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New pH-sensitive polysaccharide supramolecular hydrogel microparticles (HMPs) were constructed based on carboxymethyl β-cyclodextrin/chitosan inclusion complex (CM-β-CD/CS) and EDTA-chitosan (EDCS) in aqueous solution. The incorporation of components in HMPs was characterized by ultraviolet, fluorescence and FTIR spectroscopy. The morphology measurements of HMPs were investigated by particle size analyzer and fluorescence microscope. These results showed that CM-β-CD was integrated on the CS by electrostatic interactions, while the hydrogen bonding between CM-β-CD/CS complex and EDCS resulted in the formation of self-assembled HMPs. The swelling and shear rheological behaviors of the HMPs were also investigated, confirming the pH sensitive of the HMPs. In vitro drug release behaviors of the HMPs conducted in simulated gastric fluid (pH 1.2) and simulated intestinal fluid (pH 7.4) were studied by using bovine serum albumin (BSA) as model protein drug. Results indicated that the BSA-loaded HMPs exhibit highlighted pH-dependent release characteristics and the release of BSA from the HMPs could be described by the Ritger–Peppas model equation, suggesting that the HMPs might be formulated to be a promising candidate for the release of protein drugs.

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., Anti‐TNF alpha therapy attenuated the incidence and severity of ankylosing spondylitis in mice. Anti‐TNF alpha therapy modulated gut microbiota of ankylosing spondylitis in mice. Anti‐TNF alpha therapy repaired the gut barrier function of ankylosing spondylitis in mice.

Background: The detailed structure of the lumbar intervertebral foramina has been wellstudied. 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

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.

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.

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.