[Efficacy analysis of surgical combined with postoperative adjuvant therapy for T3 gallbladder carcinoma: a multicenter retrospective study].

Objective: To explore the clinical value of adjuvant therapy in patients with T3 gallbladder cancer (GBC) who have undergone R0 resection. Methods: Clinical and pathological data from 415 patients with T3 GBC who underwent surgical treatment in 7 tertiary centers in China from January 2013 to December 2018 were collected,including 251 males and 164 females,aged (61±11)years (range: 26 to 88 years). Depending on whether to receive adjuvant therapy after radical resection,the patients were divided into the radical resection group alone (group A,n=358) and the radical resection combined with the postoperative adjuvant therapy group (group B,n=57). The general data of the two groups were matched 1∶1 by propensity score matching method,and the caliper value was 0.02.Clinicopathological characteristics,overall survival and disease-free survival of the two groups were compared.The Cox regression model was used for multivariate analysis,and patients with at least one or more independent risk factors were classified as high-risk clinicopathological subtypes. Subgroup analysis was performed to assess the clinical value of adjuvant therapy after radical resection in patients with high-risk clinicopathological subtypes. Results: After the matching,there were 42 patients in each of the two groups. The incidence of gallbladder cancer and the number of dissected lymph nodes in group B after cholecystectomy were higher than those in group A (χ2=9.224,2.570,both P<0.05). There were no significant differences in overall survival rate and disease-free survival rate between the two groups before and after matching (all P>0.05). The results of the univariate and multivariate analysis showed that CA19-9>39 U/ml,nerve invasion,tumor location (liver side or bilateral),TNM stage ⅢB to ⅣB ,poorly differentiated tumor were independent prognostic factors of overall survival and disease-free survival of patients with T3 stage gallbladder cancer (all P<0.05).Three hundred and twenty-nine patients(79.3%) had high-risk clinicopathological subtypes,and the median survival time after curative resection with and without adjuvant therapy was 17 months and 34 months respectively,and the 3-year and 5-year overall survival rates were respectively 40.0%,21.3% and 46.0%,46.0% (χ2=4.042,P=0.044);the median disease-free survival time was 9 months and 13 months,and the 3-year and 5-year disease-free survival rates were 23.4%,13.6% and 30.2%,18.2% (χ2=0.992,P=0.319). Conclusions: Postoperative adjuvant therapy following radical surgery did not yield significant improvements in the overall survival and disease-free survival rates of patients diagnosed with T3 gallbladder cancer. However, it demonstrated a significant extension in the overall survival rate for patients presenting high-risk clinicopathological subtypes.

[Application of high-density polyethylene implants in adult cleft lip and palate nasal deformity and dysfunction].

Objective: Through the use of high-density polyethylene implants in adults with cleft lip and palate nasal deformities and abnormal functions, to evaluate the clinical effect of postoperative patients on improving nasal shape and symptoms. Methods: A retrospective study of 12 patients with nasal deformities after cleft lip and palate surgery in the Shanghai Ninth People's Hospital Affiliated to Shanghai JiaoTong University School of Medicine from January 2018 to January 2022 was completed, including 7 males and 5 females, with the age ranging from 18 to 29 years. All the patients underwent nasal deformity correction, and nasal septum correction was performed if necessary. High-density polyethylene implants (MEDPOR/Su-Por) were used intraoperatively. Follow-up for at least 6 months was performed to measure the relevant appearance indicators and subjective Visual Analog Scale (VAS) scores, and to compare the clinical effects before and after surgery. SPSS 22.0 software was used for statistical analysis. Results: Before and after surgery, the average VAS score of nasal obstruction decreased by (4.83±0.94) points; the average VAS score of appearance satisfaction increased by (3.92±1.08) points; the height of nasal columella was increased by (1.79±0.78)mm; the height of nasal tip was increased by (2.79±1.50)mm; the height of ipsilateral nostril was increased by (1.83±0.62)mm; the width of the ipsilateral nasal floor was reduced by (0.42±0.47)mm. All of above were statistically significant (all P<0.05). Conclusion: High-density polyethylene implants can effectively improve the shape and function of the nose in operations related to cleft lip and palate nasal deformity and abnormal functions, and are an ideal synthetic material.

[A nested case-control study on the association of neonatal cord blood selenium, iron and copper with congenital heart disease].

Objective: To investigate the relationship between the levels of selenium, iron and copper in cord blood of neonates and the risk of congenital heart disease (CHD), and analyze their interaction effects. Methods: The subjects were obtained from the birth cohort in Lanzhou area established from 2010 to 2012. A baseline survey was conducted in the first trimester, and the follow-up was conducted in the second trimester, third trimester and 42 days after delivery. The umbilical vein blood was collected from newborns at delivery, and information on their birth outcomes was extracted from medical records. A nested case-control study was used to select 97 neonates with CHD newly diagnosed by echocardiography as the case group, and 194 neonates were selected as the control group by 1∶2 matching according to their mother's age, block and CHD onset time. Inductively coupled ion mass spectrometry was used to detect the concentrations of selenium, iron and copper in neonatal cord blood. The element exposure was categorized into three groups, the low, medium and high concentrations, according to the quartiles Q1 and Q3 of selenium, iron and copper concentrations in the control group. The association between cord blood selenium, iron and copper concentrations and CHD was analyzed by conditional logistic regression model using medium concentration as the reference standard. The association of their interactions with CHD was analyzed by a phase multiplication model. Results: The M (Q1, Q3) concentration of neonatal cord blood copper was 746.12 (467.48, 759.74) µg/L in the case group and 535.69 (425.21, 587.79) µg/L in the control group, with a statistically significant difference between the two groups (P<0.05). After adjustment for confounders, logistic regression models showed that the risk of CHD development was increased in neonates with either high copper in cord blood (OR=4.062, 95%CI: 2.013-8.199) or high copper combined with high iron (OR=3.226, 95%CI: 1.343-7.750). No correlation was observed between selenium and iron concentrations and the development of CHD in neonates. There was a multiplicative interaction between copper and iron in cord blood on the risk of developing CHD (OR=1.303, 95%CI: 1.056-1.608). Conclusion: There is a multiplicative interaction between iron and copper elements. The high copper and the high copper combined with high iron in umbilical cord blood are risk factors for neonatal CHD.

Validation of a commercial software dose calculation for Y-90 microspheres.

PURPOSE: Several new commercial software packages have become available that can calculate the tumor and normal tissue dose distributions from post-treatment PET-CT scans for Y-90 microsphere treatments of liver lesions. This work seeks to validate the MIM SurePlan Liver Y90 software by comparing its results to a previously developed Monte Carlo derived voxel dose kernel calculation method. METHODS: We analyzed 10 patients who had treatments for metastatic liver cancer and created contours on post Y-90 treatment PET-CT images. We then performed dose calculations using three methods and compared the results. The first two methods calculated the dose using MIM SurePlan Liver Y90's LDM (Local Deposition Method) and the VSV (Voxel S Value) algorithms. The third method calculated the dose using a publicly available Fluka Monte Carlo-derived dose kernel (MCK) calculation (used as ground truth). We investigated 3D Gamma passing rates and several dosimetric parameters. RESULTS: A total of 3%/3 mm 3D gamma passing rates averaged 99.3% for the VSV and 78.9% for LDM. Compared to the MCK distribution, the differences for combined target GTV V70Gy and normal liver and/or lobe mean doses were small. Larger differences were seen in GTV mean doses and D95, likely due to large dose gradients in the treated regions combined with differences in dose kernel, dose grid and finite volume effects. CONCLUSIONS: The MIM SurePlan Liver Y90 VSV algorithm agreed well with the MCK calculation for patients treated with Y-90 microspheres based on the gamma analysis and several dosimetric parameters. Larger dosimetric differences in lesion mean doses and D95 suggests that these metrics are less robust to changes in calculation grid location and finite volume effects for small lesions.

[Advances in the study of the role of adenosine 2A receptor in liver injury].

Adenosine, as an endogenous purine nucleoside, is widely distributed in various tissues and organs of the body. It binds to adenosine receptors to regulate a variety of important biological processes. Adenosine 2A receptors have a close relationship with the occurrence and development of various clinical diseases. This article reviews the research progress of adenosine 2A receptors in non-alcoholic fatty liver disease, acute immune hepatitis, liver ischemia-reperfusion injury, liver fibrosis, etc., in order to provide new research strategies for the prevention and treatment of these diseases.

Abelacimab for Prevention of Venous Thromboembolism.

BACKGROUND: The role of factor XI in the pathogenesis of postoperative venous thromboembolism is uncertain. Abelacimab is a monoclonal antibody that binds to factor XI and locks it in the zymogen (inactive precursor) conformation. METHODS: In this open-label, parallel-group trial, we randomly assigned 412 patients who were undergoing total knee arthroplasty to receive one of three regimens of abelacimab (30 mg, 75 mg, or 150 mg) administered postoperatively in a single intravenous dose or to receive 40 mg of enoxaparin administered subcutaneously once daily. The primary efficacy outcome was venous thromboembolism, detected by mandatory venography of the leg involved in the operation or objective confirmation of symptomatic events. The principal safety outcome was a composite of major or clinically relevant nonmajor bleeding up to 30 days after surgery. RESULTS: Venous thromboembolism occurred in 13 of 102 patients (13%) in the 30-mg abelacimab group, 5 of 99 patients (5%) in the 75-mg abelacimab group, and 4 of 98 patients (4%) in the 150-mg abelacimab group, as compared with 22 of 101 patients (22%) in the enoxaparin group. The 30-mg abelacimab regimen was noninferior to enoxaparin, and the 75-mg and 150-mg abelacimab regimens were superior to enoxaparin (P<0.001). Bleeding occurred in 2%, 2%, and none of the patients in the 30-mg, 75-mg, and 150-mg abelacimab groups, respectively, and in none of the patients in the enoxaparin group. CONCLUSIONS: This trial showed that factor XI is important for the development of postoperative venous thromboembolism. Factor XI inhibition with a single intravenous dose of abelacimab after total knee arthroplasty was effective for the prevention of venous thromboembolism and was associated with a low risk of bleeding. (Funded by Anthos Therapeutics; ANT-005 TKA EudraCT number, 2019-003756-37.).

[Evaluation of the effects auricular reconstruction with Medpor combined with hearing rehabilitation].

Objective: To investigate the clinical effects of single-stage auricular reconstruction and hearing rehabilitation in children with microtia and external auditory canal atresia. Methods: Sixty eight cases of microtia with external auditory canal atresia (53 males and 15 females, age from 7 to 12 years, with a median age of 8.8 years), who received operations in Shanghai Ninth People's Hospital, Shanghai Jiaotong University School of Medicine from July 2017 to December 2019 were collected.A total of 28 cases received auricle reconstruction with high-density polyethylene (Medpor) framework and hearing reconstructions, among which 20 patients received the traditional external auditory canal and middle ear repair (EACR), and eight patients were implanted bone conduction device bone bridge(BB) simultaneously.In the control group, 40 patients only received Medpor frame implantation for auricle plasty. Postoperative changes in auricle morphology and auditory function and postoperative complications were evaluated. Results: After three to thirty months follow-ups, the auricles shape recovered well in all three groups. The average scores of 14 fine structures in the auricles were 9.43(EACR) and 10.67(BB) points. The average score of auricle symmetry were 6.83(EACR) and 6.00(BB) points. There was no significant difference compared to the auricle reconstruction group (8.23/6.20 points). P>0.05. After surgery, the average hearing improvement in the BB group was 43.33 dB HL and the average speech recognition threshold declined 42.28 dB HL. In the EACR group, the average hearing improvement was 4.13 dB HL and the average speech recognition threshold declined 11.36 dB HL. No vertigo, tinnitus, cerebrospinal fluid leakage and other complications occurred in all the patients. In the EACR group, sensorial hearing loss, auricle stent fracture, ear canal restenosis and ear canal atresia occurred in one patient respectively. In the auricle group, one auricle stent exposure and one facial branch nerve injury occurred. Nearly ten patients had difficulty in hair growth at scalp incisions. Conclusions: The operation of single-stage auricular reconstruction and hearing rehabilitation for microtia is feasible. The methods of hearing reconstruction should be determined by evaluating the development of the inner and middle ear of the patients. For those with poor mastoid development, bone bridge implantation is recommended to achieve a stable and significant hearing effect.

[A comparative study of the effects of different treatment strategies on postoperative anal function and quality of life in patients with complete obstructive left hemicolon cancer].

Objective: To compare the effects of 3 treatment strategies (emergent surgery, self-expanding metallic stents, self-expanding metallic stents plus neoadjuvant chemotherapy) on postoperative anal function and quality of life in patients with complete obstructive left hemicolon cancer. Methods: A retrospective cohort study was conducted. Clinical data of patients with complete obstructive left hemicolon cancer admitted to General Surgery Department of Beijing Chaoyang Hospital between January 2017 and October 2019 were retrospectively collected. Patient inclusion criteria: (1) complete obstructive left hemicolon cancer was confirmed through clinical manifestation and abdominal computed tomography; (2) adenocarcinoma was confirmed by postoperative pathology; (3) emergent radical resection of primary tumor was performed with temporary stoma, or radical resection of primary tumor and primary anastomosis was performed without stoma, 7 to 14 days after completion of insertion of self-expanding metallic stents. Patients who did not receive stoma reversion after emergent operation were excluded. According to different therapies, patients were divided into three groups: emergent surgery (ES) group, self-expanding metallic stents (SEMS) group and self-expanding metallic stents plus neoadjuvant chemotherapy (SEMS+NAC) group. Wexner score for incotinence (higher score indicates the worse anal function), Vaizey score (>10 indicates fecal incontinence) and low anterior resection syndrome (LARS) scale (higher score indicates the worse anal function) were applied to evaluate anal function of patients among groups at postoperative 1-, 6- and 12-month. EORTC QLQ-C30 questionnaire was used to assess the quality of life. Risk factors of decreased anal function were identified by logistic regression analysis. Results: A total of 72 patients were enrolled, including 27 (37.5%) patients in ES group, 23 (31.9%) in SEMS group and 22 (30.6%) in SEME+NAC group. The baseline characteristics including age, gender, tumor location, comorbidities, total blood loss, operation time and postoperative complications, were comparable among groups, except that the proportion of laparoscopic surgery was significantly lower in ES group (4/27, 14.9%) than that in SEMS (15/23, 65.2%) and SEMS+NAC group (16/22, 72.7%) with significant difference (P<0.001). The follow-up ended up to October 2020, and the overall follow-up rate was 79.2% (57/72). No significant differences existed in the Wexner score of patients among groups at postoperative 1-, 6- and 12-month (all P>0.05). The Vaizey scores at postoperative 1-month in ES, SEMS and SEMS+NAC group were 7 (0-17), 3 (0-7) and 4 (0-8) respectively with significant difference (H=18.415, P=0.001), and the scores in SEMS and SEMS+NAC groups were significantly lower than that in ES group (both P<0.05), while no significant difference existed between SEMS and SEMS+NAC group (P>0.05). Vaizey scores at postoperative 6- and 12-month among 3 groups were not significantly different (both P>0.05). The LARS scores at postoperative 1-month in ES, SEMS and SEMS+NAC groups were 20 (0-37), 15 (0-24) and 16 (0-28) respectively with significant difference (H=3.660, P=0.036), and the scores in SEMS and SEMS+NAC groups were significantly lower than that in ES group (both P<0.05), while no significant difference existed between SEMS and SEMS+NAC groups (P>0.05). LARS scores at postoperative 6- and 12-month among 3 groups were not significantly different (both P>0.05). The QLQ-C30 score revealed that the social function of patients in SEMS group and SEMS+NAC group was significantly better than that in ES group (both P<0.05), while no significant difference existed between SEMS and SEMS+NAC group (P>0.05). The logistic regression analysis revealed that only ES was an independent risk factor of decreased anal function (OR=2.264, 95% CI: 1.098-4.667, P=0.027). Conclusion: Compared to ES, SEMS may improve quality of life and short-term anal function of patients with complete obstructive left hemicolon cancer.

Outcomes of obese compared to non-obese veterans undergoing open inguinal hernia repair: a case-control study.

BACKGROUND: The optimal approach for inguinal hernia repair in the obese remains elusive. Minimally invasive techniques show equivocal results compared to the open method. None of the current analyses include a non-obese control group because the differences in factors leading to complications vary widely between these two cohorts. MATERIALS AND METHODS: In the present study, we matched (1:1) obese to non-obese patients undergoing an open inguinal hernia repair. Matching was performed by age, hernia type (bilateral, inguinal, femoral, recurrent, primary, direct, pantaloon, and scrotal component), type of repair (tissue repair vs. mesh), concurrent umbilical hernia repair, current smoking, ASA Class, a history of DM and COPD. RESULTS: Demographics in the unmatched cohorts demonstrated significantly (p < 0.05) wide differences between obese (n = 319) and non-obese (n = 1137) veterans: age (58.0- vs. 63.4-year-old), indirect hernia (37.7% vs. 45.5%), scrotal component (14.4% vs. 9.9%), current smoking (23.5% vs. 34.4%), DM (20.8% vs. 13.1%), OSA (13.2% vs. 3.6%), COPD (12.2% vs. 18.5%), and BPH (16.9% vs. 23.3). After matching, there were 300 obese and 300 non-obese patients available for analysis. There was no difference in 30-day morbidity between obese and non-obese patients in the unmatched (11.0% vs. 7.9%; p = 0.09) and matched (10.7% vs. 8.1%, p = 0.27) cohorts. Similarly, no differences in inguinodynia and recurrence were observed in either matched or unmatched cohorts. CONCLUSION: Obese patients pose no further risk in outcomes compared to non-obese veterans undergoing open inguinal hernia repair. The best technique for an inguinal hernia repair in obese patients should rest on the comfort and the experience of the surgeon.

Losartan prevents bladder fibrosis and protects renal function in rat with neurogenic paralysis bladder.

AIMS: To investigate the effect of losartan on preventing bladder fibrosis and protecting renal function in rats with neurogenic paralysis bladder (NPB). MATERIALS AND METHODS: Rats were assigned to the transecting spinal nerves group (TSNG), transecting spinal nerves + losartan group (LSTG), and control group (CG). On Day 32 postsurgery, bladder capacity (BC), bladder compliance (ΔC), bladder leakage pressure (Pves.leak ) of TSNG and LSTG while BC, ΔC, and bladder threshold pressure (Pves.thre ) of CG were measured by cystometry in each cohort. Renal function and the expression quantity of Angiotensin Ⅱ (Ang II) in blood were detected, in addition Ang II, Ang II Type 1 receptor (AT1), transformation growth factor ß1 (TGFß1), Collagen Ⅲ, and collagen fibrin in the bladder tissue were detected too. RESULTS: ΔC in TSNG and LSTG decreased significantly compared to the CG. Pves.leak in TSNG and LSTG were significantly higher than Pves.thre in CG. Renal function of both TSNG and LSTG decreased significantly compared with the CG, but renal function in LSTG was better than in TSNG. Ang Ⅱ in blood and bladder tissue in TSNG and LSTG increased significantly compared with CG. AT1 was expressed in the bladder tissue of all rats. The TGFß1, Collagen Ⅲ, and collagen fibrin expression level increased significantly in TSNG compared with LSTG and CG, while these levels were not significantly different between CG and LSTG. CONCLUSION: Losartan might prevent NPB fibrosis by stopping the upregulated signaling of Ang II/AT1/TGFß1 and consequently may reduce kidney damage from occurring.

[Clinical value of extended radical resection for pT3 stage gallbladder cancer].

Objective: To investigate the clinical value of extended radical resection for stage pT3 gallbladder cancer (GBC). Methods: The clinical and pathological data of 323 patients with stage pT3 GBC who received regional radical resection or extended radical resection in 7 domestic hepatobiliary centers in China from January 2013 to December 2018 were retrospectively analyzed. The propensity score matching method was used to select 36 cases in each of the regional radical resection group (group A1) and the extended radical resection group (group B1). The surgical indicators and overall survival rates of the two groups were compared, and prognostic factors were analyzed. Results: The number of positive lymph nodes [2(0,3)] and the total number of lymph nodes removed [3(1,4)] in group B1 were both higher than those in group A1 [1(0,1), 4(2,7)] (all P<0.05). There was no significant difference in other clinical and pathological factors between the two groups (all P>0.05). The 1, 3, and 5-year survival rates of group A1 were 75%, 44%, and 29%, respectively, which were significantly higher than those of group B1 of 50%, 15%, and 11% (χ(2)=11.311, all P<0.001). Extensive radical resection (HR=2.161, 95%CI: 1.222-3.821), hepatic parenchymal invasion (HR=2.324, 95%CI: 1.305-4.139), positive lymph node rate ≥1/3 (HR=2.927, 95%CI: 1.641-5.220), and ⅢB/ⅣB staging (HR=3.325, 95%CI: 1.750-6.320) are risk factors for the prognosis of GBC patients (all P<0.05), of which extended radical resection (HR=1.969, 95%CI: 1.083-3.581) was an independent risk factor for prognosis (P<0.05). When the ratio of positive lymph nodes was<1/3 and the tumor invaded the hepatic parenchyma, the overall survival rate of group B1 was significantly lower than that of group A1 (all P<0.05). Conclusions: The overall survival rate in patients with stage pT3 GBC whose lymph node positive rate<1/3 and/or hepatic parenchymal invaded cannot be improved by extended radical resection. Extended radical resection is an independent risk factor for patient prognosis.

Development and validation of a staging system for gastric adenocarcinoma after neoadjuvant chemotherapy and gastrectomy with D2 lymphadenectomy.

BACKGROUND: Neoadjuvant chemotherapy followed by gastrectomy with D2 lymphadenectomy is commonly used for patients with locally advanced gastric adenocarcinoma. The eighth AJCC ypTNM staging system was validated based on patients undergoing more limited lymphadenectomy (less than D2). The aim of this study was to develop a system for accurate staging of patients with locally advanced gastric adenocarcinoma who receive neoadjuvant chemotherapy followed by gastrectomy with D2 lymphadenectomy. METHODS: A modified system of ypTNM was developed, based on overall survival (OS) of patients receiving neoadjuvant chemotherapy followed by gastrectomy with D2 lymphadenectomy at Memorial Sloan Kettering Cancer Center, and validated using data from an international cohort of patients who had similar treatment. RESULTS: Of 325 patients in the derivation cohort, 33 (10·2 per cent) had ypT0 N0/+ tumours, which are not classifiable under the AJCC system. The 5-year OS rate for modified ypTNM stages I, II, IIIA and IIIB was 89, 71, 42·3 and 10 per cent respectively, compared with 82, 65·2 and 24·1 for AJCC stages I, II and III respectively. The concordance index (0·730 versus 0·709), estimated area under the curve (0·765 versus 0·740) and time-dependent receiver operating characteristic (ROC) curve throughout the observation period were all superior for modified ypTNM staging. For the validation cohort of 186 patients, the modified system was again better at separating patients into prognostic groups for OS. CONCLUSION: The modified ypTNM staging system improves the accuracy of OS prediction for patients treated with neoadjuvant chemotherapy followed by gastrectomy with D2 lymphadenectomy.

EphrinB2/EphB4 Signaling Regulates DPSCs to Induce Sprouting Angiogenesis of Endothelial Cells.

Dental pulp stem cells (DPSCs) are capable of facilitating angiogenesis resembling pericytes when located adjacent to endothelial cells (ECs). Nevertheless, the precise mechanisms orchestrating their proangiogenic functions remain unclear. Using a 3-dimensional (3-D) fibrin gel model, we aimed to investigate whether EphrinB2/EphB4 signaling in DPSCs plays a role in supporting vascular morphogenesis mediated by ECs, together with the underlying mechanism involved. The EphrinB2/EphB4 signaling was inhibited either by a pharmacological inhibitor of EphB4 receptor or by knocking down the expressions of EphrinB2 and EphB4 using lentiviral small hairpin RNA (shRNA). DPSCs were either encapsulated in fibrin gel together with human umbilical vein endothelial cells (HUVECs) or cultured as a monolayer on top of HUVECs to investigate both paracrine and juxtacrine interactions simultaneously. Following 10 d of direct coculture, we found that pharmacological inhibition of EphrinB2/EphB4 signaling severely impaired vessel formation and laminin deposition. When directly cocultured with HUVECs, knockdown of EphrinB2 or EphB4 in DPSCs significantly inhibited endothelial sprouting, resulting in less capillary sprouts with reduced vessel length (P < 0.05). By contrast, when DPSCs were not in direct contact with HUVECs, attenuation of EphrinB2 or EphB4 expression levels in DPSCs did not exert any significant effects on capillary morphogenesis. Noticeably, exogenous stimulation with soluble EphrinB2-Fc or EphB4-Fc (1 µg/mL) enhanced vascular endothelial growth factor (VEGF) secretion from DPSCs, thereby moderately promoting angiogenic cascades in the fibrin matrix. This study, for the first time, reveals a crucial role of EphrinB2/EphB4 signaling in regulating the capacity of DPSCs to induce sprouting angiogenesis. These findings advance our understanding of postnatal angiogenesis and may have future regenerative medicine applications.

[Accuracy analysis of computer assisted navigation for condylectomy via intraoral approach].

OBJECTIVE: To explore the application accuracy of virtual preoperative plan after the condylectomy via intraoral approach under computer assisted surgical navigation, and to analyze the location and cause of the surgical deviation to provide reference for the surgical procedure improvement in the future. METHODS: In the study, 23 cases with condylar hypertrophy (11 with condylar osteochondroma and 12 with condylar benign hypertrophy) in Department of Oral and Maxilloficial Surgery, Peking University School and Hospital of Atomatology from December 2012 to December 2016 were treated by condylectomy via intraoral approach under computer assisted surgical navigation. The patient's spiral CT data were imported into ProPlan software before operation, and the affected mandibular ramus was reconstructed three-dimensionally. The condylar osteotomy line was designed according to the lesion range, and the preoperative design model was generated and introduced into the BrainLab navigation system. Under the guidance of computer navigation, the intraoral approach was used to complete the condylar resection according to the preoperative design of the osteotomy line. Cranial spiral CT of the craniofacial region was taken within one week after operation. three-dimensional reconstruction of the mandibular ramus at the condylectomy side was performed, and the condylar section was divided into six segments (anterolateral, anterior, anteromedial, posteromedial, posterior, and posterolateral) and the corresponding regional measurement points P1 to P6 were defined. Then the preoperative virtual model and the postoperative actual model were matched by Geomagic studio 12.0 to compare the differences and to analyze the accuracy of the operation. RESULTS: All the patients had successfully accomplished the operation and obtained satisfactory results. Postoperative CT showed that the condyle lesion was completely resected, and the condylar osteotomy line was basically consistent with the surgical design. No tumor recurrence or temporomandibular joint ankylosis during the follow-up period. The postoperative accuracy analysis of the condylar resection showed that the confidence intervals measured by the six groups of P1 to P6 were (-2.26 mm, -1.89 mm), (-2.30 mm, -1.45 mm), (-3.37 mm, -2.91 mm), (-2.83 mm, -1.75 mm), (-1.13 mm, 0.99 mm), and(-1.17 mm, 0.17 mm), where P3 group was different from the other 5 groups. There was no significant difference between the P5 and P6 groups and the difference between the other four groups was statistically significant. CONCLUSION: Under the guidance of computer navigation, the intraoral approach can be performed more accurately. The surgical deviation of each part of the osteotomy surface is mainly due to excessive resection. The anterior medial area of the anterior medial condyle represents the most excessive resection. The posterior and posterior lateral measurement points represent the posterior condylar area. The average deviation is not large, but the fluctuation of the deviation value is larger than that of the other four groups. The accuracy of computer-assisted subtotal resection has yet to be improved.

Correction: Perinatal Choline Supplementation Reduces Amyloidosis and Increases Choline Acetyltransferase Expression in the Hippocampus of the APPswePS1dE9 Alzheimer's Disease Model Mice.

[This corrects the article DOI: 10.1371/journal.pone.0170450.].

Perinatal Choline Supplementation Reduces Amyloidosis and Increases Choline Acetyltransferase Expression in the Hippocampus of the APPswePS1dE9 Alzheimer's Disease Model Mice.

Prevention of Alzheimer's disease (AD) is a major goal of biomedical sciences. In previous studies we showed that high intake of the essential nutrient, choline, during gestation prevented age-related memory decline in a rat model. In this study we investigated the effects of a similar treatment on AD-related phenotypes in a mouse model of AD. We crossed wild type (WT) female mice with hemizygous APPswe/PS1dE9 (APP.PS1) AD model male mice and maintained the pregnant and lactating dams on a control AIN76A diet containing 1.1 g/kg of choline or a choline-supplemented (5 g/kg) diet. After weaning all offspring consumed the control diet. As compared to APP.PS1 mice reared on the control diet, the hippocampus of the perinatally choline-supplemented APP.PS1 mice exhibited: 1) altered levels of amyloid precursor protein (APP) metabolites-specifically elevated amounts of ß-C-terminal fragment (ß-CTF) and reduced levels of solubilized amyloid Aß40 and Aß42 peptides; 2) reduced number and total area of amyloid plaques; 3) preserved levels of choline acetyltransferase protein (CHAT) and insulin-like growth factor II (IGF2) and 4) absence of astrogliosis. The data suggest that dietary supplementation of choline during fetal development and early postnatal life may constitute a preventive strategy for AD.

[Imaging analysis of temporomandibular joint anatomy changes after intraoral condylectomy combined with orthognathic surgery].

OBJECTIVE: To quantitatively analyze the changes of facial symmetry and temporomandibular joint structure at different periods after intraoral condylectomy combined with orthognathic surgery, and to evaluate the long-term stability after the operation. METHODS: Spiral CT data of 10 cases treated by intraoral condylectomy combined with orthognathic surgery were collected, and then reconstructed by ProPlan software. Mark points were drawn on the 3D-images reconstructed immediately after the operation, and 6 months and 12 months after the operation. The measurements parameters included condylar axis angle in three dimensions, condylar-glenoid relative position and condylar facial morphology related indicators. The results were statistically analyzed by the consistency test and the variance of repeated measurement data. RESULTS: The facial asymmetry of the patients was corrected after operation, the height of the affected mandibular ascending ramus(T1: [67.81±6.95]mm, T2: [64.49±6.24]mm, T3: [63.05±7.07]mm)as well as the degree of pogonion deviation decreased(T1: [2.79±4.93]mm, T2: [0.37±4.20]mm, T3: [0.33 ± 3.97]mm)(P<0.05). But the tilt angle of the occlusion plane and the degree of mandibular height asymmetry had no significant difference between all the post-operative periods(P>0.05). The post-operative 3D changes of the position and shape of the resected and its contralateral condylar showed that the bilateral condylar axis angle in the horizontal plane gradually grew after operation(affected condyle: 71.95° ± 7.47°, 74.73°±8.44°, 76.56°±5.22°; control condyle: 72.60°±5.56°, 76.00°±5.30°, 77.19°±6.20° and had significant difference between all the post-operative periods)(P<0.05), the condyle moved slowly upward on both sides(superior space on the affected side: [8.78±4.38]mm, [4.11±2.49]mm, [3.27±1.96]mm; on the control side: [3.63±1.49]mm, [2.52±1.19]mm, [2.38±1.11]mm)(P<0.05), and moved inward only on the affected side(P< 0.05). All the above changes slowed down over time, and the disc-condyle-fossa relative position tended to be stable over time as well. The condyle diameter on the inside-outside direction gradually decreased on the affected side(T1: [14.98±2.39]mm, T2: [14.04±2.68]mm, T3: [13.74±2.89]mm)(P<0.05), and the surface morphology of the resected condyle was similar to the normal side. There were also some condylar surface morphological changes on the control side, but no statistical significance was found between different periods after the peration(P>0.05). CONCLUSIONS: The intraoral condylectomy combined with orthognathic surgery can eliminate condylar lesions effectively and correct the facial asymmetry caused by condylar benign tumor and hyperplasia. The facial symmetry can be maintained well after the operation, and the post-operative condylar morphology changes tended to be stable six months after the operation.

[Feasibility of integrating 3D photos and cone-beam computed tomography images used to evaluate changes of soft and hard tissue after orthognathic surgery].

OBJECTIVE: To evaluate the feasibility of integrating 3D photos and cone-beam computed tomography (CBCT) images and to assess the degree of error that may occur during the above process, and to analyze soft and hard tissue changes after orthognathic surgery using this new method. METHODS: Ten patients with maxillofacial deformities were chosen. For each patient, CBCT scans and stereophotographic images were taken before and 3 months after surgery. 3D photos were superimposed onto the CBCT skin images using relatively immobile areas of the face as a reference. 3D color maps and mean distances were used to evaluate the errors that might occur during the process. Two reference planes were set up using certain points. The distances between Prn (pronasale),Sn (subnasale),Ls (labrale superior),ANS (anterior nasal spine),A (subspinale),UIE (upper incisor edge) to the coronal plane were calculated before and after surgery. In order to verify the repeatability of this method, we examined the distances twice at two-week intervals. Paired t test was used to evaluate the reproducibility. RESULTS: CBCT and 3D photos could be successfully fused with clinically acceptable errors. This new method could be used to evaluate soft and hard tissue changes after orthognathic surgery. The 3D color maps showed that the two images could be fused with minimal errors. The mean distances were within 0.3 mm, and the locations of landmarks on maxilla and mandible such as Ls, ANS, A, UIE changed significantly after orthognathic surgery (P<0.05).Landmarks on the nose such as Prn,Sn had little changes after surgery (P>0.1). The paired t test showed that the mean value and standard deviation were (0.08±0.98) mm. CONCLUSION: Fusing of CBCT and 3D stereophotographic images used as a new method in evaluating soft and hard tissue changes after orthognathic surgery was feasible and accurate. The virtual 3D composite craniofacial models permitted concurrent assessment of hard and soft tissues during diagnosis and treatment planning. Maxillary and mandibular locations had significant association with orthoganthic surgery while the nasal tissue was not simp affected by surgery.

[Transpalatal modified Le Fort I osteotomy for correction of maxillary hypoplasia in cleft lip and palate patients: a preliminary clinical application].

OBJECTIVE: To evaluate the surgical corrective results of maxillary hypoplasia in patients with cleft lip and palate withtranspalatal modified Le Fort I osteotomy. METHODS: In the study, 11 patients (4 women, and 7 men) with maxillary hypoplasia secondary to cleft lip and palate underwent transpalatal modified Le Fort I osteotomy at Peking University School of Stomatology from Jan. 2012 to Dec. 2013,with the mean age of 21 years ( from 18 to 27 years), Bilateral sagittal split ramus osteotomy (BSSRO)and genioplasty were performed simultaneously in 9 of them for better appearance and functional occlusion. Lateral cephalometric radiographs were taken and traced before surgery, immediately after surgery and 6 months after surgery. The position of subspinale (A) on horizontal direction, the angle of sella-nasion-subsipmale (SNA) and the angle of sella-nasion-supramental (SNB) were collected and analyzed to evaluate the results. RESULTS: All the patients were uneventful with transpalatal modified Le Fort I osteotomy. All of them had a better profile and a satisfactory occlusionafter operation.The position of A was moved forward (6.6±1.1) mm on average in horizontal direction when surgery was completed, and maintained (6.0±1.2) mm on average 6 months after surgery. The average of SNA was 75.9°±2.8° before surgery,81.6°±8.6° immediately after surgery, and maintained 81.0°±2.6° 6 months after surgery. The average of SNB was 82.6°±3.7° before surgery, 78.0°±2.4° immediately after surgery, and maintained 78.5°±2.4° 6 months after surgery. CONCLUSION: The maxillary hypoplasia in cleft lip and palate patients can be successfully corrected with transpalatal modified Le Fort I osteotomy and the functional occlusion can be achieved simultaneously. The effect of deformity correction was satisfactory. Transpalatal modified Le Fort I osteotomy can move maxilla more sufficiently, especially applicable for the patient with severe palatal scars preoperatively.