Aims Osteoarthritis (OA) is a common degenerative joint disease characterized by chronic inflammatory articular cartilage degradation. Long noncoding RNAs (lncRNAs) have been previously indicated to play an important role in inflammation-related diseases. Herein, the current study set out to explore the involvement of lncRNA H19 in OA. Methods Firstly, OA mouse models and interleukin (IL)-1β-induced mouse chondrocytes were established. Expression patterns of IL-38 were determined in the synovial fluid and cartilage tissues from OA patients. Furthermore, the targeting relationship between lncRNA H19, tumour protein p53 (TP53), and IL-38 was determined by means of dual-luciferase reporter gene, chromatin immunoprecipitation, and RNA immunoprecipitation assays. Subsequent to gain- and loss-of-function assays, the levels of cartilage damage and proinflammatory factors were further detected using safranin O-fast green staining and enzyme-linked immunosorbent assay (ELISA) in vivo, respectively, while chondrocyte apoptosis was measured using Terminal deoxynucleotidyl transferase dUTP Nick-End Labeling (TUNEL) in vitro. Results IL-38 was highly expressed in lentivirus vector-mediated OA mice. Meanwhile, injection of exogenous IL-38 to OA mice alleviated the cartilage damage, and reduced the levels of proinflammatory factors and chondrocyte apoptosis. TP53 was responsible for lncRNA H19-mediated upregulation of IL-38. Furthermore, it was found that the anti-inflammatory effects of IL-38 were achieved by its binding with the IL-36 receptor (IL-36R). Overexpression of H19 reduced the expression of inflammatory factors and chondrocyte apoptosis, which was abrogated by knockdown of IL-38 or TP53. Conclusion Collectively, our findings evidenced that upregulation of lncRNA H19 attenuates inflammation and ameliorates cartilage damage and chondrocyte apoptosis in OA by upregulating TP53, IL-38, and by activating IL-36R. Cite this article: Bone Joint Res 2022;11(8):594–607.
Background Surgery is a crucial component of the management of chronic pulmonary aspergillosis (CPA).However, there is currently less information available on Uni-port thoracoscopy(Uni-VATS) for CPA.Therefore, we created a single-center retrospective analysis of surgical procedures for CPA to demonstrate the effectiveness and security of Uni-VATS in CPA. Methods The basic information and surgical data of patients who underwent surgery at our hospital from January 2018 to June 2022 for CPA were obtained, all of whom received voriconazole antifungal medication for 3-6 months following surgery and were monitored for more than 6 months. Results A total of 110 patients met the inclusion criteria, including 59 cases in the traditional open chest incision group and 51 cases in the Uni-VATS group. There was one death among all patients due to pulmonary infection after surgery in our hospital.The mean operative time in the traditional open chest incision group and Uni-VATS group was 321.90±92.16 and 233.12±113.65 minutes, respectively.In the two groups mentioned above, the median (IQR) of intraoperative blood loss volume was 450(300-1000) and 330(100-500) ml,postoperative 24-hour drainage volume was 520(320-820) and 200(120-400) ml, postoperative second 24-hour drainage volume was 420(260-650) and 170(100-300) ml, pain scores were 9(8-10) and 4(4-5), postoperative drainage tube removal time was 15(8-21) and 8(5-16) days,postoperative hospital stay time was 18(13-23) and 12(8-18) days, and postoperative complication rate was 40.7%(24/59) and 17.6%(9/51) respectively. ConclusionUni-VATS is highly effective safe and minimally invasive for patients with CPA, and could be suggested as an alternative to traditional methods of lung surgery.
Background: Interleukin-23 (IL-23) inhibitors are widely used in clinical practice for Psoriasis , but multiple adverse events (AEs) have been reported. We aimed to describe the distribution of AEs related IL-23 inhibitors including Guselkumab, Tildrakizumab, Risankizumab, Ustekinumab. Methods: Data from January 1, 2014, to September 30, 2022 were extracted from the FDA Adverse Event Reporting System (FAERS). Disproportionality analysis including reporting odds ratio (ROR) and information component (IC) was performed to access potential signals. It was defined a signal when the lower limit of 95% confidence interval (CI) of ROR (ROR025) more than one or IC(IC025) exceeding zero, with the number of cases greater than or equal to three at the same time. Results: A total of 41,408,408 drug-AE reports were extracted from the FAERS database involving 13271168 people. 704, 13164, 62853, 11399 patients have used Tildrakizumab, Guselkumab, Ustekinumab, Risankizumab and 8, 20, 107 and 115 signals were found respectively. The “infections and infestations” has the highest incidence of SOC in Tildrakizumab(6/8), Guselkumab(5/20), Ustekinumab(50/107), Risankizumab(25/115). Conclusion: Our pharmacovigilance analysis showed that a high frequency was reported for AEs triggered by IL-23 inhibitors. IL-23 inhibitors had the potential to impair immune function resulting in a risk of infections or cancers. We need to pay special attention to Risankizumab because the drug has more AE occurrences than Ustekinumab despite Risankizumab has few reports than Ustekinumab and launched later than Ustekinumab.
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