The purpose of this study was to explore the investigative mechanism of salidroside (SAL) on LPS-induced acute lung injury (ALI)/acute respiratory distress syndrome (ARDS). The exosomes from RLE-6TN are extracted and identified by transmission electron microscopy, particle size analysis and protein marker detection, and co-cultured with NR8383 cells. The ALI/ARDS model of SD rats was established by LPS (10 mg/kg) intratracheal instillation. Following a four-hour intratracheal instillation of LPS, 50 μl of RLE-6TN exosomes were injected through the tail vein. After that, SAL and miR-146a antagomir were injected into the tail vein for 72 h, respectively. As the changes of HE stain, body weight and ALI score are observed. The expression of miR-146a, TLR4, NF-kB, IRAK1, TRAF6 and their related proteins were detected by RT-PCR and Western blot, respectively. TNF-α, IL-6, IL-8 and IL-1 β inflammatory factors were detected by ELISA. The expression of miR-146a, NF-kB, IRAK, TRAF6 and related inflammatory factors in LPS-induced NR8383 was significantly higher than that in the control group, while SAL has greatly reduced the expression of TLR4 mediated NF-kB inflammatory pathway and related inflammatory factors. SAL can significantly improve the LPS-induced lung morphological abnormalities, slowed down the rate of weight loss in rats, and reducing the ALI score. The expression trend of NF-kB, IRAK, TRAF6 and related inflammatory factors in rats’ lung tissues was consistent with that in NR8383 cells. SAL has a protective effect on ALI/ARDS caused by sepsis, which is likely to be developed to a potential treatment for the disease. To sum up, this study provides a new theoretical basis for the treatment of ALI/ARDS with SAL.

Programmed cell death 1 receptor (PD-1) and its ligands constitute an inhibitory pathway to mediate the mechanism of immune tolerance and provide immune homeostasis. Significantly, the binding partners of PD-1 and its associated ligands are diverse, which facilitates immunosuppression in cooperation with other immune checkpoint proteins. Accumulating evidence has demonstrated the important immunosuppressive role of the PD-1 axis in the tumor microenvironment and in autoimmune diseases. In addition, PD-1 blockades have been approved to treat various cancers, including solid tumors and hematological malignancies. Here, we provide a comprehensive review of the PD-1 pathway, focusing on the structure and expression of PD-1, programmed cell death 1 ligand 1 (PD-L1), and programmed cell death 1 ligand 2 (PD-L2); the diverse biological functions of PD-1 signaling in health and immune-related diseases (including tumor immunity, autoimmunity, infectious immunity, transplantation immunity, allergy and immune privilege); and immune-related adverse events related to PD-1 and PD-L1 inhibitors.

Background: Medial patellofemoral ligament reconstruction (MPFLR) is a well-established procedure for addressing recurrent patellar dislocation (RPD) in young patients. However, for RPD with genu valgum, simultaneous MPFLR and closing-wedge distal femoral osteotomy (CWDFO) may be a promising procedure yet rarely reported. This study’s purpose was to observe and analyse the clinical and imaging findings of CWDFO combined with MPFLR for RPD with genu valgum.Methods: From May 2015 to Apirl 2018, 25 patients with RPD and genu valgum were surgically treated in our department. Anteroposterior long-leg, weight-bearing, lower-extremity radiographs, lateral radiographs and computed tomography (CT) scans of the patellofemoral joint were obtained, and the femorotibial angle (FTA), mechanical lateral distal femoral angle (mLDFA), weight-bearing line rate (WBLR), patellar height, patellar lateral shift (PLS) and tibial tubercle–trochlear groove (TT-TG) distance were analysed. Validated knee scores, such as the Kujala, Lysholm, visual analogue scale (VAS) scores and Tegner socres, were evaluated preoperatively and 2 years postoperatively.Results: 25 patients, with an average age of 19.8 years (14–27), were evaluated. All patients had been able to achieve a better sports level without any problems during the 2-year follow-up period. There has been no recurrence of patellar instability. Compared with preoperation, the FTA, mLDFA, WBLR and PLS showed statistically significant improvement following the procedure (p < 0.001). Meanwhile, no significant differences in the Insall index and TT-TG distance was found. The mean Kujala score, average Lysholm score, VAS score and Tegner socres showed significant improvement postoperatively.Conclusions: CWDFO combined with MPFLR is a suitable treatment for RPD with genu valgum, as it leads to significant improvement in the clinical and imaging findings of the knee in the short term.

Background Medial patellofemoral ligament reconstruction (MPFLR) is a well-established procedure for addressing recurrent patellar dislocation (RPD) in young patients. However, despite being a promising procedure for RPD with genu valgum, there is a scarcity of reports on simultaneous MPFLR and closing-wedge distal femoral osteotomy (CWDFO). The purpose of the present study was to observe and analyse the clinical and imaging findings of CWDFO combined with MPFLR for RPD with genu valgum. Methods From May 2015 to April 2018, 25 patients with RPD and genu valgum were surgically treated in our department. Anteroposterior long-leg, weight-bearing, lower-extremity radiographs, lateral radiographs and computed tomography (CT) scans of the patellofemoral joint were obtained, and the anatomical femorotibial angle (aFTA), mechanical lateral distal femoral angle (mLDFA), weight-bearing line rate (WBLR), patellar height, patellar lateral shift (PLS) and tibial tubercle–trochlear groove (TT-TG) distance were analysed. Validated knee scores, such as the Kujala, Lysholm, visual analogue scale (VAS) scores and Tegner socres, were evaluated preoperatively and 2 years postoperatively. Results 25 patients, with an average age of 19.8 years (14–27), were evaluated. During the 2-year follow-up period, all patients were able to achieve a better sports level without any problems, with no recurrence of patellar instability. Compared with preoperation, the aFTA, mLDFA, WBLR and PLS showed statistically significant improvement following the procedure (p < 0.001). Meanwhile, no significant differences in the Insall index and TT-TG distance were found. The mean Kujala score, average Lysholm score, VAS score and Tegner socres showed significant postoperative improvement. Conclusions CWDFO combined with MPFLR is a suitable treatment for RPD with genu valgum, and can lead to significant improvement in the clinical and imaging findings of the knee in the short term.

This study was designed to investigate the changes of urinary microvesicle-bound uromodulin and total urinary uromodulin levels in human urine and the correlations with the severity of diabetic kidney disease (DKD). 31 healthy subjects without diabetes and 100 patients with type 2 diabetes mellitus (T2DM) were included in this study. The patients with T2DM were divided into three groups based on the urinary albumin/creatinine ratio (UACR): normoalbuminuria group (DM, n = 46); microalbuminuria group (DN1, n = 32); and macroalbuminuria group (DN2, n = 22). We use a specific monoclonal antibody AD-1 to capture the urinary microvesicles. Urinary microvesicle-bound uromodulin and total urinary uromodulin levels were determined by enzyme-linked immunosorbent assay (ELISA). Our results showed that the levels of urinary microvesicle-bound uromodulin in DN1 and DN2 groups were significantly higher than those in control group and DM group (P < 0.01). Multiple stepwise linear regression analysis showed that UACR was independent determinant for urinary microvesicle-bound uromodulin (P < 0.05) but not for total urinary uromodulin. These findings suggest that the levels of urinary microvesicle-bound uromodulin are associated with the severity of DKD. The uromodulin in urinary microvesicles may be a specific marker of DKD and potentially may be used to predict the onset and/or monitor the progression of DKD.