ObjectiveTo investigate the optimal ratio of goat horn replacing antelope horn in Fufang Lingjiao Jiangya pills and the blood pressure-lowering mechanism of this medicine. MethodsThe blood pressure-lowering efficacy of Fufang Lingjiao Jiangya pills with varying proportions of goat horn replacing antelope horn was evaluated on spontaneous hypertensive rats （SHR）. In this experiment， 50 SHR rats were randomly grouped as follows： model （n=8）， captopril （0.01 g·kg^-1） （n=6）， low-dose blank Fufang Lingjiao Jiangya pills （0.342 g·kg^-1） （n=6）， high-dose blank Fufang Lingjiao Jiangya pills （0.684 g·kg^-1） （n=6）， low-dose antelope horn-containing Fufang Lingjiao Jiangya pills （0.378 g·kg^-1） （n=6）， high-dose antelope horn-containing Fufang Lingjiao Jiangya pills （0.756 g·kg^-1） （n=6）， low-dose goat horn-containing Fufang Lingjiao Jiangya pills （0.378 g·kg^-1） （n=6）， and high-dose goat horn-containing Fufang Lingjiao Jiangya pills （0.756 g·kg^-1） （n=6）. Additionally， 8 WKY rats were used as the normal group. Drugs were administered by gavage for 4 weeks while an equal volume of distilled water was administered for the normal and model groups. Blood pressure was measured before administration， 3 h post administration， and biweekly thereafter. In the experiment for Fufang Lingjiao Jiangya pills with goat horn replacing antelope horn in different proportions， 48 SHR rats were randomly grouped as follows： model， blank Fufang Lingjiao Jiangya pills （0.684 g·kg^-1）， antelope horn-containing Fufang Lingjiao Jiangya pills （0.756 g·kg^-1）， 2× goat horn-containing Fufang Lingjiao Jiangya pills （0.824 g·kg^-1）， 4× goat horn Fufang Lingjiao Jiangya pills （0.969 g·kg^-1）， and 6× goat horn Fufang Lingjiao Jiangya pills （1.112 g·kg^-1）. The normal group included 8 WKY rats， and the normal group and model group received an equal volume of distilled water. The treatment lasted for 2 weeks， and blood pressure was recorded at various time points （pre-administration， 3 h post administration， and on days 4， 7， 10， and 14 of administration）. Serum levels of angiotensin-converting enzyme （ACE）， angiotensin Ⅱ（Ang Ⅱ）， renin， and interleukin-6 （IL-6） were measured by enzyme-linked immunosorbent assay. Histopathological changes in the heart， kidney， and thoracic aorta were observed by hematoxylin-eosin staining. The protein levels of ACE2， angiotensin Ⅱ type 1 receptor （AT1R）， and angiotensinogen （AGT） in the kidney tissue were determined by Western blot， while the expression of nuclear factor （NF）-κB p65 and Toll-like receptor 4 （TLR4） in the thoracic aorta tissue was assessed by immunohistochemistry. ResultsCompared with the model group， all treatment groups showed lowered blood pressure （P<0.05， P<0.01）， and the 6× goat horn-containing Fufang Lingjiao Jiangya pills group showed consistent blood pressure-lowering effect with the antelope horn-containing Fufang Lingjiao Jiangya pills group. Compared with the normal group， the model group showed elevated serum levels of ACE， Ang Ⅱ， renin， and IL-6， while the elevations were declined in the Fufang Lingjiao Jiangya pills groups （P<0.05， P<0.01）. Pathological changes in the heart， kidney， and thoracic aorta were alleviated in all the treatment groups， with the 6× goat horn- and antelope horn-containing Fufang Lingjiao Jiangya pills groups exhibited the best effect. Western blot and immunohistochemistry results showed that all the treatment groups exhibited down-regulated protein levels of AT1R， AGT， NF-κB p65， and TLR4 and up-regulated protein levels of ACE2 （P<0.05， P<0.01） compared with model group， with the 6×goat horn- and antelope horn-containing Fufang Lingjiao Jiangya pills groups showcasing the best effect. ConclusionReplacing antelope horn with 6×goat horn in Fufang Lingjiao Jiangya pills can achieve consistent blood pressure-lowering effect with the original prescription. The prescription may exert the effect by inhibiting the renin-angiotensin-aldosterone system （RAAS） and TLR4/NF-κB signaling pathways.

Important anatomical structures such as mandibular incisive canal,tongue foramen,and mouth floor vessels may be damaged during implant surgery in the mandibular anterior region,which may lead to mouth floor hematoma,asphyxia,pain,paresthesia and other symptoms.In severe cases,this can be life-threatening.The insufficient alveolar bone space and the anatomical variation of blood vessels and nerves in the mandibular anterior region increase the risk of blood vessel and nerve injury during implant surgery.In case of vascular injury,airway control and hemostasis should be performed,and in case of nerve injury,implant removal and early medical treatment should be performed.To avoid vascular and nerve injury during implant surgery in the mandibular anterior region,it is necessary to be familiar with the anatomical structure,take cone-beam computed tomography,design properly before surgery,and use digital technology during surgery to achieve accurate implant placement.This article summarizes the anatomical structure of the mandibular anterior region,discusses the prevention strategies of vascular and nerve injuries in this region,and discusses the treatment methods after the occurrence of vascular and nerve injuries,to provide clinical reference.

The canalis sinuosus,a canal containing the anterior superior alveolar nerve bundle,originates from the infraorbital canal and extends along the maxillary sinus and nasal cavity edges to the anterior maxilla.It was once regarded as an anatomical variation.However,with the widespread application of cone beam computed tomography(CBCT),the detection rate of canalis sinuosus in the population has increased.The canalis sinuosus exhibits diverse courses,branching into multiple accessory canals and terminating at the nasal floor or the anterior tooth region,with the majority traversing the palatal side of the central incisor.The anterior superior alveolar nerve bundle within the canalis sinuosus not only innervates and nourishes the maxillary anterior teeth and the corresponding soft tissues,and the maxillary sinus mucosa,but also relates to the nasal septum,lateral nasal wall,and parts of the palatal mucosa.To minimize surgical complications,strategies for preventing and treating canalis sinuosus injuries need to be investigated.Preoperatively,CBCT is used to identify the canalis sinuosus and to virtually design implant placement at a distance of more than 2 mm from the canalis sinuosus.Intraoperatively,assessing bleeding and patient comfort,complemented by precision surgical techniques such as the use of implant surgical guide plates.Postoperatively,CBCT is used to examine the relationship between the implant and the canalis sinuosus,and treatment of canalis sinuosus injuries can be tailored based on the patient's symptoms.This review summarizes the detection of canalis sinuosus in the population,its anatomical characteristics,and the physiological functions in the anterior maxilla,and discusses strategies for avoiding canalis sinuosus injuries during implant surgery,thereby enhancing clinical awareness and providing references for clinical decision-making.

Objective:To investigate the clinical outcomes of lining repair during the reconstruction of nasal defects.Methods:From January 2010 to December 2022, our team treated 15 nasal defect patients aged between 18 and 62 years with an average age of 38, including 8 males and 7 females. The range of the defect was more than one subunit in all cases. And forehead pedicled flaps were chosen for repair. For nasal reconstruction, expander was implanted to expand the central forehead flap. The choice of support depended on the range of the defect, including rib-rib cartilage composite grafts, rib cartilage grafts and ear cartilage grafts. The repair of the lining was selected with the original skin, local nasolabial flapor forehead pedicled flap to repair the mucosal defect of the nose. Postoperative follow-up was conducted to observe the effects.Results:Among the 15 patients, 8 cases underwent rib-rib cartilage composite grafts. 3 cases had rib cartilage grafts, and 4 cases had ear cartilage grafts. All the flaps survived with 1 case experiencing infection. Postoperative follow-up for 0.5 to 2 years showed that the appearance of nasal defects in all 15 cases was significantly improved, with satisfactory results.Conclusions:The repair of nasal defect lining requires a comprehensive analysis based on the specific location, range of the defect, and the selection of the donor area in order to ultimately determine the surgical approach.

Objective:To summarize the experience of Bipartition osteotomy combined with craniofacial bone remodeling in the treatment of orbital hypertelorism and midfacial dysplasia.Methods:A retrospective analysis was done by the clinical data of two patients with orbital hypertelorism with maxillofacial malformation treated in the Shanghai Ninth People’s Hospital Affiliated to Shanghai Jiao Tong University School of Medicine in July 2005 and August 2018. The Bipartition osteotomy via intracranial approach were applied for the two patients, one male and one female. The two patients aged 17 and 19, were suffered from degree Ⅰ orbital hypertelorism [interorbital distance(IOD) 32 mm and 34 mm]. With a frontal bone fenestration, the Monobloc osteotomy was done firstly to dislocate the cranio-orbital-maxilla bone graft, then the Bipartition osteotomy was performed according to the preoperative design through 3D computer aided design(CAD) and a V-shape bone graft was removed from the interorbital bone graft to split the hard palate longitudinally along the midline. After all, the whole facial bone was separated to two blocks: bilateral orbital-maxillary segments. Finally the midface had been remodeled by the bilateral orbital-maxillary segments which rotated and fixed internally. Self-rib nasal augmentation was done later. Patents’ complications, eye movement, visual acuity, olfactory sensation, nasal shape, IOD were measured through CT scan and the appearances were observed in the postoperative follow-up to determine the degree of improvement.Results:15 mm in width of interorbital bone was resected in both of the two patients, respectively. Postoperative IOD reduced by 17 mm, 19 mm, respectively. Mild cerebrospinal fluid leakage occurred in both patients after operation. They recovered after 5, 8 days of pillow-free horizontal position, respectively. The male patient developed local skin infection at the coronal incision and recovered after dressing change for 1 week. One week after operation, the female patient’s nose tip was partially broken near the nasal columella, and recovered after debridement and repairment. Follow up for 4-11 months showed that the eye movement, visual acuity, normal convergence and olfactory sensation were normal and no diplopia of 2 patients. The nasal appearances and orbital hypertelorisum of them were corrected obviously by follow-up after 4 months, but the nasal morphology and epicanthus still need further improvement.Conclusions:The Bipartition osteotomy can effectively treat the orbital hypertelorisum through the internal rotation fixation of bilateral orbital-maxillary segments, that makes the high arch palate lower and the occlusal plane of the upper jaw flattened.

Objective:To summarize the experience of Bipartition osteotomy combined with craniofacial bone remodeling in the treatment of orbital hypertelorism and midfacial dysplasia.Methods:A retrospective analysis was done by the clinical data of two patients with orbital hypertelorism with maxillofacial malformation treated in the Shanghai Ninth People’s Hospital Affiliated to Shanghai Jiao Tong University School of Medicine in July 2005 and August 2018. The Bipartition osteotomy via intracranial approach were applied for the two patients, one male and one female. The two patients aged 17 and 19, were suffered from degree Ⅰ orbital hypertelorism [interorbital distance(IOD) 32 mm and 34 mm]. With a frontal bone fenestration, the Monobloc osteotomy was done firstly to dislocate the cranio-orbital-maxilla bone graft, then the Bipartition osteotomy was performed according to the preoperative design through 3D computer aided design(CAD) and a V-shape bone graft was removed from the interorbital bone graft to split the hard palate longitudinally along the midline. After all, the whole facial bone was separated to two blocks: bilateral orbital-maxillary segments. Finally the midface had been remodeled by the bilateral orbital-maxillary segments which rotated and fixed internally. Self-rib nasal augmentation was done later. Patents’ complications, eye movement, visual acuity, olfactory sensation, nasal shape, IOD were measured through CT scan and the appearances were observed in the postoperative follow-up to determine the degree of improvement.Results:15 mm in width of interorbital bone was resected in both of the two patients, respectively. Postoperative IOD reduced by 17 mm, 19 mm, respectively. Mild cerebrospinal fluid leakage occurred in both patients after operation. They recovered after 5, 8 days of pillow-free horizontal position, respectively. The male patient developed local skin infection at the coronal incision and recovered after dressing change for 1 week. One week after operation, the female patient’s nose tip was partially broken near the nasal columella, and recovered after debridement and repairment. Follow up for 4-11 months showed that the eye movement, visual acuity, normal convergence and olfactory sensation were normal and no diplopia of 2 patients. The nasal appearances and orbital hypertelorisum of them were corrected obviously by follow-up after 4 months, but the nasal morphology and epicanthus still need further improvement.Conclusions:The Bipartition osteotomy can effectively treat the orbital hypertelorisum through the internal rotation fixation of bilateral orbital-maxillary segments, that makes the high arch palate lower and the occlusal plane of the upper jaw flattened.

OBJECT IVE To provide scientific evidence for the quality standard research of Qingyi mixture （QM）qualitatively and quantitatively. METHODS The high performance liquid chromatography （HPLC）fingerprint of QM was established ，and the chemical pattern recognition analysis was carried out. At the same time ，the contents of 8 components such as chlorogenic acid in the preparation were determined. The determination was performed on Agilent SB-C 18 column with 0.1％ phosphoric acid-acetonitrile as mobile phase （gradient elution ）at the flow rate of 0.6 mL/min. The column temperature was 35 ℃，and detection wavelength was set at 254 nm. Similarity Evaluation System of Chromatographic Fingerprint of Traditional Chinese Medicine（2012 edition），SPSS 20.0 and SIMCA 14.1 were used to perform similarity evaluation ，cluster analysis （CA），principle component analysis （PCA）and orthogonal partial least squares-discriminant analysis （OPLS-DA）of QM samples. RESULTS A total of 22 common peaks were calibrated by 15 batches of QM ，and the similarity was over 0.975. Twenty-two common peaks were assigned and 8 of them were identified. CA ，PCA and OPLS-DA divided the 15 batches of QM into two categories. Meanwhile，5 differential components were screened out ，i.e. peak 9（cichoric acid ），peak 14（baicalin），peak 18，peak 19 and peak 21 （baicalein）. The contents of 8 components，such as chlorogenic acid ，ferulic acid ，cichoric acid ，hesperidin， baicalin，salvianolic acid B ，baicalein and paeonol ，were 0.077-0.094，0.165-0.190，0.100-0.114，0.083-0.107，0.556-0.615，0.288-0.314，0.152-0.188 and 0.114-0.128 mg/g，respectively. CONCLUSIONS The established HPLC fingerprint and content determination method can provide reference for the quality standard research of QM.

Objective:For severe skin defects which are deep to dermis, engineered skin with epidermis and dermis (bilayered) is required. Based on the success of engineering epidermis with GT/PCL electrospun membranes, our study was to investigate whether this membrane could be also used for engineering bilayered skin graft.Methods:From 2013 to 2019, we first prepared three GT/PCL electrospun membranes with different proportion (70∶30; 50∶50; 30∶70) in our laboratory; the biocompatibility of the membrane was evaluated in vitro by seeding fibroblasts or keratinocytes on the membranes. Then the outcome of GT/PCL membranes repairing skin defects in the nude mouse was investigated.Results:Cell attachment and proliferation were significantly improved with increase of gelatin. Histological analyses showed that bilayered skin engineered with GT/PCL (70∶30) group could form relatively better structure after 3 weeks of cultivation in vitro. Further in vivo transplantation studies revealed that scaffolds were not degraded in all three groups, indicating that these materials were not suitable for engineering bilayered skin although they had good biocompatibility.Conclusions:The higher gelatin membranes possess better biocompatibility. Further in vivo transplantation studies reveal that bilayered skin engineered with GT/PCL membranes is able to repair skin defects in the nude mouse.

Objective:To identify the gene mutations associated with facial cleft-related orbital hypertelorism in 3 pairs of monozygotic twins with different phenotypes (with/without hypertelorism) and to investigate their mechanisms.Methods:From May 2014 to May 2019, 3 pairs of monozygotic twins, 2 males and 4 females, aged 5-18 years, were treated in Ninth People’s Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, one with normal orbital distance and widening of orbital distance was caused by facial fissure. Among the twins, there was 1 case of orbital hypertelorism and the other case of without orbital hypertelorism, and the hypertelorism was caused by facial cleft. To screen for mutations in hypertelorism, whole genome sequencing was performed on 3 pairs of twins. The Sanger method was used to sequence the exons of 33 patients with facial fissure associated hypertelorism and 50 healthy individuals in the same period to identify the genes selected by the whole genome sequencing. The periosteal tissues were obtained from patients and healthy people during plastic surgery. The cells were cultured, the activity of alkaline phosphatase was measured, and the osteogenic differentiation was identified by alizarin red staining, real-time quantitative PCR and Western blotting were used to detect the mRNA and protein expression of signal transduction pathways in periosteal cells.Results:Whole genome sequencing analysis showed that in all three sets of twins, a new synonymous mutation (c.1479G>A, p. Q493Q) was found in the MAML3. In Sanger exon sequencing, 17(51.5%) of 33 patients with hypertelorism carried the mutation, while no mutation was detected in 50 normal controls. The result of periosteum-derived cytology showed that the expression of MAML3 mRNA and protein in the patient-derived cells was lower than that in the healthy-derived cells. Three, 7, 14 days after osteoinduction, the ALP activity in the cells from the patients was higher than that from the healthy subjects (8.540±1.450, 20.740±2.514, 24.090±3.213 vs. 5.268±0.482, 11.680±1.527, 13.200±0.592; all P<0.05). Fourteen days after osteoinduction, the result of alizarin red staining showed that there were more erythema formation in the cells from the patients than those from the healthy subjects, these result suggest that MAML3 mutation may lead to over-differentiation of human periosteal-derived cells. The mRNA and protein expression levels of hes1 and hes5 downstream of the Notch signal pathway were down-regulated in the periosteal cells of the patients, while Wnt3a and β-catenin mRNA and protein expression levels were up-regulated in the Wnt signal pathway. Conclusions:The MAML3 gene (c.1479G>A, p. Q493Q) mutation is one of the causative genes of facial cleft-related hypertelorism. Notch and Wnt/β-catenin signaling pathway play an important role in the pathogenesis of hypertelorism.

Objective:To evaluate the clinical value and effect of the application of computer navigation system in orbital-zygomatic fibrous dysplasia.Methods:From March 2016 to December 2018, 16 patients with orbital-zygomatic fibrous dysplasia admitted to Shanghai 9th People’s Hospital, Shanghai Jiao Tong University School of Medicine were included in this study. CT scans and computer aided designs were finished preoperatively. By mirrored and compared with the healthy side, preoperative-designed lesion removal area was determined and surgical regions were highlighted. Digital reference frame was fixed rigidly to patient’s forehead. After accurate registration, lesion area was removed with the aid of surgical navigation system according to preoperative-designed plan restrictively through lower eyelid-intraoral approach. The symmetric morphology of orbital-zygomatic region was analyzed postoperatively. Zygomaxillare, oribitale, zygomaticand lower orbital point of zygomatic maxillary were marked both in preoperative and postoperative three-dimensional reconstructions, and the distance between them and mid-sagittal plane was measured. Paired- t tests were applied in this study for symmetric analysis. Results:In this study, 16 patients with orbital zygomatic bone fiber dysplasia assisted by computer navigation were included, consisted of 12 males and 4 females, ranging from 18 years old to 35 years old. The differences of preoperative symmetric analysis in zygomaxillare, oribitale, zygomatic had statistical significance( P<0.01). The difference of preoperative symmetric analysis in lower orbital point of zygomatic maxillary had no statistical significance( P>0.05). The differences of postoperative symmetric analysis in zygomaxillare, oribitale, zygomatic and lower orbital point of zygomatic maxillary had no statistical significance( P>0.05). The difference in zygomaxillare decreased from(10.1±6.2) mm to(2.7±6.4) mm. The difference in oribitale(ORI)decreased from(7.7±4.6) mm to(1.9±3.9) mm. The difference in zygomatic decreased from(8.5±7.5) mm to(0.7±1.5)mm. The difference in lower orbital point of zygomatic maxillary decreased from(1.9±3.5) mm to(0.6±2.1) mm. The morphology of the affected side and the healthy side was symmetrical. The contour was natural and no postoperative complications occurred. The postoperative satisfaction rate was high. Conclusions:Computer navigation system can solve the problem of limited exposure of lower eyelid-intraoral approach in orbital-zygomatic fibrous dysplasia and significantly improve the accuracy, effectiveness and safety during surgery.