Inflammation-driven endothelial dysfunction is the major initiating factor in atherosclerosis, while the underlying mechanism remains elusive. Here, we report that the non-canonical stimulator of interferon genes (STING)-PKR-like ER kinase (PERK) pathway was significantly activated in both human and mice atherosclerotic arteries. Typically, STING activation leads to the activation of interferon regulatory factor 3 (IRF3) and nuclear factor-kappa B (NF-κB)/p65, thereby facilitating IFN signals and inflammation. In contrast, our study reveals the activated non-canonical STING-PERK pathway increases scaffold protein bromodomain protein 4 (BRD4) expression, which encourages the formation of super-enhancers on the proximal promoter regions of the proinflammatory cytokines, thereby enabling the transactivation of these cytokines by integrating activated IRF3 and NF-κB via a condensation process. Endothelium-specific STING and BRD4 deficiency significantly decreased the plaque area and inflammation. Mechanistically, this pathway is triggered by leaked mitochondrial DNA (mtDNA) via mitochondrial permeability transition pore (mPTP), formed by voltage-dependent anion channel 1 (VDAC1) oligomer interaction with oxidized mtDNA upon cholesterol oxidation stimulation. Especially, compared to macrophages, endothelial STING activation plays a more pronounced role in atherosclerosis. We propose a non-canonical STING-PERK pathway-dependent epigenetic paradigm in atherosclerosis that integrates IRF3, NF-κB and BRD4 in inflammatory responses, which provides emerging therapeutic modalities for vascular endothelial dysfunction.

Disturbance of macrophage-associated lipid metabolism plays a key role in atherosclerosis. Crosstalk between autophagy deficiency and inflammation response in foam cells (FCs) through epigenetic regulation is still poorly understood. Here, we demonstrate that in macrophages, oxidized low-density lipoprotein (ox-LDL) leads to abnormal crosstalk between autophagy and inflammation, thereby causing aberrant lipid metabolism mediated through a dysfunctional transcription factor EB (TFEB)-P300-bromodomain-containing protein 4 (BRD4) axis. ox-LDL led to macrophage autophagy deficiency along with TFEB cytoplasmic accumulation and increased reactive oxygen species generation. This activated P300 promoted BRD4 binding on the promoter regions of inflammatory genes, consequently contributing to inflammation with atherogenesis. Particularly, ox-LDL activated BRD4-dependent super-enhancer associated with liquid-liquid phase separation (LLPS) on the regulatory regions of inflammatory genes. Curcumin (Cur) prominently restored FCs autophagy by promoting TFEB nuclear translocation, optimizing lipid catabolism, and reducing inflammation. The consequences of P300 and BRD4 on super-enhancer formation and inflammatory response in FCs could be prevented by Cur. Furthermore, the anti-atherogenesis effect of Cur was inhibited by macrophage-specific Brd4 overexpression or Tfeb knock-out in Apoe knock-out mice via bone marrow transplantation. The findings identify a novel TFEB-P300-BRD4 axis and establish a new epigenetic paradigm by which Cur regulates autophagy, inhibits inflammation, and decreases lipid content.

Objective:To investigate the clinical effect and safety of mid-face lifting combined with compound fat transplantation in facial rejuvenation.Methods:From October 2016 to May 2020, 26 patients with mid-facial aging were enrolled, including 10 males and 16 females, with an average age of (47±6) years (38-65 years). The facial superficial musculoaponeurotic system was stripped, folded and suspended through the temporal hairline incision to lift the middle of the face. Liposuction was performed and compound fat was prepared, in which structural fat was injected into the area marked with loss of facial volume before operation, and extravascular matrix component gel was injected into the static wrinkle dermis. Six and 12 months after operation, the global aesthetic improvement scale of the observer and the global aesthetic improvement scale of the patient were scored, and the postoperative complications and patients＇ satisfaction were counted.Results:At the end of 6 months, improvements in mid face were reported in all patients by blinded reviewers. 12 months after operation, 53.8% (14 cases) of patients had significant improvement in facial aging, 30.8% (8 cases) had moderate improvement, and 15.4% (4 cases) had slight improvement; 25 patients (96%) were satisfied with the postoperative results. Postoperative hemorrhage occurred in one patient, scar hyperplasia occurred in one patient, and no obvious complications occurred in the other patients.Conclusions:The method of midface lifting combined with compound fat transplantation can improve the facial soft tissue and supplement the facial missing capacity, improve the static wrinkles of the face, and comprehensively solve the aging problem of midface. It has a definite clinical effect, fewer complications, and is safe and reliable. It has definite clinical effect with less complications.

Objective:To evaluate the clinical effect of ultrapulse fractional CO 2 laser in the treatment of mild to moderate orbital aging in Asians. Methods:From January 2018 to December 2018, 36 patients (72 eyes) with mild to moderate orbital aging were enrolled, 22 women and 14 men, with an average age of 32.4 years. Each patient was randomly divided into two groups. In the traditional operation group, 36 eyes received blepharoplasty through traditional inferior conjunctival approach. In the ultrapulsed fractional CO 2 laser group, 36 eyesunderwent blepharoplasty through the lower eyelid conjunctival approach assisted by optoelectronics. Both groups were treated with ultrapulsed fractional CO 2 laser for periorbital aging. The operation time, detumescence time and postoperative complications were compared. At the same time, the periorbital skin relaxation was treated by the combination of the two groups. The patients were followed up for 12 months. Results:In the traditional operation group, 11 cases were evaluated as Barton grade Ⅰ preoperatively, and the efficacy score was 0.64±0.21. In 25 cases of Barton grade Ⅱ the efficacy score was 1.34±0.34. 17 cases were Barton Ⅰ in photoelectric assisted group, and the efficacy score was 0.92±0.18. In 19 cases of Barton grade Ⅱ, the efficacy score was 1.71±0.42. There was a statistically significant difference between the two groups in Barton Ⅰ efficacy score, P<0.05 ( P=0.016); There was also a statistically significant difference between the two groups in efficacy score of Barton Ⅱ, P<0.05 ( P=0.039). The operation time of the photoelectric assisted group was (12.00±1.82) minutes, and the edema duration was (4.0±1.8) days. The duration of operation in the conventional surgery group was (16.00±3.75) minutes, and the duration of edema was (7.0±2.4) days. The operation time and edema duration in the photoelectric assisted group were both shorter than those in the traditional operation group, and the differences were statistically significant ( P<0.05). Conclusions:The blepharoplasty through traditional inferior conjunctival approach assisted with ultrapulsed fractional CO 2 laser has no obvious bleeding, with shorter operation time, swelling reduction time and the number of complications than the traditional operation.This method can solve the symptoms of blepharoplasty, lower eyelid skin relaxation and wrinkles around eyes. This method is worthy of promotion in the treatment of patients with mild to moderate periorbital aging.

Objective:To explore the clinical effects of pre-expanded anterior perforator flap of transverse cervical artery in extensive facial and cervical scar reconstruction and contralateral pre-expanded thoracic random flap in relay in donor site repair.Methods:A retrospective cohort study was conducted. From May 2008 to December 2018, 10 patients with extensive facial and cervical scar after burns were treated in the Fourth Medical Center of PLA General Hospital, including 8 males and 2 females, aged 10-55 years. In the first stage of operation, two skin and soft tissue expanders of the same volume (with rated capacity of 250-600 mL) were respectively placed in the right side and left side of the chest according to the size of scar, and then the skin was expanded. The total amount of normal saline injected was 2 to 4 times of the rated capacity of the expander. In the second stage, the defect with area of 12 cm×8 cm-23 cm×15 cm caused by scar resection and release was repaired with unilateral pre-expanded anterior perforator flap of transverse cervical artery with area of 12 cm×9 cm-24 cm×16 cm. The contralateral pre-expanded thoracic random flap with the same area as that of the above-mentioned perforator flap was extended to repair the secondary defect with area of 8 cm×6 cm-17 cm×14 cm formed after transfer of the above-mentioned perforator flap. The exploration of perforating branch of transverse cervical artery, flap transfer and survival, injury repair, and complications were observed. The appearance and related function of donor and recipient sites and satisfaction of patients were followed up.Results:The perforating branches of transverse cervical artery appeared stably in the 10 patients. All the flaps were transferred to the recipient area without tension and survived. Both facial and cervical injuries were repaired successfully with no common complications. During the follow-up of 6 months-8 years, the color and texture of the pre-expanded anterior perforator flap of transverse cervical artery matched with the surrounding tissue, the functions of head raising and neck rotation of patients were significantly improved compared with those before operation, the color and texture of the flap transplanted in the first donor site matched with the original skin, linear scar left at the surgical incision, and 9 patients were satisfied with the restoration of the appearance and function of donor and recipient sites.Conclusions:The color and texture of the pre-expanded anterior perforator flap of transverse cervical artery match well with the face and neck, and the repairable area is large. After the perforator flap is removed, the secondary wound can be repaired with the pre-expanded thoracic random flap at the same time, and the injury of the chest donor site is alleviated. This relay repair method is a good choice for reconstructing extensive facial and cervical scar.

Objective:To compare the safety and efficacy of medial-lateral pinning (MLP) and lateral pinning (LP) in pediatric supracondylar humeral fractures.Methods:According to PRISMA procedure, the randomized controlled trial (RCT) of pediatric supracondylar humeral fractures in PubMed (Medline), EMBASE, the Cochrane Library databases (Cochrane Controlled Trials Register for RCTs) and Wanfang Data from 1 January, 1990 to 1 January, 2020 were retrieved. Two researchers independently extracted the data and evaluated the quality of the original studies; the random-effects model was used for analysis.Results:A total of 4 679 original literatures were retrieved and 11 literatures were finally included, involving 920 children. Meta analysis results showed that there were no statistical differences in excellent ratio of elbow joint function (Flynn criteria), incidence of iatrogenic nerve injury and incidence of pin tract/ superficial infection between MLP group and LP group: 74.3% (255/343) vs. 72.9% (250/343), 6.1% (16/262) vs. 1.6% (4/246) and 5.3% (14/264) vs. 7.6% (20/262); RR = 0.98, 0.43 and 1.31; 95% CI 0.90 to 1.07, 0.18 to 1.03 and 0.64 to 2.67, P>0.05; the incidence of reduction loss in MLP group was significantly lower than that in LP group: 16.6% (51/307) vs. 23.9% (72/301), and there was statistical difference ( RR = 1.39, 95% CI 1.02 to 1.89, P = 0.04). Conclusions:MLP fixation and LP fixation are equally efficacious for supracondylar humeral fractures in children. MLP fixation may reduce the risk of reduction loss without increasing the risk of iatrogenic nerve injury. Manual reduction and MLP percutaneous Kirschner wire fixation for the treatment of displaced supracondylar humeral fractures in children is recommended.

Objective: To explore the subunit strategy for perineal defect reconstruction and flap selection. Methods: This is a respective study of 21 patients, with perineal defect, during January 2008 to December 2018. All patients were admitted to the fifth section of Burn and Plastic Surgery in the Fourth Medical Center of the People′s Liberation Army General Hospital. There were 10 males and 11 females, aged from 4 to 68 years old, with the mean age of 26.4 years. The causes of injury included burn (n=11), trauma (n=2), Paget′s disease (n=2), Brown′s disease (n=2), perineal squamous cell carcinoma (n=3)and hemangioma (n=1). The perineum is divided into 4 subunits, according to the anatomical structure: a front area monsveneris or pubic symphysis, 2 middle areas (labia or scrotum) and a posterior area (anal). The defects ranged 23 cm×11 cm-5 cm×3 cm after perineal lesions were removed. Appropriate flaps were selected based on tissue defect. Results: Nine patients were repaired with superficial inferior epigastric artery flap, 3 patients were repaired with superficial circumflex iliac artery flap, and 2 patients were repaired with combined superficial inferior epigastric artery flap and superficial circumflex iliac artery island flap. Internal pudendal arterial perforator flap was performed in 5 patients, and anterolateral thigh perforator flap in 2 patients. The size of flap was 25 cm×12 cm-6 cm×3 cm. All flaps survived, and incisions were primary healing. Patients were followed up for 6 months to 9 years, with an average of 13 months. The patients were satisfied with the appearances and functions of the recipient and doner sites. Scars were concealed well. Conclusions Appropriate flap can be chosen to repair perineal defects, based on the subunit principle in perineum, in order to restore function and appearance, and achieve satisfactory clinical outcomes.

Objective: To explore the clinical application of ultra-pulsed CO₂ laser skin abrasion combined with micro-skin graft in the treatment of skin depigmentation. Methods: From January 2010 to June 2014, depigmented skin specimens were used for ultra-pulsed CO₂ laser skin abrasion treatment, at 0, 10, 20, 30, 40, 50, 60 mJ. HE stain was performed to observe the abrasion depth under the 100 times microscope view. The most appropriate parameter was set to completely remove the epidermis, and leave dermis undamaged. From January 2011 to December 2017, 16 patients with skin depigmentation, 12 males and 4 females, aged 12-47 years, were treated with super-pulsed carbon dioxide laser and autologous microdermis transplantation. At 1, 3, 6 and 12 months after the operation, patients′ photos were record. The color improvement was analyzed using Image-Pro Plus 6.0 software. Results: The laser energy for complete epidermis removal is different at different sites. It is 50 mJ for back skin, 40 mJ for face and hand skin and 30 mJ for neck skin. After one year of follow-up, there was no hypertrophy scar caused by over-abrasion in all 16 patients. Combined with the micro-skingrafting, 15 patients with skin depigmentation were completely resolved, with more than 90%color improvement rate. The improvement rate was 75% in a patient with un-uniform appearance, due to part failure of micro-skin graft. The neck movement and uncertain fixation were the reasons. Conclusions The appropriate energy parameters can control the abrasion depth to avoid the hypertrophic scar. Combined with micro-skin graft, the depigmentation area can be improved with uniform color and reliable effect.

Objective To explore a method for repairing the appearance and function of the cheek aesthetic unit.Methods A single volume of 100 ml to 150 ml of tissue expander was implanted at the lower edge of the injury area on the cheek.The first injection was performed 5 days after the operation and twice a week after the injection.It took an average of about 4 months to complete the expansion,with 3-5 times over expanded.The lesions were resurfaced with the expanded flaps,and long term follow-up was observed for flap survival.Results 17 cases of cheek lesions had been successfully reconstructed,with the color,texture of the expanded flaps well matched to the surrounding skin after 3-12 months follow-up.The facial expression functions and configurations were satisfied.Conclusions Excessive expansion of the prefabricated skin flap of the jaw and neck can repair the cheek aesthetic unit successfully,which is a practical method and meets the needs of aesthetic unit repair.

OBJECTIVETo investigate the quantitative analysis based on three-dimensional computed tomography (3D-CT) in contouring surgery of complex craniofacial fibrous dysplasia (FD).

METHODS14 patients with craniofacial FD underwent 3D-CT scan. Axial images of patients with craniofacial FD were reconstructed into 3D model by using Mimics 10.0. Anatomical landmarks were located and the coordinate of the landmarks obtained. The differences between the right landmarks and the left were calculated and analyzed. Quantitative contouring surgery was performed based on the quantitative analysis result.

RESULTSWith the detail data from the 3D-CT analysis, the surgery of contouring was more safe and accurate with less operation time, less bleeding and good results.

CONCLUSIONSThe method of 3D CT quantitative analysis can provide precise information in the diagnosis and treatment planning of craniofacial deformity. Based on the result of 3D-CT quantitative analysis, the operations can be performed more accurately and safely with good symmetric consequence.

Aged ; Craniofacial Abnormalities ; diagnostic imaging ; Facial Bones ; abnormalities ; diagnostic imaging ; Fibrous Dysplasia, Polyostotic ; diagnostic imaging ; Humans ; Imaging, Three-Dimensional ; methods ; Tomography, X-Ray Computed ; methods