Objective To analyze the colistin heteroresistance in Pseudomonas aeruginosa strains and their in vitro susceptibility to antibiotics used in combination.Methods Two hundred and ninety-seven carbapenem-resistant Pseudomonas aeruginosa strains were selected for this study.Broth microdilution method was used to determine the minimum inhibitory concentrations of colistin and other antimicrobials against the Pseudomonas aeruginosa strains.The colistin heterogeneity of 20 colistin sensitive strains was analyzed by using population analysis profiles.The time-kill curves of 3 randomly selected colistin heteroresistant strains were used to determine the bacteriostatic activity of colistin.Chequer-board method was used to measure the combination efficacy of colistin with other antimicrobials including imipenem,meropenem,biapenem,ceftazidime,levofloxcin,piperacillin/tazobactam and cefoperazone/sulbactam.Results The colistin sensitive Pseudomonas aeruginosa strains accounted for 99.66％ of the 297 isolates.Population analysis profiles displayed that 35％ of the 20 isolates were colistin heteroresistant and 20％ of the 20 isolates were heterogeneous.It showed that when colistin was used in combination with other drugs,they mainly had synergistic and additive effects on heteroresistant isolates,but additive and indifferent effects on non-heterogeneous isolates.Conclusion Multidrug resistant Pseudomonas aeruginosa strains were highly susceptible to colistin,but heteroresistant and heterogeneous strains were common.The efficacy of colistin against heteroresistant isolates could be enhanced by using in combination with other drugs.

Objective To study the risk factors of post-hepatectomy hepatic decompensation (PHD) in patients with hepatocellular carcinoma.MethodWe reviewed 562 patients with Child-Pugh A classification,who underwent partial hepatectomy for hepatocellular carcinoma at Zhongshan Hospital,Fudan University between July 1st 2007 to December 31st 2007,to study the risk factors of hepatic decompensation.ResultsPreoperative high total bilirubin (TB) and low prealbumin (PA) were independent risk factors of PHD by logistic multivariate analysis ROC analysis revealed the cut-offs of preoperative PA predicting PHD were 0.14 g/L (sensitivity 41.4％; specificity 83.1％).The incidence of PHD was 16.0％ when TB≥20.4 μmol/L and PA＜0.14 g/L(OR=7.276,P=0.002).ConclusionThe Child-Pugh A patients recovered well when the preoperative liver function was as follows:TB＜20.4 μmol/L and PA≥0.14 g/L.

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 explore a new method for the treatment of nasal deformity in the middle part of facial cleft.Methods Eight patients with craniofacial cleft midface depression were treated with nasal reconstruction,nasal reconstruction plus pear shaped hole week osteotomy forward,pyriform aperture osteotomy advancement by using the auxiliary week preoperative design and postoperative surgical navigation system,and the preoperative design and postoperative CT data fit was compared.Results All the 8 patients were satisfied with results of the operation.There was no significant difference in CT data between preoperative simulation design and postoperative follow-up.Conclusions The expanded forehead flap in nasal reconstruction surgery has good effect on congenital craniofacial cleft nasal defect,and surgical navigation assisted pyriform hole osteotomy advancement for correction of congenital craniofacial cleft caused by midface depression to achieve a precise osteotomy,has good application value.

Objective:To measure the changes in the orbital and nasal parameters before and after Tessier box osteotomy with primary aesthetic rhinoplasty concurrently with byotogenous costochondral graft.Methods:From 2013 to 2018, 60 hypertelorism patients were treated in our craniofacial center. Correction involved a classic Tessier box osteotomy combined with aesthetic augmentation and reconstruction of the nasal dorsum using a costochondral graft. All patients underwent photographic and tomographic documentation both before and 12 months after surgery. Patients underwent morphometric analysis to document the changes in interorbital distance (IOD) and aesthetic nasal parameters, including the nasal dorsum and alar width, the nasal dorsal height, and the index of nasal apex protrusion versus nasal length.Results:All patients were satisfied with the outcome of the combined orbital and nasal repair. Morphometric analysis indicated that the IOD and aesthetic nasal parameters all improved following surgery. The resorption rate of the costochondral graft was 16-19%, and graft warpage was nearly absent. Although complications so as infection, cerebrospinal fluid leak or hyposomia, no severe or life-threatening complications occurred.Conclusions:Tessier box osteotomy with primary aesthetic rhinoplasty using costochondral grafts has showed to be efficacious in the treatment of patients with hypertelorism.

Objective:To retrospect the treatment and clinical effect of craniometaphyseal dysplasia(CMD), and summarize the experience of cranial reconstruction and nasal deformity correction in the management of this case.Methods:From June 2004 to June 2018, three male CMD patients of Shanghai Ninth People’s Hospital who received treatment. One patient was 1 year-old child who received drug therapy. A 5 year-old boy was treated with nasal cavity expansion and orbital hypertelorism for plastic and reconstructive surgery. The 7 year-old patient received cranial reconstruction and nasal deformity correction. Moreover, surgical treatments from 1967 to 2017 in the literatures on CMD were reviewed.Results:Indicators (Ca, ATP, PTH) in the laboratory of the first child returned to normal after medication treatment, and there was no obvious abnormality in the following 2 months. Nasal cavity of the second case was enlarged and function of the nose was improved, and interorbital distance was reduced by 16-17 mm. However, cranial facial deformation was not ameliorated obviously. For the third patient, scaphocephaly deformity was significantly improved. Skull thickness decreased from 3cm to 1-2 cm, the anteroposterior diameter of the skull was shortened up to 6 cm. The immediate review of dd dimer was 4.25 mg/L, FDP was 20.6 μg/ml, which was significantly higher than preoperative tests (dd dimer 0.98 mg/L, FDP 7.24 μg/ml). Two weeks after surgery, the patient received skull debridement due to ineffective anti-infective treatment. Ten months later, the child was admitted to the hospital because of infection. CT scan showed bone resorption, and we treated him with skull debridement and cranioplasty. Following 16 months, the patient was in a stable condition without complications until now.Conclusions:Drug therapy has a potential role in CMD treatment. However, surgery is the only effective management of it, although there will be a high risk and many complications, and the patients need repeated operations.

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.

Objective:To quantitatively assess the degree of bone resorption following cranial bone remodeling for children and adolescent congenital cranial deformity cases in Crouzon syndrome.Methods:A total of 14 congenital cranial deformity patients (mean age 7.7 years) who underwent cranial bone remodeling between Mar. 2014 and Dec. 2018 were selected from Shanghai Ninth People’s Hospital, and retrospectively reviewed. They were treated with modified monobloc osteotomy and distraction osteogenesis. Craniectomy and cranial bone remodeling were performed, and the follow-up period was one week(t1) and one year(t2). The patients were scanned by spiral CT at the two following time points. Then data were imported into Mimics to acquire the three-dimensional model of skull. Bone volume was measured with Mimics Research 18.0 after three-dimensional CT reconstruction. The resorption rate was calculated as (V t1-V t2)/V t1×100%(V t1 represented bone volume before distraction osteogenesis, V t2 represented bone volume after distraction osteogenesis), followed by statistical analysis. Results:Among the 14 patients, bone resorption occurred in 11 patients and the resorption rate after 1 year was 3.482%. There was no significant difference between bone volumes at 1 week and 1 year after surgery( t=0.851, P=0.410). Conclusions:Bone resorption following cranial bone remodeling for children and adolescents with congenital cranial deformity did exist, however, it was acceptable. Therefore, the surgical treatment of cranial remodeling and distraction osteogenesis is advisable for children and youth with congenital cranial deformities over 1 year old.

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 establish an improved model of mouse partial hepatectomy for study on liver regeneration .Methods :Healthy 8~10 week old male C57BL/6 mice were anesthetized by intraperitoneal injection .Then ,common hepatic pedicle of left lateral lobe of liver and middle lobe of liver was wrapped around with 6-0 proline suture .6-0 proline was fixed on the sur-face of right middle lobe of liver ,which was 0 .2 cm away from the hepatic pedicle .Hepatic pedicle was ligated and left lateral lobe and middle lobe of liver were resected 0 .2 cm away from ligature .The postoperative survival rate and the situation of liver weight vecovery at 3rd day ,7th day ,and 14th day after the operation were observed .Results:An improved mouse model of partial hepatectomy ,of which left lateral lobe of liver and middle lobe of liver were resected ,was established .The weight of removed liver accounted for 66 .7% of total liver and the survival rate of mice was 100% .After liver resection ,the compensa-tory regeneration of remaining liver achieved 58 .2% of the total liver weight at the 3rd day ,78 .0% at the 7th day ,and 93 .2%at the 14th day after the operation .Conclusions :An improved mouse model of partial hepatectomy was successfully established for study on liver regeneration ,which has advantages such as simplicity ,operability and high success rate .