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Background/purpose(s): The gut microbiota and its metabolites play crucial roles in pathogenesis of arthritis, highlighting gut microbiota as a promising avenue for modulating autoimmunity. However, the characterization of the gut virome in arthritis patients, including osteoarthritis (OA) and gouty arthritis (GA), requires further investigation. Methods: We employed virus-like particle (VLP)-based metagenomic sequencing to analyze gut viral community in 20 OA patients, 26 GA patients, and 31 healthy controls, encompassing a total of 77 fecal samples. Results: Our analysis generated 6819 vOTUs, with a considerable proportion of viral genomes differing from existing catalogs. The gut virome in OA and GA patients differed significantly from healthy controls, showing variations in diversity and viral family abundances. We identified 157 OA-associated and 94 GA-associated vOTUs, achieving high accuracy in patient-control discrimination with random forest models. OA-associated viruses were predicted to infect pro-inflammatory bacteria or bacteria associated with immunoglobulin A production, while GA-associated viruses were linked to Bacteroidaceae or Lachnospiraceae phages. Furthermore, several viral functional orthologs displayed significant differences in frequency between OA-enriched and GA-enriched vOTUs, suggesting potential functional roles of these viruses. Additionally, we trained classification models based on gut viral signatures to effectively discriminate OA or GA patients from healthy controls, yielding AUC values up to 0.97, indicating the clinical utility of the gut virome in diagnosing OA or GA. Conclusion: Our study highlights distinctive alterations in viral diversity and taxonomy within gut virome of OA and GA patients, offering insights into arthritis etiology and potential treatment and prevention strategies. [ABSTRACT FROM AUTHOR]

Background: Hox gene family is an important transcription factor that regulates cell process, and plays a role in the process of adipocytes differentiation and fat deposition. Previous transcriptome sequencing studies have indicated that the Homeobox A9 gene (HOXA9) is a candidate gene for regulating the process of bovine lipid metabolism, but the function and specific mechanism of action remain unclear. Therefore, this study aims to explore the role of HOXA9 in the proliferation, differentiation and apoptosis of bovine preadipocytes through gain-of-function and lose-of-function. Result: It found HOXA9 highly expressed in bovine adipose tissue, and its expression level changed significantly during adipocytes differentiation process. It gave a hint that HOXA9 may be involved in the process of bovine lipid metabolism. The results of HOXA9 gain-of-function experiments indicated that HOXA9 appeared to act as a negative regulator not only in the differentiation but also in the proliferation of bovine preadipocytes, which is mainly reflected that overexpression of HOXA9 down-regulate the mRNA and protein expression level of PPARγ, CEBPα and FABP4 (P < 0.05). The mRNA expression level of CDK1, CDK2, PCNA, CCNA2, CCNB1, CCND1 and CCNE2, as well as the protein expression of CDK2 also significantly decreased. The decrease of lipid droplets content was the main characteristic of the phenotype (P < 0.01), which further supported the evidence that HOXA9 was a negative regulator of preadipocytes differentiation. The decrease of cell proliferation rate and EdU positive rate, as well as the limitation of transition of preadipocytes from G0/G1 phase to S phase also provided evidence for the inhibition of proliferation. Apart from this above, we noted an interesting phenomenon that overexpression of HOXA9 showed in a significant upregulation of both mRNA and protein level of apoptosis markers, accompanied by a significant increase in cell apoptosis rate. These data led us not to refute the fact that HOXA9 played an active regulatory role in apoptosis. HOXA9 loss-of-function experiments, however, yielded the opposite results. Considering that HOXA9 acts as a transcription factor, we predicted its target genes. Dual luciferase reporter assay system indicated that overexpression of HOXA9 inhibits activity of PCNA promoter. Conclusion: Taken together, we demonstrated for the first time that HOXA9 played a role as a negative regulatory factor in the differentiation and proliferation of preadipocytes, but played a positive regulatory role in apoptosis, and it may play a regulatory role by targeting PCNA. This study provides basic data for further exploring the regulatory network of intramuscular fat deposition in bovine. [ABSTRACT FROM AUTHOR]

Background: Rectovaginal fistula (RVF) is an abnormal channel formed by epithelial tissue between the anterior wall of the rectum and the posterior wall of the vagina, which manifests as vaginal gassing and defecation. It is one of the common complications of female pelvic surgeries. With the increased number of proctectomies for rectal cancer, the number of postoperative rectovaginal fistulas also increases. Once RVF occurs, the failure rate is still high with various treatments available. RVF causes great suffering to women and is still a major problem in treatment. Therefore, it is significant for female rectal cancer patients to prevent RVF after rectal cancer surgery. In this study, we introduce a new method to prevent RVF during rectal cancer radical operation. Methods: In this randomized controlled trial (RCT), all operations are performed according to the principle of total mesorectal excision (TME) radical resection in rectal cancer surgery. All eligible participants will be divided into two groups: the experimental group and the control group. Experimental group: the anterior rectal wall of about 1 cm distal to the anastomosis was dislocated. Before the anastomosis of the rectal end, a fat flap (usually left side) containing the ovarian vascular pedicle was dislocated, measured by 10–15 cm in length and 2 cm in width. The fat flap containing the ovarian vascular pedicle was packed and fixed anterior to the anastomotic stoma with fibrin glue. Control group: surgery will be carried out in accordance with the TME principle. Participants will be compared on several variables, including the incidence of RVF after operation (primary outcomes), the occurrence time of postoperative RVF, the occurrence time of RVF after stoma closure, and other postoperative complications, such as anastomotic leakage, chylous leakage, and intestinal obstruction (secondary outcomes). The follow-up data collection will be conducted according to the follow-up time point, and the baseline data will also be collected for follow-up analysis. By comparing the incidence of rectovaginal leakage between the experimental group and the control group, we aim to explore the feasibility of this method for the prevention of postoperative RVF. Discussion: This RCT will explore the feasibility of packing with a laparoscopic dislocated fat flap containing an ovarian vascular pedicle anterior to the anastomotic stoma after rectal cancer surgery to prevent RVF. Trial registration: Chinese Clinical Trial Registry (ChiCTR) registration ChiCTR2000031449. Registered on June 26, 2019. All items of the WHO Trial registration data set can be found within the protocol. [ABSTRACT FROM AUTHOR]