Using whole exome sequencing to identify susceptibility genes associated with nonsyndromic cleft lip with or without cleft palate.

Cleft lip and palate is a common congenital birth defect in humans. Its incidence rate in China is as high as 1.82%, and is now a frequent deformity observed among the Chinese population; moreover, it varies across regions. Although the etiology of nonsyndromic cleft lip with or without cleft palate (NSCL/P) has been widely investigated, the results are inconsistent. The specific genes and mechanisms responsible for NSCL/P have not been fully understood. Whole exome sequencing (WES) is a new strategy for studying pathogenic genes. WES studies on NSCL/P have not been conducted in East China. Therefore, the aim of this study was to screen candidate genes of NSCL/P in East China using WES and analyze the temporal and spatial expressions of the candidate genes during embryonic palatal development. WES was performed in 30 children with NSCL/P from East China to screen candidate genes. A bioinformatics analysis was performed using commercially available software. Variants detected by WES were validated by immunohistochemistry and western blotting. After WES, 506,144 single-nucleotide variant sites were found. The results of database comparison, functional analysis, and mass spectrometry revealed that only the laminin alpha 5 (LAMA5) gene (site: rs145192286) was associated with NSCL/P. Immunohistochemistry results showed that LAMA5 expression in the medial edge epithelium changed with formation, lifting, and contact during palatogenesis. Almost no LAMA5 expression was detected in the palatal mesenchyme or after palatal fusion. Western blotting and immunohistochemistry results showed consistent trends. In conclusion, the WES results shows that the mutation at the site (rs145192286) of LAMA5 is associated with NSCL/P. The temporal and spatial expressions of LAMA5 during palatal development further demonstrate the involvement of this gene. Therefore, we speculate that LAMA5 is a new candidate pathogenic gene of NSCL/P. The identification of new pathogenic genes would help elucidate the pathogenesis of NSCL/P and provide a scientific basis for the prenatal diagnosis, prevention, and treatment of NSCL/P.

p38MAPK silencing attenuates scar proliferation after cleft palate repair surgery in rats via MRTF-A/SRF pathway.

Scarring is the primary factor of maxilla growth restriction among people who have undergone cleft palate repair surgery. p38 mitogen-activated protein kinase (p38MAPK) promotes fibrosis in a variety of organs. However, its role in post-surgery scarring on the hard palate has not been fully understood. This study is designed to investigate the role of p38MAPK in scar formation and maxilla growth of rats. We removed the mucosa on the hard palate of rats and applied the p38MAPK silencing adenovirus vector on it two weeks after surgery. Then the scarring tissue and maxilla growth were evaluated by histological and morphological examination. The effect of p38MAPK silencing on scarring-related genes in fibroblasts was also studied. We found that local injection of Ad-p38MAPK-1 in vivo effectively reduces the expression of p38MAPK and scarring-related proteins and weakens the impact of scarring on the width of the hard palate. Mechanistically, p38MAPK silencing inhibits the expression of α-smooth muscle actin (α-SMA) via mediating the production and nuclear localization of myocardin-related transcription factor A (MRTF-A) in fibroblasts. These results reveal a molecular pathway of scar formation involving p38MAPK/MRTF-A stimulation and support targeting p38MAPK as a potentially effective treatment for post-surgery scarring on the hard palate.

Virtual Surgical Planning and Three-Dimensional Printing to Aid the Anatomical Reduction of an Old Malunited Fracture of the Mandible.

ABSTRACT: Mandible fracture is a common injury in maxillofacial surgery. It causes not only maxillofacial dysfunction but also facial deformities. Malunited fractures of the mandible have been a vast challenge in clinical treatment due to the misalignment of the broken ends and the occurrence of occlusal disorders. This case report describes using virtual surgical planning and three-dimensional printing to treat a patient with malunited fracture of the mandible. Failing to perform mandibular surgery due to severe brain trauma after the car accident, the patient got malunited healing of mandible. The authors applied virtual surgical planning to perform preoperative analysis and surgical design on this patient, three-dimensional printing to fabricate occlusal plate, and models of the preoperative and postoperative mandible to guide the operation. Finally, the authors achieved the reduction and reconstruction of the mandible with satisfactory clinical results.

Evaluation of Bone Height and Bone Mineral Density Using Cone Beam Computed Tomography After Secondary Bone Graft in Alveolar Cleft.

The purpose of this study was to assess the optimal timing of subsequent dental implant placement and orthodontics after alveolar bone grafting (ABG) in patients with unilateral complete clefts of the alveolar process. Iliac bone graft surgery was performed on 60 patients. Bone mineral density (BMD) and height of the ABG areas were assessed using cone beam computed tomography at 3 and 6 months postoperatively. The heights of the labial and palatal bone graft areas were classified using the modified Bergland classification. The study found that there was no change in BMD between 3 months (mean ±â€ŠSD: 406.51 ±â€Š71.28 Hounsfield units [HU]) and 6 months (409.53 ±â€Š46.37 HU; P = 0.381). Significant changes in the distribution of bone height classifications were observed in the labial and palatal sides of the ABG between 3 and 6 months (P = 0.025 for labial bone height, P = 0.008 for palatal bone height). These results indicate that the alveolar density remained stable between 3 and 6 months, whereas bone height level declined during that period after ABG, the latter indicating bone graft absorption over time. It is, therefore, suggested that subsequent orthodontic or dental implants be placed 3 months after ABG rather than at 6 months or later.

Soft tissue perineurioma of the tongue: report of a case and review of the literature.

Perineurioma is a rare benign tumor of the peripheral nervous system distinct from schwannomas and neurofibromas. It may be intraneural or extraneural (in the soft tissue). Extraneural soft tissue perineuriomas are uncommon; rare cases have been reported in the oral cavity. We present a case of soft tissue perineurioma in the tip of the tongue. The tumor was characterized by slender spindle cells, arranged in short fascicles or whorls, and focal areas showing a distinct storiform pattern. Tumor cells showed the immunohistochemical profile of perineurial cells, including epithelial membrane antigen. Smooth muscle actin, S-100, and CD34 were not expressed by the tumor cells. The tumor was surgically excised and in 2 years there has been no recurrence. Knowledge of the tumor in the oral cavity is important to reach a correct diagnosis and to avoid unnecessary aggressive local excision.

CA1 Modulates the Osteogenic Differentiation of Dental Follicle Stem Cells by Activating the BMP Signaling Pathway In Vitro.

BACKGROUND: Carbonic anhydrase 1 (CA1) has been found to be involved in osteogenesis and osteoclast in various human diseases, but the molecular mechanisms are not completely understood. In this study, we aim to use siRNA and lentivirus to reduce or increase the expression of CA1 in Dental follicle stem cells (DFSCs), in order to further elucidate the role and mechanism of CA1 in osteogenesis, and provide better osteogenic growth factors and stem cell selection for the application of bone tissue engineering in alveolar bone fracture transplantation. METHODS: The study used RNA interference and lentiviral vectors to manipulate the expression of the CA1 gene in DFSCs during in vitro osteogenic induction. The expression of osteogenic marker genes was evaluated and changes in CA1, alkaline phosphatase (ALP), Runt-related transcription factor 2 (RUNX2), and Bone morphogenetic proteins (BMP2) were measured using quantitative real-time polymerase chain reaction (qRT-PCR) and Western blotting (WB). The osteogenic effect was assessed through Alizarin Red staining. RESULTS: The mRNA and protein expression levels of CA1, ALP, RUNX2, and BMP2 decreased distinctly in the si-CA1 group than other groups (p < 0.05). In the Lentivirus-CA1 (LV-CA1) group, the mRNA and protein expressions of CA1, ALP, RUNX2, and BMP2 were amplified to varying degrees than other groups (p < 0.05). Apart from CA1, BMP2 (43.01%) and ALP (36.69%) showed significant upregulation (p < 0.05). Alizarin red staining indicated that the LV-CA1 group produced more calcified nodules than other groups, with a higher optical density (p < 0.05), and the osteogenic effect was superior. CONCLUSIONS: CA1 can impact osteogenic differentiation via BMP related signaling pathways, positioning itself upstream in osteogenic signaling pathways, and closely linked to osteoblast calcification and ossification processes.

Virtual surgical planning/3D printing assisted fibula osteoseptocutaneous flap combined with anterolateral thigh flaps for extensive composite oromandibular defects reconstruction: a retrospective study of case series.

Oromandibular tumors or osteoradionecrosis often lead to extensive composite defects encompassing intraoral, bone and extraoral tissues. A single flap cannot simultaneously offer sufficient bone and soft tissue. The combination of free flaps could be a prospective approach to overcome the challenge. The study aims to assess the efficacy of virtual surgical planning (VSP) and 3D printing assisted fibula osteoseptocutaneous flap (FOSCF) combined with anterolateral thigh flaps (ALT) in reconstructing extensive composite defects in the oromandibular region. A retrospective analysis was conducted on 8 patients who underwent reconstruction using FOSCFs combined with ALTs. Post-surgical excision of the lesions, we obtained mean values for the defects of intraoral soft tissue, bone, extraoral soft tissue, namely, being 42.7 cm2, 96 mm, and 68.9 cm2. The mean surgical procedures took 712.5 min. A total of 16 flaps were harvested and transplanted for the 8 patients, with all successfully surviving. Postoperatively, complications manifested as localized intraoral infections in 2 cases, intermuscular vein thrombosis in another 2 cases, and pulmonary infections in 2 patients. Two patients unfortunately experienced tumor recurrence, at 12 and 3 months post-operation respectively. For the surviving 6 patients, the average follow-up period was 12.2 months. Regarding patient satisfaction, one expressed dissatisfaction with the contour of the mandible, and two exhibited moderate trismus. Objective assessments identified 1 case of oral incontinence and 2 cases where external flap contractures were observed. All 8 patients experienced restoration of masticatory function and were able to consume a soft diet within a month post-surgery. VSP/3D printing assisted FOSCFs combined with ALTs can be performed safely to reconstruct the extensive composite tissue defects in our study, with desirable esthetic and functional results, and it is a reliable option in selecting patients with defects involving multiple tissue types. However, the benefits of this method needed more cases to validate.

LAMA5: A new pathogenic gene for non-syndromic cleft lip with or without cleft palate.

BACKGROUND: This study aimed to investigate the effect of LAMA5 on palatal development in mice. METHODS: The palatine process of C57BL/6 J fetal mice on the embryonic day 13.5 (E13.5) was cultured in vitro via the rotating culture method. The LAMA5-shRNA adenovirus vector was constructed, then transfected into the palatal process of E13.5 for 48 h in vitro. A fluorescence microscope was used to visualize the fusion of palates. The expression of LAMA5 was also detected. The expression of ki67, cyclin D1, caspase 3, E-cadherin, vimentin and SHH signaling pathway-related signaling factors in the blank control group, the negative control group, and the LAMA5 interference group were detected after virus transfection. RESULTS: The bilateral palates in the LAMA5 interference group were not fused after virus transfection. PCR and WB showed that the mRNA and protein expressions of LAMA5 were decreased in the LAMA5 interference group. Furthermore, the mRNA and protein expressions of ki67, cyclin D1 and gli1 were decreased in the LAMA5 interference group, while the mRNA and protein expressions of caspase 3 were increased. However, the mRNA and protein expression of E-cadherin, vimentin, Shh and ptch1 did not significantly change in the LAMA5 interference group. CONCLUSIONS: LAMA5 silencing causes cleft palate by inhibiting the proliferation of mouse palatal cells and promoting apoptosis, which may not be involved in EMT. LAMA5 silencing can also cause cleft palate by interfering with the SHH signaling pathway.

Comparative study of stress characteristics around the adjacent teeth tissues during insertion of mini-screws with different insertion angles: A three-dimensional finite element study.

With a limited alveolar bone position, there is a high risk that mini-screws (MS) implants could cause damage to the adjacent teeth. To reduce this damage, the position and tilt angle of the MS must be optimized. The aim of this study was to assess the effect of MS implantation angle on the stress exerted on adjacent periodontal membrane and roots. A three-dimensional finite element model containing dentition, periodontal ligament, jaw and MS were established based on the CBCT images and MS scanning data. The MS was first inserted perpendicular to the surface of the bone at specific locations and then tilted at an angle of 10° and 20° to the mesial and distal teeth, respectively. The stress distribution in the periodontal tissue of the adjacent teeth was analyzed after MS implantation at different angles.The stress on the adjacent tooth root and periodontal ligament was most uniformly distributed when the MS was inserted vertically. It changed 9.4-97.7% when the axis of MS was tilted at 10-degree and 20-degree angles from the point of vertical insertion. The stresses experienced by the periodontal ligament and the root are similar. When the horizontal angle of the MS insertion was changed, the MS was closer to the adjacent tooth, resulting in greater stress near the PDL and root. It was recommended to insert the MS vertically into the alveolar bone surface to avoid root damage due to excessive stress.

Effect of a digital guide on the positional accuracy of intermaxillary fixation screw implantation in orthognathic surgery.

BACKGROUND: Intermaxillary fixation screw (IMFS) implantation is a common procedure in orthognathic surgery (OGS) performed to the temporary maxillary-mandibular fixation and stable bite relationships. The study aims to assess the accuracy of IMFS implantation with a digital guide to reduce the occurrence of root damage. METHODS: This prospective study involved 40 patients undergoing OGS at the Affiliated Hospital of Qingdao University from August 2017 to May 2021. The patients were randomly divided into two groups according to whether the IMFS implantation was with or without digital guide (20 patients in the experimental group and 20 controls). The digital guides used in the experimental group were designed according to a virtual implantation plan and printed using stereolithography. In the control group, IMFSs were directly implanted by a surgeon based on clinical experience. Postoperatively, cone-beam computed tomography was performed to compare root proximity of IMFSs between the two groups and verify the accuracy of IMFS placement. RESULTS: In the experimental group, there was no case of root damage, the incidence of the periodontal ligament (PDL) injured was 22.1%, and 77.9% IMFSs were placed without contacting adjacent anatomic structures. In the control group, the incidence of root damage had been up to 20.8%, 31.7% IMFSs injured the PDL, and only 47.5% IMFSs were placed between the roots (P < 0.001). CONCLUSION: IMFSs can be placed more accurately with surgical guides, reducing the incidence of root and PDL damages.

Inhibition of p38 mitogen-activated protein kinases may attenuate scar proliferation after cleft lip surgery in rabbits via Smads signaling pathway.

BACKGROUND: Cleft lip repair surgery always results in visible scarring. It has been proved that scar formation can be reduced by inhibiting the p38 mitogen-activated protein kinases (p38MAPKs) signaling pathway. However, the interaction between p38MAPK and Smads in scar formation is still controversial. METHODS: This study was designed to investigate whether inhibition of p38MAPK reduces postoperative scar formation of cleft lips on rabbits via the Smads signaling pathway. Scar models in rabbits after cleft lip surgery were created and their fibroblasts were extracted. Then the expression of p38MAPK was disturbed by adenovirus in vitro and Vivo. The scar thickness was measured and scar tissues were excised for Sirius red staining and immunohistochemistry to detect the expression of type I collagen (col I), type III collagen (col III), and α-smooth muscle actin (α-SMA). The underlying mechanisms of p38MAPK knockdown on the extracellular matrix and Smad signaling pathway were invested in vitro using the EdU assay, Western blot, RT PCR, and immunofluorescence. RESULTS: p38MAPK knockdown suppresses the expression of p-smad3 and p-smad2 in fibroblasts, modulating the expression of its target genes, such as α-SMA, col I, and col III. When Ad-P38MAPK-1 was injected into lip scar, it reduced the expression of scar-related genes and scar thickness when compared to the negative control groups. CONCLUSIONS: In rabbits, inhibiting p38MAPK expression prevents scar proliferation through inhibiting the Smad signaling pathway after cleft lip surgery.

Clinical study on obstructive sleep apnea following pharyngeal flap surgery.

OBJECTIVES: This study aims to investigate the incidence and severity of obstructive sleep apnea (OSA) in cleft patients with velopharyngeal insufficiency (VPI) after pharyngeal flap surgery (PFS) and explore the influence of operation age. METHODS: A retrospective study was conducted in 82 cleft patients after PFS. The patients were divided into two groups according to their age at the time of surgery. The incidence and severity of OSA were assessed at least 1.2 years (mean 6.0 years) postoperatively by polysomnography (PSG). RESULTS: The incidence rates of OSA were 20% in the adult group and 31% in the child group. No significant difference was found between the two groups (P=0.289). Patients with OSA in the adult and child groups were classified into different levels of severity (mild, moderate, severe) according to the apnea hypoventilation index (AHI). No statistically significant difference in the severity of OSA was found between the two groups (P=0.079). CONCLUSIONS: Some patients still have OSA average of 6.0 years after PFS, and operation ageis unrelated to the incidence and severity of OSA.

Sebaceous lymphadenocarcinoma of the parotid gland: A case report.

BACKGROUND: Sebaceous lymphadenoma is a benign tumor that occurs rarely in the salivary glands, most commonly in the parotid glands or periparotid lymph nodes, and even more rarely undergoes malignant transformation into a sebaceous lymphadenocarcinoma. CASE SUMMARY: We report an 82-year-old woman who presented with a painless mass in the right parotid region. We performed extended surgical resection of the parotid gland mass. Intraoperative pathology revealed a sebaceous lymphadenocarcinoma with metastasis into the periparotid cervical lymph nodes, so we also performed neck dissection and lymph node resection. Postoperative pathology confirmed the diagnosis. The literature review revealed that this was the seventh reported case of sebaceous lymphadenocarcinoma and the second reported case of cervical lymph node metastasis and infiltration of the skin of the parotid gland. CONCLUSION: Treatment of sebaceous lymphadenocarcinoma depends on the typing and clinical staging of the cancer. Extensive resection is the first choice, and adjuvant radiotherapy should be given to patients with high-grade tumors or those at an advanced clinical stage.

MicroRNA-299-3p/FOXP4 Axis Regulates the Proliferation and Migration of Oral Squamous Cell Carcinoma.

MicroRNAs are noncoding RNAs of 21 to 23 nucleotides in length that play important roles in almost all biological pathways. The roles of microRNA-299-3p in the development and progression of oral squamous cell carcinoma remain unclear. Expression level of microRNA-299-3p in oral squamous cell carcinoma cell lines was analyzed. Then, the effects of microRNA-299-3p on oral squamous cell carcinoma cell proliferation and migration were investigated. Moreover, bioinformation algorithm and Western blot were conducted to explore whether forkhead box P4 was a direct target of miR-299-3p. We showed that microRNA-299-3p expression was significantly reduced in oral squamous cell carcinoma cell lines. Next, overexpression of microRNA-299-3p was found to inhibit oral squamous cell carcinoma cell proliferation and migration but promote apoptosis. In addition, forkhead box P4 was identified as a functional target of microRNA-299-3p. Our results provide a new perspective for the mechanisms underlying the progression of oral squamous cell carcinoma and a novel target for the treatment of oral squamous cell carcinoma.

CBCT-based bone quality assessment in decompression of large odontogenic cystic lesions.

OBJECTIVES: Bone quality comprises bone mineral density and trabecular microstructure. The aim of this study was to explore the effectiveness of cone-beam computed tomography (CBCT) in evaluating bone quality of large odontogenic cystic lesions after decompression using CBCT and BoneJ software, and to determine whether secondary definitive surgery can be guided using CBCT data. METHODS: Twenty-seven patients with large odontogenic cystic lesions treated by decompression were evaluated by CBCT. Medical history and perioperative details were analyzed. RESULTS: The [Formula: see text]CT values for all patients with cystic lesions decreased after decompression, with no differences for age, sex, and histology (p > 0.05). Bone volume fraction and trabecular number of new cancellous bone (0.012%, 0.17/mm3) were lower than those of normal cancellous bone (0.189%, 0.47/mm3) (p < 0.05), while new cancellous bone trabecular separation (11.344 ± 2.556 mm) was stronger than normal cancellous bone trabecular separation (4.833 ± 2.232 mm) (p < 0.05). There were no differences in trabecular thickness between new cancellous bone (3.812 ± 1.593 mm) and normal cancellous bone (4.598 ± 3.573 mm) (p = 0.746). The [Formula: see text]CT values of five patients with favorable osteogenesis were - 72, -86, - 86, -47, and - 55, those of three patients with moderate osteogenesis were - 107, -120, and - 71, and those of two patients with poor osteogenesis were - 165 and - 127 during secondary definitive surgery. CONCLUSIONS: CBCT is considered beneficial for evaluating bone quality of large odontogenic cystic lesions after decompression, while providing potentially useful information for referral to secondary definitive surgery.

The relationship between maternal corticosteroid use and orofacial clefts-a meta-analysis.

The aim was to evaluate the relationship between maternal corticosteroid use during first trimester of pregnancy and risk of orofacial clefts (OC). The overall findings showed a certain association between maternal corticosteroid use and occurrence of OC, compared with non-users (OR=1.16 [95% CI: 1.01-1.33]). When study type was considered this association was significant only for case-control studies (OR=1.22 [95% CI: 1.02-1.47]), and not for cohort studies (OR=1.09 [95% CI: 0.88-1.34]) when there are many confounders (dose, route of application, disease etc.) and biases (re-call, loss-to follow-up etc.) that still need to be considered. A subgroup analysis based on the type of OC gave an overall OR of 1.41 (95% CI: 1.14-1.74) in the case-control studies for cleft lip with or without palate (CL/P) and 1.09 (95% CI: 0.80-1.48) for cleft palate only (CPO), when comparing maternal corticosteroid users with non-users. However, for cohort studies, the overall OR for CL/P is 1.06 (95% CI: 0.82-1.37) and 1.20 (95% CI: 0.83-1.75) for CPO. The absolute risk of facial cleft after prenatal exposure to corticosteroids, if any, is small.

[Evaluation of osteogenesis of alveolar bone graft by cone beam CT].

OBJECTIVE: To evaluate the osteogenesis of alveolar bone graft (ABG) in patients with alveolar cleft by cone beam CT (CBCT). METHODS: ABG surgery was performed in 20 patients with unilateral complete alveolar cleft. The patients were followed up for 3 and 6 months after surgery and the osteogenesis of the bone graft was evaluated by CBCT. The bone density and the height of labial and palatal bone graft area were analyzed. RESULTS: There was no significant difference in the bone density between 3 months [(403.79 ± 64.70) HU] and 6 months[(411.45 ± 42.62) HU ] (P = 0.329).However, there was significant difference in bone height in the labial and palatal side between 3 months and 6 months (labial P = 0.020, palatal P = 0.008). CONCLUSIONS: The osteogenesis was the best 3 months after bone graft. The following treatment can start in this stage.

[Preliminary report of botulinum toxin type A injection at trigger point for treatment of trigeminal neuralgia: experiences of 16 cases].

PURPOSE: To investigate the effects of injection of botulium toxin type A at trigger point for treatment of patients with primary trigeminal neuralgia. METHODS: Sixteen patients with primary Trigeminal Neuralgia were treated with injection of botulium toxin type A. Visual analog scores(VAS) at 1 week, 2 weeks, 1 month, 3 months and 6 months after treatment and Barrow Neurological Institute (BNI) pain evaluation criteria were utilized to measure the degree of pain. The data was analyzed with SPSS 10.0 software package. RESULTS: The VAS score was 9.12±0.65 before botulium toxin type A injection while the scores were 2.8±1.36, 2.2±1.26, 1.3±1.45, 1.3±1.45 and 1.2±2.52 at 1 week, 2 weeks, 1 month,3 months and 6 months after treatment. There was significant difference in VAS compared with before treatment. VAS score was lower and stable at 1 month, 3 months and 6 months after treatment, but no significant difference was found at 1-week and 2-week after treatment. BNI evaluation results showed good therapeutic effect 1 week after treatment, while the best therapeutic effect was noted 1-3 months after treatment. 6 months later, 1 patient had recurrence and 11 patients had complete relief of pain. CONCLUSIONS: Botulium toxin type A injection is an effective way for treatment of patients with primary trigeminal neuralgia.

[Role of p38 mitogen activated protein kinase on cyclic stretch in human facial hypertrophic scar fibroblasts differentiation into myofibroblasts].

OBJECTIVE: To explore the signal transduction mechanism of p38 mitogen activated protein kinase (p38MAPK) in human facial hypertrophic scar fibroblast (FB) differentiation into myofibroblasts (MFB). METHODS: Fibroblasts of primary culture were simple randomly assigned into two groups: cyclic stretch (control group) and cyclic stretch pre-treated with SB203580(experimental group). Expression of P-p38MAPK and α-smooth muscle actin (α-SMA) protein were examined using Western blotting and expression of transforming growth factor ß1 (TGF-ß1) mRNA and α-SMA mRNA were examined using reverse transcription PCR (RT-PCR). RESULTS: In control group, the expressions of α-SMA, p38MAPK, TGF-ß1 mRNA and α-SMA mRNA (0 h: 0.134 ± 0.011, 0.239 ± 0.015, 0.214 ± 0.018, 0.252 ± 0.010; 6 h: 0.152 ± 0.014, 0.287 ± 0.016, 0.288 ± 0.011, 0.277 ± 0.013; 12 h: 0.172 ± 0.017, 0.320 ± 0.017, 0.335 ± 0.013, 0.297 ± 0.006) , were significantly increased with loading time (6 h>0 h; 12 h>0 and 6 h). In experimental group (pre-treated with SB203580), the expressions of α-SMA, p38MAPK, TGF-ß1 mRNA,α-SMA mRNA (6 h: 0.116 ± 0.017,0.128 ± 0.016,0.134 ± 0.014,0.163 ± 0.009; 12 h: 0.149 ± 0.013,0.136 ± 0.018,0.144 ± 0.013,0.187 ± 0.010) on corresponding time decreased sharply compared with those in control groups (6, 12 h). CONCLUSIONS: The human facial hypertrophic scar fibroblasts differentiation in response to cyclic stretch was mediated by p38MAPK phosporylation.