This study investigated the effects and underlying mechanisms of vanillic acid(VA) against cardiac fibrosis(CF) induced by isoproterenol(ISO) in mice. Male C57BL/6J mice were randomly divided into control group, VA group(100 mg·kg~(-1), ig), ISO group(10 mg·kg~(-1), sc), ISO + VA group(10 mg·kg~(-1), sc + 100 mg·kg~(-1), ig), ISO + dynamin-related protein 1(Drp1) inhibitor(Mdivi-1) group(10 mg·kg~(-1), sc + 50 mg·kg~(-1), ip), and ISO + VA + Mdivi-1 group(10 mg·kg~(-1), sc + 100 mg·kg~(-1), ig + 50 mg·kg~(-1), ip). The treatment groups received the corresponding medications once daily for 14 consecutive days. On the day after the last administration, cardiac functions were evaluated, and serum and cardiac tissue samples were collected. These samples were analyzed for serum aspartate aminotransferase(AST), lactate dehydrogenase(LDH), creatine kinase-MB(CK-MB), cardiac troponin I(cTnI), reactive oxygen species(ROS), interleukin(IL)-1β, IL-4, IL-6, IL-10, IL-18, and tumor necrosis factor-α(TNF-α) levels, as well as cardiac tissue catalase(CAT), glutathione(GSH), malondialdehyde(MDA), myeloperoxidase(MPO), superoxide dismutase(SOD), total antioxidant capacity(T-AOC) activities, and cytochrome C levels in mitochondria and cytoplasm. Hematoxylin-eosin, Masson, uranium acetate and lead citrate staining were used to observe morphological and mitochondrial ultrastructural changes in the cardiac tissues, and myocardial injury area and collagen volume fraction were calculated. Flow cytometry was applied to detect the relative content and M1/M2 polarization of cardiac macrophages. The mRNA expression levels of macrophage polarization markers [CD86, CD206, arginase 1(Arg-1), inducible nitric oxide synthase(iNOS)], CF markers [type Ⅰ collagen(Coll Ⅰ), Coll Ⅲ, α-smooth muscle actin(α-SMA)], and cytokines(IL-1β, IL-4, IL-6, IL-10, IL-18, TNF-α) in cardiac tissues were determined by quantitative real-time PCR. Western blot was used to detect the protein expression levels of Coll Ⅰ, Coll Ⅲ, α-SMA, Drp1, p-Drp1, voltage-dependent anion channel(VDAC), hexokinase 1(HK1), NOD-like receptor protein 3(NLRP3), apoptosis-associated speck-like protein(ASC), caspase-1, cleaved-caspase-1, gasdermin D(GSDMD), cleaved N-terminal gasdermin D(GSDMD-N), IL-1β, IL-18, B-cell lymphoma-2(Bcl-2), B-cell lymphoma-xl(Bcl-xl), Bcl-2-associated death promoter(Bad), Bcl-2-associated X protein(Bax), apoptotic protease activating factor-1(Apaf-1), pro-caspase-3, cleaved-caspase-3, pro-caspase-9, cleaved-caspase-9, poly(ADP-ribose) polymerase-1(PARP-1), and cleaved-PARP-1 in cardiac tissues. The results showed that VA significantly improved cardiac function in mice with CF, reduced myocardial injury area and cardiac index, and decreased serum levels of AST, CK-MB, cTnI, LDH, ROS, IL-1β, IL-6, IL-18, and TNF-α. VA also lowered MDA and MPO levels, mRNA expressions of IL-1β, IL-6, IL-18, and TNF-α, and mRNA and protein expressions of Coll Ⅰ, Coll Ⅲ, and α-SMA in cardiac tissues, and increased serum levels of IL-4 and IL-10, cardiac tissue levels of CAT, GSH, SOD, and T-AOC, and mRNA expressions of IL-4 and IL-10. Additionally, VA ameliorated cardiac pathological damage, inhibited myocardial cell apoptosis, inflammatory infiltration, and collagen fiber deposition, reduced collagen volume fraction, and alleviated mitochondrial damage. VA decreased the ratio of F4/80~+CD86~+ M1 cells and the mRNA expressions of CD86 and iNOS in cardiac tissue, and increased the ratio of F4/80~+CD206~+ M2 cells and the mRNA expressions of CD206 and Arg-1. VA also reduced protein expressions of p-Drp1, VDAC, NLRP3, ASC, caspase-1, cleaved-caspase-1, GSDMD, GSDMD-N, IL-1β, IL-18, Bad, Bax, Apaf-1, cleaved-caspase-3, cleaved-caspase-9, cleaved-PARP-1, and cytoplasmic cytochrome C, and increased the expressions of HK1, Bcl-2, Bcl-xl, pro-caspase-3, pro-caspase-9 proteins, as well as the Bcl-2/Bax and Bcl-xl/Bad ratios and mitochondrial cytochrome C content. These results indicate that VA has a significant ameliorative effect on ISO-induced CF in mice, alleviates ISO-induced oxidative damage and inflammatory response, and its mechanism may be closely related to the inhibition of Drp1/HK1/NLRP3 and mitochondrial apoptosis signaling pathways, suppression of myocardial cell inflammatory infiltration and collagen fiber deposition, reduction of collagen volume fraction and CollⅠ, Coll Ⅲ, and α-SMA expressions, thus mitigating CF.
Animals ; Isoproterenol/adverse effects* ; Male ; Mice ; Signal Transduction/drug effects* ; Vanillic Acid/administration & dosage* ; Dynamins/genetics* ; Mice, Inbred C57BL ; Fibrosis/genetics* ; Apoptosis/drug effects* ; Mitochondria/metabolism* ; NLR Family, Pyrin Domain-Containing 3 Protein/genetics* ; Myocardium/metabolism* ; Humans

Objective To observe the clinical effect of platelet-rich fibrin (PRF) on prevention of postoperative hemorrhage and facial traumatic swelling in patients with mandibular angle osteotomy.Methods Twenty-five patients with mandibular angle hypertrophy were included in this study from January 2014 to November 2015.Split face comparative study was carried out to use the left and right sides as the experimental side and the control side,respectively.The PRF in the experimental side was placed in the mandibular osteotomy,while the control side was placed in platelet-poor plasma (PPP).After operation,the drainage volume and facial swelling degree were measured.Results The drainage volume of the experimental group (PRF group) was (20.35 ±7.40) ml,the control group (PPP group) was (43.23±11.96) ml,and the difference was statistically significant (P＜0.05).There was no such case without swelling in postoperative third day.The facial swelling score on the experimental side was (1.19±0.40),the control side was (2.62±0.64),and two groups of postoperative facial swelling scores were significantly different (P＜0.05).Conclusions The PRF can reduce postoperative bleeding and facial swelling after mandibular angle osteotomy.

Objective Aged facial contour presents changing facial skeleton and sagging soft tissue.We performed reshaping the facial skeleton simultaneouly during the rhytidectomy to achieve a youthful facial contour.Methods It was a retrospective observational study based on 26 elderly women (42-60 years) that complained of aged face and boosing of the orbital rim,prominent zygoma and mandibular angle.All of them had undergone reduction boosing,malar and mandible combined with rhytidectomy from January 2010 to December 2015.Results The facial skeleton was reshaped with face-lift successfully.No fatal bleeding,respiratory obstruction,cardiovascular accident,severe facial edema,permanent facial nerve injury and other major complications occurred.All of the patients recovered safely.Follow-up for 3-24 months showed that the facial contour and aging were improved,and the youthful face form was preserved.Conclusions The face contour correction combined with face-lift is an effective technique to restore the youthful for elderly patients.

Objective To summarize the experience of clinical application of combining double suture fixation and resection of partial fat retro-orbicularis oculus in some specially difficult blepharoplasty.Methods During upper blepharoplasty,patients with heaviness and bulkiness in the both upper eyelid and lateral upper orbital region,we combined double suture fixation and resection partial fat retro-orbicularis oculus.First,partial pretarsal bulky fat was resected,and to form skin-orbicularisoculi composite below incision line.And then,some thickened fat retro-orbicularis oculus was resected,which was also named preseptal and retro-orbicularis oculus fat (ROOF).Double suture fixation techniques were applied to form dynamic and physiological double eyelid.Results 146 cases had satisfactory effectiveness,except for 2 cases with secondary operation because of some superficial double eyelid creases,and 1 case had hematoma,and 3 had transient numbness in the lateral supraorbital nerve region.They were satisfied with healthy eyelid skins,concealed incision and non-serious complications followed at 3-24 months postoperatively.Conclusions Combining double suture fixation and resection of partial fat retro-orbicularis oculus would appear to be a useful adjunct to standard blepharoplasty techniques in selected patients.