Analysis of risk factors leading to anxiety and depression in patients with prostate cancer after castration and the construction of a risk prediction model.

BACKGROUND: Cancer patients often suffer from severe stress reactions psychologically, such as anxiety and depression. Prostate cancer (PC) is one of the common cancer types, with most patients diagnosed at advanced stages that cannot be treated by radical surgery and which are accompanied by complications such as bodily pain and bone metastasis. Therefore, attention should be given to the mental health status of PC patients as well as physical adverse events in the course of clinical treatment. AIM: To analyze the risk factors leading to anxiety and depression in PC patients after castration and build a risk prediction model. METHODS: A retrospective analysis was performed on the data of 120 PC cases treated in Xi'an People's Hospital between January 2019 and January 2022. The patient cohort was divided into a training group (n = 84) and a validation group (n = 36) at a ratio of 7:3. The patients' anxiety symptoms and depression levels were assessed 2 wk after surgery with the Self-Rating Anxiety Scale (SAS) and the Self-rating Depression Scale (SDS), respectively. Logistic regression was used to analyze the risk factors affecting negative mood, and a risk prediction model was constructed. RESULTS: In the training group, 35 patients and 37 patients had an SAS score and an SDS score greater than or equal to 50, respectively. Based on the scores, we further subclassified patients into two groups: a bad mood group (n = 35) and an emotional stability group (n = 49). Multivariate logistic regression analysis showed that marital status, castration scheme, and postoperative Visual Analogue Scale (VAS) score were independent risk factors affecting a patient's bad mood (P < 0.05). In the training and validation groups, patients with adverse emotions exhibited significantly higher risk scores than emotionally stable patients (P < 0.0001). The area under the curve (AUC) of the risk prediction model for predicting bad mood in the training group was 0.743, the specificity was 70.96%, and the sensitivity was 66.03%, while in the validation group, the AUC, specificity, and sensitivity were 0.755, 66.67%, and 76.19%, respectively. The Hosmer-Lemeshow test showed a χ2 of 4.2856, a P value of 0.830, and a C-index of 0.773 (0.692-0.854). The calibration curve revealed that the predicted curve was basically consistent with the actual curve, and the calibration curve showed that the prediction model had good discrimination and accuracy. Decision curve analysis showed that the model had a high net profit. CONCLUSION: In PC patients, marital status, castration scheme, and postoperative pain (VAS) score are important factors affecting postoperative anxiety and depression. The logistic regression model can be used to successfully predict the risk of adverse psychological emotions.

CDK2 and CDK4 targeted liensinine inhibits the growth of bladder cancer T24 cells.

Bladder cancer (BCa) is a urinary tumor with limited treatment options and high mortality. Liensinine (LIEN), a natural bisbenzylisoquinoline alkaloid, has shown excellent anti-tumor effects in numerous preclinical studies. However, the anti-BCa effect of LIEN remains unclear. To the best of our knowledge, this is the first study to investigate the molecular mechanism of LIEN in the management of BCa. First, we identified the treatment-related targets of BCa; those that repeatedly occur in more than two databases, including GeneCards, Online Mendelian Inheritance in Man, DisGeNET, Therapeutic Target Database, and Drugbank. The SwissTarget database was used to screen LIEN-related targets, and those with a probability >0 were possible LIEN targets. The prospective targets of LIEN in the treatment of BCa were then determined using a Venn diagram. Second, we discovered that the PI3K/AKT pathway and senescence mediated the anti-BCa action of LIEN by using GO and KEGG enrichment analysis to explore the function of LIEN therapeutic targets. A protein-protein interaction network was created using the String website, and six algorithms of the CytoHubba plug-in were then used in Cytoscape to assess the core targets of LIEN for the therapy of BCa. The outcomes of molecular docking and dynamics simulation demonstrated that CDK2 and CDK4 proteins were the direct targets of LIEN in the management of BCa, among which CDK2 was more stable in binding to LIEN than CDK4. Finally, in vitro experiments showed that LIEN inhibited the activity and proliferation of T24 cells. The expression of p-/AKT, CDK2, and CDK4 proteins progressively decreased, while the expression and fluorescence intensity of the senescence-related protein, γH2AX, gradually increased with increasing LIEN concentration in T24 cells. Therefore, our data suggest that LIEN may promote senescence and inhibit proliferation by inhibiting the CDK2/4 and PI3K/AKT pathways in BCa.

Differences of temporomandibular joint symmetry in patients with unilateral complete cleft lip and palate at different developmental stages. / ä¸åŒå‘è‚²æ—¶æœŸå•ä¾§å®Œå ¨æ€§å”‡è ­è£‚æ‚£è€ é¢žä¸‹é¢Œå ³èŠ‚å¯¹ç§°æ€§çš„å·®å¼‚.

OBJECTIVES: Currently, the research results regarding the bilateral temporomandibular joint symmetry in patients at different ages with unilateral complete cleft lip and palate (UCLP) are still controversial. In this study, the position of condyle in the articular fossa and morphology of condyle in UCLP patients at different developmental stages was measured and analyzed to explore the asymmetry difference, which can provide a new theoretical basis for the sequential therapy. METHODS: A total of 90 patients with UCLP were divided into a mixed dentition group (31 cases), a young permanent dentition group (31 cases) and an old permanent dentition group (28 cases) according to age and dentition development. Cone beam computed tomography (CBCT) images were imported into Invivo5 software for 3D reconstruction, and the joint space, anteroposterior diameter, medio-lateral diameter, and height of condylar were measured, and its asymmetry index was calculated. RESULTS: The asymmetry index of condylar height and anteroposterior diameter among the 3 groups, from small to large, was the mixed dentition group0.05), all of them were lower than those in the old permanent dentition group (both P<0.05). Compared with the normal side, the height of fracture condyle was smaller among the 3 groups (all P<0.05), and the anterior joint space was smaller (P<0.05) and the posterior joint space was larger (P<0.05) in the mixed dentition group. CONCLUSIONS: In patients with UCLP, the asymmetry of condylar morphology increases with age, but the condylar position tends to normal. These results suggest that early treatment has important clinical significance for the morphologic development of temporomandibular joint in UCLP patients.

Prognostic values of preoperative neutrophil-to-lymphocyte ratio, platelet-to-lymphocyte ratio and lymphocyte- to-monocyte ratio for patients with muscle- invasive bladder cancer undergoing radical cystectomy. / Valor pronóstico del índice neutrófilo-linfocito, plaqueta- linfocito y linfocito-monocito preoperatorio en pacientes con cáncer músculo invasivo de vejiga sometidos a cistectomía radical.

OBJECTIVE: To study the prognosticvalues of preoperative neutrophil-to-lymphocyte ratio(NLR), platelet-to-lymphocyte ratio (PLR) and lymphocyte-to-monocyte ratio (LMR) for patients with muscle-invasive bladder cancer (MIBC) undergoing radicalcystectomy. METHODS: The clinical data of 186 MIBC patientsreceiving radical cystectomy from January 2013 toOctober 2015 were collected. Receiver operating characteristic(ROC) curves were plotted based on preoperativeNLR, PLR and LMR as well as survival of patientswithin 5 years after surgery. The NLR, PLR and LMRvalues of patients with different clinicopathologicalcharacteristics were described by frequencies.Recurrence-free survival curve was plotted using theKaplan-Meier method, and survival curves were comparedby the log-rank test. Independent risk factorsfor recurrence were explored by multivariate logistic regression analysis. NLR, PLR and LMR were utilizedto establish the recurrence risk scoring model, and theaccuracy for predicting recurrence was assessed byROC curves. RESULTS: NLR groups had significantly differentpathological grade, T stage, lymph node metastasisand tumor number. The differences in age,pathological grade, T stage, lymph node metastasisand tumor number were significant between PLRgroups. Gender, pathological grade, T stage, lymphnode metastasis, tumor number and tumor sizehad significant differences between LMR groups(Pfree survival rate between NLR≥2.45 andNLRand PLRLMR≥3.72 and LMR33.61%) (Ptumor number, lymph node metastasis, NLR, PLRand LMR were independent risk factors for MIBCpatients. After these factors were included into therecurrence risk scoring model, the area under ROCcurve was 0.821. CONCLUSIONS: Preoperative NLR, PLR and LMRare potential biomarkers for determining the prognosisof MIBC patients, and the combination of independent risk factors may work better for prognosticevaluation.

OBJETIVOS: Estudiar el valor pronósticodel índice neutrófilo-linfocito (INL), plaqueta-linfocito(IPL) y linfocito-monocito (ILM) preoperatorioen pacientes con Cáncer de Vejiga Músculo Invasivo(CVMI) sometidos a cistectomía radical.MÉTODOS: Se analizaron los datos clínicos de 186pacientes con CVMI sometidos a cistectomía desdeEnero 2013 a Octubre 2015. Se ejecutaron curvasReceiver operating characteristics (ROC) basadas enel valor preoperatorio de INL, IPL, ILM así como la supervivenciaa los 5 años de la cirugía. Los valores delos INR, IPL, ILM de los pacientes con diferentes característicasclínicopatológicas se describieron mediantefrecuencias. Se obtuvo una curva de supervivencialibre de recurrencia usando el método de Kaplan-Meier, mientras que las curvas de supervivencias secompararon con el log-rank test. Se exploraron losfactores independientes de recurrencia a través de unanálisis de regresión logística. Se usaron los INL, IPL,ILM para establecer un modelo predictive de riesgo derecurrencia cuya precision fue evaluada con curvasROC. RESULTADOS: Las diferencias fueron significativaspara los grupos INL en cuanto a grado histológico,estadio tumoral, metastasis ganglionares y númerode tumores. Las diferencias en edad, grado histológico,estadio tumoral, metastasis a ganglios linfáticosy número de tumores fueron significativas entre losgrupos IPL. Mientras que en los grupos ILM las diferenciasfueron significativas en género, grado histológico,estadio tumar, metastasis a ganglios linfáticos,número y tamaño tumoral. (Psignificativas en la tasa de recurrencia libre de enfermedaden los grupos INL≥2.45 e INL71.11%), los grupos IPL≥157.3 e IPL77.65%), y los grupos ILM≥3.72 e ILMvs. 33.61%) (Pnúmero de tumores, metastasis ganglionares,INL, IPL, ILM fueron factores de riesgo independientesen pacientes con CVMI. Después de incluir estos factoresen el modelo predictive de riesgo de recurrencia, elárea bajo la curva ROC fue 0.821. CONCLUSIONES: Los INL, IPL, ILM preoperatoriosson potenciales biomarcadores para determinar elpronóstico de pacientes con CVMI. La combinaciónde factores independientes podría mejorar la evaluaciónpronóstica.

Perceptions of orthodontists, laypersons, and patients regarding buccal corridors and facial types.

INTRODUCTION: The space on each side of the mouth, between the commissure of the mouth and the buccal surface of the last visible tooth, is called the buccal corridor. The size of the buccal corridor can affect perceptions of facial esthetics. We analyzed the perceptions of orthodontists, laypersons, and orthodontic patients regarding the size of buccal corridors in people with brachyfacial, mesofacial, and dolichofacial types. METHODS: Photographs of 1 male and 1 female model were modified digitally into brachyfacial, mesofacial, and dolichofacial types. Each facial type was further modified to create 5 sizes of buccal corridors. Orthodontists, adult orthodontic patients, and laypersons were invited to rate the photographs. RESULTS: Orthodontists rated lower than the other groups of raters when they evaluated the female model with the buccal corridors of 20% (P <0.05). Laypersons could not distinguish the changes of the buccal corridors when evaluating the male model with brachyfacial and mesofacial (P >0.05). Orthodontic patients rated significantly higher than the orthodontists and the laypersons when evaluating the dolichofacial type of both models (P <0.05). CONCLUSIONS: Orthodontists are more sensitive to the buccal corridors than are orthodontic patients and laypersons. It is only necessary to consider eliminating the patient's buccal corridors when the buccal corridor area ratio is over 15%.

miR­130b regulates PTEN to activate the PI3K/Akt signaling pathway and attenuate oxidative stress­induced injury in diabetic encephalopathy.

Diabetic encephalopathy (DE) is one of the main chronic complications of diabetes, and is characterized by cognitive defects. MicroRNAs (miRNAs/miRs) are widely involved in the development of diabetes­related complications. The present study evaluated the role of miR­130b in DE and investigated its mechanisms of action. PC12 cells and hippocampal cells were exposed to a high glucose environment to induce cell injuries to mimic the in vitro model of DE. Cells were transfected with miR­130b mimic, miR­130b inhibitor and small interfering RNA (si)­phosphatase and tensin homolog (PTEN) to evaluate the protective effect of the miR­130b/PTEN axis against oxidative stress in high glucose­stimulated cells involving Akt activity. Furthermore, the effect of agomir­130b was also assessed on rats with DE. The expression of miR­130b was reduced in the DE models in vivo and in vitro. The administration of miR­130b mimic increased the viability of high glucose­stimulated cells, prevented apoptosis, increased the activity of superoxide dismutase (SOD), decreased the malondialdehyde (MDA) content, activated Akt protein levels and inhibited the mitochondria­mediated apoptotic pathway. The administration of miR­130b inhibitor exerted opposite effects, while si­PTEN reversed the effects of miR­130b inhibitor. In vivo, the administration of agomir­130b attenuated cognitive disorders and neuronal damage, increased SOD activity, reduced the MDA content, activated Akt protein levels and inhibited the mitochondria­mediated apoptosis pathway in rats with DE. On the whole, these results suggest that miR­130b activates the PI3K/Akt signaling pathway to exert protective effects against oxidative stress injury via the regulation of PTEN in rats with DE.

Preclinical activity of cobimetinib alone or in combination with chemotherapy and targeted therapies in renal cell carcinoma.

Background: The poor outcome of advanced renal cell carcinoma (RCC) necessitates new treatments. Cobimetinib is a MEK inhibitor and approved for the treatment of melanoma. This work investigated the efficacy of cobimetinib alone and in combination with anti-RCC drugs. Methods: Proliferation and apoptosis assays were performed, and combination index was analyzed on RCC cell lines (CaKi-2, 786-O, A-704, ACHN and A489) and xenograft models. Immunoblotting analysis was conducted to investigate the MAPK pathway. Results: Cobimetinib was active against RCC cells, with IC50 at 0.006-0.8µM, and acted synergistically with standard-of-care therapy. Cobimetinib at nontoxic doses prevented tumor formation, inhibited tumor growth and enhanced efficacy of 5-fluorouracil, sorafenib and sunitinib via suppressing Raf/MEK/ERK, leading to MAPK pathway inhibition. Conclusion: Our findings demonstrate the potent anti-RCC activity of cobimetinib and its synergism with RCC standard-of-care drugs, and confirm the underlying mechanism of the action of cobimetinib.

Curcumin regulates EZH2/Wnt/ß-Catenin pathway in the mandible and femur of ovariectomized osteoporosis rats.

Osteoporosis (OP) behaves in different manners in different parts of the skeleton. This study aims to investigate the effects of curcumin on bone mass of the mandibular and femur from ovariectomized OP rats and to validate whether enhancer of zeste homolog 2 (EZH2)/Wnt/ß-Catenin pathway is involved in this process. Curcumin was administered intragastrically into ovariectomized rats for 12 weeks. The bone parameters and the morphology of the trabecular bone of the left mandible and left femur were assessed by micro-computed tomography assay. Morphological changes of the left mandible and left femur were evaluated by hematoxylin and eosin staining. The mRNA levels of EZH2, ß-Catenin, and Runx2 in the right mandible and right femur were examined by quantitative real-time polymerase chain reaction. Immunohistochemistry was performed to assess EZH2 expression. Both the mandible and femur exhibited OP-like changes in ovariectomized rats, while the mandible bone resorption was less than the femur bone resorption. Curcumin intragastric administration improved bone microstructure and promoted bone formation in the mandible and femur. Curcumin inhibited EZH2 mRNA level and induced that of ß-Catenin and Runx2 in the mandible and femur. Collectively, curcumin exerts protective effects against OP, possibly by regulating the EZH2/Wnt/ß-Catenin pathway.

Discovery of Clinical Candidate (5-(3-(4-Chlorophenoxy)prop-1-yn-1-yl)-3-hydroxypicolinoyl)glycine, an Orally Bioavailable Prolyl Hydroxylase Inhibitor for the Treatment of Anemia.

The design and discovery of a new series of (5-alkynyl-3-hydroxypicolinoyl)glycine inhibitors of prolyl hydroxylase (PHD) are described. These compounds showed potent in vitro inhibitory activity toward PHD2 in a fluorescence polarization-based assay. Remarkably, oral administration of 17, with an IC50 of 64.2 nM toward PHD2, was found to stabilize HIF-α, elevate erythropoietin (EPO), and alleviate anemia in a cisplatin-induced anemia mouse model with an oral dose of 25 mg/kg. Rat and dog studies showed that 17 has good pharmacokinetic properties, with oral bioavailabilities of 55.7 and 54.0%, respectively, and shows excellent safety profiles even at a high dose of 200 mg/kg in these animals. Based on these results, 17 is currently being evaluated in a phase I clinical trial for anemia.

Association of finasteride with prostate cancer: A systematic review and meta-analysis.

BACKGROUND: The Prostate Cancer Prevention Trial has shown a protective effect of finasteride on prostate cancer, but it also showed that finasteride can increase the risk of high-grade prostate cancer. Several studies have investigated the relationship between finasteride and prostate cancer, but these studies have shown inconsistent results. ETHICS: The protocol was approved by the institutional review board of each study center. Written informed consent will be obtained from all patients before registration, in accordance with the Declaration of Helsinki. METHODS: We performed a systematic literature review and meta-analysis to assess the association between finasteride and prostate cancer. Systematic literature searches were conducted using PubMed, EMBASE, Science Direct/Elsevier, MEDLINE, CNKI, and the Cochrane Library up to October 2018 to identify studies that involved the relationship between finasteride and prostate cancer. Meta-analysis was performed using Review Manager and Stata software. Combined ORs were identified with 95% confidence intervals (95% CI) in a random or fixed effects model. RESULTS: Eight studies were identified, including 54,335 cases of patients that used finasteride and 9197 patients who served as placebo controls. Our results illustrate that there is a significant correlation between finasteride use and prostate cancer with combined ORs of 0.70 [0.51, 0.96]. A significant correlation between finasteride use and high-grade prostate cancer was also observed with combined ORs of 2.10 [1.85, 2.38]. CONCLUSIONS: This study confirms that finasteride significantly reduced the risk of prostate cancer; however, the malignant degree of prostate cancer was increased. Studies with larger sample sizes are needed to better clarify the correlation between finasteride use and prostate cancer.

[Characteristics of mandible and mandibular dentition according to vertical facial skeletal features of adolescents].

OBJECTIVE: We aim to examine teenagers with varying vertical facial skeletal types with near-normal occlusion. We further aim to identify and study mandibular morphology and dentition characteristics to establish normal ranges and variations for future clinical reference. METHODS: According to the results of the case studies, 42 adolescents with near-normal occlusion were divided into three groups, namely, low- (7 cases), average- (23 cases) and high-angle (12 cases) groups. We used Invivo 5 software for Digital Imaging and Communications in Medicine (DICOM) data to calculate the cant of occlusal plane, axis corner of L6, ∠L1/MP, ∠L6/MP, Balkwill angle and Bonwill triangle of each group. RESULTS: Markedly, the finding shows that the cant of occlusal plane and axis corner of L6 in the low-angle group were smaller than those of the other two groups. In the average-angle group, ∠L1/MP was larger than that of the high-angle group. Lastly, in the high-angle group, ∠L6/MP was smaller than those of the two other groups. On the one hand, these differences were considered statistically significant (P<0.05). On the other hand, other measurements show that these differences were considered statistically non-significant (P>0.05). CONCLUSIONS: In the low-angle group, the parallelisation of the occlusal plane tends to be more obvious compared with the two other groups. In the coronal section of the low-angle group, the axis of the mandibular first molar is up-right, whereas it is distally tilted in the sagittal section of the high-angle group. Furthermore, a number of differences are noted in the adult groups. Factors, such as aging and development in the craniofacial region, lead to changes in functional occlusion.

[Three-dimensional analysis for changes in dentigerous cyst-associated maxillary canines after marsupialization in adolescents].

OBJECTIVE: To observe three-dimensional changes of dentigerous cyst-associated maxillary canines (DCAMC) in adolescents after marsupialization by using cone beam computed tomography (CBCT).
 Methods: A total of 34 DCAMC patients with dentigerous cyst aged 10-14 were divided into central type and lateral type, while canines on the non-cyst side served as a control. A three-dimensional reference frame was set up to analyze the position, angle changes and influential factors for DCAMC by using CBCT before operation and in 3-6 month after operation.
 Results: 1) Compared with pre-operation, there was significant vertical movement in DCAMC after marsupialization. Tip of tooth moved labially while tooth axis inclined mesiodistally; 2) Horizontal, vertical movement and mesiodistal inclination of DCAMC were significantly greater than those in the health side; 3) Compared with the lateral type DCAMC, the central type DCAMC showed a significant changes in labial inclination; 4) Horizontal movement, mesiodistal and labial inclination of lateral type DCAMC were all evidently greater than those of the central type DCAMC; 5) Vertical movement and inclination of DCAMC after marsupialization were significantly correlated to the time interval (r=0.354, 0.374, both P<0.05), while vertical movement of cuspid in health side was significantly negative correlated with the patients' age and the level of root formation (r=-0.506, -0.721, both P<0.01).
 Conclusion: DCAMC in adolescents can obtain obvious changes in position and angles after marsupialization regardless of the level of root formation, which is beneficial for further orthodontic treatment.

[Correlation between adenoid hypertrophy, maxillary sinus mucosal thickening and dentofacial development in children].

PURPOSE：To investigate the effects of adenoid hypertrophy and maxillary sinus mucosal thickening on dentofacial development. METHODS：The selected subjects were divided into 4 groups according to the inclusion criteria: group A (adenoid hypertrophy with maxillary sinus mucosal thickening), group B (adenoid hypertrophy without maxillary sinus mucosal thickening), group C (normal adenoid with maxillary sinus mucosal thickening), and group D (normal adenoid without maxillary sinus mucosal thickening). There were 20 subjects in each group, aging from 12 to 14 years old. The volume of maxillary sinus was measured by Mimics software. The adenoid, dental arch width, basal bone width and palatal height were measured by Dolphin software and dentofacial measurements were performed in the lateral cephalograms derived from cone-beam CT (CBCT). The data were analyzed with SPSS 24.0 software package. RESULTS： There was no significant difference in dentofacial measurements between group B and group D or group C and group D，except for ANB angle (P<0.05). Compared with group D, SNB, ANB, Wits appraisal, NA-APo, MP-HP, N-Me, S-Go/N-Me, N-ANS (perp HP), sum of three angles, Ar-Go of group A were significantly different (P<0.05). Neither left nor right maxillary sinus bony volume had significant difference between group B and D or group C and D. CONCLUSIONS： Both adenoid hypertrophy and maxillary sinus mucosal thickening have impact on dentofacial development. Moderate or more severe adenoid hypertrophy with maxillary sinus mucosal thickening has greater impact on dentofacial development over adenoid hypertrophy or maxillary sinus mucosal thickening alone.

[Three dimensional measurement of craniofacial hard tissues for the Han nationality with normal occlusion in Changsha area].

OBJECTIVE: To explore the influence of gender and age on the measurement of cone beam CT (CBCT) in normal and occluded craniofacial hard tissues for Han nationality in Changsha area.
 Methods: A total of 80 CBCT data of normal and occluded craniofacial hard tissues for Han nationality in Changsha area were collected, including 40 adults [16 males and 24 females, aged (17.57±1.83) years] and 40 children[16 males and 24 females, age (11.50±1.26) years]. Three-dimensional cephalometric measurements were carried out by Dolphion Imaging software, and the influence of gender and age was compared.
 Results: The symmetry of craniofacial hard tissues in male and female in the adults was good (the maximum asymmetric rate R was 6.39% and the minimum asymmetric rate R was 0.08%). There was no significant differencein the anterior palatal width, palatal width, the upper incisor protrusion distance, the lower incisor protrusion distance, hyoid-mandibular plane, basal epiglottis width, and palatal plane airway width between the males and females (all P>0.05); while the remaining indicators were significantly higher in males than those in females (all P<0.05). There was no significant gender difference in angle indicators (all P>0.05). There were significant differences in the posterior height, the maxillary length, the lower incisor protrusion, and the mandibular plane angle between the adults and the children(all P<0.05); but the rest of indicators were not significant difference (all P>0.05).
 Conclusion: The symmetry of craniofacial hard tissues for Han nationality in Changsha area is good. The gender and age affect the line space measurements but not affect the most of the angle measurements.

[Three-dimensional morphological features of temporomandibular joint in skeletal malocclusion Class III patients with different vertical skeletal facial types].

OBJECTIVE: To investigate three-dimensional morphological features of temporomandibular joint in skeletal malocclusion Class III with different vertical skeletal facial types.
 Methods: A total of 46 adults with skeletal malocclusion Class III were enrolled and allocated into a normal-angle, a high-angle and a low-angle groups. All patients were undergone cone beam computed tomography (CBCT). Images of temporomandibular joint were reconstructed and analyzed by Invivo 5. Nine measurements relevant to the positions and forms of condyle as well as joint spaces were performed.
 Results: Significant differences were not observed between the 2 sides of each group among skeletal malocclusion Class III (P>0.05). Compared with the high-angle and normal-angle patients, the low-angle patients had larger superior spaces, bigger gradients of the articular tublecle, longer condyle, and larger internal spaces between the condyle and the fossa. Compared with the low-angle and normal-angle patients, the high-angle patients had smaller condylar antero-posterior diameters.
 Conclusion: Class III malocclusion patients with different vertical skeletal patterns have different positions and forms of condyles, which should be paid attention to in clinic.

[Esthetic evaluation of frontal smile on different crown heights of lateral incisor and canine].

OBJECTIVE: To investigate the effect of different crown heights of lateral incisor and canine on smile esthetics perception between orthodontists and patients.
 Methods: A total of 31 orthodontists and 56 patients on smile aesthetics perception were investigated. We adjusted the height of lateral incisor and canine to get 20 kinds of anterior tooth area morphology by Photoshop and asked interviewees to grade. Scores of satisfaction were recorded by Likert method.
 Results: Subjects in the 2 groups preferred smiles with upper anterior teeth edge parallel to lower lip. There was better acceptance for longer canines and less satisfaction at shorter lateral incisors in patients. Patients also got higher discrete degree of evaluation results and more rigorous about smile esthetics than orthodontists.
 Conclusion: Orthodontists and patients have different satisfaction at esthetics of anterior teeth. Esthetics preference should be considered in orthodontic treatment schedule.

A squamous odontogenic tumor following an orthodontic micro-screw: A rare case report and review of the literature.

We reported a very rare case of squamous odontogenic tumor(SOT) in a 23-year-old female. The tumor arose after an implanting operation of an orthodontic micro-screw, and was definitely diagnosed by the histopathological examination. Based on the case report and a review of the literature, we discussed about the general features, differential diagnosis and pathogenesis of SOT.

Recent Advances in the Discovery of HIF-1α-p300/CBP Inhibitors as Anti-Cancer Agents.

Hypoxia-inducible factor-1 (HIF-1), a heterodimeric (containing α and ß subunits) transcription factor, is involved in hypoxia response pathway that regulates the expression of many tumorrelated genes. The stabilized HIF-1 heterodimer couples to the general co-activators p300/CBP (CREB binding protein), forming an active transcription factor to initiate hypoxic responses. Inhibiting the transcription factor-coactivator HIF-1α-p300/CBP interaction represents an attractive approach for blocking hypoxia pathway in tumors. Recently, diverse HIF-1α-p300/CBP inhibitors have been designed and their anti-tumor activities have been evaluated. The developments of inhibitors of HIF-1α- p300/CBP are discussed in this review. An outline of structures and biological activities of these inhibitors can be traced, along with the approaches for inhibitors discovery. The challenges in identifying novel and selective potent inhibitors of HIF-1α-p300/CBP are also put forward.

[Biomechanical effect of 2 anchorages on maxillary protraction with cleft lip and palate: a finite element analysis].

PURPOSE: To establish cranio-maxillary complex finite element models (FEMs) in cleft lip and palate (CLP) patients with miniplate and tooth-borne anchorage, and to investigate the biomechanical effects on maxillary protraction. METHODS: The protracting process was simulated on FEMs established from a male patient's cone beam CT (CBCT) data to analyze the displacement and stress from different appliances. RESULTS: Four FEMs of unilateral cleft lip and palate (UCLP) or bilateral cleft lip and palate (BCLP) patients' cranio-maxillary complex with MA and TA were established. The maxillary arch on both sides of the cleft moved towards the cleft side during protraction, which was more obvious in the miniplate anchorage three-dimensional finite element models(FEM-MA) than the tooth-borne anchorage three-dimensional finite element models (FEM-TA).The amount of forward, downward displacement of the inferior orbital rim, paranasal area and middle maxilla point in the FEM-MA was larger than that in the FEM-TA, while the amount of forward displacement of premaxilla and upper canine in the FEM-TA was larger than that in the FEM-MA. The FEM-MA exhibited an orthopedic effect with more favorable stress distribution on the middle maxilla point while the FEM-TA showed a dentoalveolar effect with prominent stress distribution on the upper canine point. In addition, the FEM-MA showed a larger stress distribution area and sutural stress value than did the FEM-TA. The UCLP models showed an asymmetric pattern in stress distribution and displacement, which was larger on the cleft side than that on the non-cleft side. The amount of displacement of premaxilla in the BCLP models was smaller than that in the UCLP models. CONCLUSIONS: The established models have high geomagic and biomechanical similarities. It would be more advantageous to obtain more aesthetic outcomes and better stability using the miniplate anchorage.

Affinity-Based Fluorescence Polarization Assay for High-Throughput Screening of Prolyl Hydroxylase 2 Inhibitors.

Prolyl hydroxylase domain 2 (PHD2) enzyme, a Fe(II) and 2-oxoglutarate (2-OG) dependent oxygenase, mediates key physiological responses to hypoxia by modulating the levels of hypoxia inducible factor 1-α (HIF1α). PHD2 has been shown to have the therapeutic potentials for conditions including anemia and ischemic disease. Currently, many activity-based assays have been developed for identifying PHD2 inhibitors. Here we report an affinity-based fluorescence polarization method using FITC-labeled HIF1α (556-574) peptide as a probe for quantitative and site-specific screening of small molecule PHD2 inhibitors.