Depressive symptoms in Chinese adults with risk factors for diabetes: the Shanghai High-Risk Diabetic Screen (SHiDS) study.

AIMS: To evaluate the relationship between newly diagnosed diabetes or prediabetes and depressive symptoms among individuals with risk factors for diabetes in China. We also investigated the associations of depressive symptoms with pancreatic ß-cell function and insulin resistance. METHODS: We used cross-sectional data from the Shanghai High-Risk Diabetic Screen (SHiDS) project. Between 2014 and 2017, a total of 1728 participants were enrolled in this study and underwent an oral glucose tolerance test to screen for diabetes and prediabetes. Insulin resistance was evaluated using the homeostatic model assessment of insulin resistance and the modified Matsuda index. Pancreatic ß-cell function was calculated using the homeostatic model assessment of ß-cell function, Stumvoll first- and second-phase indexes. Elevated depressive symptoms were determined using the Patient Health Questionnaire-9 (PHQ-9 score ≥ 10). RESULTS: The prevalence of elevated depressive symptoms in the total study population was 4.8% (83 of 1728). Compared with the normal glucose tolerance group, individuals with newly diagnosed diabetes were less likely to have elevated depressive symptoms even after controlling for potential confounders [adjusted odds ratio (OR) 0.35, 95% confidence interval (CI) 0.18-0.68; P = 0.002]. However, prediabetes was not associated with depressive symptoms. The odds for elevated depressive symptoms were increased in individuals with higher levels of the Stumvoll first-phase index. No association was observed between depressive symptoms and insulin resistance. CONCLUSION: Elevated depressive symptoms were less prevalent in Chinese individuals with newly diagnosed diabetes among a high-risk population for diabetes.

[Phosphonate inhibits steatosis and lobular inflammation of non-alcoholic steatohepatitis through depleting macrophages].

Objective: To explore the role of macrophages in non-alcoholic steatohepatitis (NASH) in order to provide directions for the therapeutic target of metabolic liver disease. Methods: Twenty C57BL/6 wild-type male mice at 6-8 weeks were randomly divided into two groups: 5 in the control group, methionine-and choline-deficient diet (MCD); 15 in the experimental group, MCD diet + intraperitoneal injection of disodium chlorophosphonate liposomes (to clear macrophages). Mice were fed for 4 weeks to establish NASH model. Blood, liver and spleen were collected to analyze the body mass index, liver index, spleen index, and serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST) levels. Non-alcoholic steatosis (NAS) activity score was evaluated by HE and Oil Red O staining. The relative expression level of F4/80 mRNA was compared by RT-PCR. Data comparison between groups was analyzed by t-test. Results: NASH model was successfully established by feeding the mice with MCD for four week. The expression of F4/80 mRNA (t = 4.167, P < 0.01), hepatic steatosis (t = 10.70, P < 0.05), interlobular inflammatory infiltration (t = 3.08, P < 0.05), and NAS score were decreased (t = 8.06, P < 0.05) in the experimental group. At the same time, ALT level [(817.00 ± 128.90) U/L vs. (231.20 ± 36.28) U/L, t = 5.71, P < 0.01], AST level [(1 211.00 ± 248.90) U/L vs. (505.30 ± 88.20) U/L, t = 3.32, P < 0.01] was decreased significantly. However, the spleen volume and spleen index of the experimental group were larger (0.24 ± 0.01 and 0.32 ± 0.02, t = 2.41, P < 0.05), and there was no significant effect on liver ballooning, body mass index and liver index. Conclusion: In NASH, phosphonate can consume macrophages to inhibit liver inflammation and protect the damaged liver.

[Methylene blue play a role in preventing septic liver injury by inducing macrophage polarization].

Thirty mice were used to establish a sepsis model with cecal ligation and puncture. 15 mg/kg methylene blue or isotonic saline were injected intraperitoneally to observe liver tissue pathological changes. Changes in macrophage frequency and expressional condition of M1 and M2-type hepatic inflammatory factors were detected. After LPS stimulation, the expression level of macrophage inflammatory factor were detected. The results showed that the pathological liver injury was significantly reduced in the MB mice group (P < 0.05), and the frequency of liver macrophage was not statistically significantly different (P > 0.05). MB elevation had promoted the expression of M2-type hepatic inflammatory factor (P < 0.05) and macrophage inflammatory factor (P < 0.05). MB can play a role in preventing septic liver injury by inducing macrophages polarization to M2-type.

[Preliminary results of surgical treatment of fibrous dysplasia of proximal femur in children].

Objective: To investigate the surgical treatment, clinical effect and revision reasons of children with proximal femoral fibrous dysplasia(FD). Methods: The clinical data of 26 children with polyostotic FD of proximal femur who underwent surgery at Department of Pediatric Orthopaedics, Beijing Jishuitan Hospital from June 2016 to June 2018 were retrospectively analyzed. There were 18 males and 8 females with a mean age of 9.2 years (range:5 to 16 years).One of them was McCune Albright syndrome. Fifteen cases were in first operation and 11 cases were in revision operation. The operation methods and results were reviewed,and the causes of revision were analyzed. Results: Among the 15 children who underwent the first operation,13 cases underwent osteotomy or fracture reduction and interlocking intramedullary nail(IMN) fixation;One case underwent valgus osteotomy and pediatric hip plate(PHP)internal fixation;One case underwent valgus osteotomy+lesion curettage+allogeneic bone graft+PHP fixation. Among the 11 children who underwent revision surgery,9 cases were treated with IMN fixation,1 case with PHP fixation,and 1 case with PHP fixation+allogeneic bone graft. The causes of revision included distal fixation failed in 6 cases,proximal fixation failed in 3 cases,plate fixation failed in 5 cases,and recurrence occurred after curettage and artificial bone graft in 2 cases. Patients were followed up for 1.4 years(range:1.0 to 3.5 years) after recent operation. The osteotomy or fracture healed well with good deformity correction. Postoperative complications included infection in 1 case and local bone partial resorption in 1 case. Conclusions: Osteotomy combined with rigid internal fixation is an effective surgical treatment for fibrous dysplasia of proximal femur in children. Internal fixation should cover the whole length of lesion. Intramedullary nail is the most common choice. Because the growth of height and the progress of the disease itself,this deformity is prone to recur in children,needing closely follow-up after operation.

Publisher Correction: Parenthood and risk of hip fracture: a 10-year follow-up prospective study of middle-aged women and men in China.

The original version of this article, published on 25 November 2019, unfortunately contained a mistake.

Parenthood and risk of hip fracture: a 10-year follow-up prospective study of middle-aged women and men in China.

This prospective study of Chinese adults demonstrated an inverse J-shaped association of number of children with risk of hip fracture in both men and postmenopausal women aged 50 years or older. Women with 2 or 3 children and men with 4 children had the lowest risk of hip fracture. INTRODUCTION: Women have higher absolute risks of fracture than men, which is believed to reflect differences in oestrogen exposure. The aim of this study was to compare the associations of number of children with risk of hip fracture between men and women aged over 50 years. METHODS: The China Kadoorie Biobank (CKB) recruited 133,399 women and 110,296 men, aged 50 years or older between 2004 and 2008. During 10-year follow-up, 2068 participants (1394 women and 674 men) suffered a hip fracture. Cox regression analysis was used to estimate sex-specific adjusted hazard ratios (HRs) and 95% CI for incident hip fracture. RESULTS: Over 98% of both subsets of men and women aged 50 or older reported having children. Women who had 2 or 3 children had the lowest risks of hip fracture compared with other groups. Compared with nulliparous women, the adjusted HR for hip fracture were 0.89 (95% CI; 0.72, 1.10) for 1 child, 0.79 (0.70, 0.90) for 2 children, 0.79 (0.72, 0.87) for 3 children, 0.81 (0.72, 0.91) for 4 children, and 0.95 (0.83, 1.10) for those with 5 or more children. The associations of number of children with hip fracture were broadly consistent in men of a similar age. CONCLUSIONS: The concordant effects of the number of children with risk of hip fracture between men and women suggest that the lower risks in multiparous women are not due to differences in oestrogen exposure or other biological effects, but may reflect residual confounding by socioeconomic or lifestyle factors.

[Association between family history of diabetes and incident diabetes of adults: a prospective study].

Objective: To evaluate the association betweew family history of diabetes and incident diabetes of adults. Methods: A total of 49 266 participants in the China Kadoorie Biobank (CKB) study from Wuzhong district of Suzhou city were included in the analysis, after the exclusion of those with heart disease, stroke, cancer and diabetes at baseline survey. The person-year of follow-up was calculated from the date on completion of baseline survey to the date on any firstly-occurred event, i.e., diabetes incidence, death, loss of follow-up, or December 31, 2013. Cox regression model was used to estimate the hazards ratios of the association between family history of diabetes and incident diabetes. Results: During 348 677 person-years of the follow-up (median 7.08 years), a total of 423 men and 791 women were diagnosed as having diabetes. Compared to those without diabetic family history, participants with family history of diabetes showed a higher risk of diabetes, with a HR (95%CI) of 1.90 (1.57-2.29), and the risk increased with the number of relatives suffering from diabetes (Pfor trend<0.05). The family history of maternal type, sibling type, and sibling and parental type had a statistically significant association with the risk of diabetes. The adjusted HR (95%CI) was 2.03 (1.45-2.77), 2.07 (1.56-2.68) and 2.39 (1.14-4.34), respectively. Modification effects of tobacco smoking, alcohol drinking, body mass index and physical activity on the association between diabetic family history and risk of diabetes were not observed in the study (Pfor interaction >0.05). Conclusions: Diabetic family history is associated with the increased incident diabetes, and the risk increased with the number of relatives suffering from diabetes.

Tea consumption and bone health in Chinese adults: a population-based study.

Tea is a worldwide drink with controversial effect on bone health. The sex-specific associations are unrevealed among general population. This study showed that prolonged moderate tea consumption benefited bone health in women, while no additional benefit with stronger tea. However, tea consumption was not associated with bone health in men. INTRODUCTION: Tea consumption has been shown a potentially beneficial effect on bone health in postmenopausal women. However, little is known about such association in men, and whether stronger tea instead harms bone health due to elevated urinary excretion of calcium associated with caffeine in the tea. The aim of this study was to examine the association between various metrics of tea consumption and bone health. METHODS: The present study included 20,643 participants from the China Kadoorie Biobank (CKB), who have finished both baseline survey (2004-2008) and a re-survey (2013-2014). They were aged 38-86 years at re-survey. Tea consumption was self-reported at both baseline and re-survey. Bone mineral density (BMD) was measured using calcaneal quantitative ultrasound once at re-survey. RESULTS: Compared with non-consumers, prolonged weekly tea consumers in women was associated with higher calcaneus BMD measures, with ß (95% CI) of 0.98 (0.22, 1.74) for BUA, 4.68 (1.74, 7.61) for SOS, and 1.95 (0.81, 3.10) for SI. Among prolonged weekly tea consumers, no linear increase in BMD measures with the amount of tea leaves added was observed. The SOS and SI were higher in consumers with tea leaves 3.0-5.9 g/day than in those with < 3.0 g/day, but were reduced to non-significant for those with ≥ 6.0 g/day. Tea consumption was not associated with calcaneus BMD measures in men. CONCLUSION: Prolonged moderate tea consumption benefited bone health in women but not in men. For stronger tea consumption with more tea leaves added, neither benefit nor harm to bone health was observed.

Vascular endothelial growth factor A/Vascular endothelial growth factor receptor 2 axis promotes human dental pulp stem cell migration via the FAK/PI3K/Akt and p38 MAPK signalling pathways.

AIM: To investigate the effects of vascular endothelial growth factor A (VEGFA) and the underlying molecular mechanisms on the migration of human dental pulp stem cells (hDPSCs). METHODOLOGY: The expression of VEGFA in inflammatory pulp tissue and lipopolysaccharide (LPS)-stimulated dental pulp cells was examined by immunofluorescence staining and qRT-PCR. The migration of hDPSCs was detected using transwell migration and wound healing assays. The activation of FAK, PI3K, Akt and p38 signalling was evaluated by Western blot analysis. Silence RNA (siRNA) technology was utilized to knockdown the expression of VEGFR1 (Flt-1) and VEGFR2 (Flk-1/KDR). PF573228 (inhibitor of FAK), LY294002 (inhibitor of PI3K), SB203580 (inhibitor of p38) and SU5416 (inhibitor of VEGFR2) were employed to investigate the effect of VEGFA on the migratory mechanism of hDPSCs. Data were analysed statistically using the Student's t-test or one-way ANOVA. RESULTS: The expression levels of VEGFA in inflammatory pulp tissue in vivo and LPS-stimulated dental pulp cells in vitro were significantly greater than those in the control groups (P < 0.05). Vascular endothelial growth factor A promoted the migration of hDPSCs in a concentration-dependent manner. Several signalling pathways, including FAK, PI3K, Akt and p38, were activated by VEGFA in a dose- and time-dependent manner in hDPSCs. The VEGFA-induced migration of hDPSCs was significantly inhibited with drug inhibitors such as PF573228, LY294002, SB203580 or SU5416 (P < 0.05). These signalling pathways activated by VEGFA stimulation were significantly suppressed by pre-treatment with inhibitor of VEGFR2 (SU5416) or transfection with siRNA of VRGFR2 (P < 0.05) but not VEGFR1 siRNA. CONCLUSIONS: Vascular endothelial growth factor A/VEGFR2 axis promoted the migration of hDPSCs via the FAK/PI3K/Akt and p38 MAPK signalling pathways. These findings reveal a novel molecular mechanism for cell migration of hDPSCs, which may contribute to the remodelling of pulp tissue and dentine.

Lipopolysaccharide-induced DNA damage response activates nuclear factor κB signalling pathway via GATA4 in dental pulp cells.

AIM: To investigate the role of GATA-binding protein 4 (GATA4) in the inflammatory response induced by DNA double-strand breaks (DSBs) in human dental pulp cells (hDPCs). METHODOLOGY: Lipopolysaccharide (LPS) was used for stimulating inflammation in dental pulp tissue in vivo and hDPCs in vitro. Expression levels of GATA4 and γ-H2A.X (a marker for DSBs) were detected at different stages of pulpitis in a rat model and human pulp tissues by immunohistochemistry. Real-time quantitative polymerase chain reaction and Western blot were performed to assess expression of GATA4 and γ-H2A.X and the activation of nuclear factor κB (NF-κB) in hDPCs stimulated by LPS. The comet assay was used for detecting the extent of DSBs in hDPCs. Immunocytochemistry and Western blot were utilized to evaluate expression of γ-H2A.X and GATA4 and activation of NF-κB in hDPCs pre-treated with inhibitors of DNA damage response or transfected with GATA4 small interfering RNA before the treatment of LPS. Data were analysed statistically using one-way anova or Kruskal-Wallis tests. RESULTS: The expression of GATA4 and activation of DNA damage response and NF-κB in inflamed pulp tissue and LPS-treated hDPCs were identified. Significantly decreased expression of GATA4 and significantly decreased inflammatory processes in hDPCs were demonstrated via suppression of DNA damage response (P < 0.05). In GATA4-knockdown cells, the expression of γ-H2A.X did not change, but nuclear translocation of p65 was significantly suppressed (P < 0.05) upon induction by LPS. CONCLUSIONS: Lipopolysaccharide-induced DSBs activated the NF-κB signalling pathway in hDPCs, and GATA4 acts as a positive moderator of the progress. The involvement of GATA4 in this pathology may serve as a therapeutic target in pulpitis.

[Association study of genetic variations in SLCO1B3 gene with prognosis in breast cancer patients treated with neoadjuvant chemotherapy of TA regimen].

Objective: To assess the association of single nucleotide polymorphisms (SNPs) in SLCO1B3 gene with prognosis of breast cancer (BC) patients treated with neoadjuvant chemotherapy of TA regimen (taxane and antharcycline drugs). Methods: 439 female BC patients were recruited and treated with neoadjuvant chemotherapy of TA regimen. A blood sample (2 ml) of peripheral blood was collected from each patient before chemotherapy. Tagging SNPs (tag-SNPs) were selected. We investigated the association of tag-SNPs with prognosis, by Sequenom Mass ARRAY system platform, characterizing tag-SNPs. The hazard ratio (HR) and 95% confidence interval (CI) for progression or death were calculated by multivariable-adjusted Cox regression model. Results: Seven tag-SNPs (rs11045689, rs200104106, rs3764006, rs3834935, rs4149117, rs7305323 and rs73241801) were selected for study. Compared with individuals carrying the rs11045689 GG genotype, individuals carrying rs11045689 AA genotype performed worse PFS and OS, with the HR (95% CI) for progression being 1.39 (1.11~1.75) and the HR (95% CI) for death being 1.38 (1.04~1.83). Compared with individuals carrying the rs73241801 CC genotype, individuals carrying rs73241801 TT genotype performed better OS (P=0.041), with the HR (95% CI) for death being 0.65 (0.44~0.94). The number of risk allele was significantly associated with PFS (P=0.012) and OS (P=0.017) of BC patients by accumulation analysis. Compared with individuals carrying one or less than one risk allele, individuals carrying four risk alleles performed worse PFS and OS, with the HR (95% CI) for progression being 1.37 (1.09~1.72) and the HR (95% CI) for death being 1.36 (1.02~1.81). Conclusion: The variations of rs11045689 and rs73241801 in SLCO1B3 gene were significantly associated with prognosis of BC patients treated with neoadjuvant chemotherapy of TA regimen, which might serve as biomarkers for predicting prognosis of BC patients treated with neoadjuvant chemotherapy.

[Experimental study of silybin-phospholipid complex intervention on amiodarone-induced fatty liver in mice].

Objective: To probe into the mechanism and interventional effects of silybin-phospholipid complex on amiodarone-induced steatosis in mice. Methods: Eight-week-old male C57BL/6 mice were divided into three groups (5 mice in each group): a control group (WT) with normal diet, a model group with amiodarone 150mg/kg/d by oral gavage (AM), and an intervention group on amiodarone 150mg/kg/d combined with silybin-phospholipid complex(AM+SILIPHOS. All mice were fed their assigned diet for one week. Then, one week later, serum alanine aminotransferase, aspartate aminotransferase, triglyceride, total cholesterol and high-density lipoprotein were detected of each group. A liver pathological change was observed by oil red O and H&E staining. Ultrastructural pathological changes of hepatocytes were observed to evaluate the intervention effect by transmission electron microscopy. RT-q PCR was used to detect the expression of peroxisome proliferator-activated receptor alpha and its regulated lipid metabolism genes CPTI, CPTII, Acot1, Acot2, ACOX, Cyp4a10 and Cyp4a14 in liver tissues. Intra-group comparison was done by paired t-test. One-way ANOVA was used for comparison between groups and semi-quantitative data were tested using Mann-Whitney U test. Results: Oil Red O and H&E staining results of liver tissue in the intervention group showed that intrahepatic steatosis was significantly reduced when compared to model group. Transmission electron microscopy showed that the model group had pyknotic nuclei, mitochondrial swelling, structural damage, and lysosomal degradation whereas the intervention group had hepatic nucleus without pyknosis, reduced mitochondrial swelling and slight structural damage than that of model group. RT-q PCR results showed that the expression of peroxisome proliferator-activated receptor alpha, CPTI, CPTII, Acot1, Acot2, ACOX, Cyp4a10 and Cyp4a14 were increased in the model group but the expression of CPTI, Cyp4a14, Acot1 and peroxisome proliferator-activated receptor alpha were decreased in the intervention group (P < 0.05). Conclusion: Silybin-phospholipid complex can alleviate amiodarone-induced steatosis, and its mechanism may play a role in protecting mitochondrial function and regulating fatty acid metabolism. Thus, silybin-phospholipid complex has potential intervention effect on amiodarone-induced fatty liver.

Recent advances on topical antimicrobials for skin and soft tissue infections and their safety concerns.

Antimicrobial resistance of disease-related microorganisms is considered a worldwide prevalent and serious issue which increases the failure of treatment outcomes and leads to high mortality. Considering that the increased resistance to systemic antimicrobial therapy often needs of the use of more toxic agents, topical antimicrobial therapy emerges as an attractive route for the treatment of infectious diseases. The topical antimicrobial therapy is based on the absorption of high drug doses in a readily accessible skin surface, resulting in a reduction of microbial proliferation at infected skin sites. Topical antimicrobials retain the following features: (a) they are able to escape the enzymatic degradation and rapid clearance in the gastrointestinal tract or the first-pass metabolism during oral administration; (b) alleviate the physical discomfort related to intravenous injection; (c) reduce possible adverse effects and drug interactions of systemic administrations; (d) increase patient compliance and convenience; and (e) reduce the treatment costs. Novel antimicrobials for topical application have been widely exploited to control the emergence of drug-resistant microorganisms. This review provides a description of antimicrobial resistance, common microorganisms causing skin and soft tissue infections, topical delivery route of antimicrobials, safety concerns of topical antimicrobials, recent advances, challenges and future prospective in topical antimicrobial development.

Astrocyte elevated gene-1 participates in the production of pro-inflammatory cytokines in dental pulp cells via NF-κB signalling pathway.

AIM: To identify the role of astrocyte elevated gene-1 (AEG-1) and the mechanism underlying the inflammatory response in dental pulp cells. METHODOLOGY: Astrocyte elevated gene-1 expression was detected at different stages of pulpitis in a rat model using immunohistochemistry. RT-qPCR and Western blot were used to assess AEG-1 expression in human dental pulp cells stimulated by lipopolysaccharide (LPS). The LPS-induced expression of inflammatory cytokine genes was quantified by RT-qPCR in cells transfected with AEG-1 or negative control (NC) siRNA. Immunofluorescence and Western blot were utilized to evaluate the activation of NF-κB signalling in AEG-1 knockdown cells. AEG-1 expression was also investigated by Western blot in dental pulp cells pre-treated with inhibitors of NF-κB and PI-3K signalling before the addition of LPS. Data were analysed statistically using one-way anova. RESULTS: The exposure of dental pulp tissue to LPS resulted in acute inflammation with necrosis and AEG-1 expression in the pulp tissue beneath the perforation. In LPS-stimulated dental pulp cells, AEG-1 mRNA and protein were significantly up-regulated (P < 0 .05) in a time- and dose-dependent manner. In AEG-1 knockdown cells, the synthesis of IL-1, IL-6 and TNF-α mRNA was suppressed significantly (P < 0.05) upon LPS induction. AEG-1 knockdown also inhibited nuclear translocation of p65. Suppression of NF-κB and PI-3K abrogated the LPS-induced up-regulation of AEG-1. CONCLUSION: Astrocyte elevated gene-1 participated in inflammatory cytokine synthesis via NF-κB signalling in the dental pulp. Both NF-κB and PI-3K signalling are involved in LPS-induced AEG-1 expression in dental pulp cells.

Patterns and correlates of major depression in Chinese adults: a cross-sectional study of 0.5 million men and women.

BACKGROUND: Worldwide 350 million people suffer from major depression, with the majority of cases occurring in low- and middle-income countries. We examined the patterns, correlates and care-seeking behaviour of adults suffering from major depressive episode (MDE) in China. METHOD: A nationwide study recruited 512 891 adults aged 30-79 years from 10 provinces across China during 2004-2008. The 12-month prevalence of MDE was assessed by the Modified Composite International Diagnostic Interview-short form. Logistic regression yielded adjusted odds ratios (ORs) of MDE associated with socio-economic, lifestyle and health-related factors and major stressful life events. RESULTS: Overall, 0.7% of participants had MDE and a further 2.4% had major depressive symptoms. Stressful life events were strongly associated with MDE [adjusted OR 14.7, 95% confidence interval (CI) 13.7-15.7], with a dose-response relationship with the number of such events experienced. Family conflict had the highest OR for MDE (18.9, 95% CI 16.8-21.2) among the 10 stressful life events. The risk of MDE was also positively associated with rural residency (OR 1.5, 95% CI 1.4-1.7), low income (OR 2.3, 95% CI 2.1-2.4), living alone (OR 2.6, 95% CI 2.3-3.0), smoking (OR 1.4, 95% CI 1.3-1.6) and certain other mental disorders (e.g. anxiety, phobia). Similar, albeit weaker, associations were observed with depressive symptoms. Among those with MDE, about 15% sought medical help or took psychiatric medication, 15% reported having suicidal ideation and 6% reported attempting suicide. CONCLUSIONS: Among Chinese adults, the patterns and correlates of MDE were generally consistent with those observed in the West. The low rates of seeking professional help and treatment highlight the great gap in mental health services in China.

Peptide 11R-VIVIT stimulates osteoblastogenesis through regulating the expression of nuclear factor of activated T cells cytoplasmic 1.

Osteoporosis is characterized by the imbalance of two relatively independent processes-osteoblastogenesis and osteoclastogenesis. Calcineurin (Cn)/nuclear factor of activated T cells (NFAT)(Cn/NFAT) signaling pathway is involved in these two processes in bone metabolism, but its potential as a target to treat osteoporosis needs to be defined. The aim of this study is to investigate the inhibition of polypeptide 11R-VIVIT onCn/NFAT signaling pathway. Rat calvaria (RC) cells were prepared from experimental model of osteoporosis in rat.11R-VIVIT wasused to treat cultured RC cells from wide type (WT) rat or from osteoporosis (OP) rat, we then measured the expressions of NFATc1, osteopontin (OPN), osteocalcin (OC), cytokines, NFκB subunit p65 by real time PCR, western blot or immunofluorescence. Then ALP expression and staining, and alizarin red S (ARS) staining were employed to study the osteoblastodifferentiation. 11R-VIVIT regulates the expression of NFATc1, and some other molecules in Cn/NFAT signaling pathway, such as OPN and OC, at transcriptional level and protein level. Further, it can regulate the expression of inflammatory cytokine like IL-1beta, IL-10 and TNF-alpha and NFκB activity. Further, 11R-VIVIT can accelerate osteoblastodifferentiation of RC cells demonstrated by ALP and ARS staining.11R-VIVIT can stimulate the bone formation by decreasing NFATc1 expression and regulating the expression of inflammation related molecules.

Hypodontia, a prospective predictive marker for tumor?

Tooth agenesis and tumor are two totally different diseases occurring at different ages. In the past 10 years, more and more evidences suggested there was a relationship between them. High prevalence of breast, colon, lung, and ovary tumor was observed in tooth agenesis patients. But it is still controversial. Therefore, to have a greater understanding of the possible association, a critical review on molecular association for genes involving tooth agenesis and tumorigenesis is necessary. In this current review, we summarized the reported cases of tooth agenesis with different kinds of tumors and the molecular relationship between these two diseases through causative genes. The results indicated tooth agenesis might be a prospective predictive marker for tumor. Through this review, we want to draw more attention on this topic and hope it will be an effective way to predict the risk of tumor.

Dopamine D1 receptor agonist A-68930 inhibits NLRP3 inflammasome activation and protects rats from spinal cord injury-induced acute lung injury.

STUDY DESIGN: Randomized experimental study. OBJECTIVES: The study aimed to investigate the therapeutic efficacy and molecular mechanisms of A-68930 in a rat model of spinal cord injury (SCI)-induced acute lung injury (ALI). SETTING: China. METHODS: The influences of A-68930 on the pulmonary edema, histological changes, proinflammatory cytokines levels, myeloperoxidase (MPO) activity and NLRP3 inflammasome protein expression were estimated. RESULTS: SCI significantly promoted NLRP3 inflammasome activation, increased proinflammatory cytokine productions and MPO activity, and induced pulmonary edema and tissue damage in the SCI group as compared with the control group. A-68930 administration significantly inhibited NLRP3 inflammasome activation and reduced inflammatory cytokines levels and MPO activity. Moreover, A-68930 administration attenuated pulmonary edema and histopathology. CONCLUSION: Our experimental findings indicated that A-68930 exhibited a protective effect on SCI-induced ALI by the alleviations of inflammatory response with the inhibition NLRP3 inflammasome activation 72 h post injury. The present study indicated that A-68930 could be a potentially efficient therapeutic strategy for the treatment of SCI-induced ALI.

Quercetin suppresses NLRP3 inflammasome activation and attenuates histopathology in a rat model of spinal cord injury.

STUDY DESIGN: Randomized experimental study. OBJECTIVES: To investigate the molecular mechanisms of quercetin in spinal cord injury (SCI) rats. SETTING: China. METHODS: One hundred female Sprague-Dawley rats were randomly assigned into four groups: sham group, SCI group, SCI+Vehicle (Veh) group, and the SCI+Quercetin (Que) group. The influences of quercetin on proinflammatory cytokine levels, histological changes and locomotion scale were estimated. RESULTS: SCI significantly promoted nucleotide-binding domain-like receptor protein 3 (NLRP3) inflammasome activation and increased proinflammatory cytokine productions in the SCI group as compared with the sham group. Quercetin administration significantly decreased reactive oxygen species production, inhibited NLRP3 inflammasome activation and reduced inflammatory cytokine levels. Moreover, quercetin administration attenuated histopathology and promoted locomotion recovery. CONCLUSION: Quercetin can attenuate tissue damage and improve neurological function recovery, and the mechanism may be related to the inhibition of NLRP3 inflammasome activation.