[Umbelliferone improves chronic hypoxia-induced pulmonary hypertension by inhibiting the RhoA/ROCK signaling pathway and autophagy].

This study aimed to investigate the effects of hypoxia on RhoA/Rho-kinase (ROCK) signaling pathway and autophagy in pulmonary artery smooth muscle cells (PASMCs), and to explore the underlying mechanism of Umbelliferone (Umb) in ameliorating chronic hypoxic pulmonary hypertension. PASMCs were cultured from Sprague-Dawley (SD) rats and randomly divided into control group, hypoxia group, hypoxia + Umb intervention group and normoxia + Umb intervention group. Alpha smooth muscle actin (α-SMA) and LC3 were assessed by immunofluorescence staining. Protein expression of RhoA, ROCK2, p-MYPT1, LC3-II, Beclin-1, p62, C-Caspase 3, Bax and Bcl-2 was analyzed by Western blotting. In in vivo study, SD rats were divided into control group, hypoxia group and hypoxia + Umb intervention group. Weight ratio of the right ventricle (RV)/left ventricle plus septum (LV+S) was detected, and pulmonary arterial morphological features were examined by HE staining. The results indicated that compared with the control group, the LC3-II/LC3-I ratio and expression of Beclin-1 were significantly increased, while p62 expression was significantly decreased, and the expressions of RhoA, ROCK2 and p-MYPT1 were significantly increased in PASMCs of hypoxia group (P < 0.05). The changes of LC3-II/LC3-I ratio, the expressions of Beclin-1, p62, RhoA, ROCK2 and p-MYPT1 in PASMCs were reversed by Umb treatment (P < 0.05). Consistently, the pulmonary arterial wall was thickened and the RV/(LV+S) ratio was increased in hypoxic rats, which were significantly improved by Umb treatment (P < 0.05). These results suggest that Umb can improve hypoxia-induced pulmonary hypertension by inhibiting the RhoA/ROCK signaling pathway and autophagy in PASMCs.

Inhibiting TLR4 signaling by linarin for preventing inflammatory response in osteoarthritis.

Osteoarthritis (OA) is one of the most common degenerative diseases, ultimately leading to long-term joint pain and severe articular malformation. Controlling local chronic inflammation is a crucial strategy for delaying OA development. Linarin is a natural flavonoid glycoside that is widely available in Compositae, Chrysanthemum indicum and Dendrocalamus and processes protective effects in several animal models. The purpose of our work was to study the protective effect of Linarin for OA. Cellular experiments data showed that Linarin suppressed lipopolysaccharide (LPS)-caused the overproduction of nitric oxide (NO), prostaglandin E2 (PGE2), interleukin-6 (IL-6) and tumour necrosis factor-alpha (TNF-α) in chondrocyte. In addition, LPS-stimulated expression of cyclooxygenase-2 (COX-2) and inducible nitric oxide nitrate (iNOS) was decreased by Linarin pre-treatment. Together, Linarin prevented the catabiosis of extracellular matrix caused by LPS. For mechanism, Linarin inhibited the formation of Toll-like receptor 4 (TLR4) / myeloid differentiation protein-2 (MD-2) dipolymer complex and subsequently intervened NF-κB activation. Our mouse DMM model further clarified the protection of Linarin in vivo. In summary, our results suggested that Linarin may be a potential effective agent for OA.

A biomechanics study on ligamentous injury in anterior-posterior compression type II pelvic injury.

BACKGROUND: Anterior-posterior compression (APC) type II pelvis fracture is caused by the destruction of pelvic ligaments. This study aims to explore ligaments injury in APC type II pelvic injury. METHOD: Fourteen human cadaveric pelvis samples with sacrospinous ligament (SPL), sacrotuberous ligament (SBL), anterior sacroiliac ligament (ASL), and partial bone retaining unilaterally were acquired for this study. They were randomly divided into hemipelvis restricted and unrestricted groups. We recorded the separation distance of the pubic symphysis and anterior sacroiliac joint, external rotation angle, and force when ASL ruptured. We observed the external rotation damage to the pelvic bone and ligaments. RESULT: When ASL failed, there was no significant difference in pubic symphysis separation (28.6 ± 8.4 mm to 23.6 ± 8.2 mm, P = 0.11) and anterior sacroiliac joint separation (11.4 ± 3.8 mm to 9.7 ± 3.9 mm, P = 0.30) between restricted and unrestricted groups. The external rotation angle (33.9 ± 5.5° to 48.9 ± 5.2°, P < 0.01) and force (553.9 ± 82.6 N to 756.6 ± 41.4 N, P < 0.01) were significantly different. Pubic symphysis separation between two groups ranged from 14 to 40 mm. In the restricted group, both SBL and SPL were injured. SPL ruptured first, and then SBL and the interosseous sacroiliac ligament were damaged while the posterior ligament remained unharmed. In the unrestricted group, interosseous sacroiliac ligament and posterior sacroiliac ligaments were damaged, while SBL and SPL were not. When the ASL, SBL, and SPL all failed, pubic symphysis and anterior sacroiliac joint separation between two groups increased significantly (from 28.6 ± 8.4 to 42.0 ± 7.6 mm, 11.4 ± 3.8 to 16.7 ± 4.2 mm respectively, all P < 0.05). CONCLUSION: Pelvic external rotation injury is either hemipelvic restricted or unrestricted, which can result in different outcomes. When the ASL ruptures, the unrestricted group needs greater external rotation angle and force, without SBL or SPL injury, while both SBL and SPL were injured in another group. When ASL fails in two groups, pubic symphysis separation fluctuates considerably. Finally, when the ASL ruptures, SBL and SPL may be undamaged.

Astilbin prevents osteoarthritis development through the TLR4/MD-2 pathway.

Osteoarthritis has become one of the main diseases affecting the life of many elderly people with high incidence of disability, and local chronic inflammation in the joint cavity is the most crucial pathological feature of osteoarthritis. Astilbin is the main active component in a variety of natural plants such as Hypericum perforatum and Sarcandra glabra, which possess antioxidant and anti-inflammatory effects. At present, there is no study about the protective effect of Astilbin for osteoarthritis. The purpose of this study was to investigate the effect of Astilbin in human OA chondrocytes and mouse OA model, which was established by surgery-mediated destabilization of the medial meniscus (DMM). In vitro, we found that Astilbin pre-treatment inhibited lipopolysaccharide (LPS)-induced overproduction of inflammation-correlated cytokines such as nitric oxide (NO), prostaglandin E2 (PGE2), tumour necrosis factor α (TNF-α) and interleukin 6 (IL-6), and suppressed overexpression of inflammatory enzymes such as inducible nitric oxide synthase (iNOS) and cyclooxygenase 2 (COX-2). Astilbin, on the other hand, prevented the LPS-induced degradation of extracellular matrix (ECM) by down-regulating MMP13 (matrix metalloproteinases 13) and ADAMTS5 (a disintegrin and metalloproteinase with thrombospondin motifs 5). Moreover, by inhibiting the formation of the TLR4/MD-2/LPS complex, Astilbin blocked LPS-induced activation of TLR4/NF-κB signalling cascade. In vivo, Astilbin showed the chondro-protective effect in the surgical-induced OA mouse models. In conclusion, our findings provided evidence that develops Astilbin as a potential therapeutic drug for OA patients.

Combined antisclerostin antibody and parathyroid hormone (1-34) synergistically enhance the healing of bone defects in ovariectomized rats.

Osteoporotic bones heal more slowly and ineffectively than normal bones. A combination of antibodies against sclerosing protein (Scl-Ab), and parathyroid hormone 1-34 (PTH 1-34) may improve healing. A standard osteoporotic rat model was established 12 weeks after bilateral ovarian resection (OVX). Bone defects were created in the right femora of 80 rats, which were randomly divided into 4 groups: control, Scl-Ab (25 mg/kg twice weekly), PTH (60 µg/kg of PTH 1-34 three times a week) and PTH plus Scl-Ab. After 12 weeks of treatment the rats were sacrificed and blood and the distal femora were harvested for biochemical evaluation, histology, microcomputed tomography and biomechanical testing. Compared to the control group, monotherapy and combination therapy with PTH and/or Scl-Ab promoted the formation of new bone, enhanced maximum femoral loading and increased the levels of procollagen type I N­terminal propeptide (PINP) and osteocalcin. The administration of PTH + Scl-Ab maximally enhanced bone defect healing. Combination treatment was better than either treatment alone, indicating a synergistic effect.

Comparison of sinus tarsi approach versus extensile lateral approach for displaced intra-articular calcaneal fractures Sanders type IV.

PURPOSE: Displaced intra-articular calcaneus fractures Sanders type IV(DIACFS IV) can result in an unsatisfactory prognosis and a high complication rate. Our investigation intends to compare the outcomes of DIACFS IV treated by open reduction and internal fixation (ORIF) via sinus tarsi approach (STA) with these via extensile lateral approach (ELA). METHODS: Sixty-nine patients (82 ft) with DIACFS IV who were treated with ORIF (29 in STA group and 40 in ELA group) were retrospectively assessed. Median follow-up was 50 months in two groups. Radiographic results were reviewed pre-operatively and post-operatively, and relative complications were collected. Clinical outcomes were evaluated using the American Orthopaedic Foot and Ankle Society (AOFAS) score and visual analog scale (VAS). RESULTS: The wound-healing complication rate was 14.28% in STA group and 34.04% in ELA group (p = .043), and overall complication rate was 54% and 77% (p = .056), respectively. Seven cases of sural nerve injury only occurred in ELA group. The post-operative radiographs of the calcaneus (Böhler's angle, height, width, and length) were significantly different from those measured pre-operatively in each group. And these data were parallel between the two groups. In STA and ELA groups, the average AOFAS was 75.45 versus 72.44 (p = .496), and the mean VAS was 23.95 versus 30.93 (p = .088), respectively. CONCLUSION: Similar clinical and radiographic outcomes are achieved between STA and ELA. And STA has a lower incidence of wound healing complication and sural nerve injury. Therefore, ORIF via STA can be a considerable management for DIACFS IV.

Vacuum-assisted closure combined with a closed suction irrigation system for treating postoperative wound infections following posterior spinal internal fixation.

BACKGROUND: Wound infections after posterior spinal surgery are a troublesome complication; patients are occasionally forced to remove the internal fixation device, which can lead to instability of the spine and injury to the spinal cord. The purpose of this study was to evaluate the efficacy of modified vacuum-assisted closure (VAC) for treating an early postoperative spinal wound infection. METHODS: We conducted a retrospective study of 18 patients with wound infections after posterior spinal surgery from 2014 to 2017 at a single tertiary center. All patients included in the study received modified VAC treatment (VAC combined with a closed suction irrigation system, CSIS) until the wound satisfied the secondary closure conditions. Detailed information was obtained from the medical records. RESULTS: Wound size decreased significantly after 1 week of the modified VAC treatment. Three patients were treated with VAC three times and one patient received the VAC treatment four times; the remaining patients received the VAC treatment twice. The patients had excellent wound beds after an average of 8 days. The wound healed completely after an average of 17 days, and the average hospital stay was 33 days. There was no recurrence of infection at the 1-year follow-up. CONCLUSIONS: This study demonstrates that VAC combined with a CSIS is a safe, reliable, and effective method to treat a wound infection after spinal surgery. This improved VAC procedure provides an excellent wound bed to facilitate wound healing and shorten the hospital stay.

Does Timing of Surgery Affect Treatment of the Terrible Triad of the Elbow?

BACKGROUND This study investigated the influence of surgical timing on the treatment of terrible triad of the elbow (TTE). MATERIAL AND METHODS After exclusion, 63 patients were enrolled in this study: 20 patients were classified into the emergency group (group A, within 24 h after injury), 26 into the early surgery group (group B, from 4 to 14 days after injury), and 17 into the delayed surgery group (group C, more than 14 days after injury). All patients underwent the same approach, and elbow motion and complication rates were recorded and compared. RESULTS Fifty-eight patients were followed up (mean 20.5±1.9 months), and 5 patients had lost partial final data. At 1 month after the operation, elbow motion in group A was higher than in group B and group C (P<0.01); however, 3 or more months later, there was no distinct difference between group A and group B (P>0.05), while both group A and group B showed better outcomes than group C at all time points (P<0.05). Moreover, group A and group B had better higher elbow motion, MEPS, excellent and good rate than group C at the final clinical visit (all P<0.05). No postoperative pain or complication rate differences were found among the 3 groups except for elbow stiffness (2 in group A, 3 in group B, and 7 in group C) (P<0.05) which required reoperation to enhance elbow function. CONCLUSIONS Emergency or early operation for TTE patients were more effective than delayed operation.