The study on synthesis and vitro hypolipidemic activity of novel berberine derivatives nitric oxide donors.

Berberine was used as the lead compound in the present study to design and synthesize novel berberine derivatives by splicing bromine bridges of different berberine carbon chain lengths coupled nitric oxide donors, and their lipid lowering activities were assessed in a variety of ways. This experiment synthesized 17 new berberine nitric oxide donor derivatives. Compared with berberine hydrochloride, most of the compounds exhibited certain glycerate inhibitory activity, and compounds 6a, 6b, 6d, 12b and 12d showed higher inhibitory activity than berberine, with 6a, 6b and 6d having significant inhibitory activity. In addition, compound 6a linked to furazolidone nitric oxide donor showed better NO release in experiments; In further mechanistic studies, we screened and got two proteins, PCSK9 and ACLY, and docked two proteins with 17 compounds, and found that most of the compounds bound better with ATP citrate lyase (ACLY), among which there may be a strong interaction between compound 6a and ACLY, and the interaction force was better than the target drug Bempedoic Acid, which meaning that 6a may exert hypolipidemic effects by inhibiting ACLY; moreover, we also found that 6a may had the better performance in gastrointestinal absorption, blood-brain barrier permeability, Egan, Muegge class drug principle model calculation and bioavailability.

SSK1-Loaded Neurotransmitter-Derived Nanoparticles for Alzheimer's Disease Therapy via Clearance of Senescent Cells.

Age is a significant contributor to the onset of AD. Senolysis has been recently demonstrated to ameliorate aging-associated diseases that showing a great potential in AD therapy. However, due to the presence of BBB, the anti-AD activity of senolytics are significantly diminished. SSK1 is a prodrug that can be activated by ß-gal, a lysosomal enzyme commonly upregulated in senescent cells, and thus selectively eliminates senescent cells. Furthermore, the level of ß-gal is significantly correlated with conventional AD genes from clinical sequencing data. SSK1-loaded neurotransmitter -derived lipid nanoparticles are herein developed (SSK1-NPs) that revealing good BBB penetration and bioavailability of in the body. At the brain lesion, SSK1-NP treatment significantly reduces the expression of genes associated with senescence, induced senescent cells elimination, decreased amyloid-beta accumulation, and eventually improve cognitive function of aged AD mice. SSK1-NPs, a novel nanomedicine displaying potent anti-AD activity and excellent safety profile, provides a promising strategy for AD therapy.

Prevalence and Related Factors of Attention Deficit Hyperactivity Disorder in School-age Children With Atopic Dermatitis.

Context: Atopic dermatitis (AD) is a chronic inflammatory skin disease and commonly affects children. AD is associated with a high incidence of ADHD, the most common psychological and neurobehavioral disorder in children and adolescents. If clinicians don't identify ADHD and intervene early, preschool children can experience adverse effects. Objective: The study intended to investigate the prevalence of attention deficit hyperactivity disorder (ADHD) in preschool children with AD, analyze the associated factors, and provide insights for early identification of risk factors and the development of interventions to reduce the likelihood of ADHD occurrence. Design: The research team performed a prospective, observational, case-control study. Setting: The study took place at the Zhoushan branch of Ruijin Hospital at the Shanghai Jiaotong University School of Medicine in Zhoushan, Zhejiang, China. Participants: Participants were 80 school-aged children diagnosed with AD and admitted to the hospital between May 2019 and May 2023. Groups: Based on the presence or absence of ADHD, the research team divided the children into two groups: (1) the Simple AD group with 71 participants with AD only, and the AD + ADHD group, with 9 participants with AD and ADHD. Outcome Measures: The research team: (1) collected and analyzed participants' demographic and clinical data, including an assessment of the AD severity using the SCORing Atopic Dermatitis (SCORAD) scale and the presence of sleep disorders using the Children's Sleep Habits Questionnaire (CSHQ); (2) assessed the presence of ADHD using the Swanson, Nolan, and Pelham-IV rating scales (SNAP-IV); (3) analyzed the factors influencing the occurrence of ADHD in AD children, using univariate and multivariate logistic regression analysis. Results: Among the 80 school-age children with AD, 9 participants (11.25%) had received a diagnosis of ADHD. The AD + ADHD group's age (P < .001); body mass index (BMI), with P < .001; AD severity (P = .013); rate of sleep disorders (P = .001); and levels of serum interleukin 6 (IL-6), with (P < .001), interleukin 4 (IL-4), with (P < .001), and nerve growth factor (NGF), with (P < .001) were all significantly greater than those of the Simple AD group. The univariate logistic regression analysis indicated that age (P = .014), BMI (P = .024), AD severity (P = .022), sleep disorders (P = .042), and levels of IL-6 (P = .044), IL-4 (P = .045), and NGF (P = .046) were all significantly related to the development of ADHD in school-age children with AD. The multivariate logistic regression analysis revealed that sleep disorders (P = .018) and elevated levels of serum IL-6 (P = .032), IL-4 (P = .021), and NGF (P = .016 ) were independent risk factors for ADHD (OR = 2.651, 3.074, 2.686, 3.340). Conclusions: School-aged children with AD are more likely to develop ADHD, which is mainly associated with sleep disorders and elevated levels of serum IL-6, IL-4, and NGF. Clinicians should give attention to these risk factors and implement early interventions to reduce the risk of children with AD developing ADHD.

Deep learning-based detection and classification of lumbar disc herniation on magnetic resonance images.

Background: The severity assessment of lumbar disc herniation (LDH) on MR images is crucial for selecting suitable surgical candidates. However, the interpretation of MR images is time-consuming and requires repetitive work. This study aims to develop and evaluate a deep learning-based diagnostic model for automated LDH detection and classification on lumbar axial T2-weighted MR images. Methods: A total of 1115 patients were analyzed in this retrospective study; both a development dataset (1015 patients, 15 249 images) and an external test dataset (100 patients, 1273 images) were utilized. According to the Michigan State University (MSU) classification criterion, experts labeled all images with consensus, and the final labeled results were regarded as the reference standard. The automated diagnostic model comprised Faster R-CNN and ResNeXt101 as the detection and classification network, respectively. The deep learning-based diagnostic performance was evaluated by calculating mean intersection over union (IoU), accuracy, precision, sensitivity, specificity, F1 score, the area under the receiver operating characteristics curve (AUC), and intraclass correlation coefficient (ICC) with 95% confidence intervals (CIs). Results: High detection consistency was obtained in the internal test dataset (mean IoU = 0.82, precision = 98.4%, sensitivity = 99.4%) and external test dataset (mean IoU = 0.70, precision = 96.3%, sensitivity = 97.8%). Overall accuracy for LDH classification was 87.70% (95% CI: 86.59%-88.86%) and 74.23% (95% CI: 71.83%-76.75%) in the internal and external test datasets, respectively. For internal testing, the proposed model achieved a high agreement in classification (ICC = 0.87, 95% CI: 0.86-0.88, P < 0.001), which was higher than that of external testing (ICC = 0.79, 95% CI: 0.76-0.81, P < 0.001). The AUC for model classification was 0.965 (95% CI: 0.962-0.968) and 0.916 (95% CI: 0.908-0.925) in the internal and external test datasets, respectively. Conclusions: The automated diagnostic model achieved high performance in detecting and classifying LDH and exhibited considerable consistency with experts' classification.

High-Throughput Screening of Functional Neo-Antigens and Their Specific T-Cell Receptors via the Jurkat Reporter System Combined with Droplet Microfluidics.

T-cell receptor (TCR)-engineered T cells can precisely recognize a broad repertoire of targets derived from both intracellular and surface proteins of tumor cells. TCR-T adoptive cell therapy has shown safety and promising efficacy in solid tumor immunotherapy. However, antigen-specific functional TCR screening is time-consuming and expensive, which limits its application clinically. Here, we developed a novel integrated antigen-TCR screening platform based on droplet microfluidic technology, enabling high-throughput peptide-major histocompatibility complex (pMHC)-to-TCR paired screening with a high sensitivity and low background signal. We introduced DNA barcoding technology to label peptide antigen candidate-loaded antigen-presenting cells and Jurkat reporter cells to check the specificity of pMHC-TCR candidates. Coupled with the next-generation sequencing pipeline, interpretation of the DNA barcodes and the gene expression level of the Jurkat T-cell activation pathway provided a clear peptide-MHC-TCR recognition relationship. Our proof-of-principle study demonstrates that the platform could achieve pMHC-TCR paired high-throughput screening, which is expected to be used in the cross-reactivity and off-target high-throughput paired testing of candidate pMHC-TCRs in clinical applications.

Automated Magnetic Resonance Image Segmentation of Spinal Structures at the L4-5 Level with Deep Learning: 3D Reconstruction of Lumbar Intervertebral Foramen.

OBJECTIVE: 3D reconstruction of lumbar intervertebral foramen (LIVF) has been beneficial in evaluating surgical trajectory. Still, the current methods of reconstructing the 3D LIVF model are mainly based on manual segmentation, which is laborious and time-consuming. This study aims to explore the feasibility of automatically segmenting lumbar spinal structures and increasing the speed and accuracy of 3D lumbar intervertebral foramen (LIVF) reconstruction on magnetic resonance image (MRI) at the L4-5 level. METHODS: A total of 100 participants (mean age: 42.2 ± 14.0 years; 52 males and 48 females; mean body mass index, 22.7 ± 3.2 kg/m2 ), were enrolled in this prospective study between March and July 2020. All participants were scanned on L4-5 level with a 3T MR unit using 3D T2-weighted sampling perfection with application-optimized contrast with various flip-angle evolutions (SPACE) sequences. The lumbar spine's vertebra bone structures (VBS) and intervertebral discs (IVD) were manually segmented by skilled surgeons according to their anatomical outlines from MRI. Then all manual segmentation were saved and used for training. An automated segmentation method based on a 3D U-shaped architecture network (3D-UNet) was introduced for the automated segmentation of lumbar spinal structures. A number of quantitative metrics, including dice similarity coefficient (DSC), precision, and recall, were used to evaluate the performance of the automated segmentation method on MRI. Wilcoxon signed-rank test was applied to compare morphometric parameters, including foraminal area, height and width of 3D LIVF models between automatic and manual segmentation. The intra-class correlation coefficient was used to assess the test-retest reliability and inter-observer reliability of multiple measurements for these morphometric parameters of 3D LIVF models. RESULTS: The automatic segmentation performance of all spinal structures (VBS and IVD) was found to be 0.918 (healthy levels: 0.922; unhealthy levels: 0.916) for the mean DSC, 0.922 (healthy levels: 0.927; unhealthy levels: 0.920) for the mean precision, and 0.917 (healthy levels: 0.918; unhealthy levels: 0.917) for the mean recall in the test dataset. It took approximately 2.5 s to achieve each automated segmentation, far less than the 240 min for manual segmentation. Furthermore, no significant differences were observed in the foraminal area, height and width of the 3D LIVF models between manual and automatic segmentation images (P > 0.05). CONCLUSION: A method of automated MRI segmentation based on deep learning algorithms was capable of rapidly generating accurate segmentation of spinal structures and can be used to construct 3D LIVF models from MRI at the L4-5 level.

A Novel Proteogenomic Integration Strategy Expands the Breadth of Neo-Epitope Sources.

Tumor-specific antigens can activate T cell-based antitumor immune responses and are ideal targets for cancer immunotherapy. However, their identification is still challenging. Although mass spectrometry can directly identify human leukocyte antigen (HLA) binding peptides in tumor cells, it focuses on tumor-specific antigens derived from annotated protein-coding regions constituting only 1.5% of the genome. We developed a novel proteogenomic integration strategy to expand the breadth of tumor-specific epitopes derived from all genomic regions. Using the colorectal cancer cell line HCT116 as a model, we accurately identified 10,737 HLA-presented peptides, 1293 of which were non-canonical peptides that traditional database searches could not identify. Moreover, we found eight tumor neo-epitopes derived from somatic mutations, four of which were not previously reported. Our findings suggest that this new proteogenomic approach holds great promise for increasing the number of tumor-specific antigen candidates, potentially enlarging the tumor target pool and improving cancer immunotherapy.

Economic Evaluation of Transcatheter Aortic Valve Replacement Compared to Surgical Aortic Valve Replacement in Chinese Intermediate-Risk Patients.

Background: Aortic stenosis (AS) is a severe disease that causes heart failure and sudden death. Transcatheter aortic valve replacement (TAVR) and surgical aortic valve replacement (SAVR) are both recommended for patients with intermediate surgical risk, but the cost-effectiveness of TAVR compared to SAVR in China has not been investigated. Methods: A combined decision tree and Markov model were conducted to compare the cost-effectiveness of TAVR versus SAVR with a 5-year simulation. The primary outcome was the incremental cost-effectiveness ratio (ICER), a ratio of incremental costs to incremental quality-adjusted life-year (QALY). One-way sensitive analysis and probabilistic sensitivity analysis (PSA) were conducted to test the robustness of the model. Results: After a simulation of 5 years, the costs of TAVR and SAVR were 54,573 and 35,002 USD, respectively, and the corresponding effectiveness was 2.826 versus 2.712 QALY, respectively. The ICER for the TAVR versus SAVR comparison was 170,056 USD/QALY, which was three times higher than the per capita gross domestic product (GDP) in China. One-way sensitive analysis showed that the cost of the TAVR device impacted the ICER. The TAVR could be cost-effective only in the case where its cost is lowered to 29,766 USD. Conclusion: TAVR is currently not cost-effective in China, but it could be cost-effective with a reduction of costs to 29,766 USD, which is approximately 65% of the current price.

Alzheimer's Disease Enhanced Tonic Inhibition is Correlated With Upregulated Astrocyte GABA Transporter-3/4 in a Knock-In APP Mouse Model.

Cognitive decline is a major symptom in Alzheimer's disease (AD), which is strongly associated with synaptic excitatory-inhibitory imbalance. Here, we investigated whether astrocyte-specific GABA transporter 3/4 (GAT3/4) is altered in APP knock-in mouse model of AD and whether this is correlated with changes in principal cell excitability. Using the APP NL-F/NL-F knock-in mouse model of AD, aged-matched to wild-type mice, we performed in vitro electrophysiological whole-cell recordings combined with immunohistochemistry in the CA1 and dentate gyrus (DG) regions of the hippocampus. We observed a higher expression of GAD67, an enzyme that catalyses GABA production, and GAT3/4 in reactive astrocytes labelled with GFAP, which correlated with an enhanced tonic inhibition in the CA1 and DG of 12-16 month-old APP NL-F/NL-F mice compared to the age-matched wild-type animals. Comparative neuroanatomy experiments performed using post-mortem brain tissue from human AD patients, age-matched to healthy controls, mirrored the results obtained using mice tissue. Blocking GAT3/4 associated tonic inhibition recorded in CA1 and DG principal cells resulted in an increased membrane input resistance, enhanced firing frequency and synaptic excitation in both wild-type and APP NL-F/NL-F mice. These effects exacerbated synaptic hyperactivity reported previously in the APP NL-F/NL-F mice model. Our data suggest that an alteration in astrocyte GABA homeostasis is correlated with increased tonic inhibition in the hippocampus, which probably plays an important compensatory role in restoring AD-associated synaptic hyperactivity. Therefore, reducing tonic inhibition through GAT3/4 may not be a good therapeutic strategy for AD.

Indole-3-Acetic Acid Alters Intestinal Microbiota and Alleviates Ankylosing Spondylitis in Mice.

Ankylosing spondylitis (AS) is a systemic, chronic, and inflammatory autoimmune disease associated with the disorder of intestinal microbiota. Unfortunately, effective therapies for AS are lacking. Recent evidence has indicated that indole-3-acetic acid (IAA), an important microbial tryptophan metabolite, can modulate intestinal homeostasis and suppress inflammatory responses. However, reports have not examined the in vivo protective effects of IAA against AS. In this study, we investigated the protective effects and underlying mechanisms through which IAA acts against AS. We constructed a proteoglycan (PG)-induced AS mouse model and administered IAA (50 mg/kg body weight) by intraperitoneal injection daily for 4 weeks. The effects of IAA on AS mice were evaluated by examining disease severity, intestinal barrier function, aryl hydrocarbon receptor (AhR) pathway, T-helper 17 (Th17)/T regulatory (Treg) balance, and inflammatory cytokine levels. The intestinal microbiota compositions were profiled through whole-genome sequencing. We observed that IAA decreased the incidence and severity of AS in mice, inhibited the production of pro-inflammatory cytokines (tumor necrosis factor α [TNF-α], interleukin [IL]-6, IL-17A, and IL-23), promoted the production of the anti-inflammatory cytokine IL-10, and reduced the ratios of pro-/anti- inflammatory cytokines. IAA ameliorated pathological changes in the ileum and improved intestinal mucosal barrier function. IAA also activated the AhR pathway, upregulated the transcription factor forehead box protein P3 (FoxP3) and increased Treg cells, and downregulated the transcription factors retinoic acid receptor-related orphan receptor gamma t (RORγt) and signal transducer and activator of transcription 3 (STAT3) and decreased Th17 cells. Furthermore, IAA altered the composition of the intestinal microbiota composition by increasing Bacteroides and decreasing Proteobacteria and Firmicutes, in addition to increasing the abundances of Bifidobacterium pseudolongum and Mucispirillum schaedleri. In conclusion, IAA exerted several protective effects against PG-induced AS in mice, which was mediated by the restoration of balance among the intestinal microbial community, activating the AhR pathway, and inhibiting inflammation. IAA might represent a novel therapeutic approach for AS.

Genome-wide profiling of prognosis-related alternative splicing signatures in sarcoma.

BACKGROUND: Sarcomas (SARCs) are rare malignant tumors with poor prognosis. Increasing evidence has suggested that aberrant alternative splicing (AS) is strongly associated with tumor initiation and progression. We considered whether survival-related AS events might serve as prognosis predictors and underlying targeted molecules in SARC treatment. METHODS: RNA-Seq data of the SARC cohort were downloaded from The Cancer Genome Atlas (TCGA) database. Survival-related AS events were selected by univariate and multivariate Cox regression analyses. Metascape was used for constructing a gene interaction network and performing functional enrichment analysis. Then, prognosis predictors were established based on statistically significant survival-related AS events and evaluated by receiver operator characteristic (ROC) curve analysis. Finally, the potential regulatory network was analyzed via Pearson's correlation between survival-related AS events and splicing factors (SFs). RESULTS: A total of 3,610 AS events and 2,291 genes were found to be prognosis-related in 261 SARC samples. The focal adhesion pathway was identified as the most critical molecular mechanism corresponding to poor prognosis. Notably, several prognosis predictors based on survival-related AS events showed excellent performance in prognosis prediction. The area under the curve of the ROC of the risk score was 0.85 in the integrated predictor. The splicing network proved complicated regulation between prognosis-related SFs and AS events. Also, driver gene mutations were significantly associated with AS in SARC patients. CONCLUSIONS: Survival-related AS events may become ideal indictors for the prognosis prediction of SARCs. Corresponding splicing regulatory mechanisms are worth further exploration.

Anti-TNF-α therapy alters the gut microbiota in proteoglycan-induced ankylosing spondylitis in mice.

Ankylosing spondylitis is a chronic, progressive disease, and its treatment is relevant to the gut microbiota. Anti-tumor necrosis factor-alpha (anti-TNF-α) therapy alters the gut microbiota in many diseases, including inflammatory bowel disease. However, little is known about the effect of TNF-α blocker treatment on the gut microbiota in ankylosing spondylitis. Herein, the effect of a TNF-α blocker on the gut microbiota in proteoglycan-induced arthritis was investigated. Proteoglycan-induced mice were treated with an rhTNFR:Fc solution of etanercept (5 µg/g) for 4 weeks. rhTNFR:Fc treatment attenuated the arthritis incidence and severity of arthritis in the proteoglycan-induced mice and decreased inflammation in the ankle joints and ameliorated ileal tissue destruction. Moreover, high gut permeability occurred, and zonula occludens-1 and occludin protein levels were reduced in proteoglycan-induced mice. These levels were significantly restored by the administration of rhTNFR:Fc. The serum TNF-α and IL-17 levels were also decreased. In addition, flora analysis via 16S rDNA high-throughput sequencing revealed that rhTNFR:Fc treatment restored the gut microbiota composition to a composition similar to that in control mice. In conclusion, anti-TNF-α therapy attenuated proteoglycan-induced arthritis progression and modulated the gut microbiota and intestinal barrier function. These results provide new insights for anti-TNF-α therapy strategies via regulating the gut microbiota in ankylosing spondylitis.

Clinical Anatomy and Possible Clinical Significance of the Intervertebral Vein in the Lumbar Intervertebral Foramina.

BACKGROUND: The detailed structure of the lumbar intervertebral foramina has been well-studied. Nevertheless, detailed descriptions of branches of the intervertebral vein (IV) through the lumbar intervertebral foramina are lacking. OBJECTIVES: This study aimed to provide an anatomical basis for invasive treatment targeting the branches of the IV using an approach through the lumbar intervertebral foramina, particularly for the purposes of transforaminal epidural steroid injection. STUDY DESIGN: This research involved a dissection-based study of 10 embalmed human cadavers. SETTING: The research took place at The Third Affiliated Hospital of Southern Medical University. METHODS: One hundred lumbar intervertebral foramina from 10 embalmed cadavers were studied. Branches of the IV in the intervertebral foramina were observed. The length and diameter of the veins were measured using a Vernier caliper. RESULTS: At a rate of 100%, branches of the IV were observed in the 100 lumbar foramina examined in our study. The following 4 types of branches of the IV were routinely found: Type I in 27 (27%) of the IV foramina, in which a superior branch of the IV ran along the inferior margin of the vertebral pedicle; Type II in 18 (18%) of the intervertebral foramina, in which an inferior branch of the IV ran along the superior margin of the inferior vertebral pedicle; Type III in 41 (41%) of the intervertebral foramina, in which the IV was divided into a superior and inferior branch; and Type IV in 14 (14%) of the intervertebral foramina, in which the IV was divided into 2 superior branches and an inferior branch. LIMITATIONS: The greatest weakness of this study is that it lacks actual clinical verification. Future clinical trials are expected to contribute more objective data concerning the IV branches. Due to the relative changes in vascular position during dissection, the relevant data warrant improvement. CONCLUSIONS: The lumbar IVs are an important part of the anatomical structure of the intervertebral foramina. Adequate knowledge of the IV may be of clinical importance to physicians performing transforaminal epidural steroid injection. KEY WORDS: Clinical anatomy, intervertebral veins, lumbar vertebra, Kambin's triangle, safe triangle, intervertebral foramina, vertebral venous system, inadvertent injection, transforaminal epidural steroid injection.

Percutaneous coronary intervention for a Chinese familial hypercholesterolemia homozygous under the guidance of optical coherence tomography.

Homozygous familial hypercholesterolemia developed into severe cardiovascular consequences early. Untreated HoFH usually cannot survive over 30 years old. Acute coronary syndrome(ACS) caused by plaque rupture is one of the main causes of death in HoFH. As the highest resolution intravascular imaging technique, optical coherence tomography(OCT) can clearly show the thickness and structural characteristics of atherosclerotic plaque caps. In this study, a Chinese male HoFH received percutaneous coronary intervention for unstable angina. After analyzed his genetic and follow-up data, OCT was performed during interventional therapy. Multiple lipid rich plaques accompanied with inflammatory cell infiltration and a thin-cap fibroatheroma(TCFA) were noted, which reflected the vulnerability of plaques. The utility of OCT had certain guiding significance for strategy of interventional therapy and the long-term drug management. And this case suggested that it was important to undergo OCT examination for patients with HoFH who required percutaneous coronary intervention.

Rifaximin Alters Intestinal Microbiota and Prevents Progression of Ankylosing Spondylitis in Mice.

Recently, accumulating evidence has suggested that gut microbiota may be involved in the occurrence and development of ankylosing spondylitis (AS). It has been suggested that rifaximin have the ability to modulate the gut bacterial communities, prevent inflammatory response, and modulate gut barrier function. The goal of this work is to evaluate the protective effects of rifaximin in fighting AS and to elucidate the potential underlying mechanism. Rifaximin were administered to the proteoglycan (PG)-induced AS mice for 4 consecutive weeks. The disease severity was measured with the clinical and histological of arthritis and spondylitis. Intestinal histopathological, pro-inflammatory cytokine levels and the intestinal mucosal barrier were evaluated. Then, western blot was performed to explore the toll-like receptor 4 (TLR-4) signal transducer and NF-κB expression. Stool samples were collected to analyze the differences in the gut microbiota via next-generation sequencing of 16S rDNA. We found that rifaximin significantly reduced the severity of AS and resulted in down-regulation of inflammatory factors, such as TNF-α, IL-6, IL-17A, and IL-23. Meanwhile, rifaximin prevented ileum histological alterations, restored intestinal barrier function and inhibited TLR-4/NF-κB signaling pathway activation. Rifaximin also changed the gut microbiota composition with increased Bacteroidetes/Firmicutes phylum ratio, as well as selectively promoting some probiotic populations, including Lactobacillales. Our results suggest that rifaximin suppressed progression of AS and regulated gut microbiota in AS mice. Rifaximin might be useful as a novel treatment for AS.

The Morphology and Clinical Significance of the Extraforaminal Ligaments at the T1-T12 Levels.

STUDY DESIGN: A dissection-based study of 10 embalmed human cadavers. OBJECTIVE: The purpose of this study was to describe the extraforaminal ligaments in the exit regions of the T1-T12 intervertebral foramina and to discuss their possible clinical significance. SUMMARY OF BACKGROUND DATA: The ligaments at the lumbar intervertebral foramina have been well studied. However, detailed descriptions of the extraforaminal ligaments at the T1-T12 levels are lacking. METHODS: Two hundred forty T1-T12 intervertebral foramina from 10 embalmed cadavers were studied. The presence of the ligament was noted. The quantity, morphology, distributions, proximal attachments, distal attachments, and spatial orientations of the extraforaminal ligaments in the exit regions of the T1-T12 intervertebral foramina were examined. The length, width, diameter, and thickness of the ligaments were measured with digital calipers by three independent investigators. RESULTS: A total of 564 extraforaminal ligaments were identified in the 229 intervertebral foramina; no ligaments were found in the other 11 intervertebral foramina, resulting in an occurrence rate of extraforaminal ligaments of 95.42%. One hundred thirty-six (24.11%) of the extraforaminal ligaments were radiating ligaments, and 428 (75.89%) were transforaminal ligaments. Radiating ligaments had a tendency to be abundant at T1 and T9-T12 and sparse at T2-T8. There were 245 (43.44%) ligaments at the anterior aspect of the exit regions of the intervertebral foramina, 225 (39.89%) ligaments at the posterior aspect, 64 (11.35%) ligaments at the inferior aspect, and 30 (5.32%) ligaments at the superior aspect. CONCLUSION: In the exit region of thoracic intervertebral foramina, there are two types of extraforaminal ligaments. They may serve as a protective mechanism against traction and play a role in the positioning of the nerves in the intervertebral foramen. Transforaminal ligaments may be an underlying cause of rib or chest pain after thoracic fracture and may be of clinical importance to surgeons. LEVEL OF EVIDENCE: N/A.