[Three-dimensional finite element analysis of traumatic mechanism of mandibular symphyseal fracture combined with bilateral intracapsular condylar fractures].

OBJECTIVE: To analyze the biomechanical mechanism of mandibular symphyseal fracture combined with bilateral intracapsular condylar fractures using finite element analysis (FEA). METHODS: Maxillofacial CT scans and temporomandibular joint (TMJ) MRI were performed on a young male with normal mandible, no wisdom teeth and no history of TMJ diseases. The three-dimensional finite element model of mandible was established by Mimics and ANSYS based on the CT and MRI data. The stress distributions of mandible with different angles of traumatic loads applied on the symphyseal region were analyzed. Besides, two models with or without disc, two working conditions in occlusal or non-occlusal status were established, respectively, and the differences of stress distribution between them were compared. RESULTS: A three-dimensional finite element model of mandible including TMJ was established successfully with the geometry and mechanical properties to reproduce a normal mandibular structure. Following a blow to the mandibular symphysis with different angles, stress concentration areas were mainly located at condyle, anterior border of ramus and symphyseal region under all conditions. The maximum equivalent stress always appeared on condylar articular surface. As the angle between the external force and the horizontal plane gradually increased from 0° to 60°, the stress on the mandible gradually concentrated to symphysis and bilateral condyle. However, when the angle between the external force and the horizontal plane exceeded 60°, the stress tended to disperse to other parts of the mandible. Compared with the condition without simulating the disc, the stress distribution of articular surface and condylar neck decreased significantly when the disc was present. Compared with non-occlusal status, the stress on the mandible in occlusal status mainly distributed on the occlusal surface, and no stress concentration was found in other parts of the mandible. CONCLUSION: When the direction of external force is 60° from the horizontal plane, the stress distribution mainly concentrates on symphyseal region and bilateral condylar surface, which explains the occurrence of symphyseal fracture and intracapsular condylar fracture. The stress distribution of condyle (including articular surface and condylar neck) decreases significantly in the presence of arti-cular disc and in stable occlusal status when mandibular symphysis is under traumatic force.

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.

[Three-dimensional imaging study on the anatomical morphology of trabecular bone of the condyle based on the distribution of volume of interests].

Objective: To analyze the anatomical morphological characteristics of the trabecular bone of human mandibular condyle by observing the distribution of volume of interests (VOI). Methods: The micro-CT images of a right condyle specimen of a 61-year-old adult male was analyzed in this study. The cylindrical VOI with both diameter and height of 2 mm were arranged, according to a certain pattern, as many as possible at various levels within the trabecular bone of the condyle. Each VOI had no intersection area. The selected VOI were divided into 5 parts: medial part, middle part, lateral part, anterior part and posterior part, with 6 layers from top to bottom. And the distribution of the overall anatomical morphological characteristics of three-dimensional (3D) images of the trabecular bone of the condyle was analyzed by using seven morphological parameters of each VOI, i.e. bone mineral density (BMD), bone volume/total volume (BV/TV), bone surface area/bone volume (BS/BV), trabecular thickness (Tb.Th), trabecular bone number (Tb.N), trabecular spacing (Tb.Sp) and trabecular bone pattern factor (Tb.Pf). Results: In the present study, totally 34 VOI were selected from the condyle specimen.The morphological distribution of the VOI was uneven in the 3D structure of the trabecular bone of the human condyle. BMD, BV/TV, Tb.N and Tb.Th were much higher at the middle part, while showed the smallest at the medial part. The anterior part demonstrated much higher parameters than the posterior part at the first, second, fifth and sixth layers, respectively, however, the posterior part showed much higher parameters than the anterior part at the third and fourth layers, respectively. The BMD was much higher at the first [(332.66±97.11) mg/cm3] and sixth [(255.79±45.68) mg/cm3] layers, while the lowest at the second layer [(255.79±41.06) mg/cm3]. The BV/TV and Tb.N were much higher at the first layer, with the lowest at the fifth layer. The Tb.Th at the first layer [(0.11±0.03) mm] was much higher than the others, which were similarly lower. The BS/BV, Tb.Sp and Tb.Pf were lower at the first layer and much higher at the medial and lateral parts, while were lower at the middle and anterior parts. The posterior part demonstrated much higher BS/BV, Tb.Sp and Tb.Pf than the anterior part at the first, fifth and sixth layers, respectively. However, the anterior part showed much higher scores than the posterior part at the third and fourth layers, respectively. The ANOVA results showed that the 7 morphological parameters of VOI were not statistically significant amongst the 6 layers (P>0.05). However, the 6 out of the 7 parameters, i.e. BV/TV, BS/BV, Tb.Th, Tb.N, Tb.Sp and Tb.Pf, were statistically significant amongst the five parts (P<0.05), while the only parameter of BMD was not statistically significant (P>0.05). Conclusions: The anatomical distribution characteristics of the trabecular bone of condyle were analyzed by using 3D imaging measurement based on the VOI. The results showed uneven distributions and indicated that the method of dividing the trabecular bone of mandibular condyle into VOI sets, which accorded with its specific anatomical characteristics, was feasible for further reference.

A newborn with coronavirus (COVID-19) disease: A brief report.

There are few neonates reported with COVID-19 disease. To date there is no clear evidence of vertical transmission of the virus before birth. We report a 4-day old infant born to an asymptomatic mother who developed infection with SARS-CoV-2, likely from contact with parents during the postnatal period.

[Clinical features and outcomes of cancer-related versus non-cancer-related sepsis in pediatric intensive care unit].

Objective: To compare the clinical features and outcomes of cancer-related and non-cancer-related sepsis in children who were admitted pediatric intensive care unit (PICU). Methods: The clinical history of patients with sepsis, who were admitted to PICU in Shanghai Children's Hospital, Shanghai Jiao Tong University from August 2016 to July 2019, were retrospectively reviewed. A total of 768 patients were divided into the cancer-related sepsis group (135 cases) and the non-cancer-related sepsis group (633 cases). The patients in the cancer-related group were further categorized into three subgroups including hematological malignancy (80 cases), solid tumor (43 cases) and hemophagocytic lymphohistiocytosis (HLH) (12 cases). The variables of clinical features, laboratory tests, pathogens, management strategies and in-hospital mortality were compared between the two groups by student t test, Mann-Whitney U test or Chi-square test. Results: The patients with cancer-related sepsis accounted for 17.6% of all patients (135/768). Regarding the site of initial infection, the incidence of gastrointestinal infection (43.0% (58/135) vs. 28.6% (181/633), χ(2)=10.718, P=0.001), blood stream infection (29.6% (40/135) vs. 17.1% (108/633), χ(2)=11.297, P=0.001) and skin and soft tissue infection (22.2% (30/135) vs. 4.1% (26/633), χ(2)=54.013, P<0.01) were higher in the patients with cancer-related sepsis than in those with non-cancer-related sepsis. On first PICU admission, the levels of hemoglobin (71 (61, 83) vs. 106 (92, 116) g/L, Z=13.594, P<0.01), white blood cell (1.4 (0.3, 5.2) vs. 9.8 (5.8, 15.1)×10(9)/L, Z=11.213, P<0.01), platelet count (51 (15, 121) vs. 286 (192, 384)×10(9)/L, Z=13.336, P<0.01), CD19(+)cells (0.106 (0.008, 0.274) vs. 0.325 (0.224, 0.454), Z=6.555, P<0.01), and neutrophil (0.449 (0.170, 0.730) vs. 0.683 (0.537, 0.800), Z=5.974, P<0.01) were significantly lower in patients with cancer-related sepsis; however, the levels of C-reactive protein (82 (25, 155) vs. 36 (11, 86) mg/L, Z=-5.257, P<0.01), procalcitonin (1.5 (0.3, 12.0) vs. 0.8 (0.2, 4.0) µg/L, Z=-2.767, P=0.006), CD8(+)cells (0.329 (0.253, 0.514) vs. 0.209 (0.156, 0.275), Z=-5.699, P<0.01), interleukin (IL) -6 (0.1 (0.1, 522.4) vs. 0.1 (0.1, 0.1) ng/L, Z=-2.747, P=0.006), IL-8 (0.1 (0.1, 177.0) vs. 0.1 (0.1, 4.5) ng/L, Z=-2.087, P=0.037), and IL-10 (0.1 (0.1, 42.7) vs. 0.1 (0.1, 6.6) ng/L, Z=-2.148, P=0.032) were significantly higher in patients with cancer-related sepsis. Similarly, the rate of continuous renal replacement therapy (CRRT) (34.8% (47/135) vs. 16.9% (107/633), χ(2)=26.267, P<0.01) and the use of intravenous immunoglobulin (IVIG) (83.0% (112/135) vs. 66.2% (419/633), χ(2)=14.667, P<0.01) were significantly higher in cancer-related sepsis group. Moreover, the incidence of co-infection with fungi was also higher in cancer-related sepsis group (14.1% (19/135) vs. 0.5%(3/633), χ(2)=73.965, P<0.01), and so was the number of multiple organ dysfunction (3 (2, 5) vs. 2 (1, 3), Z=-6.988, P<0.01). Finally, the in-hospital mortality rate of cancer-related sepsis and non-cancer-related sepsis were 36.3% (49/135) and 9.3% (59/633), respectively, also significantly different (χ(2)=67.000, P<0.01). There was no difference in the in-hospital mortality among children with hematologic tumors, solid tumors and HLH (35.0% (28/80) vs. 32.6% (14/43) vs. 7/12, χ(2)=2.838, P=0.242). Conclusions: The site of initial infection, inflammatory markers on PICU admission, and co-infection pathogen during hospitalization are different between patients with cancer-related sepsis and non-cancer-related sepsis. Besides, the in-hospital mortality of cancer-related sepsis is about 4-fold that of non-cancer-related sepsis. The monitoring of clinical features and organ dysfunction, and timely treatment are crucial for cancer-related sepsis.

[Stress change of periodontal ligament of the anterior teeth at the stage of space closure in lingual appliances: a 3-dimensional finite element analysis].

OBJECTIVE: To analyze the stress distribution in the periodontal ligament (PDL) under different loading conditions at the stage of space closure by 3D finite element model of customized lingual appliances. METHODS: The 3D finite element model was used in ANSYS 11.0 to analyze the stress distribution in the PDL under the following loading conditions: (1) buccal sliding mechanics (0.75 N,1.00 N,1.50 N), (2) palatal sliding mechanics (0.75 N,1.00 N,1.50 N), (3) palatal-buccal combined sliding mechanics (buccal 1.00 N + palatal 0.50 N, buccal 0.75 N + palatal 0.75 N, buccal 0.50 N+ palatal 1.00 N). The maximum principal stress, minimum principal stress and von Mises stress were evaluated. RESULTS: (1) buccal sliding mechanics(0.75 N,1.00 N,1.50 N): maximum principal stress: at the initial of loading, maximum principal stress, which was the compressed stress, distributed in labial PDL of cervix of lateral incisor, and palatal distal PDL of cervix of canine. With increasing loa-ding, the magnitude and range of the stress was increased. Minimum principal stress: at the initial of loading, minimum principal stress which was tonsil stress, distributed in palatal PDL of cervix of lateral incisor and mesial PDL of cervix of canine. With increasing loading, the magnitude and range of minimum principal stress was increased. The area of minimum principal stress appeared in distal and mesial PDL of cervix of central incisor. von Mises stress:it distributed in labial and palatal PDL of cervix of lateral incisor and distal PDL of cervix of canine initially. With increasing loading, the magnitude and range of stress was increased towards the direction of root. Finally, there was stress concentration area at mesial PDL of cervix of canine. (2) palatal sliding mechanics(0.75 N,1.00 N,1.50 N): maximum principal stress: at the initial of loading, maximum principal stress which was the compressed stress, distributed in palatal and distal PDL of cervix of canine, and distal-buccal and palatal PDL of cervix of lateral incisor. With increasing loading, the magnitude and range of the stress was increased. Minimum principal stress: at the initial of loading, minimum principal stress which was tonsil stress, distributed in distal-interproximal PDL of cervix of lateral incisor and mesial-interproximal PDL of cervix of canine. With increasing loading, the magnitude and range of the stress was increased.von Mises stress: von Mises stress distributed in palatal and interproximal PDL of cervix of canine. With increasing loading, the magnitude and range of stress was increased. Finally, von Mises stress distributing area appeared at distal-palatal PDL of cervix of canine. (3) palatal-buccal combined sliding mechanics: maximum principal stress: maximum principal stress still distributed in distal-palatal PDL of cervix of canine. Minimum principal stress: minimum principal stress distributed in palatal PDL of cervix of lateral incisor when buccal force was more than palatal force. As palatal force increased, the stress concentrating area transferred to mesial PDL of cervix of canine.von Mises stress: it was lower and more well-distributed in palatal-buccal combined sliding mechanics than palatal or buccal sliding mechanics. CONCLUSION: Using buccal sliding mechanics,stress majorly distributed in PDL of lateral incisor and canine, and magnitude and range of stress increased with the increase of loading; Using palatal sliding mechanics, stress majorly distributed in PDL of canine, and magnitude and range of stress increased with the increase of loading; With palatal-buccal combined sliding mechanics, the maximum principal stress distributed in the distal PDL of canine. Minimum principal stress distributed in palatal PDL of cervix of lateral incisor when buccal force was more than palatal force. As palatal force was increasing, the minimum principal stress distributing area shifted to mesial PDL of cervix of canine. When using 1.00 N buccal force and 0.50 N palatal force, the von Mises stress distributed uniformly in PDL and minimal stress appeared.

[Construction and assessment of a three-dimensional finite element model of mandibualr second molar mesialization using customized lingual appliance and mini-implant].

Objective: To construct a three-dimensional (3D) finite element model and analyze the biomechanical characteristics during mandibular second molar mesialization using customized lingual appliances and mini-implant. Methods: One adult student volunteer from The First Affiliated Hospital of Zhengzhou University with lower left first molar extraction was selected. After CT scanning, Mimics, Geomagic, ANSYS were employed to develop a 3D finite element model including customized lingual brackets, stainless steel lingual arch wire, buccal buckles, lower dentition, periodontal ligaments and alveolar bone. Four different loading methods (1. the force of 1.470 N loaded at the lingual side only; 2, 3, 4. the forces of 0.490, 0.735 and 0.980 N loaded at both buccal and lingual sides, respectively.) were included. The initial displacements of the lower second molar and stress distribution in the periodontal ligaments were analyzed. Results: More uniform stress distributions in the periodontal membrane of mandibular left second molar were found when the mesial force were loaded at both buccal and lingual sides than the force loaded at lingual side only. More inclination of the second molar was observed when force loaded at both sides than at lingual side only. With the values of the force increased, the mesial inclination potential of the second molar, the initial movement of the second molar and the stress distribution in the periodontal membrane increased. Under the force of 0.735 N at both buccal and lingual sides, mesially inclined initial displacements of the mandibuar second molar were observed and the stress values of von Mises was in the suitable area. Conclusions: Less second molar rotation was found when the force loaded at both buccal and lingual sides than loaded at lingual side only. However, force loaded at both sides would increase the measial inclination potential of the second molar.

[The role of postmastectomy radiotherapy in clinical T1-3N1M0 breast cancer patients with pathological negative lymph nodes after neoadjuvant chemotherapy and mastectomy].

Objective: To analyze the outcomes of clinical T1-3N1M0 breast cancer patients with pathological negative axillary lymph nodes (ypN0) after neoadjuvant chemotherapy (NAC) and mastectomy, and investigate the role of postmastectomy radiotherapy (PMRT). Methods: A total of 185 patients with clinical T1-3N1M0 breast cancer treated between 1999 and 2013 were retrospectively reviewed. All patients were treated with NAC and mastectomy, and achieved ypN0. Of them, 89 patients received additional PMRT and 96 patients did not. 101 patients had clinical stage Ⅱ disease. 84 patients had clinical stage Ⅲ disease. The rates of locoregional recurrence (LRR), distant metastasis (DM), disease-free survival (DFS), and overall survival (OS) were calculated using the Kaplan-Meier method, and differences were compared using the log-rank test. Univariate analysis was used to interpret the impact of clinical features and treatment on patients' outcome. Results: The 5-year rates of LRR, DM, DFS, and OS for all patients were 4.5%, 10.4%, 86.6%, and 97.1%, respectively. For patients with and without PMRT, the 5-year LRR rates were 1.1% and 7.5% (P=0.071), the 5-year DM rates were 5.1% and 15.0% (P=0.023), the 5-year DFS rates were 95.0% and 79.0% (P=0.008), and the 5-year OS rates were 100.0% and 94.5% (P=0.089) respectively. In univariate analysis, lymph-vascular space invasion (LVSI) was poor prognostic factor of LRR (P=0.001), < 40 years old and lack of PMRT was a poor prognostic factor for DM (P<0.05), lack of PMRT was a poor prognostic factor for DFS (P=0.008), primary lesion residual and mild-moderate pathological response to NAC were poor prognostic factors for OS (P<0.05). In the subgroup of Stage Ⅲ disease, for patients with and without PMRT, the 5-year LRR rates were 1.9% and 14.4% (P=0.041), the 5-year DFS rates were 91.9% and 67.4% (P=0.022), respectively. In the subgroup of Stage Ⅱ disease, for patients with and without PMRT, the 5-year DM rates were 0 and 11.5% (P=0.044), the 5-year DFS rates were 100.0% and 84.9% (P=0.023), respectively. Conclusions: The LRR rate of clinical T1-3N1M0 breast cancer patients who achieved ypN0 after NAC and mastectomy was low. PMRT decreased the DM rate and increased DFS rate in all patients, and significantly decreased the LRR rate in Stage Ⅲ disease. PMRT should be considered for patients with Stage Ⅲ disease, and further research is warranted to investigate the benefit of PMRT for Stage Ⅱ disease.

[Efficacy of continuous blood purification in treatment of severe acute pancreatitis in children].

Objective: To explore the therapeutic role of bedside continuous blood purification(CBP) in children with severe acute pancreatitis(SAP). Method: The clinical and laboratory data of 11 children with SAP who were admitted to Pediatric Intensive Care Unit (PICU) of Shanghai Children's Hospital from June 2013 to May 2016 were analyzed, including using pediatric critical illness score (PCIS) and pediatric risk of score mortality (PRISM)-Ⅲ score to assessing the severity of the disease.For those patients with severe organ dysfunction, CBP treatment was used when conventional therapy was not efficient.The evolution and prognosis of the disease were observed and analyzed.The measurement data were analyzed by Wilcoxon signed rank test. Result: From June 2013 to May 2016, 11 cases with SAP were treated in PICU, of whom 7 cases had combined multiple organ dysfunction syndrome(MODS). After conservative treatment for 12-24 h, 6 cases with SAP deteriorated aggressively and were treated with CBP.PRISMA and PRISMA flex machines were used with Gambro PRISMA filter, and continuous venovenous hemodiafiltration(CVVHDF) or high volume hemofiltration (HVHF) were chosen as the therapy model.All 6 SAP patients survived after bedside CBP treatment(the median time spent on CBP were 48.5(48.0, 55.5) h). The serum concentration of amylase before and after the CBP treatment were respectively 675(495, 1 334)vs.176(136, 246) U/L, lipase 551(385, 1 075)vs.143(117, 185) U/L, CRP 168(125, 192) vs. 67(28, 87) mg/L, and inflammatory cytokines(TNF alpha 67.2(51.0, 72.9)vs. 22.6(19.3, 31.0) ng/L, IL-6 47.8(35.2, 88.4)vs. 23.6(20.3, 42.9) ng/L, IL-10 21.3(16.8, 23.9)vs. 35.6(26.5, 38.6) ng/L), which were obviously improved after CBP treatment(all P<0.05). And after CBP treatment, partial pressure of oxygen(PaO(2))/fraction of inspiration O(2)(FiO(2)) (192(101, 208)and 240(207, 267) mmHg, 1 mmHg=0.133 kPa), MAP (58.3(56.3, 62.5) and 83.3(74.0, 87.4) mmHg) and PCIS scores (66(62.5, 72)and 92(89, 94) scores) were higher (all P<0.05). Conclusion: CBP in critically ill with SAP can rapidly reduce blood amylase and lipase, help to keep the stable internal environment, block the systemic inflammatory response, improve the organ functions and maintain the fluid balance.CBP treatment may be a potential therapy in children with SAP.

[Prognostic value of sequencing of radiotherapy and chemotherapy following breast-conserving surgery for patients with breast cancer].

Objective: To evaluate the prognostic value of sequencing of adjuvant radiotherapy and chemotherapy following breast-conserving surgery for patients with breast cancer. Methods: A total of 1 154 patients withT1-2N0-3M0 breast cancer retrospectively reviewed. All patients received sequential radiotherapy and chemotherapy following breast-conserving surgery. Among them, 603 patients received radiotherapy first and 551 patients received chemotherapy first. Log-rank tests were used to determine significance of disease-free survival (DFS) and overall survival (OS) rates in the Kaplan-Meier curve. Results: The 5-year DFS and OS rates for all patients were 93.0% and 97.8%. The 5-year OS rate was 98.6% in the radiotherapy first group and 96.4% in the chemotherapy first group (P=0.191), and the corresponding DFS rate was 92.7% and 93.2% (P=0.430), respectively. Among the patients with Luminal A subtype, the 5-year OS rate was 99.6% in the radiotherapy first group and 97.8% in the chemotherapy first group (P=0.789). Among the patients with Luminal B subtype, the 5-year OS rate was 94.2% and 96.0%, respectively (P=0.680). Among the patients with triple negative breast cancer, the 5-year OS rate was 100% and 90.9%, respectively, with statistically significant differences (P=0.019). Among the patients with HER-2 positive breast cancer, The 5-year DFS rate was 80.1% and 100%, respectively (P=0.045). Conclusions: The OS and DFS rates in the chemotherapy first group are not significantly different from those of radiotherapy first group after breast-conserving surgery. Patients with HER-2 positive breast cancer in chemotherapy first group have a much higher DFS rate than that of radiotherapy first group, whereas patients with triple negative breast cancer in radiotherapy first group have a better OS rate than that of chemotherapy first group. Further research is warranted to investigate the benefit of different molecular types in different sequencing of radiotherapy and chemotherapy after breast-conserving surgery.

[Study on apoptosis mechanism of H9c2 cardiomyocytes induced by N, N-dimethylformamide].

Objective: To observe the change levels of nuclear factor-kappa B (NF-κB) p65 protein in cytoplasm and nuclear, phosphorylation of inhibitor of kappa B (p-IκB) protein and cytochrome C (Cyt-c) , cleaved cysteinyl aspartate specific proteinase-3 (Cleaved caspase-3) , B-cell lymphoma/leukemia-2 (Bcl-2) in cytoplasm in the process of N, N-dimethylformamide (DMF) -induced apoptosis in H9c2 cardiomyocytes, and explore the tentative mechanism of apoptosis. Methods: H9c2 cardiomyocytes were exposed to 200 mmol/L DMF. Western blotting was used to detect the protein expression levels of p65 in cytoplasm and nuclear, p-IκB after exposure for 0, 2, 4, 6, 8, 12 h, and the protein expression levels of Cyt-c, Cleaved caspase-3, Bcl-2 in cytoplasm after exposure for 0, 2, 4, 8, 12, 24 h. Immunofluorescencecytochemistry (IFC) was used to observe the location of Cyt-c after 200 mmol/L DMF exposure for different times. Results: The levels of p65 in cytoplasm and nuclear and p-IκB among groups were statistically significant (F were 7.79, 33.11, 90.25, respectively, all P<0.01) . Compared with the control group, the levels of p65 in cytoplasm of 2, 4, 6 h group were significantly decreased (all P<0.01) ; the levels of p65 in nuclear of 2, 4, 6, 8 h were significantly increased (all P<0.01) ; the levels of p-IκB of 2, 4, 6 h group were significantly increased (all P<0.01) . The levels of Cyt-c, Cleaved caspase-3 and Bcl-2 among groups were statistically significant (F were 51.42, 503.68, 73.37, respectively, all P<0.01) . Compared with the control group, the levels of Cyt-c of 8, 12 h group were significantly increased (both P<0.01) ; the levels of Cleaved caspase-3 of 2, 4, 8, 12, 24 h were significantly increased (all P<0.01) ; the levels of Bcl-2 of 2, 4, 8, 12, 24 h group were significantly decreased (all P<0.01) . IFC showed that Cyt-c was released from the mitochondria to the cytoplasm gradually as the extension of the exposure time. Conclusion: NF-κB signaling pathway and mitochondrial pathway are involved in the mechanism of DMF-induced apoptosis in H9c2 cardiomyocytes.

[Finite element analysis of the maxillary central incisor with traditional and modified crown lengthening surgery and post-core restoration in management of crown-root fracture].

OBJECTIVE: To construct three-dimensional finite element models with modified crown lengthening surgery and post-core restoration in management of various crown-root fracture types, to investigate the intensity and distribution of stressin models mentioned above, and to compare and analyze the indications of traditional and modified crown lengthening surgeries from the mechanic point of view. METHODS: Nine three-dimensional finite element models with modified crown lengthening surgery and post-core restoration were established and analyzed by micro-CT scanning technique, dental impression scanner, Mimics 10.0, Geomagic studio 9.0 and ANSYS 14.0 software. The von Mises stress of dentin, periodontal ligament, alveolar bone, post and core, as well as the periodontal ligament area and threshold limit value were calculated and compared with the findings of traditional crown lengthening models which had been published earlierby our research group. RESULTS: The von Mises stress intensity of modified crown lengthening models were: dentin>post>core>alveolar bone>periodontal ligament. The maximum von Mises stress of dentin(44.37-80.58 MPa)distributed in lingual central shoulder. The periodontal ligament area of the modified crown lengthening surgery was reduced by 6% to 28%, under the same crown-root fracture conditions, the periodontal ligament area of modified crown lengthening models was larger than that of the traditional crown lengthening models. In modified crown lengthening surgery models, the von Mises stress of periodontal ligament of B3L1m, B3L2m, B3L3m models exceeded their limit values, however, the von Mises stress of periodontal ligament of the B2L2c, B2L3c, B3L1c, B3L2c, B3L3c models exceeded their limit values in traditional crown lengthening surgery models. CONCLUSIONS: The modified crown lengthening surgery conserves more periodontal supporting tissues, which facilitates the long-term survival of teeth. The indication of modified crown lengthening surgery is wider than traditional method. The maxillary central incisors with labial fracture at gingival margin level and with palatal fracture at or below the alveolar crest level are not the indication of the crown lengthening surgery.

Effect of the Schneiderian membrane on the formation of bone after lifting the floor of the maxillary sinus: an experimental study in dogs.

A titanium membrane was used to isolate the Schneiderian membrane of the bony walls of the sinus so that we could investigate their role on the formation of bone after sinus lifts compared with a control group (conventional raising of the sinus floor) in which we did not use a membrane to isolate any area. Three canine models of lifting the sinus floor using the lateral window technique were established: conventional lifting of the floor (control group), raising of the floor with the mucosa shielded (mucosal shielding group), and raising of the floor with the bony wall shielded (bony wall shielding group). The formation of bone one and three months after the sinus floor had been lifted was compared in each group both grossly and by histopathological examination. An appreciable amount of new bone had formed in the control group, with abundant areas near the inferior bony wall, and some near the raised Schneiderian membrane. Similarly, new bone had also formed in the mucosal shielding group, with abundant new bone near the inferior bony wall, but none near the raised Schneiderian membrane. However, there was considerably less new bone in the bony wall shielding group, with none in tissues adjacent to the inferior bony wall and little in tissues near the raised Schneiderian membrane. The Schneiderian membrane has osteogenic capability and participates in the formation of bone after the sinus floor has been lifted. However, its osteogenic role is weaker than that of the surrounding bony wall of the maxillary sinus.

Dopamine-2 receptor activation suppresses PACAP expression in gonadotrophs.

Pituitary adenylate cyclase-activating polypeptide (PACAP) is expressed at a high level in the fetal pituitary and decreases profoundly between embryonic day 19 and postnatal day 1 (PN1), with a further decrease from PN1 to PN4. In this series of experiments, we investigated the hypothesis that dopamine 2 receptor (Drd2) activation interrupts a cAMP-dependent feed-forward loop that maintains PACAP expression at a high level in the fetal pituitary. Using single-cell RT-PCR of pituitary cell cultures from newborn rats, Drd2 mRNA was identified in gonadotrophs that were also positive for PACAP mRNA. PACAP expression in pituitary cultures from embryonic day 19 rats was suppressed by the PACAP6-38 antagonist and by the Drd2 agonist bromocriptine. Increasing concentrations of bromocriptine inhibited cAMP production as well as cAMP signaling based on cAMP response element-luciferase activity, decreased PACAP promoter activity, and decreased PACAP mRNA levels in αT3-1 gonadotroph cells. Furthermore, blockade of dopamine receptors by injecting haloperidol into newborn rat pups partially reversed the developmental decline in pituitary PACAP mRNA that occurs between PN1 and PN4. These results provide evidence that dopamine receptor signaling regulates PACAP expression under physiological conditions and lend support to the hypothesis that a rise in hypothalamic dopamine at birth abrogates cAMP signaling in fetal gonadotrophs to interrupt a feed-forward mechanism that maintains PACAP expression at a high level in the fetal pituitary. We propose that this perinatal decline in pituitary PACAP reduces pituitary follistatin which permits GnRH receptors and FSH-ß to increase to facilitate activation of the neonatal gonad.

Targeted pituitary overexpression of pituitary adenylate-cyclase activating polypeptide alters postnatal sexual maturation in male mice.

The neuropeptide pituitary adenylate cyclase activating polypeptide (PACAP) is present in high concentrations within the hypothalamus, suggesting that it may be a hypophysiotropic factor, whereas pituitary expression suggests a paracrine function. PACAP stimulates gonadotropin secretion and enhances GnRH responsiveness. PACAP increases gonadotropin α-subunit (αGSU), lengthens LHß, but reduces FSHß mRNA levels in adult pituitary cell cultures in part by increasing follistatin. PACAP stimulates LH secretion in rats; however, acceptance of PACAP as a regulator of reproduction has been limited by a paucity of in vivo studies. We created a transgenic mouse model of pituitary PACAP overexpression using the αGSU subunit promoter. Real-time PCR was used to evaluate PACAP, follistatin, GnRH receptor, and the gonadotropin subunit mRNA in male transgenic and wild-type mice of various ages. Transgenic mice had greater than 1000-fold higher levels of pituitary PACAP mRNA; and immunocytochemistry, Western blot, and ELISA analyses confirmed high peptide levels. FSH, LH, and testosterone levels were significantly suppressed, and the timing of puberty was substantially delayed in PACAP transgenic mice in which gonadotropin subunit and GnRH receptor mRNA levels were reduced and pituitary follistatin expression was increased. Microarray analyses revealed 1229 of 45102 probes were significantly (P < 0.01) different in pituitaries from PACAP transgenic mice, of which 83 genes were at least 2-fold different. Genes involved in small molecule biochemistry, cancer, and reproductive system diseases were the top associated networks. The GnRH signaling pathway was the top canonical pathway affected by pituitary PACAP excess. These experiments provide the first evidence that PACAP affects gonadotropin expression and sexual maturation in vivo.

Bone marrow-derived mesenchymal stem cells are capable of mediating hepatitis B virus infection in injured tissues.

UNLABELLED: We have previously showed that endothelial progenitor cells (EPCs) through uptake of hepatitis B virus (HBV) may play a critical role in mediating extrahepatic HBV diseases. However, it remains to be elucidated whether mesenchymal stem cells (MSCs) are capable of mediating HBV trans-infection into extrahepatic tissues. METHODS AND RESULTS: In this study, we showed that HBV antigens, HBV DNA and the viral particles were detected in MSCs after 3 days virus challenge. Neither HBV covalently closed circular DNA nor pregenomic RNA were detected in MSCs. Intravenously transplantation of HBV-exposed MSCs into myocardial infarction mouse model resulted in incorporation of HBV into injured heart and other damaged tissues. CONCLUSION: These results indicate that MSCs could serve as an additional extrahepatic virus reservoir, which may play a role at least in part in mediating HBV trans-infection into the injured tissues through the process of MSCs recruitment.

A L.E.A.P.S. heteroconjugate vaccine containing a T cell epitope from HSV-1 glycoprotein D elicits Th1 responses and protection.

The L.E.A.P.S. heteroconjugate vaccine antigen (JgD), composed of a T cell epitope from glycoprotein D (gD(8-23)) of herpes simplex virus (HSV) linked with a peptide sequence from beta-2-microglobulin (aa38-50), elicited protection against lethal intraperitoneal (IP) challenge and prevented disease signs in most, and limited disease progression, for the rest of BALB/c mice challenged in the epidermal abrasion-zosteriform spread mouse infection model. JgD elicited a Th1 response in vaccinated mice as indicated by delayed type hypersensitivity (DTH) responses to HSV antigen, and gD and virion specific antibodies with an IgG2a/IgG1 >1. Vaccination with the JgD peptide delayed the onset of disease signs, reduced severity of the disease and reduced mortality rates in mice with different MHC backgrounds as compared to their respective control mice. CD8 cells were demonstrated as important for initiation of the immune response to JgD and CD4 cells and interferon gamma (IFN-gamma) for delivering immune protection in BALB/c mice, as indicated in monoclonal antibody ablation studies. JgD, and other J-L.E.A.P.S. vaccine antigens, appear to prime T cells to initiate a Th1 response, which is subsequently boosted upon viral challenge to result in protection.

Multiple mechanisms for HSV-1 induction of interferon alpha production by peripheral blood mononuclear cells.

UV-inactivated, infectious, and other forms of herpes simplex virus 1 (HSV-1) induced interferon (IFN) production by different routes in myeloid origin mononuclear cells (MOMC) (consisting predominantly of monocytes). GM-CSF activated the MOMC (G-MOMC) to produce greater amounts of interferon while differentiation to DC, by the addition of granulocyte macrophage colony stimulating factor (GM-CSF) and calcium ionophore (GA-MOMC), reduced the levels of interferon production upon challenge with some HSV strains. UV-inactivated virus induced more interferon than infectious virus. L-fucose, an antagonist of the mannose receptor, inhibited the induction of IFN-alpha by UV-inactivated virus and gB(-) virus (defective in penetration) in MOMC and GA-MOMC but not G-MOMC. L-fucose had little effect on interferon induction by infectious HSV-1. The insensitivity of the G-MOMC to fucose inhibition distinguishes these interferon producing cells from the pDC2 cells previously described as natural interferon producing cells. The mannose receptor appears to be involved in the response to non-infectious forms of HSV but infectious virus appears to use a different pathway. These studies suggest that non-infectious virions and HSV infected cell debris effectively stimulate monocytes and pre-dendritic cells to produce IFN-alpha to initiate host protection against HSV infection.