Construction of human 3D striato-nigral assembloids to recapitulate medium spiny neuronal projection defects in Huntington's disease.

The striato-nigral (Str-SN) circuit is composed of medium spiny neuronal projections that are mainly sent from the striatum to the midbrain substantial nigra (SN), which is essential for regulating motor behaviors. Dysfunction of the Str-SN circuitry may cause a series of motor disabilities that are associated with neurodegenerative disorders, such as Huntington's disease (HD). Although the etiology of HD is known as abnormally expanded CAG repeats of the huntingtin gene, treatment of HD remains tremendously challenging. One possible reason is the lack of effective HD model that resembles Str-SN circuitry deficits for pharmacological studies. Here, we first differentiated striatum-like organoids from human pluripotent stem cells (hPSCs), containing functional medium spiny neurons (MSNs). We then generated 3D Str-SN assembloids by assembling striatum-like organoids with midbrain SN-like organoids. With AAV-hSYN-GFP-mediated viral tracing, extensive MSN projections from the striatum to the SN are established, which formed synaptic connection with GABAergic neurons in SN organoids and showed the optically evoked inhibitory postsynaptic currents and electronic field potentials by labeling the striatum-like organoids with optogenetic virus. Furthermore, these Str-SN assembloids exhibited enhanced calcium activity compared to that of individual striatal organoids. Importantly, we further demonstrated the reciprocal projection defects in HD iPSC-derived assembloids, which could be ameliorated by treatment of brain-derived neurotrophic factor. Taken together, these findings suggest that Str-SN assembloids could be used for identifying MSN projection defects and could be applied as potential drug test platforms for HD.

Exact reaction coordinates for flap opening in HIV-1 protease.

The primary goal of protein science is to understand how proteins function, which requires understanding the functional dynamics responsible for transitions between different functional structures of a protein. A central concept is the exact reaction coordinates that can determine the value of committor for any protein configuration, which provide the optimal description of functional dynamics. Despite intensive efforts, identifying the exact reaction coordinates (RCs) in complex molecules remains a formidable challenge. Using the recently developed generalized work functional, we report the discovery of the exact RCs for an important functional process-the flap opening of HIV-1 protease. Our results show that this process has six RCs, each one is a linear combination of ~240 backbone dihedrals, providing the precise definition of collectivity and cooperativity in the functional dynamics of a protein. Applying bias potentials along each RC can accelerate flap opening by [Formula: see text] to [Formula: see text] folds. The success in identifying the RCs of a protein with 198 residues represents a significant progress beyond that of the alanine dipeptide, currently the only other complex molecule for which the exact RCs for its conformational changes are known. Our results suggest that the generalized work functional (GWF) might be the fundamental operator of mechanics that controls protein dynamics.

Seismic constraints and geodynamic implications of differential lithosphere-asthenosphere flow revealed in East Asia.

During the last 50 Ma, the East Asian continent has been a zone of massive continental collision and lithospheric deformation. While the consequences of this for Asian surface and lithospheric deformation have been intensively studied over the past 4 decades, the relationships between lithospheric deformation and underlying asthenospheric flow have been more difficult to constrain. Here we present a high resolution 3-D azimuthal anisotropy model for the northeastern Tibetan Plateau and its eastward continuation based on surface-wave tomography and shear-wave splitting measurements. This model shows that eastward lateral flow of asthenosphere beneath the northeastern Tibetan Plateau is being blocked by thick Ordos and Sichuan cratonic keels. The damming effect of these keels induces flow to first rotate around the Ordos keel and then transition into strong east-west flow beneath the thinner lithosphere that forms the lithospheric suture between the two cratonic keels. We further find that asthenosphere flow directions can differ from those of overlying lithosphere, with the asthenosphere neither being passively dragged by overlying lithosphere, nor being able to drag the overlying plate to mimic its subsurface flow. Finally, the region of eastward-channeled asthenospheric flow from Tibet underlies a belt of stronger intracontinental deformation in eastern China.

Carrier frequency and incidence estimation of deficiency of adenosine deaminase 2 in the Chinese population based on massive exome sequencing data.

Deficiency of adenosine deaminase 2 (DADA2) is an autosomal recessive autoinflammatory disease characterised by early onset stroke, recurrent fever, and diverse vascular pathologies, caused by loss-of-function homozygous or compound heterozygous variants of ADA2. This research aimed to determine the carrier frequency and expected incidence of DADA2 in China, using massive exome sequencing (ES) data. A total of 50 likely pathogenic/pathogenic variants (LP/PVs) were identified among 69,413 Chinese individuals, including 20 novel and rare variants (<0.0022 % allele frequency), expanding the known spectrum of PVs in ADA2. The overall carrier frequency in the Chinese population was 1.05 % (732/69,413) and the estimated incidence of DADA2 was approximately one in 92,251 individuals. The present study provides an accurate estimation of the prevalence of DADA2 in China, supporting genetic counseling, early diagnosis treatment, and prognostic evaluation.

Ultra-Processed Food Consumption and Long-Term Risk of Irritable Bowel Syndrome: A Large-Scale Prospective Cohort Study.

BACKGROUND & AIMS: The considerable disease burden of irritable bowel syndrome (IBS) has coincided with the increase of ultraprocessed food (UPF) consumption over the past few decades. However, epidemiologic evidence for an association is lacking. We aimed to examine the long-term risk of IBS associated with UPF consumption in a large-scale prospective cohort. METHODS: Participants who completed 24-hour dietary recalls during 2009 to 2012 from the UK Biobank, and free of IBS, celiac disease, inflammatory bowel disease, and any cancer at baseline, were included (N = 178,711; 53.1% female). UPF consumption was defined according to the NOVA food classification system, expressed as a percentage of UPF content in the total diet intake (as grams per day). The primary outcome was incident IBS. A Cox proportional hazard model was performed to estimate associated risk. RESULTS: The mean UPF consumption was 21.0% (SD, 11.0%) of the total diet. During a median of 11.3 years of follow-up, 2690 incident IBS cases were identified. An 8% higher risk of IBS (hazard ratio, 1.08; 95% CI, 1.04-1.12) was associated with every 10% increment of UPF consumption. Compared with the lowest quartile of UPF consumption, the highest quartile was associated with a significantly increased risk of incident IBS (hazard ratio, 1.19; 95% CI, 1.07-1.33; Ptrend < .001). Subgroup analyses by age, sex, body mass index, smoking, and alcohol drinking status also showed similar results, except for the never/previous drinking subgroup. Further sensitivity analyses confirmed the positive association with a higher UPF consumption. CONCLUSIONS: Our findings provide evidence that a higher UPF consumption is associated with an increased risk of incident IBS, with a significant dose-response relationship.

Self-Enhanced Electrochemiluminesence of Dye-Doped Polymer Dots for Coreactant-Free Visualized Detection of Iodide Ions.

The monitoring of radioactive iodide levels is of great significance in environmental science and cancer radiotherapy. In this work, a high-throughput, radiation-resistant, and visualized electrochemiluminescence (ECL) strategy was developed for detection of iodide ions. Herein, the hydrophobic ruthenium derivative (Ru(bpy)3[B(C6F5)4]2) (bpy = bipyridyl) was doped in tertiary amine-coupled polymer dots (N-PFO Pdots) to synthesize self-enhanced Pdots (Ru@Pdots), which showed extremely high ECL intensity in absence of coreactant. Due to the efficient ECL resonance energy transfer between Ru(bpy)3[B(C6F5)4]2 and N-PFO, the Ru@Pdots exhibited 18 times higher ECL intensity compared with bare N-PFO Pdots. Besides, Ru@Pdots also showed 220-times higher ECL intensity compared with Ru(bpy)3[B(C6F5)4]2 doped coreactant-dependent Pdots (Ru@PFO Pdots). Using Ru@Pdots as ECL emitters, an ECL imaging array was designed for iodide ion detection, which exhibited a detection range of 0.8 nM-4 µM and a limit of detection of 0.1 nM. In this strategy, iodide ions were oxidized as iodide free radicals on the surface of the electrode, which could further consume the nitrogen radical of Ru@Pdots and effectively quench the ECL signal. This method also showed good specificity, radiation-resistant performance, and accuracy in actual seawater sample testing, which indicated its value in marine environmental monitoring, nuclear security, and cancer radiotherapy.

Hepatotoxicity of epidermal growth factor receptor - tyrosine kinase inhibitors (EGFR-TKIs).

Drug-induced liver injury (DILI) is one of the most frequently adverse reactions in clinical drug use, usually caused by drugs or herbal compounds. Compared with other populations, cancer patients are more prone to abnormal liver function due to primary or secondary liver malignant tumor, radiation-induced liver injury and other reasons, making potential adverse reactions from liver damage caused by anticancer drugs of particular concernduring clinical treatment process. In recent years, the application of epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs) has changed the treatment status of a series of solid malignant tumors. Unfortunately, the increasing incidence of hepatotoxicitylimits the clinical application of EGFR-TKIs. The mechanisms of liver injury caused by EGFR-TKIs were complex. Despite more than a decade of research, other than direct damage to hepatocytes caused by inhibition of cellular DNA synthesis and resulting in hepatocyte necrosis, the rest of the specific mechanisms remain unclear, and few effective solutions are available. This review focuses on the clinical feature, incidence rates and the recent advances on the discovery of mechanism of hepatotoxicity in EGFR-TKIs, as well as rechallenge and therapeutic strategies underlying hepatotoxicity of EGFR-TKIs.

Prospective Investigation of Optical Genome Mapping for Prenatal Genetic Diagnosis.

BACKGROUND: Optical genome mapping (OGM) is a novel assay for detecting structural variants (SVs) and has been retrospectively evaluated for its performance. However, its prospective evaluation in prenatal diagnosis remains unreported. This study aimed to prospectively assess the technical concordance of OGM with standard of care (SOC) testing in prenatal diagnosis. METHODS: A prospective cohort of 204 pregnant women was enrolled in this study. Amniotic fluid samples from these women were subjected to OGM and SOC testing, which included chromosomal microarray analysis (CMA) and karyotyping (KT) in parallel. The diagnostic yield of OGM was evaluated, and the technical concordance between OGM and SOC testing was assessed. RESULTS: OGM successfully analyzed 204 cultured amniocyte samples, even with a cell count as low as 0.24 million. In total, 60 reportable SVs were identified through combined OGM and SOC testing, with 22 SVs detected by all 3 techniques. The diagnostic yield for OGM, CMA, and KT was 25% (51/204), 22.06% (45/204), and 18.14% (37/204), respectively. The highest diagnostic yield (29.41%, 60/204) was achieved when OGM and KT were used together. OGM demonstrated a concordance of 95.56% with CMA and 75.68% with KT in this cohort study. CONCLUSIONS: Our findings suggest that OGM can be effectively applied in prenatal diagnosis using cultured amniocytes and exhibits high concordance with SOC testing. The combined use of OGM and KT appears to yield the most promising diagnostic outcomes.

Diagnostic value of a novel salivary gland ultrasound scoring system in IgG4-related sialadenitis.

OBJECTIVES: To develop a novel ultrasound scoring system for the major salivary glands in patients with immunoglobulin G4-related sialadenitis (IgG4-RS) and assess its diagnostic value in a multicenter cohort of Chinese patients. METHODS: Twenty clinicians (rheumatologists, stomatologists, and radiologists) participated. The study was conducted in four steps: (1) defining the ultrasonography (US) elements, (2) developing a novel ultrasound scoring system for US of the salivary glands, (3) evaluation of inter- and intra-reader reliabilities using the new ultrasound scoring system, and (4) assessing the diagnostic value of this novel ultrasound scoring system in IgG4-RS patients in a Chinese multicenter cohort. RESULTS: A novel ultrasound scoring system for the salivary glands was developed, with total scores ranging from 0 to 34. The inter- and intra-reader reliabilities of the ultrasound scoring system were excellent (0.972 and 0.940, respectively). A total of 470 people were recruited in this study; 187 patients were diagnosed with IgG4-RS, and the remaining 283 people were diagnosed with non-IgG4-RS. Patients with IgG4-RS had significantly higher US scores than the non-IgG4-RS group (mean US score=16 vs. 4, P < 0.001). The calculated area under the curve (AUC) for the total US score was 0.852 (95% CI: 0.814-0.891). The total US scores≥9 showed a sensitivity of 75.4% and a specificity of 91.9%. Association analysis showed a positive correlation between total US scores and serum IgG4 levels and hypocomplementemia (r=0.221, r=0.349; P = 0.002) and a negative correlation between total US scores and serum C3 and C4 levels (r=-0.210, r=-0.303; P = 0.005, P < 0.001). CONCLUSIONS: A novel semiquantitative ultrasound scoring system for patients with IgG4-RS was developed, with good diagnostic performance. The inter- and intra-reader reliabilities were excellent. US scores were correlated with IgG4, C3, and C4 levels and hypocomplementemia.

Characterization of lncRNA and mRNA profiles in ciliary body in experimental myopia.

Currently, researchers have mainly focused on the role of the tissues of the posterior segment of the eyes in the development of myopia. However, the ciliary body, an anterior ocular tissue that contracts to initiate the process of accommodation, may also play an important role in the progression of myopia due to the increased demand for near work. In the present study, we established a lens-induced myopia (LIM) animal model in guinea pigs and investigated the molecular changes in the ciliary body associated with the development of myopia based on RNA sequencing. As a result, 871 differentially expressed (DE) mRNAs and 19 DE lncRNAs were identified in the ciliary body between the LIM group and the normal control group. In addition, the lncRNA-mRNA co-expression analysis was performed to explore the target genes of lncRNAs, which were mainly enriched in the Rap1 signaling pathway, cytokine-cytokine receptor interaction, and complement and coagulation cascades pathways based on the functional enrichment analysis. Among the target genes of lncRNAs, three hub genes, including Ctnnb1, Pik3r1, and Itgb1, were found to be involved in the Rap1 signaling pathway. Interestingly, two crucial genes, Grk1 and Pde6a, which are mainly expressed in retinal photoreceptors, were enriched in visual perception in the ciliary body in functional analysis and were verified to be expressed in the ciliary body. These findings indicate the molecular pathogenetic role of the ciliary body in myopia and provide new insights into the underlying mechanism of myopia development. Further studies are needed to explore the specific contributions of these identified lncRNAs and mRNAs to the development of myopia.

Long-term risk of cardiovascular disease associated with MASLD and different cardiometabolic risk factors in IBD patients: A prospective cohort study.

BACKGROUND: To examine the cardiovascular disease (CVD) risks associated with metabolic dysfunction-associated steatotic liver disease (MASLD) and different numbers of cardiometabolic risk factors (CMRFs) in patients with inflammatory bowel disease (IBD) based on a long-term prospective cohort. METHODS: Prevalent IBD patients at baseline who were free of CVD, cancer, alcoholic liver disease, cancer and hepatitis B/C virus seropositive were included (N = 4204). MASLD, MASLD subtypes [pure MASLD, MASLD with increased alcohol intake (MetALD)], lean/non-lean MASLD and CMRFs at baseline were defined according to the latest criteria proposed by AASLD and EASL. The primary outcome was incident CVD, including ischaemic heart disease (IHD), heart failure (HF) and stroke. Multivariable Cox proportional hazard models were used to estimate the relationship. RESULTS: Overall, 1528 (36.4%) were diagnosed with MASLD at baseline. During a median of 13.1-year follow-up, 503 incident CVDs were identified. Compared with IBD-only, IBD-MASLD patients had an increased risk of CVD (HR = 1.77, 95%CI: 1.26-2.49), especially in those with MetALD (HR = 2.34, 1.34-4.11) and lean MASLD (HR = 2.30, 1.13-4.66). As the number of CMRFs increased, the risks of CVD were significantly increased (p trend <0.001), with a 116% and 92% excess risk in MASLD with 3 CMRFs (HR = 2.16, 1.48-3.15) and ≥4 CMRFs (HR = 1.92, 1.27-2.91). Similar excess risk of incident IHD and HF was observed in IBD-MASLD, either pure MASLD or MetALD, as well as lean/non-lean MASLD. CONCLUSIONS: MASLD is associated with increased CVD risk in IBD patients, with greater risk as number of CMRFs increased and evidently higher risk in MetALD and lean MASLD patients.

Utidelone plus pembrolizumab as the fourth-line combination treatment in non-small cell lung cancer with EGFR mutation: a case report.

Utidelone is an ebomycin derivative chemotherapeutic drug, which can promote tubulin polymerization and stabilize microtubule structure, so as to induce apoptosis. The drug is an innovative drug independently developed by China with independent intellectual property rights. Phase II clinical trials for advanced breast cancer are being approved by National Medical Products Administration for the treatment of advanced breast cancer. However, there is no report on the application in non-small cell lung cancer (NSCLC) patients with the epidermal growth factor receptor (EGFR) mutation. This case is a patient with EGFR mutant stage IV NSCLC who has progressed after third-line targeted therapy. The fourth line was treated with utidelone combined with pabolizumab. The patient had progressed after targeted therapy with oxitinib, ametinib, and vometinib. Due to the patient's physical reasons, the traditional platinum drugs were not suitable, so the patient was treated with utidelone combined with pabolizumab. The curative effect was evaluated as SD after two cycles and progesterone receptor after four cycles. At present, it is still in the maintenance of reduction of utidelone combined with pabolizumab, and the tumor continues to shrink. Although peripheral neurotoxicity occurred during treatment, it improved after symptomatic treatment. The treatment of EGFR mutant stage IV NSCLC with utidelone combined with pabolizumab has good effect and mild adverse reactions.

Bidirectional association between type 2 diabetes and irritable bowel syndrome: A large-scale prospective cohort study.

AIM: To examine the bidirectional association between type 2 diabetes (T2D) and irritable bowel syndrome (IBS) in a large prospective population cohort. METHODS: Participants free of IBS at baseline in the UK Biobank were included in the analysis of T2D and incident IBS (cohort 1), with 11 140 T2D patients and 413 979 non-T2D patients. Similarly, those free of T2D at baseline were included in the analysis of IBS and incident T2D (cohort 2), with 21 944 IBS patients and 413 979 non-IBS patients. Diagnoses of T2D and IBS were based on International Classification of Disease-10 codes. The Cox proportional hazards model was used to estimate adjusted hazard ratios (HRs). RESULTS: In cohort 1, 8984 IBS cases were identified during a median 14.5-year follow-up. Compared with non-T2D, T2D patients had a 39.0% increased risk of incident IBS (HR = 1.39, 95% confidence interval [CI]: 1.23-1.56, P < .001), with a higher IBS risk in those with higher fasting blood glucose levels (HR = 1.43, 95% CI: 1.19-1.72, P < .001) or longer T2D duration (HR = 1.47, 95% CI: 1.23-1.74, P < .001). In cohort 2, 29 563 incident T2D cases were identified. IBS patients had an 18.0% higher risk of developing T2D versus non-IBS patients (HR = 1.18, 95% CI: 1.12-1.24, P < .001). A similar excess T2D risk was observed in IBS patients with a duration of either less than 10 years, or of 10 years or longer. Further sensitivity analysis and subgroup analysis indicated consistent findings. CONCLUSIONS: T2D and IBS exhibit a bidirectional association, with an increased risk of co-morbidity. Awareness of this association may improve the prevention and management of both diseases.

Interaction of lncRNA-CR33942 with Dif/Dorsal Facilitates Antimicrobial Peptide Transcriptions and Enhances Drosophila Toll Immune Responses.

The Drosophila Toll signaling pathway mainly responds to Gram-positive (G+) bacteria or fungal infection, which is highly conserved with mammalian TLR signaling pathway. Although many positive and negative regulators involved in the immune response of the Toll pathway have been identified in Drosophila, the roles of long noncoding RNAs (lncRNAs) in Drosophila Toll immune responses are poorly understood to date. In this study, our results demonstrate that lncRNA-CR33942 is mainly expressed in the nucleus and upregulated after Micrococcus luteus infection. Especially, lncRNA-CR33942 not only modulates differential expressions of multiple antimicrobial peptide genes but also affects the Drosophila survival rate during response to G+ bacterial infection based on the transiently overexpressing and the knockdown lncRNA-CR33942 assays in vivo. Mechanically, lncRNA-CR33942 interacts with the NF-κB transcription factors Dorsal-related immunity factor/Dorsal to promote the transcriptions of antimicrobial peptides drosomycin and metchnikowin, thus enhancing Drosophila Toll immune responses. Taken together, this study identifies lncRNA-CR33942 as a positive regulator of Drosophila innate immune response to G+ bacterial infection to facilitate Toll signaling via interacting with Dorsal-related immunity factor/Dorsal. It would be helpful to reveal the roles of lncRNAs in Toll immune response in Drosophila and provide insights into animal innate immunity.

Ultrasound-MR fusion imaging combined with intraductal cooling via PTCD during microwave ablation of perihilar liver tumors: a retrospective pilot study.

PURPOSE: To explore the feasibility and safety of a microwave ablation (MWA) strategy involving intraductal chilled saline perfusion (ICSP) via percutaneous transhepatic cholangial drainage (PTCD) combined with ultrasound-magnetic resonance (US-MR) fusion imaging for liver tumors proximal to the hilar bile ducts (HBDs). METHODS: Patients with liver tumors proximal to the HBDs (≤5 mm) who underwent MWA at our hospital between June 2020 and April 2023 were retrospectively analyzed. The strategy of US-MR fusion imaging combined with PTCD-ICSP was used to assist the MWA procedures. The technical success, technique efficacy, local tumor progression, intrahepatic distant recurrence and complications were recorded and analyzed. RESULTS: In total, 12 patients with 12 liver tumors were retrospectively enrolled in this study. US-MR fusion imaging was utilized in all patients, and PTCD-ICSP assistance was successfully used for 4 nodules abutting HBDs (0 mm). The rates of technical success, technique efficacy, local tumor progression and intrahepatic distant recurrence were 91.7%, 83.3%, 0% and 8.3%, respectively. The major complication of biliary infection occurred in only one patient who had previously undergone left hemihepatectomy and bile-intestinal anastomosis. CONCLUSIONS: MWA for liver tumors proximal to HBDs assisted by US-MR fusion imaging combined with PTCD-ICSP was feasible and safe. This strategy made MWA of liver tumors abutting HBDs possible.

Screening and Predictive Biomarkers for Down Syndrome Through Amniotic Fluid Metabolomics.

BACKGROUND: Down syndrome (DS) is a congenital disorder caused by the presence of an extra copy of all or part of chromosome 21. It is characterized by significant intellectual disability, distinct facial features, and growth and developmental challenges. The utilization of metabolomics to analyze specific metabolic markers in maternal amniotic fluid may provide innovative tools and screening methods for investigating the early pathophysiology of trisomy 21 at the functional level. METHODS: Amniotic fluid samples were obtained via amniocentesis from 57 pregnancies with DS and 55 control pregnancies between 173/7 and 240/7 weeks of gestation. The targeted metabolomics focused on 34 organic acids, 17 amino acids, and 5 acylcarnitine metabolites. The untargeted metabolomics analysis concentrated on lipid profiles and included 602 metabolites that met quality control standards. Principal Component Analysis, Orthogonal Partial Least Squares Discriminant Analysis (OPLS-DA), and false discovery rate (FDR) adjustments were applied. MetaboAnalystR 5.0 was used to perform the metabolic pathway analysis on the identified differential metabolites. RESULTS: Fifty differential metabolites, including L-glutamine, eight organic acids, and 41 lipids, were significantly altered in DS based on three criteria: VIP > 1 in the OPLS-DA model, FDR-adjusted p-value < 0.05, and |log2FC| > log2(1.5) from a volcano plot of all detected metabolites. An analysis of 212 differential metabolites, selected from both targeted and untargeted approaches (VIP > 1 in the OPLS-DA model and FDR-adjusted p-value < 0.05), revealed significant changes in nine metabolic pathways. Fourteen key metabolites were identified to establish a screening model for DS, achieving an area under the curve of 1.00. CONCLUSIONS: Our results underscore the potential of metabolomics approaches in identifying concise and reliable biomarker combinations that demonstrate promising screening performance in DS.

The Evaluation of Outcomes after Thoracic Endovascular Aortic Repair for Type B Aortic Dissection in Mainland China.

BACKGROUND: To assess the mortality and outcomes after thoracic endovascular aortic repair (TEVAR) in patients with type B aortic dissection (TBAD) in mainland China, and to compare these outcomes with data from Western countries, while analyzing the potential reasons for differences among different countries. METHODS: An extensive literature search spanning from January 1999 to October 2023 was conducted using PubMed, Cochrane Library, and Embase databases for studies on endovascular treatment for TBAD. This systematic review and meta-analysis adhered to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses statement. Data extraction and analysis followed the guidelines outlined in the Preferred Reporting Items for Systematic Reviews and Meta-Analyses statement. Primary outcomes were in-hospital mortality and mid-term (< 5 years) mortality. RESULTS: Based on 25 publications (3,080 patients), pooled estimate for in-hospital mortality was 2.2% (95% confidence interval, 1.6%-2.9%). Major perioperative complications included stroke (2.4% [1.8%-3.3%]), spinal cord ischemia (1.4% [1.0%-2.2%]), retrograde type A aortic dissection (1.2% [0.8%-1.8%]), type I endoleak (5.6% [3.6%-8.6%]), visceral ischemia (1.0% [0.5%-2.1%]), and acute renal failure (2.8% [2.0%-3.8%]). Mid-term mortality was 5.1% (3.6%-7.3%), and secondary intervention rate was 4.9% (4.0%-6.0%) with 1.7% (1.0%-2.9%) conversion rate to open surgery. In subgroup analysis based on uncomplicated TBAD, in-hospital and mid-term mortality was 0.5% (0.2%-1.5%) and 0.6% (0.2-1.7%), respectively. Compared with data from Western countries, mainland Chinese patients had a lower mortality. CONCLUSIONS: In mainland China, the outcomes of endovascular treatment for TBAD are comparable to those of Western countries. The large number of patients undergoing TEVAR in mainland China and its good performance support the use of TEVAR in uncomplicated TBAD.

Ultrasomics differentiation of malignant and benign focal liver lesions based on contrast-enhanced ultrasound.

OBJECTIVES: To establish a nomogram for differentiating malignant and benign focal liver lesions (FLLs) using ultrasomics features derived from contrast-enhanced ultrasound (CEUS). METHODS: 527 patients were retrospectively enrolled. On the training cohort, ultrasomics features were extracted from CEUS and b-mode ultrasound (BUS). Automatic feature selection and model development were performed using the Ultrasomics-Platform software, outputting the corresponding ultrasomics scores. A nomogram based on the ultrasomics scores from artery phase (AP), portal venous phase (PVP) and delayed phase (DP) of CEUS, and clinical factors were established. On the validation cohort, the diagnostic performance of the nomogram was assessed and compared with seniorexpert and resident radiologists. RESULTS: In the training cohort, the AP, PVP and DP scores exhibited better differential performance than BUS score, with area under the curve (AUC) of 84.1-85.1% compared with the BUS (74.6%, P < 0.05). In the validation cohort, the AUC of combined nomogram and expert was significantly higher than that of the resident (91.4% vs. 89.5% vs. 79.3%, P < 0.05). The combined nomogram had a comparable sensitivity with the expert and resident (95.2% vs. 98.4% vs. 97.6%), while the expert had a higher specificity than the nomogram and the resident (80.6% vs. 72.2% vs. 61.1%, P = 0.205). CONCLUSIONS: A CEUS ultrasomics based nomogram had an expert level performance in FLL characterization.

Risk Factors and Prediction Nomogram of Local Regeneration after Ultrasound-guided Microwave Ablation of Uterine Fibroids.

STUDY OBJECTIVE: To explore the risk factors associated with local regeneration of the treated uterine fibroids (UFs) after microwave ablation (MWA) and to develop a nomogram model for predicting the risk of local regeneration. DESIGN: Retrospective study. SETTING: The Eighth Affiliated Hospital of Sun Yat-Sen University. PATIENTS: Patients with UFs who underwent MWA at our hospital between October 2020 and April 2023 were included. INTERVENTION: MWA was used for the treatment of UFs. MEASUREMENTS AND MAIN RESULTS: A total of 47 patients with 68 fibroids were included into this study. Over a median follow-up of 13 months (interquartile range, 8-22 months), local regeneration occurred in 11 UFs. The clinical and imaging characteristics of these patients were recorded and compared. Risk factors for local regeneration were determined through univariate and multivariate Cox regression analysis. Multivariate analysis revealed that the fertility desires, larger size of UFs (≥95.3 cm3), and hyperenhancement of UFs on contrast-enhanced ultrasound were independent risk factors for local regeneration after MWA. A predictive nomogram was constructed to predict the local regeneration after MWA of UFs. The concordance index (C-index) (C-index, 0.924; internal validation C-index, 0.895) and the 1- and 2-year area under the curve values (0.962, 0.927) all indicated that the nomogram had good predictive performance. Calibration and decision curve analysis curves further confirmed the model's accuracy and clinical utility. CONCLUSION: Fertility desires, larger size of UFs, and hyperenhancement on contrast-enhanced ultrasound were independent predictors of UFs local regeneration after MWA in our study. The nomogram constructed based on the abovementioned independent risk factors may help predict which UFs will develop local regeneration after MWA.

Association of ambient PM2.5 and its components with in vitro fertilization outcomes: The modifying role of maternal dietary patterns.

Despite the associations of dietary patterns and air pollution with human reproductive health have been demonstrated, the interaction of maternal preconception diet and PM2.5 and its components exposure on in vitro fertilization (IVF) treatment outcomes has not been investigated. A total of 2688 couples from an ongoing prospective cohort were included. Principle component analysis with varimax rotation was performed to determine dietary patterns. One-year and 85-day average PM2.5 and its components exposure levels before oocyte retrieval were estimated. Generalized linear regression models were conducted to assess the association of dietary patterns and PM2.5 and its components exposure with IVF outcomes. Interactive effects of dietary patterns on the association between PM2.5 and its components and IVF outcomes were evaluated by stratified analyses based on different dietary patterns. A positive association between the "Fruits-Vegetables-Dairy" pattern and normal fertilization (p-trend = 0.009), Day 3 available embryos (p-trend = 0.048), and top-quality embryos (p-trend = 0.041) was detected. Conversely, women with higher adherence to the "Puffed food-Bakery-Candy" pattern were less likely to achieve Day 3 available embryos (p-trend = 0.042) and top-quality embryos (p-trend = 0.030), clinical pregnancy (p-trend = 0.049), and live birth (p-trend = 0.020). Additionally, increased intake of animal organs and seafood improved the odds of live birth (p-trend = 0.048). Exposure to PM2.5, SO42-, organic matter (OM), and black carbon (BC) had adverse effects on embryo development and pregnancy outcomes. Furthermore, our findings indicated that the effects of PM2.5 components exposure on normal fertilization and embryo quality were modified by the "Grains-Tubers-Legumes". Moreover, moderate intake of animal organs and seafood appeared to attenuate the effect of NO3- and NH4+ on the risk of early abortion. Our findings provide human evidence of the interaction between dietary patterns and PM2.5 exposure on IVF outcomes during preconception, implicating the potential for dietary interventions in infertile women to improve reproductive outcomes under conditions of unavoidable ambient air-pollutant exposure.