Mechanism and potential contributing factors to temporomandibular joint osteoarthritis.

OBJECTIVE: To investigate the mechanism of and potential contributing factors to temporomandibular joint osteoarthritis (TMJOA) caused by oestrogen deficiency with a persistent high bite force. MATERIALS AND METHODS: A TMJOA model was generated by subjecting 6-week-old female rats to ovariectomy (OVX) and feeding them a hard feed. The rats (n = 12/group) were divided into sham (control); OVX; OVX+hard feed (HF); OVX+hard feed+local-joint injection of 17ß-oestradiol (an oestrogen) (E2); and OVX+hard feed+local-joint injection of rapamycin (an autophagy activator) (RAPA)groups. Condyles were stained with haematoxylin-eosin and Safranin O Fast Green. The expression of Beclin 1, LC3 and p-mTOR in condylar cartilages was analysed. RESULTS: Tissue staining revealed thinner condylar cartilage, varying numbers or fewer hypertrophic chondrocytes, and lower proteoglycan content in the cartilage matrix of the OVX group. These characteristics were more pronounced in the HF group, but were significantly recovered in the E2 and RAPA groups. Immunohistochemical staining revealed significantly lower autophagic flux in OVX/HF groups and a higher one in E2/RAPA groups. CONCLUSIONS: A persistent high bite force could aggravate TMJOA induced by oestrogen deficiency, and the application of oestrogen or rapamycin could delay its progression. Additionally, autophagy may play a role in the development of TMJOA.

Effect of 17ß-estradiol on the proliferation of condylar chondrocytes.

OBJECTIVES: To study the effects of 17ß-estradiol (E2) on the regulation of the proliferation of condylar chondrocytes and provide a preliminary discussion on the role of phosphorylate-mammalian target of rapamycin (p-mTOR) in this regulatory process. METHODS: Condylar chondrocytes were isolated from 6-week-old female rats for primary culture. Drug treatment with different concentrations of E2 and/or rapamycin (RAPA) was carried out on second-generation cells. Cell Counting Kit 8 was used to measure the cell viability of condylar chondrocytes after culture for 24, 48, or 72 h, and reverse transcription-polymerase chain reaction (RT-PCR) was applied to detect the relative gene expression of estrogen receptor alpha (ERα), estrogen receptor beta (ERß), collagen type Ⅱ (COLⅡ), autophagy-related gene 6 (Beclin-1), and autophagy-related gene 5 (ATG-5). Western blot was employed to determine the relative protein expression of ERα, ERß, Beclin-1, lipid-modified light chain 3B (LC3-Ⅱ), and p-mTOR. RESULTS: E2 could significantly promote the proliferation of chondrocytes cultured in vitro, and maximum promotion was achieved at a concentration of 10-8 mol·L-1. RAPA could significantly inhibit cell proliferation. E2 at aconcentration of 10-8 mol·L-1 could greatly improve the gene expression levels of ERα and COLⅡ (P<0.01) with the protein levels of ERα and p-mTOR (P<0.05), and decrease the gene expression levels of Beclin-1 and ATG-5 (P<0.05) with the protein levels of Beclin-1 and LC3-Ⅱ (P<0.05). RAPA could also enhance the relative protein expression of Beclin-1 and LC3-Ⅱ (P<0.01), and reduce the expression of p-mTOR (P<0.01). Treatment with the ERα antagonist significantly reduced the expression of p-mTOR in cells (P<0.01). CONCLUSIONS: At a concentration of 10-8 mol·L-1, E2 could effectively activate the phosphorylation of mTOR through the ERα-p-mTOR pathway, inhibit cell autophagy, and promote the proliferation of condylar chondrocytes.

Mechanical thrombectomy for acute occlusion of the posterior inferior cerebellar artery: A case report.

BACKGROUND: Mechanical thrombectomy (MT) has been demonstrated to be useful for the treatment of ischemic stroke in patients with large vessel occlusions. However, recanalization by MT is not recommended for distal vessels such as second-order branches of the middle cerebral artery and posterior inferior cerebellar artery (PICA). Because of the small size and tortuosity of these arteries, the risks of using the available endovascular devices outweigh the benefits of treatment. However, MT appears to be effective in patients with primary distal vessel occlusion in eloquent areas, those with a high National Institutes of Health Stroke Scale score, and those ineligible for recombinant tissue plasminogen activator therapy. Here, we report the use of MT for treating acute occlusion of the PICA using a direct-aspiration first-pass technique (ADAPT). CASE SUMMARY: In this case, the patient received acute occlusion of the PICA with ADAPT when right internal carotid artery stenting was performed. CONCLUSION: With the introduction of advanced endovascular devices, MT may now be a feasible treatment for acute occlusion of the PICA.

Cognitive dysfunction in a patient with migraine and APT1A2 mutation: a case report.

BACKGROUND: Hemiplegic migraine (HM) is a rare type of migraine with aura. Some reports have described the clinical manifestations in HM patients with the ATP1A2 mutation. But the impact of the ATP1A2 mutation on cognitive profile in HM patients has not been evaluated in detail. Here we report a patient with cognitive dysfunction in specific area. CASE PRESENTATION: A 15-year-old boy with an aura that included disturbances in consciousness, associated with fever, vomiting, hemiplegia, and aphasia. He was diagnosed with HM with the ATP1A2 mutation before. He had trouble in mathematics and depicting three-dimensional things. CONCLUSIONS: The HM with ATP1A2 patient could develop permanent cognitive dysfunction. Therefore, the cognitive quotient should be carefully and comprehensively evaluated.

A novel 3D heteropoly blue type photo-Fenton-like catalyst and its ability to remove dye pollution.

A environment-friendly 3D inorganic heteropoly blue (HPB) Ba2Na2 [HPWV4WVI8O40]·26H2O was directly synthesized by hydrothermal method and characterized by means of ICP, IR, XPS, X-ray single crystal and X-ray powder diffraction. It was an efficient heterogeneous photo-Fenton-like catalyst to degrade anionic dye methyl orange under visible light irradiation. It removed cationic dyes methylene blue in neutral environment and rhodamine B in acidic condition via flocculation. The removal efficiency of methylene blue and rhodamine B by flocculation was more than 95%. Moreover, it could degrade methyl orange and flocculate rhodamine B at the same time. For MO and MO-RhB solutions, the degradation rates of MO in 60 min were 85.5% and 49.1%, respectively. Furthermore, the possible pathways for the production of active species in the MO degradation reaction were discussed. This is the first HPB constructed with 4e-reduced phosphotungstate, Ba and Na ions, having the properties of photo-Fenton-like catalyst and flocculant.

A heteropoly blue as environmental friendly material: An excellent heterogeneous Fenton-like catalyst and flocculent.

The first 3D heteropoly blue Ba2Na4[SiW4VW8VIO40]·19H2O (1) as heterogeneous Fenton-like catalyst and flocculent was hydrothermally synthesized and fully characterized by various methods 1 was an efficient Fenton-like catalyst for degradation of phenol with degradation rate of 92.1% (visible light irradiation), and 89.0% (no light) in 90min, respectively. The degradation efficiency of anionic dye methyl orange was 97.0% in 5min, when 1 was used as photo-Fenton-like catalyst under visible light. And 1 was a nice flocculent for cationic dyes methylene blue and rhodamine B, the removal rates were both above 95%. Moreover, 1 could degrade methyl orange and flocculate rhodamine B at the same time, but the degradation rate decreased from 100% to 77.5% in 60min, while the flocculation of RhB in 10min was not affected.

Drug Discovery against Psoriasis: Identification of a New Potent FMS-like Tyrosine Kinase 3 (FLT3) Inhibitor, 1-(4-((1H-Pyrazolo[3,4-d]pyrimidin-4-yl)oxy)-3-fluorophenyl)-3-(5-(tert-butyl)isoxazol-3-yl)urea, That Showed Potent Activity in a Psoriatic Animal Model.

Psoriasis is a chronic T-cell-mediated autoimmune disease, and FMS-like tyrosine kinase 3 (FLT3) has been considered as a potential molecular target for the treatment of psoriasis. In this investigation, structural optimization was performed on a lead compound, 1-(4-(1H-pyrazolo[3,4-d]pyrimidin-4-yloxy)phenyl)-3-(4-chloro-3-(trifluoromethyl)phenyl)urea (1), which showed a moderate inhibitory activity againt FLT3. A series of pyrazolo[3,4-d]pyrimidine derivatives were synthesized, and structure-activity relationship analysis led to the discovery of a number of potent FLT3 inhibitors. One of the most active compounds, 1-(4-(1H-pyrazolo[3,4-d]pyrimidin-4-yloxy)-3-fluorophenyl)-3-(5-tert-butylisoxazol-3-yl)urea (18b), was then chosen for in-depth antipsoriasis studies because this compound displayed the highest potency in a preliminary antipsoriasis test. Compound 18b exhibited significant antipsoriatic effects in the K14-VEGF transgenic mouse model of psoriasis, and no recurrence was found 15 days later after the last administration. Detailed mechanisms of action of compound 18b were also investigated. Collectively, compound 18b could be a potential drug candidate for psoriasis treatment.

Cytokine-induced killer cells combined with dendritic cells inhibited liver cancer cells.

OBJECTIVES: To investigate the prognosis of advanced liver cancer patients treated with CIK-DCs and the mechanism of apoptosis of HEPG 2 cells. METHODS: 67 patients were enrolled in the study. Peripheral blood mononuclear cells (PBMCs) were separated, of which adherent PBMCs used granulocyte 2 macrophage colony2 stimulating factor (GM2CSF), tumor necrosis factor 2α (TNF2α), and interleukin 24 (IL24) to induce DCs, which were sensitized with antigen of autologous or exogenous cancer cells to obtain Ag-DCs; suspended PBMCs used interferon 2γ (IFN2γ), IL-2, and CD 3 monoclonal antibody (CD3mAb) respectively, to induce CIK cells. DCs and CIK cells were cultured together. Flow cytometry was used to detect the phenotypes of DCs and CIK cells, and the blood retransfused into patients. Western blot and flow cytometer were used to analyze the growth cycle of HepG 2 cells and the expression of BAX and PCNA. RESULTS: No patients underwent complete remission, 5 obtained partial remission and 29 had stable disease. Of the 31 patients whose lesions could not be evaluated, 17 received effective treatment, showing that the immune response was enhanced. In vitro laboratory experiments revealed that DC-CIK cells markedly affected the growth cycle of HepG 2 cells. Analysis showed that DC-CIK cells enhanced the gene expression of BAX and inhibited the activity of PCNA. CONCLUSIONS: Co-cultured DCs and CIK cells inhibit the proliferation and migration of liver cancer cells by down-regulating PCNA and up-regulating BAX. This approach may be an effective method to treat advanced liver cancer.

[Evaluation of therapeutic effect of children's dental treatment under general anesthesia: 111 cases report].

OBJECTIVE: To retrospectively evaluate the efficiency of dental treatment under general anesthesia (GA) in child patients, and analyze the related factors. METHODS: The records of patients treated under GA in the Department of Pediatric Dentistry, Peking University School and Hospital of Stomatology, between Aug 2008 and Jun 2012 were collected and analyzed. Two hundred and twenty eight records were found, of which 111 patients under 18 years old who were recalled more than 3 months after GA were selected randomly. The unplanned treatments including caries, failed restoration, root canal treatment and space maintenance fall-off etc. were recorded and analyzed. The survival rate and median survival time of the teeth were calculated, and a multivariate analysis was performed by Cox proportional hazard model. RESULTS: Totally, there were 1 415 teeth treated under GA. The median survival time was 825 days, 77.0% of the teeth were present during their recall period. The median time of the first unplanned treatment was 215 days, and the failed restoration was the main reason for the unplanned treatment. Other factors such as the age at treatment, gender, total number of decayed teeth, reason for GA, and living place were found unassociated with the survival rate. CONCLUSION: The effect of dental treatment under GA is satisfied. Regular dental visit after GA is very important for children's dental health.

The effect of intranasal carbon dioxide on the acute response to nasal challenge with allergen.

Intranasal carbon dioxide (CO(2)) was shown to reduce symptoms of seasonal allergic rhinitis (SAR). This study was designed to evaluate the effect of CO(2) on nasal allergen challenge. We conducted a randomized, controlled, crossover trial in 12 subjects with SAR outside their pollen season. Thirty minutes after a 20-second exposure to CO(2) or no exposure, subjects underwent a unilateral, localized, nasal allergen challenge. Filter paper disks were placed on the nasal septum to deliver a sham challenge followed by 2 increasing doses of either grass or ragweed allergen. Secretions were collected from both sides of the septum to evaluate the nasonasal reflex and were assayed for histamine. Nasal and eye symptoms were recorded. The primary outcome measure was the contralateral, reflex, secretory response to allergen as measured by secretion weights. Secondary outcome measures included ipsilateral nasal secretion weights, nasal and eye symptoms, levels of histamine in nasal secretions, and eosinophils in nasal scrapings. Subjects reported a transient burning sensation during exposure to CO(2). Compared with no treatment, active treatment resulted in a significant reduction in sneezes (p = 0.05), contralateral secretion weights (p = 0.04), and bilateral runny nose symptoms (p = 0.01). Ipsilateral secretion weights were numerically reduced. Histamine levels in ipsilateral nasal secretions increased significantly when the subjects received sham treatment but did not increase after pretreatment with CO(2). Treatment with nasal CO(2) resulted in partial reduction of the acute response to allergen challenge. Reflex responses were reduced, supporting an effect on neuronal mechanisms, which predict usefulness in the treatment of allergic rhinitis. Registered with the U.S. National Institutes of Health clinicaltrials.gov. Identifier: NCT00618410.