A Novel Surgical Technique for Augmented Corticotomy-Assisted Orthodontics: Bone Grafting With Periosteum.

PURPOSE: To introduce grafting fixed with the periosteum (dumpling technique) as an alternative surgical technique for augmented corticotomy-assisted orthodontics in the lower anterior region and evaluate the preliminary outcomes. MATERIALS AND METHODS: Eleven patients (9 women, 2 men; mean age, 21.4 yr) with a thin alveolus or alveolar defect in the lower anterior region by clinical and radiographic examination underwent an augmented corticotomy using the new dumpling technique. Cone-beam computerized tomography was used to evaluate morphologic changes of the lower anterior ridge before treatment (T0) and 1 week (T1) and 6 months (T2) after the bone-augmentation procedure. Repeated-measures analysis of variance with Bonferroni multiple-comparison test was used to compare variables at each time point. RESULTS: No severe postsurgical complications occurred in any patient. The mean alveolar bone thickness of the labial plate increased from T0 to T1 (P < .001) and decreased from T1 to T2 (P < .001). However, compared with T0, there was still a significant increase in horizontal bone thickness at T2 (P < .05). The vertical alveolar bone level increased from T0 to T1 (P < .001) and was maintained from T1 to T2 (P > .05). No significant differences were found in root length of the lower anterior teeth at these 3 time points (P > .05). CONCLUSIONS: In this preliminary study, the dumpling technique for augmented corticotomy-assisted surgical orthodontics showed alveolar bone augmentation by increasing the vertical alveolar height and the horizontal bone thickness in the labial aspect of the anterior mandibular area. However, long-term follow-up is necessary.

GDF15-mediated upregulation of ferroportin plays a key role in the development of hyperferritinemia in children with hemophagocytic lymphohistiocytosis.

BACKGROUND: Growth differentiation factor 15 (GDF15), a divergent TGFß superfamily, has recently been implicated in the modulation of iron homeostasis, acting as an upstream negative regulator of hepcidin, the key iron regulatory hormone produced primarily by hepatocytes. However, little is known about possible roles that GDF15 might play in the regulation of iron homeostasis and development of hyperferritinemia in children with hemophagocytic lymphohistiocytosis (HLH). PROCEDURES: We compared serum GDF15 level and mRNA expressions of GDF15 and key molecules of iron metabolism, and made correlations between their expressions in children with HLH and control children. RESULTS: Serum GDF15 level was remarkably higher in HLH group than that in controls, with median serum concentration of 1,700 and 260 pg/ml, respectively (P < 0.001). In addition, GDF15 mRNA was significantly upregulated but independent of hypoxia-inducible factor-mediated oxygen signaling pathway. More importantly, GDF15 induction was positively correlated to upregulation of ferroportin, the only cellular iron exporter, and to upregulation of ferritin heavy chain. CONCLUSIONS: Our study suggests that GDF15 induction helps suppress further activation of macrophages in stressful physiologic states as HLH, and is intimately implicated in the development of hyperferritinemia by modulating the hepcidin-ferroportin axis, resulting in enhanced ferroportin-mediated iron efflux.

Marsupialization facilitates eruption of dentigerous cyst-associated mandibular premolars in preadolescent patients.

PURPOSE: The purpose of the present study was to investigate the eruption of dentigerous cyst (DC)-associated mandibular premolars after marsupialization in preadolescents. PATIENTS AND METHODS: The present study was a retrospective cohort study of preadolescent patients with DCs who were treated as outpatients at the Department of Oral and Maxillofacial Surgery, Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine. For our study, the data from these patients were collected, and the eruption of the premolar teeth, along with related factors, such as the interval to eruption, cusp depth, angulation, cyst size, and eruption space, were analyzed for the cyst group compared with the noncyst control group. RESULTS: The mean age of the patients was 9.1 years. All teeth associated with DCs erupted successfully after marsupialization. The follow-up panoramic radiograph showed that the cysts had disappeared and had been replaced by regenerated bone. The initial panoramic radiograph showed the angulation of the teeth in the cyst group had a significantly larger inclination angle than did the teeth in the noncyst group (P < .05). However, no significant difference was found for cusp depth, root formation, or space measurement. The gender, age, cusp depth, angulation, and eruption space were not factors influencing the eruption of the DC-associated tooth for preadolescent patients in the present study. In addition, the cyst-associated teeth took less time to erupt than the teeth in the control group. CONCLUSIONS: The results of the present study suggest that DC-associated mandibular premolars can erupt spontaneously after marsupialization in preadolescents.

An orthodontic technique for minimally invasive extraction of impacted lower third molar.

PURPOSE: To present a novel orthodontic approach for minimally invasive extraction of impacted mandibular third molars (M3s) close to the inferior alveolar nerve (IAN). PATIENTS AND METHODS: Eight patients (8 M3s) requiring extraction of M3s were included in this study; there were 2 cases of horizontal impaction, 4 of mesioangular impaction, and 2 of vertical impaction. Cone-beam computed tomogram showed that the roots of impacted M3s in 2 cases interrupted the cortices of the mandibular canal, and those in the other 6 cases were very close to the IAN. Orthodontic treatment was performed in this study. The crowns of 5 impacted teeth were surgically exposed before the application of the orthodontic device, whereas bonding was performed directly to the occlusal surface of the other 3 M3s, which had partially erupted. The opposing maxillary M3s were removed in 3 cases. One-step orthodontic extraction was applied to vertically impacted M3s and 2-step treatment was applied to horizontally or mesioangularly impacted M3s. Success was defined as the separation of the impacted tooth from the IAN as visualized on cone-beam computed tomogram. RESULTS: After orthodontic treatment, all impacted M3s were extruded and separated from the IAN (mean, 6.6 months; range, 4 to 10 months), without any neurologic consequences. The average time of extraction was 5 minutes. In all 8 cases, new bone formation occurred distal to the adjacent second molar. CONCLUSION: This orthodontic technique may be a minimally invasive approach for the extraction of impacted M3s adjacent to the IAN, with a decreased risk of paresthesias and with osteoperiodontal advantages.

Resveratrol induces apoptosis and autophagy in T-cell acute lymphoblastic leukemia cells by inhibiting Akt/mTOR and activating p38-MAPK.

OBJECTIVE: To explore the effects of resveratrol-induced apoptosis and autophagy in T-cell acute lymphoblastic leukemia (T-ALL) cells and potential molecular mechanisms. METHODS: The anti-proliferation effect of resveratrol-induced, apoptosis and autophagy on T-ALL cells were detected by using MTT test, immunofluorescence, electronic microscope, and flow cytometry, respectively. Western blotting was performed for detecting changes of apoptosis-associated proteins, cell cycle regulatory proteins and state of activation of Akt, mTOR, p70S6K, 4E-BP1, and p38-MAPK. RESULTS: Resveratrol inhibited the proliferation and induced apoptosis and autophagy in T-ALL cells in a dose and time-dependent manner. It also induced cell cycle arrest at G0/G1 phase via up regulating cyclin-dependent kinase (CDK) inhibitors p21 and p27 and down regulating cyclin A and cyclin D1. Western blotting revealed that resveratrol significantly decreased the expression of antiapoptotic proteins (Mcl-1 and Bcl-2) and increased the expression of proapoptotic proteins (Bax, Bim, and Bad), and induced cleaved-caspase-3 in a time-dependent manner. Significant increase in ratio of LC3-II/LC3-I and Beclin 1 was also detected. Furthermore, resveratrol induced significant dephosphorylation of Akt, mTOR, p70S6K, and 4E-BP1, but enhanced specific phosphorylation of p38-MAPK which could be blocked by SB203580. When autophagy was suppressed by 3-MA, apoptosis in T-ALL cells induced by resveratrol was enhanced. CONCLUSION: Our findings have suggested that resveratrol induces cell cycle arrest, apoptosis, and autophagy in T-ALL cells through inhibiting Akt/mTOR/p70S6K/4E-BP1 and activating p38-MAPK signaling pathways. Autophagy might play a role as a self-defense mechanism in T-ALL cells treated by resveratrol. Therefore, the reasonable inhibition of autophagy in T-ALL cells may serve as a promising strategy for resveratrol induced apoptosis and can be used as adjuvant chemotherapy for T-ALL.

Rapamycin sensitizes glucocorticoid resistant acute lymphoblastic leukemia CEM-C1 cells to dexamethasone induced apoptosis through both mTOR suppression and up-regulation and activation of glucocorticoid receptor.

OBJECTIVE: To explore the role of glucocorticoid (GC) receptor (GR) in rapamycin's reversion of GC resistance in human GC-resistant T-acute lymphoblastic leukemia (ALL) CEM-C1 cells. METHODS: CEM-C1 cells were cultured in vitro and treated with rapamycin at different concentrations with or without 1 µmol/L dexamethasone (Dex). 3-(4, 5-dimethylthiazol-2-yl)-2, 5-diphenyltetrazolium bromide (MTT) test was performed to assess cell proliferation. The cell cycle and cell apoptosis were analyzed by flow cytometry. The expression of GRα mRNA was determined by real-time quantitative RT-PCR. The expression of GR, p-70S6K, Mcl-1, and Bim proteins was detected by Western blot. RESULTS: When incubated with rapamycin at different concentrations, CEM-C1 cells showed significant growth inhibition in a time- and concentration-dependent manner. The growth inhibition was synergistically increased when CEM-C1 cells were treated with rapamycin plus 1 µmol/L Dex. CEM-C1 cells treated with rapamycin alone showed no apparent apoptosis, and were arrested at G0/G1 phase. After the treatment with Dex plus rapamycin, CEM-C1 cells demonstrated apparent apoptosis and increased the cell cycle arrested at G0/G1 phase. Rapamycin combined with Dex up-regulated GRα, phosphorylated GR(p-GR), and pro-apoptotic protein Bim-EL in CEM-C1 cells, but inhibited the expression of p-p70S6K, a downstream target protein of mTOR (mammalian target of rapamycin). CONCLUSION: After the treatment with rapamycin plus Dex, Dex resistant CEM-C1 cells induce growth inhibition and apoptosis. The underlying mechanism may involve inhibition of the mTOR signaling pathway and also be associated with up-regulation of GR expression and activation of GC-GR signaling pathway.

Clinical and prognostic characteristics of 95 cases of Langerhans cell histiocytosis in children: a single-institute experience from 2013 to 2020.

BACKGROUND: This study aimed to understand the clinical characteristics and outcomes of children with Langerhans cell histiocytosis (LCH) in China. METHODS: We conducted a retrospective study of 95 paediatric patients with LCH in West China Second University Hospital of Sichuan University between July 2013 and August 2020. RESULTS: The onset age of multisystem LCH (MS-LCH) patients with risk organ (RO) involvement was younger than that of MS-LCH without RO involvement (p = .002) and single system LCH (p < .001) patients; bone was the most frequently involved organ, followed by the skin. Of all, the BRAF-V600E mutation was detected in 48 out of 84 patients who underwent gene analysis. Additionally, in our study, BRAF p.N486_T491 > K, BRAF p.L485_P490delinsF, BRAF p.R506_K507insLLR, ARAF p.Q349_F351delinsL and MAP2K1 p.Q58_E62del were known mutations in the mitogen-activated protein kinase (MAPK) pathway. The BRAF-V600E genotype in the tissue and plasma prior to therapy were detected in 16 patients, and the concordance was only 37.5% (6/16). According to the modified LCH-III-based-protocol, JLSG-02 protocol chemotherapy, and vemurafenib, the estimated five-year overall survival, event-free survival (EFS) and cumulative reactivation rates of 95 patients were 98.8%, 74.6% and 24.5%, respectively. The EFS rate in good responders was better than that in poor responders at 12-week (HR = 0.022, 95%CI 0.002-0.231, p = .002), and EFS was not affected by age, RO involvement or BRAF-V600E mutation. Regarding sequelae, nine patients had central diabetes insipidus and two had growth retardation. CONCLUSIONS: In this study, LCH was a highly heterogeneous disease characterized molecularly by MAPK-pathway activating mutations. Vincristine, prednisone and cytarabine-based chemotherapy combined with vemurafenib improved the prognosis of childhood LCH. In future, prospective clinical trials and novel therapeutic strategies should be developed to improve outcomes in paediatric patients with LCH.KEY MESSAGEChildren with Langerhans cell histiocytosis in China present highly heterogeneous clinical characteristics, with up to 60% of cases harbouring mutations in MAPK pathway.Treatment response at 12-week is associated with EFS in our study.Vincristine, prednisone and cytarabine-based chemotherapy combined with vemurafenib improved the prognosis of Chinese childhood LCH, but the reactivation rate is still high.

[Expression of transferrin receptor 2 in mononuclear cells from children with acute leukemia].

OBJECTIVE: To study the expression of TFR2 mRNA in mononuclear cells of bone marrow and peripheral blood from children with acute lymphoblastic leukemia, and to explore possible correlations between TFR2 expression and a panel of prognostic/risk factors. METHODS: Bone marrow or peripheral mononuclear cells were isolated from 56 children with newly diagnosed acute lymphoblastic leukemia (ALL) and 15 normal children as control. TFR2 mRNA expression level in mononuclear cell was determined by real-time fluorescence quantitative RT-PCR. RESULTS: Relative expression level of TFR2 mRNA in prednisone good responders (median: 0.0848) was significantly higher than that in prednisone poor responders (median: 0.0126) (P = 0.038). The medians of TFR2 mRNA expression levels in low-risk, moderate-risk and high-risk ALL were 0.1677, 0.0728 and 0.0125 respectively (P = 0.003). The medians of TFR2 mRNA expression levels in three ALL groups with initial WBC counts less than 50 x 10(9)/L, from 50 x 10(9)/L to 100 x 10(9)/L and more than 100 x 10(9)/L were 0.0974, 0.0294 and 0.0078 (P = 0. 013). In addition, the relative TFR2 mRNA level in B-lineage ALL was significantly higher than that in T-ALL, with medians of 0.0636 and 0.0065 respectively (P = 0.004). Ranked correlation analysis revealed that TFR2 expression was negatively correlated to initial white blood cell count, percentage of blast cells and absolute numbers of blasts in peripheral blood, with ranked correlation coefficients of -0.398, -0.307 and 0.421 respectively (correponding P values were 0.003, 0.022 and 0.001). CONCLUSION: TFR2 might be a novel prognostic factor for ALL.

[Diffuse large B-cell lymphoma with expression of anaplastic lymphoma kinase protein: clinicopathologic and immunohistochemical study of 5 cases].

OBJECTIVE: To study the clinicopathologic features of diffuse large B-cell lymphoma (DLBCL) with expression of anaplastic lymphoma kinase (ALK) protein. METHODS: Nine hundred and forty-five (945) cases of DLBCL (including 177 consultation cases) diagnosed according to the 2001 World Health Organization classification of tumors of hematopoietic and lymphoid tissues were enrolled into the study. Immunohistochemical study for anti-ALK-11 was performed using LSAB technique. The ALK-positive cases were further confirmed by immunohistochemical study using EnVision technique. Only ALK-positive cases by EnVision technique were further analyzed by immunostaining for antigens including CD20, CD3, CD30, EMA, granzyme-B, TIA-1 and PC. Immunoglobulin heavy chain gene rearrangement study was also performed and follow-up data collected. RESULTS: There were altogether 5 (4 males and 1 female) cases of DLBCL showing expression of ALK protein. The age of the patients ranged from 34 to 72 years. All were primary nodal DLBCL. One case belonged to clinical stage I, 2 in stage II and 2 in stage III. The duration of follow up ranged from 4 to 32 months. Three patients subsequently died and the longest survival was 32 months. Morphologic subtypes included centroblastic 2, anaplastic 1, immunoblastic with plasmacytoid differentiation 1 and plasmablastic 1. Immunohistochemically, 4 cases were CD20 positive (including 2 centroblastic, 1 anaplastic and 1 immunoblastic cases). The plasmablastic case expressed kappa light chain and was negative for CD20. Rearrangement of immunoglobulin heavy chain gene was demonstrated in all 5 cases studied. As for ALK protein staining, a mixed membranous and cytoplasmic (1 immunoblastic case), granular cytoplasmic (2 centroblastic and 1 anaplastic cases) and mixed nuclear and cytoplasmic (1 plasmablastic case) patterns were observed. CONCLUSIONS: Expression of ALK protein is a rare phenomenon in DLBCL and can be seen in centroblastic, anaplastic, immunoblastic and plasmablastic subtypes. It is often associated with aggressive clinical behavior and worse prognosis. A new pattern of ALK protein expression, mixed membranous and cytoplasmic, is reported.

Three-D imaging of dental alveolar bone change after fixed orthodontic treatment in patients with periodontitis.

OBJECTIVES: The objective of this study was to radiographically quantify bone height and bone density in patients with periodontitis after fixed orthodontic treatment using cone beam computed tomography (CBCT). MATERIALS AND METHODS: A total of 81 patients including 40 patients with chronic periodontitis (group 1) and 41 patients with normal periodontal tissues (group 2) were selected. CBCT scanning for anterior teeth were taken before and after orthodontic treatment. Measurements of bone height and bone density were performed using CBCT software. RESULTS: The group 1 presented a statistically lesser bone density and bone height when compared to group 2 before treatment. There was a significant loss of bone density for both groups after orthodontic treatment, but bone density loss was significantly greater in the group 1. There was no statistically significant bone height change in two groups after treatment. CONCLUSIONS: This study demonstrated that orthodontic treatment can preserve bone height but not capable of maintaining bone density, especially for patients with periodontitis. It is indicated that the change of bone density may be more susceptible than that of bone height when radiographically evaluating bone status under this combined periodontal and orthodontic therapy.

Case studies on local orthodontic traction by minis-implants before implant rehabilitation.

OBJECTIVE: Dentition defect with malocclusion is a common occurrence in the clinical work. To restore proper occlusion, preprosthetic corrections of these malposed teeth are often indispensible. The use of orthodontic mini-implants as temporary anchorage devices provides a plausible treatment for those patients with local problems. The aim of this study was to present two cases using local orthodontic traction in conjunction with mini-implants to provide necessary conditions for implant rehabilitation in three dimensional space. Clinical consideration: Two cases who had dentition defect with malocclusion were included in the present study. As both of them rejected crown reduction or orthodontics treatment, local orthodontic traction by mini-implants was used to restore normal space for implant rehabilitation in three dimensions. Careful mechanics analysis and personalized mechanical device were under consideration. The results showed that the biological responses of the corrected teeth and the surrounding bony structures appeared normal and acceptable. Moreover the patients achieved an ideal local occlusion with a short treatment time. CONCLUSION: In conclusion local orthodontic traction by mini-implants was a less-invasive and short-term method with favorable effects and less necessary occlusal adjustments.

Low-dose anisomycin sensitizes glucocorticoid-resistant T-acute lymphoblastic leukemia CEM-C1 cells to dexamethasone-induced apoptosis through activation of glucocorticoid receptor and p38-MAPK/JNK.

Glucocorticoid (GC) resistance in children with acute lymphoblastic leukemia (ALL) usually resulted in the failure of treatment. Exploring new agents to overcome GC resistance is important. Here we reported for the first time that low-dose anisomycin has the potential to sensitize GC-resistant T-ALL CEM-C1 cells to dexamethasone (DEX). Compared with the use of DEX or low-dose anisomycin alone, co-treatment with them resulted in a significant increase of growth inhibition, apoptosis and cell cycle arrest in CEM-C1 cells through induction of activated caspase-3 and up-regulation of Bim, p21and p27, and down-regulation of Mcl-1, Bcl-2, c-myc, cyclin A and cyclin D1. Furthermore, co-treatment remarkably activated glucocorticoid receptor (GR), p38-MAPK and JNK, and all of them were canceled only by the GR inhibitor RU486, indicating GR might be an at the upstream of GR-p38-MAPK/JNK pathway. We conclude that low-dose anisomycin sensitizes GC-resistant CEM-C1 cells to DEX and this effect is mediated, at least in part, by activation of the GR-p38-MAPK/JNK signaling pathway.

Pro-apoptotic protein BIM in apoptosis of glucocorticoid-sensitive and -resistant acute lymphoblastic leukemia CEM cells.

Although glucocorticoids (GCs) have been used to treat acute lymphoblast leukemia (ALL) for decades, the mechanisms of GC sensitivity and resistance in ALL cells are poorly understood. This study investigated the role and mechanisms of pro-apoptotic protein BIM in apoptosis of GC-sensitive and- resistant ALL cells. The dramatic apoptosis was observed in GC-sensitive CEM-C7 cells after incubated with DEX for 48 h, while not in GC-resistant CEM-C1 cells. The significant up-regulation of BIM in CEM-C7 cells induced by DEX was also observed, but no up-regulation of BIM was detected in DEX-induced CEM-C1 cells. When treated with DEX plus RU486, a glucocorticoid receptor blocker, the apoptosis and BIM expression of CEM-C7 cells were canceled. P38MAPK-blocking pharmacon SB203580 also significantly inhibited the up-regulation of BIM in CEM-C7 cells. These suggested that the absence of BIM up-regulation is one of the important mechanisms of GC resistance, GC-GR conjugation is indispensible in both GC-induced apoptosis and up-regulation of BIM, and p38 MAPK signal pathway is also involved in this process.

[TfR2 mRNA expression in bone marrow mononuclear cells of children with hyperplastic anemia and its implications].

The aim of this study was to investigate the expression of transferrin receptor 2 (TfR2) mRNA in bone marrow mononuclear cells (BMMNC) of children with hyperplastic anemia (HA), to analyze the correlation of TfR2 mRNA expression level with Hb level, bone marrow erythroid hyperplasia, iron status in body and underlying diseases, and to evaluate the role of TfR2 in erythroid hemopoiesis and the useful value in diagnosis of HA. The experiment was divided into 2 groups: test group, in which 40 patients with HA were enrolled, and control group in which 10 patients without erythroid disorders and hematological malignancies confirmed by bone marrow examination were enrolled. The bone marrow samples of patients in mentioned above 2 groups were collected, the TfR2 mRNA expression in BMMNC of patients with HA was detected by fluorescence-quantitative PCR, the correlation of HA with bone marrow erythroid hyperplasia, iron status of body and underlying diseases was analyzed. The results showed that the relative level of TfR2 mRNA expression in HA patients was significantly higher than that in control patients. The TfR2 mRNA expression level negatively correlated with Hb level in peripheral blood (r = -0.715), while it positively correlated with ratio of bone marrow erythroblasts (r = 0.533). It is concluded that TfR2 mRNA expression in HA patients increases and closely correlates with hyperplasia status of bone marrow and anemia level in peripheral blood.

ALK-positive extramedullary plasmacytoma with expression of the CLTC-ALK fusion transcript.

Anaplastic lymphoma kinase (ALK)-positive non-Hodgkin lymphoma (NHL) was long thought to be a disease occurring uniquely in T or null-cell lymphomas. More recently, however, a small number of B-lineage lymphomas have been reported to express ALK fusion genes. These tumors often exhibit a plasmablastic morphology, a finding which prompted our interest in looking for ALK fusions in plasma cell neoplasms. We studied 46 cases of extramedullary plasmacytoma by immunostaining with anti-ALK antibody and fluorescence in situ hybridization (FISH) analysis using an ALK break-apart probe and found one case to be ALK protein-positive and demonstrated the disruption of the ALK gene in this case. Immunohistochemistry showed that the tumor cells were strongly positive for CD138, VS38c, and epithelial membrane antigen, but lacked expression of CD20, CD79a, CD45, and CD30. Both RT-PCR and genomic DNA-PCR confirmed the CLTC-ALK fusion. This finding expands the lists of the ALK-positive tumors, and ALK-positive extramedullary plasmacytoma may benefit from the treatment of ALK inhibitor in the future.

[Research on periodontal changes on the compression side during rapid tooth movement into newly distracted bone].

PURPOSE: To investigate periodontal remodeling mechanism on the compression side during early tooth movement into newly distracted bone. METHODS: Ten male Beagle dogs were selected. Distraction osteogenesis was performed on randomized side as experimental group, while the fourth premolars were extracted on the other side as control group. Then the third premolars were distalized with 30g orthodontic force instantly after the cessation of distraction or extraction. The distance of the tooth movement was measured with a sliding caliper every week. Each distance was measured 3 times and the mean value was recorded. The measurement data were analysed with paired t test by SPSS 18.0 software package. Beagle dogs were killed in the first, second, fourth week after tooth movement. Slices were obtained for HE staining and TRAP staining to observe the periodontal tissue on the compression side. RESULTS: The average moving velocity of the teeth in the distracted bone was (1.055±0.054)mm per week, which was significantly faster than that in the control group(P<0.05).There was no apparent lag period in the experimental group. In addition, there was no hyalinization observed on the compression side of the periodontal tissue in the experimental group, while the amount and area of distribution of the TRAP-positive cells on the compression side was significantly larger and strongly expressed. CONCLUSIONS: The moving velocity of the teeth in the newly distracted bone was significantly faster, and no apparent lag period, which may be related to no hyalinization and more early-appeared, vigorous and wide-distributed osteoclasts on the compression side of the periodontal tissue.

[The role of CBCT in evaluation of alveolar bone state during orthodontic-periodontal treatment].

PURPOSE: To evaluate the role of cone beam computed tomography (CBCT) in evaluation of alveolar bone state during orthodontic-periodontal treatment. METHODS: Twenty patients with periodontal disease seeking for orthodontic-periodontal therapy were selected. The first stage of orthodontics included alignment and leveling arches (treatment) and the average period was 6 months. CBCT for anterior teeth was taken before and after treatment, and alveolar bone density and height were recorded with landmark identification designed by ourselves in this study. The data was analyzed with SPSS16.0 software package for paired t test and interclass correlations (ICC) assessments. RESULTS: Paired t test showed that the alveolar density was significantly reduced after treatment (P=0.02) and no significant change of alveolar height was observed before and after treatment (P=0.74). The value of ICC was more than 0.9 for all intra-observer and inter-observer assessments. CONCLUSIONS: The alveolar bone density decreased during orthodontic treatment and CBCT could be used in evaluation of alveolar bone state. The landmark identification designed by ourselves can offer consistent and reproducible data. Supported by Research Fund of Science and Technology Commission of Shanghai Municipality(Grant No.08DZ2271100). Dr.MA ZG and FAN LF Contributed equally to the study.

[Study on activation of AKT/mTOR pathway in anaplastic large cell lymphoma].

OBJECTIVE: To study the expression of anaplastic lymphoma kinase (ALK) and the phosphorylation status of AKT, mammalian target of rapamycin (mTOR), 4E-binding protein 1 (4E-BP1) and ribosomal protein S6 kinase (p70S6K) and their interrelationships and clinical pathological significance in anaplastic large cell lymphoma (ALCL) patients. METHODS: Immunohistochemical and EnVision methods were used to detect the expression of ALK, p-AKT, p-mTOR, p-4E-BP1 and p-p70S6K. RESULTS: Among the 81 ALCL patients, 51 (63.0%) expressed ALK, whereas the other 30 (37.0%) did not. Patients with ALK(+) ALCL had a better prognosis than those with ALK-ALCL (P < 0.05). Out of the 71 ALCL samples studied, p-AKT was detected in 54 (76.1%) samples and its phosphorylation was correlated with ALK expression (P < 0.05); p-mTOR was detected in 57 (80.3%) samples and its expression was correlated with both ALK and p-AKT (P < 0.05); p-4E-BP1 and p-p70S6K were detected in 64 (90.1%) and 66 (93.0%) samples respectively, and their expressions were related with p-mTOR (P < 0.05), but not with ALK or p-AKT (P > 0.05). COX Proportional Hazard Model analysis showed that both the expression of ALK and the B symptoms affected the prognosis (P < 0.05), moreover, the former had greater impact than the later. CONCLUSION: Expressions of p-AKT, p-mTOR, p-4E-BP1 and p-p70S6K are detected in ALCL, while ALK(+) cases have higher incidence than those with ALK(-) cases. Phosphorylation of AKT and mTOR is correlated with ALK expression, suggesting that there is an activated pathway of AKT/mTOR in patients with ALK(+) ALCL, but the activation have no obvious prognostic significance.

[Blockage of mTOR signaling pathway by rapamycin contributes to inhibition of tumor cell proliferation in ALK-positive lymphoid cell strains].

OBJECTIVE: To investigate the relationship between mTOR signaling pathway and ALK-positive lymphoid cell lines. METHODS: The expression of the downstream effector proteins of mTOR were analyzed by Western blot before and after Karpas299, BaF3/NPM-ALK and BaF3 cell lines treated with rapamycin. Effect of rapamycin on cell proliferation was detected by MTT assay. FACS was used to analyze apoptosis and cell cycles. RESULTS: mTOR signaling phosphoproteins, p-p70S6K and p-4E-BP1 were highly expressed in ALK(+) Karpas299, BaF3/NPM-ALK and parental BaF3 cell lines, and they were dephosphorylated after 1 h withdrawal of IL-3 in BaF3 cells. After 48 h exposure to 10 nmol/L rapamycin, p-p70S6K and p-4E-BP1 proteins expression were decreased, and mainly for the former. The relative inhibitory rate to its control cells was 24.4% in Karpas299, 37.8% in BaF3/NPM-ALK and 61.6% in BaF3. The apoptotic ratio was increased from (11.97 +/- 0.11)% to (15.87 +/- 0.62)% in Karpas299 (P < 0.05), from (3.23 +/- 0.11)% to (7.67 +/- 0.49)% in BaF3 (P < 0.05) and from (1.90 +/- 0.47)% to (2.80 +/- 0.27)% in BaF3/NPM-ALK (P > 0.05). The fraction of G(1) phase cells increased from (37.63 +/- 1.91)% to (69.77 +/- 5.44)% in BaF3/NPM-ALK, from (31.13 +/- 2.51)% to (40.70 +/- 1.47)% in Karpas299 and (53.57 +/- 2.22)% to (63.70 +/- 1.20)% in BaF3 (P < 0.05). CONCLUSION: NPM-ALK kinase can activate mTOR signaling pathway. Rapamycin can inhibit the proliferation of ALK(+) lymphoid cells by blocking mTOR signaling pathway and inducing cell cycling arrest at G(1) phase.