Comparison the treatment of anterior inferior tibiofibular ligament anatomical repair and syndesmosis screw fixation for syndesmotic injuries in ankle fracture.

BACKGROUND: The fixation method of syndesmotic injuries in ankle fractures remains controversial. The goal of the study was to compare radiographic and clinical outcomes between anterior inferior tibiofibular ligament (AITFL) anatomical repair with syndesmosis screw fixation in syndesmotic injuries. METHODS: We analyzed 62 patients who were treated with AITFL anatomical repair or syndesmosis screw fixation for syndesmotic injuries in an advanced teaching hospital between March 2016 and March 2019. Fixation was performed with AITFL anatomical repair in 30 patients (AAR group) and syndesmosis screw in 32 patients (SS group). Radiographic evaluations were the differences in mean anterior and posterior (A difference and P difference) tibiofibular distance between injured and uninjured ankle computed tomography (CT) scan at 6 months postoperatively. Clinical evaluation of patients was done using the American Orthopaedic Foot & Ankle Society (AOFAS) Ankle Hindfoot Score, the Olerud-Molander Ankle (OMA) score and visual analogue scale (VAS) score at 1, 3, 6 months and 1, 2 years postoperatively. RESULTS: The A difference and P difference on CT was no differences (1.6 ± 0.8 mm, 1.3 ± 0.7 mm vs. 1.5 ± 0.7 mm, 1.2 ± 0.7 mm) between the two groups (All of P > 0.05). The AAR group had higher mean AOFAS score (65.6 ± 5.9, 82.3 ± 4.2, 87.6 ± 5.6 vs. 61.8 ± 5.2, 79.1 ± 4.0, 83.8 ± 4.9; P = 0.008, 0.003, 0.007) and higher mean OMA score (45.7 ± 8.7, 79.2 ± 6.5, 84.1 ± 5.3 vs. 40.4 ± 7.3, 74.8 ± 6.3, 80.3 ± 5.8; P = 0.012, 0.009, 0.010)) at 1, 3 and 6 months postoperatively. The AAR group had lower mean VAS scores (2.6 ± 1.2, 1.7 ± 0.7 vs. 3.4 ± 1.2, 2.2 ± 1.1; P = 0.018, 0.038) at 1 and 3 months postoperatively. CONCLUSIONS: The results of this study suggest that the AITFL anatomical repair technique could effectively improve ankle function during daily activity. Therefore, AITFL anatomical repair technique is expected to become a better fixation method for syndesmotic injuries.

11S Glycinin Up-Regulated NLRP-3-Induced Pyroptosis by Triggering Reactive Oxygen Species in Porcine Intestinal Epithelial Cells.

11S glycinin is a major soybean antigenic protein, which induces human and animal allergies. It has been reported to induce intestinal porcine epithelial (IPEC-J2) cell apoptosis, but the role of pyroptosis in 11S glycinin allergies remains unknown. In this study, IPEC-J2 cells were used as an in vitro physiological model to explore the mechanism of 11S glycinin-induced pyroptosis. The cells were incubated with 0, 1, 5, and 10 mg·ml-1 11S glycinin for 24 h. Our results revealed that 11S glycinin significantly inhibited cell proliferation, induced DNA damage, generated active oxygen, decreased mitochondrial membrane potential, and increased the NOD-like receptor protein 3 (NLRP-3) expression of IPEC-J2 cells in a dose-dependent manner. Further, IPEC-J2 cells were transfected with designed sh-NLRP-3 lentivirus to silence NLRP-3. The results showed that 11S glycinin up-regulated the silenced NLRP-3 gene and increased the expression levels of apoptosis-related spot-like protein (ASC), caspase-1, the cleaved gasdermin D, and interleukin-1ß. The IPEC-J2 cells showed pyrolysis morphology. Moreover, we revealed that N-acetyl-L-cysteine can significantly inhibit the production of reactive oxygen species and reduce the expression levels of NLRP-3 and the cleaved gasdermin D. Taken together, 11S glycinin up-regulated NLRP-3-induced pyroptosis by triggering reactive oxygen species in IPEC-J2 cells.

Systematic Study on a Quantitative Analysis of Multicomponents by Single Marker (QAMS) Method for Simultaneous Determination of Eight Constituents in Pneumonia Mixture by UPLC-MS/MS.

Pneumonia mixture was formulated and is available to treat children acute pneumonia and acute bronchitis in our hospital for nearly forty years, but there are few studies of its quality evaluation or control. In this paper, a new strategy for quality evaluation of pneumonia mixture was explored and verified through qualitative and quantitative analyses of multicomponents by single marker (QAMS) by UPLC-MS/MS. Baicalein was selected as an internal reference, and the relative correction factors (RCFs) and the relative retention time (RRT) of (R, S)-goitrin, amygdalin, chlorogenic acid, pseudoephedrine hydrochloride, ephedrine hydrochloride, ammonium glycyrrhizinate, and baicalin were established. The robustness and durability of the QAMS method were investigated. RCF values calculated by the average (AVG) method and linear regression (LRG) method had good repeatability and were acceptable for quantitative analysis, and the RTT combined with the exact masses of precursor and fragment ions and their abundance could be adopted for accurately positioning the chromatographic peak of the eight constituents. The consistency and feasibility of the QAMS method were verified by comparing the contents of the seven components calculated by a classic and validated external standard method (ESM) with those of the QAMS method, which reduces analytical cost and time of detection and avoids the problem of the diversity and large quantity of reference standards. The results demonstrated that the QAMS method developed in this paper could provide a new, alternative, and promising method to comprehensively and effectively determine multicomponents and control the quality of pneumonia mixture or even a group of similar medicines.

Stemona alkaloids suppress the positive feedback loop between M2 polarization and fibroblast differentiation by inhibiting JAK2/STAT3 pathway in fibroblasts and CXCR4/PI3K/AKT1 pathway in macrophages.

This study aimed to investigate the interaction between macrophages and fibroblasts in pulmonary fibrosis and the effects of total alkaloids of Stemona tuberosa (STA, 9 alkaloids with relative content of 91.2%) on them. The culture medium of LPS- or IL-4-induced macrophages was used as conditioned medium (CM) to co-culture with fibroblasts to study the effect of macrophages on the differentiation of fibroblasts. Similarly，the CM of TGF-ß1-induced fibroblasts was co-culture with macrophages to study the effect of fibroblasts on the polarization of macrophages. The results showed that the TGF-ß1 level in IL-4-induced (M2) rather than LPS-induced (M1) macrophages was significantly high (p < 0.001), and the SDF-1 level in TGF-ß1-induced fibroblasts (MF) was significantly high (p < 0.001). The expressions of α-SMA and Col-1 in M2-CM-induced fibroblasts and Arg-1 and CXCR4 in MF-CM-induced macrophages were significantly increased (p < 0.01). STA effectively decreased the expressions of α-SMA (p < 0.05, 0.01 at 10, 100 µg/mL), Col-1 (p < 0.05, 0.05, 0.01 at 1, 10, 100 µg/mL), Arg-1 (p < 0.01 at 1, 10, 100 µg/mL) and CXCR4 (p < 0.01, 0.001 at 10, 100 µg/mL), which were consistent with the experimental results in vivo. These results suggested that there was a positive feedback loop between M2 polarization and fibroblast differentiation in pulmonary fibrosis. Further studies showed that the transcription of sdf-1 gene in MF was initiated by JAK2/STAT3 pathway and the M2 polarization was promoted by SDF-1/CXCR4/PI3K/AKT1 pathway. STA blocked the feedback loop by suppressing JAK2/STAT3 pathway in fibroblasts and CXCR4-PI3K/AKT1 pathway in macrophages.

Neotuberostemonine attenuates bleomycin-induced pulmonary fibrosis by suppressing the recruitment and activation of macrophages.

Neotuberostemonine (NTS) is one of the main antitussive alkaloids in the root of Stemona tuberosa Lour. This study aimed to investigate the effects of NTS on bleomycin (BLM)-induced pulmonary fibrosis in mice and the underlying mechanism. After BLM administration, NTS were orally administered to mice at 20 and 40mg/kg per day from days 8 to 21, with nintedanib as a positive control. The effect of NTS on BLM-induced mice was assessed via histopathological examination by HE and Masson's trichrome staining, TGF-ß1 level and macrophage recruitment by immunohistochemical staining, expression of profibrotic media and M1/M2 polarization by western blot. RAW 264.7 cells were used to evaluate whether NTS (1, 10, 100µM) directly affected macrophages. The results revealed that NTS treatment significantly ameliorated lung histopathological changes and decreased inflammatory cell counts in the bronchoalveolar lavage fluid. The over-expression of collagen, α-SMA and TGF-ß1 was reduced by NTS. Furthermore, NTS markedly lowered the expression of MMP-2 and TIMP-1 while raised the expression of MMP-9. A further analysis showed that NTS was able to decrease the recruitment of macrophages and to inhibit the M2 polarization in mice lung tissues. The experiment in vitro showed that NTS significantly reduced the arginase-1 (marker for M2) expression in a dose-dependent manner but down-regulated the iNOS (marker for M1) expression only at 100µM. In conclusion, our study demonstrated for the first time that NTS has a significant protective effect on BLM-induced pulmonary fibrosis through suppressing the recruitment and M2 polarization of macrophages.