95% CI: 1.20-1.42), ulcerative colitis (OR=1.31, 95% CI: 1.14-1.50), Sjögren's syndrome (OR=1.61, 95% CI: 1.24-2.09), and Graves' disease (OR=1.45, 95% CI: 1.24-1.70) than controls. However, there appeared to be no significant association between PD and systemic lupus erythematosus (OR=0.82, 95% CI: 0.66-1.03), multiple sclerosis (OR=2.02, 95% CI: 0.87-4.70), rheumatoid arthritis (OR=0.79, 95% CI: 0.61-1.03), or celiac disease (OR=1.16, 95% CI: 0.79-1.69). This study supports the existence of a strong link between AIDs and PD. When PD and AIDs are identified, clinicians need to be aware of the possibility of coexistence. However, there are some limitations of this study, such as the apparent heterogeneity of some of the results and the fact that most of the included study types were retrospective. Therefore, future larger prospective cohort studies are needed to further explore the interaction between PD and AIDs. Systematic review registration: INPLASY, identifier INPLASY202280088.

Human forebrain organoids-based multi-omics analyses reveal PCCB's regulation on GABAergic system contributing to schizophrenia.

Identifying genes whose expression is associated with schizophrenia (SCZ) risk by transcriptome-wide association studies (TWAS) facilitates downstream experimental studies. Here, we integrated multiple published datasets of TWAS (including FUSION, PrediXcan, summary-data-based Mendelian randomization (SMR), joint-tissue imputation approach with Mendelian randomization (MR-JTI)), gene coexpression, and differential gene expression analysis to prioritize SCZ candidate genes for functional study. Convergent evidence prioritized Propionyl-CoA Carboxylase Subunit Beta ( PCCB ), a nuclear-encoded mitochondrial gene, as an SCZ risk gene. However, the PCCB ’s contribution to SCZ risk has not been investigated before. Using dual luciferase reporter assay, we identified that SCZ-associated SNP rs35874192, an eQTL SNP for PCCB , showed differential allelic effects on transcriptional activities. PCCB knockdown in human forebrain organoids (hFOs) followed by RNA-seq revealed dysregulation of genes enriched with multiple neuronal functions including gamma-aminobutyric acid (GABA)-ergic synapse, as well as genes dysregulated in postmortem brains of SCZ patients or in cerebral organoids derived from SCZ patients. The metabolomic and mitochondrial function analyses confirmed the deceased GABA levels resulted from reduced tricarboxylic acid cycle in PCCB knockdown hFOs. Multielectrode array recording analysis showed that PCCB knockdown in hFOs resulted into SCZ-related phenotypes including hyper-neuroactivities and decreased synchronization of neural network. In summary, this study utilized hFOs-based multi-omics data and revealed that PCCB downregulation may contribute to SCZ risk through regulating GABAergic system, highlighting the mitochondrial function in SCZ.

Human forebrain organoid-based multi-omics analyses of PCCB as a schizophrenia associated gene linked to GABAergic pathways.

Identifying genes whose expression is associated with schizophrenia (SCZ) risk by transcriptome-wide association studies (TWAS) facilitates downstream experimental studies. Here, we integrated multiple published datasets of TWAS, gene coexpression, and differential gene expression analysis to prioritize SCZ candidate genes for functional study. Convergent evidence prioritized Propionyl-CoA Carboxylase Subunit Beta (PCCB), a nuclear-encoded mitochondrial gene, as an SCZ risk gene. However, the PCCB's contribution to SCZ risk has not been investigated before. Using dual luciferase reporter assay, we identified that SCZ-associated SNPs rs6791142 and rs35874192, two eQTL SNPs for PCCB, showed differential allelic effects on transcriptional activities. PCCB knockdown in human forebrain organoids (hFOs) followed by RNA sequencing analysis revealed dysregulation of genes enriched with multiple neuronal functions including gamma-aminobutyric acid (GABA)-ergic synapse. The metabolomic and mitochondrial function analyses confirmed the decreased GABA levels resulted from inhibited tricarboxylic acid cycle in PCCB knockdown hFOs. Multielectrode array recording analysis showed that PCCB knockdown in hFOs resulted into SCZ-related phenotypes including hyper-neuroactivities and decreased synchronization of neural network. In summary, this study utilized hFOs-based multi-omics analyses and revealed that PCCB downregulation may contribute to SCZ risk through regulating GABAergic pathways, highlighting the mitochondrial function in SCZ.

Establishment and verification of an osteoporosis risk model in patients with rheumatoid arthritis: a valuable new model.

To establish a model for osteoporosis risk in patients with rheumatoid arthritis and validate the model. A newly generated predictive model has been suggested to have good differentiation, calibration, and clinical validity and may be a useful clinical model for predicting osteoporosis in patients with rheumatoid arthritis. PURPOSE: To establish a prediction model for osteoporosis risk in patients with rheumatoid arthritis and validate the model internally and externally. METHODS: A total of 270 patients with rheumatoid arthritis who underwent bone mineral density measurement at our hospital from June 2019 to June 2020 were enrolled in the study. The patients were divided into two groups according to their entry time: a training set containing the first 2/3 of the patients (n = 180) and a validation set containing the remaining 1/3 of the patients (n = 90). Binary logistic regression analysis was used to establish the regression models, and the concordance index (C-index), calibration plot, and decision curve analysis were used to evaluate the prediction model. RESULTS: Five variables, including age (X1), course of disease (X2), the disease activity score using 28 joint counts (DAS28) (X4), anti-cyclic citrullinated peptide antibody (CCP) (X7), and 7-joint ultrasonic bone erosion (X14), were selected to enter the model. The prediction model is Logit Y = - 12.647 + 0.133X1 + 0.011X2 + 0.754X4 + 0.001X7 + 0.605X14. The model had good differentiation; the C-index in the internal verification was 0.947 (95% CI is 0.932-0.977) and the C-index in the external verification was 0.946 (95% CI is 0.940-0.994). The calibration plot of the model showed excellent consistency between the prediction probability and actual probability. When > 0.483 was taken as the cutoff value for the diagnosis of osteoporosis, the sensitivity, specificity, positive likelihood ratio, negative likelihood ratio, and Jordan index of the model were 90.24%, 87.76%, 7.37, 0.11, and 78.00%, respectively. CONCLUSION: A newly generated predictive model has been suggested to have good differentiation, calibration, and clinical validity and may be a useful clinical model for predicting osteoporosis in patients with rheumatoid arthritis.

Risk scoring system for recurrence after simultaneous resection of colorectal cancer liver metastasis.

BACKGROUND: The simultaneous resection of synchronous colorectal cancer liver metastasis (SCRLM) has been widely applied. It is necessary to establish a risk scoring system to predict post-operative recurrence, especially in patients with neoadjuvant treatment. METHODS: The medical records of 221 patients undergoing simultaneous resection of CRLM were assessed in this study with a further 128 patients allocated to a validation group. All patients in the study group were classified according to their history of neoadjuvant treatment and univariate and multivariate analyses were applied to study independent risk factors. A score model was then generated according to the factors included. Our data set were also applied to validate three other existing scoring models [Fong clinical recurrence score (CRS), Konopke, and Zakaria disease-free survival (DFS) score], and the concordance index was calculated for comparison among these models. RESULTS: CRLM involving more than three nodes positive for a primary tumor was considered an independent risk factor for progression in patients without neoadjuvant treatment and all score models could discretely stratify patients according to disease free survival. In patients receiving neoadjuvant treatment, CRLM involving more than one node and transfusion invasion were major determinants in patients after treatment. However, only our scoring system and Fong's CRS score could discretely discriminate patients. In the validation group, patients were significantly classified with the score system. CONCLUSIONS: Existing score models had better values for determining prognosis in patients with SCRLM, especially in those undertaking neoadjuvant treatment. Larger cohorts, along with more detailed clinical features and multicenter validation should be undertaken before utilization.

Evaluation of Skeletal Muscle Microcirculation and Reserve Function of the Type 2 Diabetes with Contrast-Enhanced Ultrasonography.

OBJECTIVE: This study aimed to discuss clinical application value of contrast-enhanced ultrasonography on lesion skeletal muscle microcirculation and arterial perfusion reserve in type 2 diabetes mellitus and complicated microvessels. METHODS: Patients in the control group, type 2 diabetes mellitus (DM) group, diabetic microangiopathy (DM + MC) group underwent contrast-enhanced ultrasonography before and after temporary arterial occlusion to observe blood perfusion of gastrocnemius muscle; draw the time-intensity curve of arteriole, muscular tissue, and venule, and obtain perfusion parameters such as contrast agent arrival time and contrast agent transit time. Blood glucose, insulin, insulin resistance index, and relevant blood rheology parameters were measured. RESULTS: Contrast agent transit time of the DM + MC group before arterial occlusion was significantly longer than that of the DM group and control group (P < 0.05). Contrast agent transit time of the DM + MC group after temporary arterial occlusion was significantly longer than that of the DM group and control group (P < 0.05). Contrast agent transit time of △artery-muscle, △artery-vein, and △muscle-vein of the DM group and control group and △artery-muscle of the DM + MC group after arterial occlusion was significantly shortened, when compared with that before arterial occlusion (P < 0.05). For △muscle-vein and △artery-vein contrast agent transit time in the DM + MC group, the difference was not statistically significant. By comparing blood glucose, insulin, insulin resistance index, and relevant blood rheology parameters among the DM + MC group, DM group, and control group, the difference was statistically significant, and there was a good correlation. CONCLUSION: Contrast-enhanced ultrasonography can be used to evaluate skeletal muscle microcirculation disturbance and arterial reserve function of patients who had type 2 diabetic microangiopathy.