The feasibility of contrast-enhanced CT to identify the adhesive renal venous tumor thrombus of renal cell carcinoma.

OBJECTIVE: To identify adhesive renal venous tumor thrombus (RVTT) of renal cell carcinoma (RCC) by contrast-enhancement CT (CECT). MATERIALS AND METHODS: Our retrospective study included 53 patients who underwent preoperative CECT and pathologically confirmed RCC combined with RVTT. They were divided into two groups based on the intra-operative findings of RVTT adhesion to the venous wall, with 26 cases in the adhesive RVTT group (ARVTT) and 27 cases in the non-adhesive group (NRVTT). The location, maximum diameter (MD) and CT values of tumors, the maximum length (ML) and width (MW) of RVTT, and length of inferior vena cava tumor thrombus were compared between the two groups. The presence of renal venous wall involvement, renal venous wall inflammation, and enlarged retroperitoneal lymph node was compared between the two groups. A receiver operating characteristic curve was used to analyze the diagnostic performance. RESULTS: The MD of RCC and the ML and MW of the RVTT were all larger in the ARVTT group than in the NRVTT group (p = 0.042, p < 0.001, and p = 0.002). The proportion of renal vein wall involvement and renal vein wall inflammation were higher in the ARVTT group than in NRVTT groups (both p < 0.001). The multivariable model including ML and vascular wall inflammation to predict ARVTT could achieve the best diagnostic performance with the area under the curve, sensitivity, specificity, and accuracy of 0.91, 88.5%, 96.3%, and 92.5%, respectively. CONCLUSION: The multivariable model acquired by CECT images could be used to predict RVTT adhesion. CLINICAL RELEVANCE STATEMENT: For RCC patients with tumor thrombus, contrast-enhanced CT could noninvasively predict the adhesion of tumor thrombus, thus predicting the difficulty of surgery and contributing to the selection of an appropriate treatment plan. KEY POINTS: • The length and width of the tumor thrombus could be used to predict its adhesion to the vessel wall. • Adhesion of the tumor thrombus can be reflected by inflammation of the renal vein wall. • The multivariable model from CECT can well predict whether the tumor thrombus adhered to the vein wall.

Clinical Application of CT Navigation in treatment of Lumbar Spondylolisthesis with Minimally Invasive Surgery - Transforaminal Lumbar Interbody Fusion.

OBJECTIVE: To explore the clinical effect of the application of CT navigation in the treatment of lumbar spondylolisthesis with minimally invasive surgery - transforaminal lumbar interbody fusion (MIS-TLIF). METHODS: A retrospective study was conducted on 30 patients with lumbar spondylolisthesis who were continuously treated in linyi central hospital from May 2018 to March 2019.The patients were divided into two groups,15 patients treated with MIS-TLIF with the aid of CT navigation during the operation were included into an observation group. Another 15 patients were treated with open transforaminal lumbar interbody fusion as the control group. The baseline information, including gender, age and course of disease, perioperative period and imaging conditions, and VAS and ODI scores of patients in the two groups were collected and analyzed. RESULTS: Fifteen patients were included into the observation group, including 9 male and 6 female patients with an average age of 52.60 ± 6.31 and a course of disease of 16.33 ± 6.00 months. The other 15 patients were included into the observation group, including seven male and eight female patients with an average age of 52.87 ± 7.38 and a course of disease of 19.13 ± 9.89 months. The difference in the gender, age and course of disease between the two groups had no statistical significance (P > 0.05). However, the difference in the duration of operation and intraoperative blood loss between the two groups had statistical significance (P< 0.05). There were no statistically significant differences in wound complications, neurological complications, preoperative slippage rate, postoperative slippage rate, slippage reduction rate and screw placement accuracy (P > 0.05). VAS scores of the two groups were statistically significant from six months after surgery (P < 0.01). There was no significant difference in ODI between the two groups at any time point (P >, 0.05). VAS and ODI scores were improved at each time point compared with those before surgery. CONCLUSION: The minimally invasive transforaminal lumbar fusion performed with the aid of CT navigation during the operation shortens the duration of operation and the amount of bleeding, reduces the back pain, is beneficial to the early postoperative functional exercise, and speeds up the postoperative recovery.

A survey on the prevalence and risk indicators of erosive tooth wear among adolescents in Guangzhou, South China.

BACKGROUND: Erosive tooth wear (ETW) has become a crucial oral health problem over the decades in China. OBJECTIVES: To explore the prevalence and risk indicators of ETW among adolescents in Guangzhou, south China. METHODS: A cross-sectional survey of 720 participants was conducted in Guangzhou, using an equal-sized, stratified, multistage random sampling approach. The participants were from two different age groups (12- and 15-year-olds), 360 per group. The ratio of males to females was 1:1 in each group. ETW was recorded utilising the basic erosive wear examination (BEWE) index as the dependent variable. Independent variables included age, gender, region, socioeconomic status, dietary factors, oral health measures and others. RESULTS: The prevalence rates (weighted) of ETW and dentin exposure (DE) were 56.1% and 26.2% among adolescents in Guangzhou, with mean teeth (weighted) of 1.8 ± 2.5 and 0.6 ± 1.5, respectively. No matter the prevalence or the mean teeth, the 15-year-olds were higher than the 12-year-olds; the mean teeth of ETW of males was higher than that of females; the mean teeth of ETW and DE of the adolescents of low socioeconomic status were higher than those of high socioeconomic status. Medium to high risk levels were found for 10.1%. In the multiple regression model, age, gender and taking acidic foods/drinks before sleep were associated with ETW. CONCLUSIONS: Moderate ETW in the permanent dentition was common among adolescents in Guangzhou. However, the teeth involved were low. Dietary factors and demographics were the main risk indicators.

Epigenetic Modulation in Periodontitis: Interaction of Adiponectin and JMJD3-IRF4 Axis in Macrophages.

Emerging evidence suggests an important role for epigenetic mechanisms in modulating signals during macrophage polarization and inflammation. JMJD3, a JmjC family histone demethylase necessary for M2 polarization is also required for effective induction of multiple M1 genes by lipopolysaccharide (LPS). However, the effects of JMJD3 to inflammation in the context of obesity remains unknown. To address this deficiency, we firstly examined the expression of JMJD3 in macrophage isolated from bone marrow and adipose tissue of diet induced obesity (DIO) mice. The results indicated that JMJD3 was down-regulated in obesity. Adiponectin (APN), a factor secreted by adipose tissue which is down-regulated in obesity, functions to switch macrophage polarization from M1 to M2, thereby attenuating chronic inflammation. Intriguingly, our results indicated that APN contributed to JMJD3 up-regulation, reduced macrophage infiltration in obese adipose tissue, and abolished the up-regulation of JMJD3 in peritoneal macrophages isolated from DIO mice when challenged with Porphyromonas gingivalis LPS (pg.lps). To elucidate the interaction of APN and JMJD3 involved in macrophage transformation in the context of inflammation, we designed the loss and gain-function experiments of APN in vivo with APN(-/-) mice with experimental periodontitis and in vitro with macrophage isolated from APN(-/-) mice. For the first time, we found that APN can help to reduce periodontitis-related bone loss, modulate JMJD3 and IRF4 expression, and macrophage infiltration. Therefore, it can be inferred that APN may contribute to anti-inflammation macrophage polarization by regulating JMJD3 expression, which provides a basis for macrophage-centered epigenetic therapeutic strategies.

Changes in the hemolytic activity of Candida species by common electrolytes.

BACKGROUND: Hemolysins are crucial virulence factors which help pathogens to survive and persist in the host. This study investigated whether common electrolytes will affect the hemolysins of Candida species. The hemolysins from 25 Candida isolates were investigated using a plate specially designed for Candida species in the presence of three electrolytes, CaCl2, NaCl and KCl, at different concentrations. The hemolytic activity was determined after 48 h and the hemolytic index was calculated. RESULTS: All three electrolytes caused a decrease in the hemolytic activity. Significant differences existed between varying concentrations of NaCl, while no significant differences existed for the CaCl2 and KCl groups. Additionally, the peripheral hemolytic index was highly correlated with the hemolytic index (r = 0.656, p < 0.001). CONCLUSIONS: Our findings indicate that electrolytes reduce hemolysis by Candida species and a correlation exists between the peripheral hemolytic index and the translucent hemolytic index.

Dental fear and its possible relationship with periodontal status in Chinese adults: a preliminary study.

BACKGROUND: The aim of the present study was to describe the characteristics of dental fear of Chinese adult patients with periodontal disease and provide information for clinical assessment. METHODS: A total of 1203 dental patients completed questionnaires that included Corach's Dental Anxiety Scales (DAS), Dental Fear Survey (DFS) and the short-form Dental Anxiety Inventory (S-DAI). Among all the patients, 366 cases were self-reported periodontal disease. The general characteristics were described, such as socio-demographics, dental attendances and oral health behaviors. The statistical analysis was performed by t-test, Mann-Whitney U test and linear regression respectively to evaluate correlations between dental fear and general characteristics according to the three scales. RESULTS: The prevalence of dental fear was 74% among 1203 patients, 23.4% of total with high dental fear, while 27.3% in the patients with periodontal disease. The average score of DAS and DFS for patients with periodontal disease was significantly higher than those without periodontal disease. The regression analysis indicated that gender, age, periodontal status, dental attendances and oral health behaviors were correlated with dental fear. Among 366 patients with periodontal disease, gender, dental attendances and oral health behaviors had correlation with dental fear. The analysis of DFS scale exhibited that 'drilling with handpiece' and 'injecting the anesthetic' were the most important factors to contribute to dental fear. CONCLUSIONS: There was high prevalence of dental fear in Chinese adult patients, particularly in patients with periodontal disease, and high level of dental fear may lead to poor periodontal status.

Effect and possible mechanism of network between microRNAs and RUNX2 gene on human dental follicle cells.

To investigate whether crosstalk between RUNX2 and miRNAs is involved in tooth eruption regulated by dental follicle cells (DFCs) and the possible molecular mechanism. Blood samples and embedded dental follicles were collected from patients with cleidocranial dysplasia, and RUNX2 gene mutations were analyzed, then RUNX2(+/m) DFCs were isolated and identified. The characteristics of RUNX2(+/m) DFCs were analyzed. The differential expression of miRNAs was detected between the RUNX2(+/m) DFCs and RUNX2(+/+) DFCs by microarray, and target genes were predicted by miRGen. miR-146a was chosen for further investigation, and its effects in DFCs were analyzed by transfecting its mimics and inhibitors, and expression of genes involved in tooth eruption were detected. A novel insertion mutation (c.309_310insTG) of RUNX2 gene was identified which had an effect on the characteristics of DFCs. Compared with the RUNX2(+/+) DFCs, there were 69 microRNAs more than twofold up-regulated and 54 microRNAs more than twofold down-regulated in the RUNX2(+/m) DFCs. Among these, miR-146a decreased significantly in RUNX2(+/m) DFCs, and expression of RUNX2, CSF-1, EGFR, and OPG was significantly altered when miR-146a was overexpressed or inhibited. RUNX2 gene mutation contributes to the characteristic change of DFCs, and the crosstalk between RUNX2 gene and miRNAs may be one of the key regulatory mechanisms of differentiation of DFCs.

miR-488-3p Represses Malignant Behaviors and Facilitates Autophagy of Osteosarcoma Cells by Targeting Neurensin-2.

OBJECTIVE: Osteosarcoma (OS) is a primary bone sarcoma that primarily affects children and adolescents and poses significant challenges in terms of treatment. microRNAs (miRNAs) have been implicated in OS cell growth and regulation. This study sought to investigate the role of hsa-miR-488-3p in autophagy and apoptosis of OS cells. METHODS: The expression of miR-488-3p was examined in normal human osteoblasts and OS cell lines (U2OS, Saos2, and OS 99-1) using RT-qPCR. U2OS cells were transfected with miR-488-3p-mimic, and cell viability, apoptosis, migration, and invasion were assessed using CCK-8, flow cytometry, and Transwell assays, respectively. Western blotting and immunofluorescence were employed to measure apoptosis- and autophagy-related protein levels, as well as the autophagosome marker LC3. The binding sites between miR-488-3p and neurensin-2 (NRSN2) were predicted using online bioinformatics tools and confirmed by a dual-luciferase assay. Functional rescue experiments were conducted by co-transfecting miR-488-3p-mimic and pcDNA3.1-NRSN2 into U2OS cells to validate the effects of the miR-488-3p/NRSN2 axis on OS cell behaviors. Additionally, 3-MA, an autophagy inhibitor, was used to investigate the relationship between miR-488-3p/NRSN2 and cell apoptosis and autophagy. RESULTS: miR-488-3p was found to be downregulated in OS cell lines, and its over-expression inhibited the viability, migration, and invasion while promoting apoptosis of U2OS cells. NRSN2 was identified as a direct target of miR-488-3p. Over-expression of NRSN2 partially counteracted the inhibitory effects of miR-488-3p on malignant behaviors of U2OS cells. Furthermore, miR-488-3p induced autophagy in U2OS cells through NRSN2-mediated mechanisms. The autophagy inhibitor 3-MA partially reversed the effects of the miR-488-3p/NRSN2 axis in U2OS cells. CONCLUSION: Our findings demonstrate that miR-488-3p suppresses malignant behaviors and promotes autophagy in OS cells by targeting NRSN2. This study provides insights into the role of miR-488-3p in OS pathogenesis and suggests its potential as a therapeutic target for OS treatment.

Aberrant pulmonary immune response of obese mice to periodontal infection.

Obesity and periodontitis constitute mutual risk factors in respiratory disorders; this study aimed to explore the pulmonary immune response to periodontal infection using combined animal models with diet-induced obesity (DIO). Thirty-two C57 BL/6J mice were randomly divided into low-fat (LF) or high-fat (HF) diet groups and fed an LF diet as a control or an HF diet to induce obesity. The 30-week mice in the diet group were divided into periodontal ligation group (10 days using Porphyromonas gingivalis ATCC 33277) or sham-ligation group. The expressions of the macrophage-specific maker (F4/80), macrophage chemotactic protein1 (MCP1), and inflammatory cytokines in lung tissues were analyzed. The mRNA and protein levels of F4/80, MCP1, interleukin (IL)-1ß, and IL-6 expressions were significantly upregulated by obesity in lung tissues. However, the mRNA and protein levels of F4/80, MCP1, and IL-6 were downregulated by periodontitis in DIO mice relative to that of the HF control group. Periodontitis increased tumor necrosis factor-α level of lung tissues under LF, while IL-10 was not affected by obesity regardless of periodontitis. Periodontitis may aggravate pulmonary immune response in obese rodents. This may relate to the imbalance of the pro- and anti-inflammatory cytokine status of lung lesions, which tends to attenuate the infiltration of alveolar macrophages.

Study Progress on Inorganic Fibers from Industry Solid Wastes and the Key Factors Determining Their Characteristics.

Compared to basalt and glass fibers, the production of inorganic fiber from industry solid wastes is an effective method to not only save natural resources but also recycle waste resources. Because the preparation of the fibers requires high temperature treatment, the production process is associated with high energy consumption and high carbon emissions. How to resolve these problems is a current research challenge in this field. Herein, we reviewed the study progress on these fibers and further discussed the key factors determining their characteristics, including chemical composition, melt structure, and viscosity of melt. In production, the matching of solid waste blends containing enough total content of SiO2 and Al2O3, and a suitable amount of MgO and CaO, is beneficial to the structure control of the melt. The study found that the melt consisted of Q2 and Q3; and that Q3 content more than Q2 was more suitable for fiber production and its performance improvement. Such a melt structure can be achieved by controlling the degree of depolymerization and the temperature. New ultrasonic technology can shorten the homogenization time; its application is hoped to save energy and reduce carbon emissions. These conclusions will offer important guidance for the development of inorganic fibers from industry solid wastes in the future.

Preparation, thermal stability and mechanical properties of inorganic continuous fibers produced from fly ash and magnesium slag.

A large number of industrial solid waste resources urgently need to be recycled, so, fast-expanding the utilization area of these waste resources is a pressing task in today's China. The production of various slag wool fibers is an effective way due to the huge demand of thermal insulation materials. Besides, the preparation of slag continuous fibers is also a good choice because of its wide application fields. Two fly ash-based continuous fibers were successfully prepared by fly ash and magnesium slag, or add less feldspar, through melting at high temperature, following spinning into continuous fibers. Their samples were treated at different temperatures from 100 to 700 °C, and then investigate tensile strength and thermal resistance. As the same fly ash-based fibers, the tensile strength of two fibers in this study increase 115% and 28.3% than the fibers previously reported. Their utilization rates of solid waste resources are up to 100% and 80%, and far higher than 45% of the same fiber reported. FT-IR, SEM, Solid-state NMR analysis indicates that thermal action makes the 29Si structure without Al(Q3,Q2, and Q1) transfer to 29Si structure containing Al(Q4(3Al),Q4(2Al), Q4(1Al)), meanwhile, AlVI (AlO6 octahedron) was destroyed completely and converted into AlV (AlO5) and AlIV (Al[SiO]3). Only some Al atoms participated in the formation of network structure in fiber, they contributed to the strength of fibers.

Effect of cleidocranial dysplasia-related novel mutation of RUNX2 on characteristics of dental pulp cells and tooth development.

Cleidocranial dysplasia (CCD) is an autosomal-dominant disorder caused by a lack of function of one or more alleles of the RUNX2 gene. Mutations of the RUNX2 gene were analyzed in a family with CCD, and a novel nonsense mutation was identified, c. 1096G > T, p.E366X, which was predicted to cause a number of potential dysfunctions. Western blot analysis showed that the novel mutation created a shortened protein product, which lost 155 aa in the C-terminal domain. The mutant protein was detected to be localized mostly in the cytoplasm, not in the nucleus, which demonstrated that transport of the RUNX2 protein into the nucleus was disturbed by the p.E366X mutation. For the first time, RUNX2(+/m) dental pulp cells (DPCs) were isolated from two permanent incisors of the CCD patient. Compared to RUNX2(+/+) controls, RUNX2(+/m) DPCs presented an impeded progression from the G1 to the S phase in the cell cycle, a lower rate of proliferation, weaker ability of calcification, and distinct ultrastructure. More interestingly, the ultrastructural analysis and energy dispersive X-ray spectrometry (EDS) analysis showed that the CCD tooth exhibited insufficient mineralization of enamel and dentin. This study suggests that the truncated RUNX2 mutant protein may be responsible for the alterations of RUNX2(+/m) DPCs, and RUNX2 gene may be involved in dental development by affecting the cell growth and differentiation, which provides new insights into understanding of dental abnormalities in CCD patients.

Severity and prevalence of plaque-induced gingivitis in the Chinese population.

UNLABELLED: This study investigated the prevalence and severity of gingivitis and plaque in a representative Chinese population of adults. METHODS: Using the Loe-Silness gingivitis index (GI) and the modified Quigley-Hein plaque index (PULI), researchers examined 1143 patients from Guangzhou, Shenyang, and Nanjing for the presence of gingivitis and plaque. A two-tailed t-test was used to determine significant differences in the GI and PLI scores between gender and urban/rural areas. The data pertaining to study sites and age groups were compared using the Kruskal-Wallis one-way analysis of variances (ANOVA) by ranks. The correlation between GI/PLI and age was examined using the Pearson correlation coefficient. Age differences among three sites were analyzed with the one-way ANOVA. RESULTS: The age and urban/rural compositions (mean age 42.2 years) paralleled the 2008 China census. The overall average and standard deviation of GI and PLI were 1.101 +/- 0.239 and 3.394 +/- 0.578, respectively. Age significantly correlated with GI and PLI (P < .0001). The PLI in males was significantly higher (P < .0001) than in females; however, no significant difference was noted between GI in males compared to females. Patients in rural areas showed a significantly higher GI and PLI (t = 7.723, P < .0001; t = 7.072, P < .0001) than those in urban ones. CONCLUSIONS: Clinical trials evaluating a product's antigingivitis efficacy should recruit participants from a population that represents accurately the intended product users. Variables should include gender, race, age, and geography.

Common single nucleotide polymorphisms in cyclooxygenase-2 and risk of severe chronic periodontitis in a Chinese population.

AIM: Several common single nucleotide polymorphisms (SNPs) of the cyclooxygenase-2 (COX-2) gene have been reported to be functional. The association between -1195GA, -765GC and 8473TC of COX-2, and severe chronic periodontitis (CP) in a Chinese population was investigated. MATERIAL AND METHODS: 148 cases of healthy controls (control group) and 146 cases of severe CP were recruited in this study. Genotypes of -1195GA, -765GC and 8473TC were determined by polymerase chain reaction restriction fragment length polymorphism (PCR-RFLP). The distributions of genotypes and haplotypes were compared by chi(2) test and the odds ratios (ORs) were calculated by logistic regression analysis. RESULTS: The prevalence of the -1195A was more prevalent in CP group (60.62%) than control group (51.35%), and the distributions of the -765C and 8473C were higher in control group (6.76% and 21.96%) compared with CP group (3.08% and 15.07%). Only genotype distribution of -1195GA was significant when p-value was corrected for multiple testing (p(c)=0.033). The adjusted ORs for the -1195AA/GA, -765GC and 8473CC/TC were 2.49 (95% CI=1.33-4.69, p=0.005), 0.45 (95% CI=0.20-1.04, p=0.061) and 0.67 (95% CI=0.41-1.11, p=0.118). Subjects with the haplotype AGT had a significantly higher risk of periodontitis than those with the most common haplotype GGT (OR=1.91, 95% CI=1.32-2.76, p(c)<0.001). CONCLUSIONS: It suggests the -1195A variant is associated with an increased risk for severe CP.

Association between vitamin D receptor gene polymorphisms and severe chronic periodontitis in a Chinese population.

BACKGROUND: Chronic periodontitis (CP) exhibits inflammation and alveolar bone loss, and severe forms of periodontitis are suggested to have a genetic basis. Vitamin D receptor (VDR) regulates bone metabolism and inflammation-related genes, and single nucleotide polymorphisms (SNPs) in the VDR gene may affect the functional activity of the VDR protein in CP. Therefore, the aim of this study was to investigate the association between VDR SNPs and severe CP in a Chinese population. METHODS: DNA was obtained from 107 patients with severe CP and 121 control subjects. The BsmI, TaqI, ApaI, and FokI SNPs of VDR genes were investigated by restriction fragment length polymorphism of polymerase chain reaction (PCR) products. The digested PCR products were electrophoresed on an 8% polyacrylamide gel and developed by the DNA silver staining method. RESULTS: The distribution of VDR TaqI genotypes and alleles between the two groups was significantly different (P = 0.019 and P = 0.039, respectively). The TT genotype and T allele seemed to increase the susceptibility of severe CP (odds ratio, 2.75; 95% confidence interval [CI]: 1.17 to 6.47; odds ratio, 2.28, 95% CI: 1.02 to 5.06, respectively) in Chinese populations. There was no significant difference in the genotype distribution or the allele frequencies of VDR BsmI, ApaI, or FokI between the two groups. CONCLUSION: TaqI SNP of VDR gene might be associated with severe CP in Chinese patients.

Aberrant Periodontal and Systemic Immune Response of Overweight Rodents to Periodontal Infection.

This study aimed to explore periodontal and systemic immune response of overweight hosts to periodontitis. Forty C57 BL/6J male mice were divided into high (HF) or low fat (LF) diet groups and fed with the two diets, respectively, for 8 weeks. Each diet group was then divided into periodontitis (P) or control (C) groups (n = 10 per group) for 10-day ligation or sham-ligation. Overweight-related parameters including body weight were measured. Alveolar bone loss (ABL) was morphometrically analyzed and periodontal osteoclasts were stained. Periodontal immune response including leukocyte and macrophage number and inflammatory cytokines were analyzed by histology and quantitative PCR. Serum cytokine and lipid levels were quantified using electrochemiluminescence immunoassays, enzyme-linked immunosorbent assays, and biochemistry. It was found that HF group had 14.4% body weight gain compared with LF group (P < 0.01). ABL and periodontal osteoclast, leukocyte, and macrophage number were higher in P group than C group regardless of diet (P < 0.05). ABL and periodontal osteoclast number were not affected by diet regardless of ligation or sham-ligation. Leukocyte and macrophage number and protein level of tumor necrosis factor α (TNF-α) in periodontium and serum interleukin-6 level were downregulated by HF diet in periodontitis mice (P < 0.05). Periodontal protein level of TNF-α was highly correlated with serum interleukin-6 and low-density lipoprotein cholesterol levels (P < 0.01). These findings indicated that impaired immune response occurs both periodontally and systemically in preobesity overweight individuals. Given a well-reported exacerbating effect of obesity on periodontitis, overweight, if let uncontrolled, might place the individuals at potential risk for future periodontal tissue damage.

Mutations in the RUNX2 gene in Chinese patients with cleidocranial dysplasia.

Cleidocranial dysplasia (CCD) is an autosomal dominant inheritable skeletal disease caused by heterozygous mutations in an osteoblast-specific transcription factor, RUNX2. Mutational analyses of RUNX2 were done on 4 unrelated Chinese patients with CCD. One nonsense and 3 missense mutations were detected, including one novel mutation, a heterozygous G to C transition mutation at nucleotide 475 in exon 2, which converts glycine to arginine at codon 159 (G159R). Two mutations, R225W and R391X, were reported in Chinese patients with CCD for the first time. Our findings show that R225 mutations interfere with nuclear accumulation of RUNX2 protein, and that a lack of nuclear RUNX2 protein accumulation is at least one of the causes of haploinsufficiency in these cases. Body stature was significantly reduced in the 3 male and 1 female cases. The cases all had malformations of the tarsometatarsal joints. In 1 case, the humeroulnar joints and humeroradial joints were abnormal, and the elbow looked like a triangle. The data suggest that an impaired runt domain contributes to the short stature of CCD patients. We postulate that RUNX2 influences joint formation by affecting the differentiation pathways of chondrocytes and osteoblasts.

A novel RUNX2 mutation in cleidocranial dysplasia patients.

Cleidocranial dysplasia (CCD) is an autosomal-dominant heritable skeletal disease caused by heterozygous mutations in the RUNX2 gene. Here, the RUNX2 gene was analyzed within a CCD family from China, and a novel missense mutation (c. 475G --> C [p.G159R]) was identified. Normal and mutant RUNX2 expression vectors were then constructed and expressed transiently in NIH3T3 cells. Immunofluorescent staining and Western blotting showed that wild-type RUNX2 protein was localized exclusively in the nucleus; however, the mutant protein was found in both the nucleus and the cytoplasm, which demonstrated that transport of the RUNX2 mutant into the nucleus was disturbed by the G159R mutation. Therefore, we suggest that G159 is very important to promote RUNX2 nuclear localization. According to clinical analysis, the patient displays severe dysplasia of bones and relatively low-grade craniofacial abnormality, and we infer that G159 may be vital for normal skeletal development, other than control of tooth number. These findings confirm that mutations in the RUNX2 gene are associated with the pathogenesis of CCD across different ethnic backgrounds.

[Mutational analysis of the cathepsin C gene in a family of Han nationality with Papillon-Lefevre syndrome].

OBJECTIVE: To investigate the mutational characteristics of the cathepsin C gene (CTSC, also known as dipeptidyl-peptidase I gene, DPP I) in a family of Han nationality with Papillon-Lefevre syndrome, and to provide the molecular basis for the phenotype. METHODS: Genomic DNAs were extracted from the proband, his parents and younger sister after informed consent. Polymerase chain reaction and direct DNA sequencing were carried out to screen the mutations of the cathepsin C gene. RESULTS: Compound heterozygous mutations of the cathepsin C gene were identified in the patient. The patient carried one frameshift mutation 116delG in exon 1, one heterozygous mutation C255S in exon 6, one missense mutation F314S and one sense mutation E335E in exon 7. The four changes were novel mutations of the cathepsin C gene, which had not been reported previously. None of the mutations were detected in normal controls. CONCLUSION: Mutations of the cathepsin C gene are probably responsible for the phenotype of Papillon-Lefevre syndrome in this family.

[Impacts of periodontitis on visceral organ weight and weight percentage in obese mice].

OBJECTIVE: This study aimed to explore the impacts of periodontitis on the visceral weight and weight percentage of obese animal models. METHODS: A total of 64 C57BL/6J mice were divided into the following diet groups: high-fat diet (HFD) group (n=36), which was fed with high-fat diet to induce obesity, and low-fat diet (LFD) group (n=28), which was fed with low-fat diet as the control. After 16 weeks on diet, each diet group was divided into periodontitis (P) and control (C) groups. The P groups were induced for periodontitis by ligation with Porphyromonas gingivalis-adhered silk for 5 or 10 days, and the C groups were sham-ligated as the control. Visceral organs were resected and weighed. The organ weight percentage was calculated. RESULTS: Compared with the LFD group, the HFD group significantly upregulated the weight and weight percentage of visceral adipose tissue and spleen (P<0.05), upregulated the weight of liver and kidney (P<0.05), and downregulated the weight percentage of liver and kidney (P<0.01). In the HFD group, the weight and weight percentage of spleen were downregulated in the P group (P<0.05), but were upregulated in the 10-day group compared with the 5-day group (P<0.05). CONCLUSIONS: Periodontitis can affect the general morphology of the viscera (especially spleen) in obese animal models. Pathological indications in terms of immunometabolism might be present in the correlation between obesity and periodontitis.