Periodontitis-induced oral microbiome alterations provide clues on how periodontitis exacerbates colitis.

AIM: To evaluate whether and how microbiota-derived metabolites associated with periodontitis aggravate colitis in mice. MATERIALS AND METHODS: A mouse model of periodontitis and colitis was constructed. Unbiased transcriptomic analyses of the colon were performed to explore important pathways through which periodontitis exacerbated colitis. Oral and gut bacteria were analysed using 16S rRNA sequencing. Gas chromatography-mass spectrometry was used to observe the alterations of oral and gut metabolites. Isolated intestinal lamina propria lymphocytes were analysed by flow cytometry. Inflammasome pathway was detected using qRT-PCR, Western blotting or ELISA. RESULTS: Periodontitis activated the colonic inflammasome pathway and altered the gut microbial composition and metabolite profiles in mice with colitis. Notably, periodontitis induced increase of the faecal metabolite isoleucine (Ile) which was synthesized by microbiota and plants. Moreover, periodontitis upregulated the Ile levels in saliva, but not in serum, indicating that Ile might be an oral pathobiont-synthesizing metabolite that transited from the oral cavity to the gut. Ile triggered the inflammasome pathway, upregulated the number of inflammatory IL-1ßhigh MHCIIhigh Ly6Chigh monocytes in colonic lamina propria, and exacerbated colitis. Further studies found that the Ile metabolite acetyl-coenzyme A positively regulated NLRP3 inflammasome by KAT5-mediated acetylation of NLRP3. CONCLUSIONS: Our study revealed that alteration in periodontitis-induced microbial metabolites deteriorated colitis in a mouse model and that this was associated with Ile production.

A Comparative Study of Bone Tissue Morphology and Bone Turnover Markers in Different Stages of Kümmell's Disease.

Although the incidence of Kümmell's disease (KD) has increased significantly in recent years, its pathological mechanism is still unclear. The aim of this study is to investigate the histomorphological characteristics and the kinetics of bone turnover markers following KD. This study involves 82 patients with KD, and fasting blood samples were collected to detect the serum concentration of bone turnover markers. A transpedicular bone biopsy was performed to collect bone biopsy specimens during vertebroplasty surgery. According to Li's staging system for KD, all cases were divided into 3 stages. Comparisons of the 3 stages and their kinetics were conducted. 19 (23.2%) patients were classified as Stage I, 39 (47.5%) as Stage II, 24 (29.2%) as Stage III. Bone histomorphological analysis showed that the ratios of WBV and FV reached a peak value (14.23 ± 0.62 and 54.63% ± 3.52%; p = 0.001 and 0.001) at Stage I. The ratios of NBV remained low (4.81% ± 2.61%) in Stage I, but reached a peak value (18.50% ± 2.77%; p = 0.001) in Stage III. Bone metabolism index level showed that the serum concentration of OST and ß-CTX continued to rise after fracture, reaching a peak value of (38.15 ± 3.84 and 1.31 ± 0.16 ng/Ml; p = 0.073 and 0.026), while PINP reached its valley value (48.57 ± 7.25 ng/Ml; p = 0.069) in Stage III. A significant and negative correlation was found between the ratio of ß-CTX and EBV/TV (p= 0.0194, r = -0.2037), and FV/TV (p= 0.0001, r = -0.5368). At the same time, ß-CTX had a positive significant correlation with the NBV/TV (p= 0.0001, r = 0.6218). Bone histomorphometric analysis and bone turnover markers showed that KD has a possibility of healing in the early stage.

Caveolin-1 mediates gene transfer and cytotoxicity of polyethyleneimine in mammalian cell lines.

Polyethyleneimine (PEI) is a cost-effective and non-viral vector for gene transfer, but the factors determining gene transfer efficiency and cytotoxicity of PEI in different mammalian cell lines remain largely unknown. In the present study, three different cell lines were chosen for investigation. Using pEGFP DNA and PEI, 21.5, 29.2, and 92.1 % of GFP-positive cells were obtained in BMSC, Hela, and 293T, respectively. In luciferase reporter assay, similar results were obtained (for luciferase activity, BMSC < Hela < 293T cells). By MTT test and cell apoptotic marker analysis, we demonstrated that high gene transfer efficiency is accompanied with high cytotoxicity of PEI. Moreover, we found that high expression level of caveolin-1 was accompanied with high gene transfer efficiency and cytotoxicity of PEI in 293T cells. More convincingly, caveolin-1 silencing in 293T could reduce both gene transfer efficiency and cytotoxicity of PEI. In contrast, caveolin-1 overexpression in BMSCs increases both gene transfer efficiency and cytotoxicity of PEI. Taken together, our study suggests that caveolin-1 may at least in part determine gene transfer efficiency and cytotoxicity of PEI in mammalian cell lines, providing caveolin-1 as a potential target for improving gene transfer efficiency when applying positively charged polyplexes to cell transfection.

Effect of Initial Crack Position on Crack Propagation Behaviors of Heavy-Duty Transmission Gear.

The tooth bending fatigue fracture is caused by the alternating loads for the heavy-duty transmission gears. The crack initiation and propagation are the two major parts in the failure process. The crack propagation behavior is mainly affected by initial crack position except for the load and material properties. In this paper, the crack propagation model of a gear is established under the considering of crack initiation location by using extended finite element method (XFEM). The model accuracy is verified by testing results of strain and fractography by conducting the single-tooth bending fatigue experiment. The influence of crack initiation locations on subsequent crack propagation behavior is analyzed. The crack length in the tooth width direction and depth direction is faster when the initial crack is located in the middle of root surface. The crack growth rate is lower for the initial crack located in the surface close to the end surface of the gear.

[Clinical application of an improved classification system of Kümmell's disease].

OBJECTIVE: To report an improved classification system of Kümmell's disease and its clinical application. METHODS: Based on CT and MRI, an improved classification system of Kümmell's disease was proposed in terms of the integrity of sagittal endplate, the integrity of posterior wall of vertebral body, and the degree of vertebral compression. Between January 2011 and March 2018, the improved classification system was used to evaluate and guide the treatment of 78 patients with Kümmell's disease. There were 13 males and 65 females. The mean age was 69.1 years (range, 54-85 years). The mean disease duration was 4.0 months (range, 1-8 months). The mean T value of bone mineral density was -3.66 (range, -3.86- -3.34).The fractures located at thoracic vertebrae in 47 cases and lumbar vertebrae in 31 cases. According to the modified classification system of Kümmell's disease, there were 11 cases of type A1, 13 cases of type A2, 2 cases of type A3, 10 cases of type B1, 18 cases of type B2, 4 cases of type B3, 4 cases of type C1, 5 cases of type C2, and 11 cases of type C3. According to the classification results, the patients of types A and B were treated with percutaneous kyphoplasty (PKP), while the patients of type C were treated with PKP or intra- vertebral fixation according to the degree of vertebral reduction. Visual analogue scale (VAS) score and Oswestry Disability Index (ODI) were used to evaluate clinical efficacy. The heights of the anterior, middle, and posterior edges of the vertebrae and the Cobb angle were measured to evaluate the reduction of the injured vertebrae and the improvement of kyphosis deformity. The complications were recorded. RESULTS: The statistical analysis showed that the improved classification system has good consistency. All patients were followed up 12-36 months (mean, 24.3 months). The heights of anterior, middle, and posterior edges of the vertebrae, Cobb angle, VAS score, and ODI of all types of patients at last follow-up showed significant differences when compared with those before operation ( P<0.05). After operation, 4 patients of type A2 had different degree of vertebral height loss; 2 patients of type B2, 3 patients of type C1, and 2 patients of type C2 developed asymptomatic bone cement leakage during PKP; 2 patients of type B3 and 3 patients of type C2 underwent percutaneous internal fixation and vertebral augmentation due to bone cement loosening. CONCLUSION: The modified classification system of Kümmell's disease can be used to guide treatment of Kümmell's disease, but the number of clinical application cases is limited, and further application and observation are needed.

Controlled water vapor transmission rate promotes wound-healing via wound re-epithelialization and contraction enhancement.

A desirable microenvironment is essential for wound healing, in which an ideal moisture content is one of the most important factors. The fundamental function and requirement for wound dressings is to keep the wound at an optimal moisture. Here, we prepared serial polyurethane (PU) membrane dressings with graded water vapor transmission rates (WVTRs), and the optimal WVTR of the dressing for wound healing was identified by both in vitro and in vivo studies. It was found that the dressing with a WVTR of 2028.3 ± 237.8 g/m(2)·24 h was able to maintain an optimal moisture content for the proliferation and regular function of epidermal cells and fibroblasts in a three-dimensional culture model. Moreover, the dressing with this optimal WTVR was found to be able to promote wound healing in a mouse skin wound model. Our finds may be helpful in the design of wound dressing for wound regeneration in the future.

High-dose methotrexate, etoposide, dexamethasone and pegaspargase (MEDA) combination chemotherapy is effective for advanced and relapsed/refractory extranodal natural killer/T cell lymphoma: a retrospective study.

Extranodal natural killer/T cell lymphoma, nasal type (ENK/TCL), is an aggressive and rare hematological malignancy. Patients with advanced and relapsed/refractory disease have very poor outcomes. In this study, we retrospectively assessed the efficacy and safety of MEDA regimen (methotrexate, etoposide, dexamethasone and pegaspargase) in the treatment of advanced and relapsed/refractory ENK/TCL patients. Thirteen patients received a total of 55 cycles of MEDA, with a median of four cycles. At the completion of treatment, the overall response rate was 76.9 %, with a complete response rate of 61.5 %. The 1-year overall survival rate was 69.2 %, and 1-year progression-free survival was 61.5 %. Treatment-related toxicity was monitored in all patients. Grade 3/4 neutropenia occurred in 46.2 % of patients. Serious infections happened in two cases (15.4 %). Grade 3/4 thrombocytopenia occurred in 30.8 % of patients, and 23.1 % received platelet transfusion. Grade 3/4 anemia was observed in 23.1 % of patients. Hepatotoxicity and low fibrinogen were common, but mild. These results show that MEDA regimen is very effective with tolerable adverse effects in the treatment of advanced and relapsed/refractory ENK/TCL. Further prospective trials are expected to validate the efficacy of MEDA in an expanded number of patients.