Generic drug products (test products: drug A, B...) are bioequivalent to an innovator product (reference product) when their bioavailabilities in the same molar dose are similar. Bioavailability is usually expressed by following pharmacokinetic parameters: the area under plasma concentration-time curve (AUC), the maximum plasma concentration (Cmax) and the time of maximum plasma concentration (tmax). This paper used a two period crossover bioequivalence study to develop convenient, friendly user interface software, BA&BE Analysis to statistically process data in clinical pharmacology studies and other areas. The method involves user input of data for analysis into a grid format, setting variables and parameters, followed by one-way analysis of variance (ANOVA), bioavailability and bioequivalence analysis of the data. The software developed in the present study should help scientists to carry out data analysis of bioavailability and bioequivalence testing quickly and easily.

Objective:To investigate the effect of eyebrow arch augmentation with personalized polyether ether ketone (PEEK) implant assisted by endoscope.Methods:From January 2019 to August 2021, 9 patients with low and flat eyebrow arch requiring eyebrow arch augmentation were treated in the plastic surgery department of the Friendship Plastic Surgery Hospital Affiliated to Nanjing Medical University. The cranial and maxillofacial CT scanning data were obtained before operation, the eyebrow arch elevation range and height were designed according to the patient's requirements, and personalized peek implants were manufactured. During the operation, a small temporal hairline incision was used to accurately separate the implantation cavity of individualized peek implants under the periosteum of the eyebrow arch implantation area with the aid of endoscope. Personalized PEEK implants were implanted under endoscope to make them fully fit with the eyebrow arch bone and fixed with titanium nails. Photos were taken and analyzed before and after operation.Results:All patients were followed up for 3 months to 2 years. Their facial expressions were normal, and there were no motor nerve injury, rejection and iatrogenic infection. The patients were satisfied with the postoperative effect. Compared with before operation, the low level of orbital bone in eyebrow area was improved, and the facial contour was three-dimensional and harmonious.Conclusions:The eyebrow arch augmentation with individualized peek implant assisted by endoscope is safe and effective. It can greatly reshape the upper contour of the face, deepen the upper eyelid fossa and improve the convex eye phenomenon, so as to achieve the cosmetic effect of enhancing the three-dimensional sense of the eyebrow orbital area, which is worthy of clinical application.

Objective:To investigate the clinical effect of W-shaped genioplasty in the correction of broad and short chin deformity.Methods:Thirty-eight patients (5 males, 33 females, aged 20 to 41 years, mean 27.3 years) complained with broad and short chin were admitted to the Affiliated Friendship Plastic Surgery Hospitalof Nanjing Medical University from January 2019 to December 2021. CBCT scan and three-dimensional reconstruction were performed to design osteotomy line and determine the distance of chin lengthening, narrowing and advancing or retrocession preoperatively. Under general anesthesia, the W-shaped osteotomy was performed using an intraoral incision, and the angle between the bilateral free bone fragments, the distance of downward and forward movement were adjusted to change the curvature, width, length and prominence of the lower edge of the chin according to the preoperative designs. The results were evaluated by clinical appearances and image analyses at a follow-up of 3-24 months.Results:The amount of vertical lengthening of the chin in 38 cases were 2 mm to 5 mm, with an average of 3.02 mm. The horizontal narrowing width distances were 3-7 mm, with an average of 5.6 mm. The patients were followed up for 3-24 months, with an average of 10.6 months. There were no complications such as hematoma, wound dehiscence, accidental fracture, surgical area infection and permanent neurosensory disorder. 38 patients had transient sensory loss in the lower lip region of varying degrees, but all recovered spontaneously during routine follow-up period. All patients were satisfied with the improvement of facial contour.Conclusions:W-shaped geinoplasty preserves the central bone of the chin and the attachment of genioglossus muscle, which does not affect the normal anatomy and physiological function of the oral cavity. After osteotomy, the bone is removed and the bilateral bone fragments move flexibly. It can effectively change the radian, width, length and protrusion of the lower edge of the chin in three dimensions, so as to correct the wide and short deformity of the chin.

Objectives:To investigate the effect of inhibition of long non-coding RNA(lnc RNA)in human metastasis associated lung adenocarcinoma transcript 1(MALAT1)on glycolipitoxicity-induced human umbilical vein endothelial cell dysfunction. Methods:Human umbilical vein endothelial cells were treated with glucose and palmitic acid in vitro to establish the glycolipitoxic endothelial cell models.Following groups were examined:control group,high-glucose and high-fat group,high-glucose and high-fat + non-targeting RAN control group,high-glucose and high-lipid+MALAT1 siRNA group,and high-glucose and high-lipid+MAPK1 siRNA group.RT-qPCR was used to detect the mRNA expression of MALAT1 and MAPK1.Western blot was used to detect the expression levels of autophagy,mitochondrial fusion division,apoptosis,and pathway-related proteins.Immunofluorescence confocal localization was used to detect the fluorescence colocalization of autophagy and lysosome-related proteins.The number of autophagolysosomes in endothelial cells was observed by transmission electron microscopy.Mitochondrial probe staining was used to detect mitochondrial morphology,immunofluorescence was used to detect intracellular reactive oxygen species(ROS)production,flow cytometry was used to detect the apoptosis of cells in each group,cell proliferation and scratch assays were used to detect the proliferation and migration ability of cells in different groups at different time points.The angiogenesis was quantified by counting the number of new blood vessels in each group. Results:Compared with the control group,the expression of lncRNA MALAT1 mRNA and the expression of phosphorylated mito-activated protein kinase 1(p-MAPK1)were upregulated(both P＜0.05)and the expression of phosphorylated mammalian target protein(p-mTOR)was downregulated in the high-glucose and high-fat group and the high-sugar and high-fat control group(all P＜0.01).Compared with the high-glucose and high-fat non-targeting RNA control group,the expressions of microtubule-associated protein 1A/1B-light chain 3(LC3)and p62 were downregulated(P＜0.01,P＜0.05),LC3 and lysosome-associated membrane protein 2(LAMP2)protein co-localized positive fluorescence particles were increased(both P＜0.01),number of lysosomes were decreased,the expression of ROS was decreased(P＜0.01),the expression level of mitochondrial fusion protein optic nerve atrophin 1(OPA1)was increased(P＜0.05),the expressions of cleaved caspase-3 and BCL-2-related X protein(BAX)were decreased and BCL-2 was increased(all P＜0.05),cell proliferation,migration,and tube-forming ability were increased(all P＜0.01),and the expression of p-MAPK1 was decreased(P＜0.05)and p-mTOR expression was increased(both P＜0.05)in the high-glucose and high-lipid+si-MALAT1 group.Compared with the high-glucose and high-fat non-targeting RNA control group,the expression of p-MAPK1 in endothelial cells was decreased and the expression of p-mTOR was increased in the high-glucose and high-lipid+si-MAPK1 group(both P＜0.01). Conclusions:Inhibition of lncRNA MALAT1 expression can reduce the level of mitophagy in glycolipidotoxic environments,reduce apoptosis of endothelial cells and improve endothelial cell function,which may be related to the regulation of MAPK1/mTOR signaling pathway.

Objective:To investigate the clinical outcomes of personalized polyetheretherketone (PEEK) implant in the correction of nasolabial fold depression.Methods:A total of 30 patients with nasolabial fold depression (5 males, 25 females, aged 26 to 52 years, mean 36.3 years) admitted to the Affiliated Friendship Plastic Hospital of Nanjing Medical University who want to undergo nasolabial fold augmentation from January 2019 to January 2021. All patients underwent CBCT scan and three-dimensional simulation, the personalized PEEK implant was designed and produced with CAD/CAM technique, the personalized PEEK was implanted during the operation. The patients were followed up for 3-12 months, and the wrinkle score and satisfaction were compared before operation and 3 months and 6 months after operation.Results:The depressions of nasolabial fold were significantly improved in all patients, and there were no complications such as hematoma and infection after operation. During the follow-up, there was no implant displacement or exposure, and the effect was stable and lasting. The scores of wrinkles at 3 months after operation (2.30±0.47) and 6 months after operation (2.17±0.38) were significantly lower than those before operation (4.03±0.67), and the scores of satisfaction were significantly higher than those before operation ( P<0.05). The scores of satisfaction at 3 months after operation (3.97±0.56) and 6 months after operation (4.23±0.57) were significantly higher than those before operation (1.70±0.60). The difference was statistically significant ( P<0.05). Conclusions:3D printing personalized PEEK prosthesis is effective in correcting nasolabial fold depression, and it is safe and stable, so it is recommended for clinical application.

Objective:To investigate the effect of electroporation-mediated local gene therapy on the expression of Wnt3a and β-catenin in callus of distraction gap during mandibular distraction osteogenesis of rabbits.Methods:The experiments were conducted in the laboratory of the Affiliated Friendship Plastic Surgery Hospital of Nanjing Medical University from September 2019 to December 2019. Forty eight New-Zealand rabbits were randomly divided into control group (group A), gene therapy group (group B) and normal saline group (group C), with 16 rabbits in each group. After bilateral mandible osteotomy and distractors were implanted, the distractors were activated at a speed of 0.8 mm/d on 4th day, postoperatively, and lasted for 7 days, followed by consolidation period. Group A distracted only, group B was subject to local injection of recombinant plasmid pIRES-hBMP2-hVEGF165 in the distraction gap and electroporation stimulation at the beginning of activation distractors; and group C local injection of the same dose of normal saline in the distraction gap and electroporation stimulation at the beginning of activation distractors. Four animals in each group were sacrificed on the day at the end of distraction, 7th, 14th, 28th days of consolidation period, respectively. The callus in the distraction gap was taken for immunohistochemical staining and RT-PCR to detect the expression of Wnt3a and β-catenin, and image analysis was performed. SPSS 22.0 statistical software was used for data analysis.Results:Immunohistochemical staining showed that Wnt3a and β-catenin were mainly located in the cytoplasm and nuclei of fibroblasts, chondrocytes and osteoblasts in callus tissue. Immunohistochemistry and RT-PCR showed that the expression of Wnt3a and β-catenin reached a peak at the end of distraction. With the disappearance of distraction tension, the expression of Wnt3a and β-catenin gradually decreased. After gene therapy intervention, the expression of Wnt3a and β-catenin was significantly increased, and the expression of Wnt3a and β-catenin in group B was the highest at each time point, with statistically significant difference compared with groups A and C ( F=96.3, P<0.01). Conclusions:Gene therapy promotes the expression of Wnt3a and β-catenin in the callus of distraction gap, regulating the balance of the bone reconstruction system and thus promoting the formation of new bone in the distraction gap.