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 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 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 summarize long-term clinical follow-up results of segment instability between the upper instrumented vertebra (UIV) and the adjacent upper vertebra (UIV+1) and to establish the optimal timing for surgery for UIV+1.Methods:A retrospective analysis was conducted on 265 patients with lumbar degenerative diseases who underwent transforaminal lumbar interbody fusion (TLIF) surgery at the Department of Spinal Surgery, Zhongda Hospital, from January 2014 to December 2018. The cohort included 119 male and 146 female patients, with an average age of 64.93 years (range: 32-86 years). Preoperative dynamic imaging measured sagittal angulation (SA) and sagittal translation (ST) of the UIV+1/UIV segment. Patients with SA>10° or ST>2 mm were categorized into the unstable group, further divided into the unstable non-fusion group and the unstable fusion group based on whether UIV+1 expansion fusion was performed. The remaining patients were classified into the stable group. Imaging indicators, Visual Analogue Scale (VAS) scores, Oswestry disability index (ODI) scores, and Japanese Orthopaedic Association (JOA) scores were compared among the groups, with JOA improvement rates calculated to assess clinical efficacy. Pearson correlation coefficient analysis was employed to examine correlations between preoperative imaging indicators and final follow-up JOA improvement rates. Receiver Operating Characteristic (ROC) curves and the maximum Youden index were utilized to determine thresholds for preoperative SA and ST.Results:The follow-up duration for all patients was 73.53±12.92 months (range: 61-108 months). The stable group (124 cases) included 61 males and 63 females, aged 64.31±9.83 years (range: 44-82 years). The unstable non-fusion group (59 cases) included 22 males and 37 females, aged 65.76±11.01 years (range: 32-86 years). The unstable fusion group (82 cases) included 36 males and 46 females, aged 65.26±8.68 years (range: 47-80 years). At the last follow-up, the unstable non-fusion group exhibited ΔSA 0.90°±1.97° and ΔST 0.77±1.27 mm, both significantly higher than the stable group's ΔSA 0.25°±1.57° and ΔST 0.34±0.34 mm ( t=3.564, P<0.001; t=2.311, P=0.022). Clinical improvements were lower in the unstable non-fusion group compared to the other two groups: VAS (2.28±0.83), ODI (5.91%±3.46%), JOA (24.11±1.78), with a JOA improvement rate of 60%. The stable group showed VAS (1.51±0.69), ODI (3.71%±1.75%), JOA (27.33±1.91), with a JOA improvement rate of 83%. The unstable fusion group had VAS (1.46±0.83), ODI (3.46%±1.81%), JOA (26.48±1.66), with a JOA improvement rate of 78%. These differences were statistically significant ( F=32.117, P<0.001; F=24.827, P<0.001; F=92.658, P<0.001; F=93.341, P<0.001). The JOA improvement rate was negatively correlated with preoperative SA ( r=-0.363, P<0.001) to a low extent, and with preoperative ST ( r=-0.596, P<0.001) to a moderate extent. ROC curve analysis determined the preoperative SA threshold as 11.5° and the preoperative ST threshold as 1.85 mm. Conclusion:Pre-existing instability of the responsible segment UIV and UIV+1 (SA>10° or ST>2 mm) may worsen during long-term follow-up after TLIF. When preoperative SA exceeds 11.5° and ST exceeds 1.85 mm between UIV and UIV+1, performing an extended fusion involving UIV+1 can ensure surgical efficacy over long-term follow-up.

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.

Objective:To evaluate the accuracy and clinical outcomes of two different three-dimensional(3D) printed digital mandibular angle osteotomy templates.Methods:Female patients with a prominent mandibular angle(PMA) admitted to the same surgical team in the Friendship Plastic Surgery Hospital of Nanjing Medical University from March 2019 to July 2020 were selected as the research subjects. They were allocated into Group A and Group B alternately according to the order of admission. Group A was the conventional digital osteotomy template(CDOT) group, and Group B was the novel digital osteotomy template(NDOT) group. All patients underwent cone-beam computed tomography(CBCT) scan and 3D reconstruction before surgery. Preoperative CT data were imported into Mimics 19.0, and personalized mandibular angle osteotomy(MAO) line and digital osteotomy template(DOT) were designed according to patients’ conditions and requirements. In Group A, the DOTs were designed according to the part of mandibular angle to be removed(CDOT). And in Group B, the DOTs were designed according to to the part of reserved mandible(NDOT). The DOTs were created with a 3D printer. All patients were underwent bilateral MAO under the guidance of these DOTs through an intraoral approach. CBCT scan was also performed on all patients within 1 week after surgery, and incision healing, complications and lower facial contouring were observed. The mean time taken for positioning DOT and performing curved osteotomy, the volume of postoperative drainage on one side within 24 hours after surgery, and the deviations between the preoperative design and 3D reconstruction mode lower mandibular margin within 1 week after surgery were compared between the two groups.Results:A total of 20 female patients with PMA were included, including 10 patients in Group A, aged 20-31 years, with an average of 24.3±2.3 years. Group B consisted of 10 patients aged 22-30 years, with an average of 24.6±2.2 years. There was no significant difference in age between 2 groups ( P>0.05). All patients were successfully performed MAO without fracture, massive bleeding, infection and other complications, and the postoperative result were satisfactory. The mean time taken to position the DOT and perform MAO one side in Group A was (18.1±1.0) min, significantly longer than that in Group B (14.2±1.4) min ( P<0.05). The volume of postoperative drainage on one side within 24 hours in Group A and Group B was (107.9±12.5) ml and (112.1±13.8) ml, respectively ( P>0.05). The deviations between preoperative design and postoperative mandibular margin, at the anterior part was (2.7±1.2) mm in Group A, which was significantly larger than that of Group B[(1.6±0.9) mm]( P<0.05), the middle part deviation of Group A and B was (1.9±0.7) mm and (1.8±0.8) mm, respectively ( P>0.05), and the posterior part deviation of Group A was (2.8±1.1) mm, which was significantly higher than that of Group B (1.8±0.8 mm)( P<0.05). Conclusions:DOT assisted MAO can achieve accurate osteotomy and reduce the operative difficulty. The NDOT is easier to be located in the operation with more stable fixation, and the surgical efficiency and accuracy of osteotomy are higher than that of CDOT.

Objective:To investigate the clinical outcomes of using autologous mandibular outer cortex "sandwich" grafting to augment mandible for correcting lower facial asymmetry with normal occlusal relationships.Methods:A retrospective analysis was conducted on the clinical data of patients with lower facial asymmetry treated at the Department of Plastic Surgery, the Affiliated Friendship Plastic Surgery Hospital of Nanjing Medical University, from January 2016 to December 2019. Preoperative cone-beam CT (CBCT) scans of the maxillofacial region were obtained to acquire three-dimensional data of the maxillofacial skeleton. Computer-aided design was used to determine the osteotomy range of the mandibular outer cortex and design osteotomy guide template. The outer cortex of the larger mandibular side (donor site) was harvested according to the osteotomy guide template and sectioned. The segmented mandibular outer cortex was then contoured to match the arc of the recipient side’s mandibular outer cortex and fixed to the inner side of the recipient mandibular outer cortex, thus increasing the width and thickness of the expanded mandible. Follow-up was conducted at 7th day and 6 months postoperatively, CBCT scan was performed to measure the changes in ramus height (Co-Go), mandibular body length (Go-Me), and mandibular outer cortex thickness, and volume, and the patient satisfaction with facial appearance (1 to 5 points, with higher scores indicating higher satisfaction), were assessed to evaluate surgical outcomes. Statistical analysis was performed using SPSS 12.0 software. Paired t-tests were used to compare patient satisfaction scores preoperatively and six months postoperatively. Repeated measurement ANOVA was used to compare Co-Go and Go-Me measurements preoperatively, 7th day, and 6 months postoperatively. If a statistically significant difference is found, further analysis using post-hoc testing(Tukey’s HSD test) will be conducted to examine the data. Results:Sixteen patients with lower facial asymmetry were included, comprising of 5 males and 11 females, aged 18 to 40 years, with an average age of 25.2 years. Surgical method included contralateral mandibular outer cortex "sandwich" grafting to the expanded mandible in 9 cases and simultaneous genioplasty in 7 cases. Follow-up ranged from 6 months to 5 years, with an average follow-up of 18.6 months. All patients experienced numbness of the lower lip postoperatively, which resolved within six months, and no severe complications occurred. The symmetry of lower facial contour improved significantly and remained stable. Patient satisfaction score for facial appearance increased from (1.63±0.62) points preoperatively to (4.19±0.75) points six months postoperatively( P<0.01). The differences in Co-Go on the donor side and Go-Me on the recipient side across the three time points(preoperatively, 7th day and 6 months postoperatively) were not statistically significant(all P>0.05). However, the differences in Go-Me on the donor side and Co-Go on the recipient side across the three time points were statistically significant(all P<0.05). On the donor side, the mandibular outer cortex thickness decreased by a maximum of 6 mm on 7th day postoperatively and increased by a maximum of 2 mm at 6 months postoperatively compared to 7th day. On the recipient side, mandibular outer cortex thickness increased by a maximum of 6 mm on 7th day postoperatively and decreased by a maximum of 2 mm at six months postoperatively compared to 7th day. The volume of the mandibular outer cortex on the recipient side increased by (4 415.94±1 017.21)mm 3 at 7th day postoperatively compared to preoperatively, and decreased by (202.63±300.85)mm 3 at 6 months postoperatively. Conclusion:For lower facial asymmetrical with normal occlusal relationships and no occlusal plane deviation, contralateral mandibular outer cortex "sandwich" bone grafting can effectively increase the width and volume of the mandible on the grafted side, achieving favorable clinical outcomes.

Objective:To evaluate the accuracy and clinical outcomes of two different three-dimensional(3D) printed digital mandibular angle osteotomy templates.Methods:Female patients with a prominent mandibular angle(PMA) admitted to the same surgical team in the Friendship Plastic Surgery Hospital of Nanjing Medical University from March 2019 to July 2020 were selected as the research subjects. They were allocated into Group A and Group B alternately according to the order of admission. Group A was the conventional digital osteotomy template(CDOT) group, and Group B was the novel digital osteotomy template(NDOT) group. All patients underwent cone-beam computed tomography(CBCT) scan and 3D reconstruction before surgery. Preoperative CT data were imported into Mimics 19.0, and personalized mandibular angle osteotomy(MAO) line and digital osteotomy template(DOT) were designed according to patients’ conditions and requirements. In Group A, the DOTs were designed according to the part of mandibular angle to be removed(CDOT). And in Group B, the DOTs were designed according to to the part of reserved mandible(NDOT). The DOTs were created with a 3D printer. All patients were underwent bilateral MAO under the guidance of these DOTs through an intraoral approach. CBCT scan was also performed on all patients within 1 week after surgery, and incision healing, complications and lower facial contouring were observed. The mean time taken for positioning DOT and performing curved osteotomy, the volume of postoperative drainage on one side within 24 hours after surgery, and the deviations between the preoperative design and 3D reconstruction mode lower mandibular margin within 1 week after surgery were compared between the two groups.Results:A total of 20 female patients with PMA were included, including 10 patients in Group A, aged 20-31 years, with an average of 24.3±2.3 years. Group B consisted of 10 patients aged 22-30 years, with an average of 24.6±2.2 years. There was no significant difference in age between 2 groups ( P>0.05). All patients were successfully performed MAO without fracture, massive bleeding, infection and other complications, and the postoperative result were satisfactory. The mean time taken to position the DOT and perform MAO one side in Group A was (18.1±1.0) min, significantly longer than that in Group B (14.2±1.4) min ( P<0.05). The volume of postoperative drainage on one side within 24 hours in Group A and Group B was (107.9±12.5) ml and (112.1±13.8) ml, respectively ( P>0.05). The deviations between preoperative design and postoperative mandibular margin, at the anterior part was (2.7±1.2) mm in Group A, which was significantly larger than that of Group B[(1.6±0.9) mm]( P<0.05), the middle part deviation of Group A and B was (1.9±0.7) mm and (1.8±0.8) mm, respectively ( P>0.05), and the posterior part deviation of Group A was (2.8±1.1) mm, which was significantly higher than that of Group B (1.8±0.8 mm)( P<0.05). Conclusions:DOT assisted MAO can achieve accurate osteotomy and reduce the operative difficulty. The NDOT is easier to be located in the operation with more stable fixation, and the surgical efficiency and accuracy of osteotomy are higher than that of CDOT.