[Epidemiological and Etiologic characteristics of Meningococcal meningitis in Xinjiang Uygur Autonomous Region,1960-2019].

Objective: To understand the epidemiological and etiologic characteristics of meningococcal meningitis in Xinjiang Uygur Autonomous Region (Xinjiang). Methods: The epidemiological data about the meningococcal meningitis cases in Xinjiang from 1960 to 2019 were collected from the China information system for disease control and prevention and the Center for Disease Control and Prevention of Xinjiang. The epidemiological characteristics were analyzed. Clinical specimens from suspected cases were cultured and tested by real-time PCR method. A survey on the carriage rate of Neisseria meningitides (Nm) in the healthy population was performed. The serogroups of isolates were determined by serum-agglutination and PCR methods. Multi-locus sequence typing was used for subtyping the isolates. Results: The incidence rates of meningococcal meningitis in Xinjiang from 1960 to 2019 were 0.02/100 000-81.32/100 000, with the mortality as 1.05%-20.78%. The five districts with the most cases were Kashi prefecture, Aksu prefecture, Urumqi city, Changji Hui autonomous prefecture, and Hotan prefecture. Before 1990, serogroup A (81.82%) was the commonest group for cases and contacts. After 1990, 14.00% of the cases were caused by serogroups B, C, W, and Y. There was no predominant serogroup for contacts with serogroups B, C, W, Y, and C accounting for 23.28%, 18.53%, 15.52%, 9.91% and 7.33% respectively. The general Nm carriage rate was 15.50%, with the population of 16 - 20 years age group having the highest rate (25.53%). Serogroups B (52.11%), W (20.66%), C (12.21%), and Y (9.39%) occupied 52.11%, 20.66%, 12.21% and 9.39% respectively. The commonest clonal lineages of Nm isolates were ST-4821, ST-175, and ST-5 clonal complexes, while the ST-5 and ST-4821 clonal complexes were the major ones for invasive strains. Conclusions: There appeared regional differences in the incidence rates of Xinjiang meningococcal meningitis, and the carriage rate of Nm was high. The serogroups have been changing. It is necessary to strengthen the prevention and control of meningococcal meningitis to prevent any potential outbreak.

KLF13 loss-of-function variation contributes to familial congenital heart defects.

OBJECTIVE: Congenital heart defect (CHD) represents the most common form of human developmental abnormality and contributes to substantial morbidity, mortality, and socioeconomic burden worldwide. Accumulating evidence underscores the strong genetic basis of CHD. Nevertheless, CHD is of pronounced genetic heterogeneity, and the genetic determinants underlying CHD in most patients are still unclear. This study was mainly sought to identify the causative gene for CHD in a consanguineous Chinese family. PATIENTS AND METHODS: Whole-exosome sequencing and bioinformatics analyses were performed in a Chinese family with CHD (double-outlet right ventricle and ventricular septal defect), which was transmitted in an autosomal dominant pattern. A total of 312 unrelated healthy individuals were then genotyped for the identified genetic variation. The functional effect of the identified variation was characterized by utilizing a Dual-Luciferase reporter assay system. RESULTS: A novel heterozygous variation, NM_015995.3: c.370G>T; p.(Glu124*), was identified in the KLF13 gene, which encodes Kruppel-like factor 13 key to proper heart development. Genetic analysis of the pedigree unveiled that the variation co-segregated with CHD, with complete penetrance. The variation was absent from 624 control chromosomes. The biological analysis revealed that the Glu124*-mutant KLF13 protein failed to transactivate its cardiac target genes ACTC1 and ANP. Furthermore, the variation disrupted the synergistic transactivation between KLF13 and GATA4, as well as GATA6, two other genes that have been recognized to cause CHD. CONCLUSIONS: These findings firstly indicate that genetically defective KLF13 predisposes to familial CHD, implying potential implications for genetic counseling and an improved prophylactic strategy in a subset of CHD patients.

Locomotor transition: how squid jet from water to air.

The amazing multi-modal locomotion of flying squid helps to achieve fast-speed migration and predator-escape behavior. Observation of flying squid has been rarely reported in recent years, since it is challenging to clearly record the flying squid's aquatic-aerial locomotion in a marine environment. The existing reports of squid-flying events are rare and merely record the in-air motion. Therefore, the water-air locomotor transition of flying squid is still unknown. This paper proposes the idea of using CFD to simulate the process of the flying squid (Sthenoteuthis oualaniensis (S. oualaniensis)) launching from water into air. The results for the first time reveal the flow field information of squid in launching phase and show the kinematic parameters of flying squid in quantification. Both a trailing jet and pinch-off vortex rings are formed to generate launching thrust, and the formation number L ω /D ω is 5.22, demonstrating that the jet strategy is to produce greater time-averaged thrust rather than higher propulsion efficiency. The results also indicate that the maximum flying speed negatively correlates with the launch angle, indicating that a lower launch angle could result in a larger flying speed for the flying squid to escape. These findings explore the multi-modal locomotion of flying squid from a new perspective, helping to explain the trade-off strategy of water-to-air transition, and further enhance the performance of aquatic-aerial vehicles.

Using Meglumine Diatrizoate to improve the accuracy of diagnosis of cracked teeth on Cone-beam CT images.

AIM: To explore in a laboratory setting the feasibility of using Meglumine Diatrizoate (MD) to improve the accuracy of diagnosis of cracked teeth on cone-beam CT (CBCT) images. METHODOLOGY: Twenty-four teeth were cracked artificially by soaking them cyclically in liquid nitrogen and hot water. The number and position of crack lines were evaluated with a dental operating microscope and used as the gold standard. The artificially cracked teeth were then examined using routine scanning (RS) and enhanced scanning (ES) modes, respectively. For the ES mode, MD was painted on the surface of the crack lines, and then, CBCT scanning with the same parameters was performed after 10 min. A radiological graduate student and an experienced radiologist evaluated the presence or absence of crack lines, respectively. The differences between the RS and ES modes were determined and assessed using McNemar's test. Inter-examiner agreement and intra-examiner agreement were assessed using kappa analysis. RESULTS: Fifty-seven crack lines were found in the 24 cracked teeth. In the RS mode, the accuracy of detection of crack lines was 23% (radiological graduate student) and 32% (experienced radiologist), whereas in the ES mode, the accuracy was 61% (radiological graduate student) and 65% (experienced radiologist). The inter-examiner agreement was 0.693 in RS mode and 0.849 in ES mode. The intra-examiner agreement was 0.872 and 0.949 for the radiological graduate student in RS and ES mode respectively; and one for the experienced radiologist both in RS and ES mode. CONCLUSIONS: Compared with routine scanning mode, more crack lines could be detected in enhanced scanning mode using Meglumine Diatrizoate as a contrast medium. MD could be a potential contrast medium to improve the accuracy of detection of crack lines on CBCT images.

[A cross-sectional study of seroepidemiology of viral hepatitis among Uighurs in Shufu of Xinjiang].

Objective: To explore the status of seroepidemiology on hepatitis A, B and C among students and residents aged equal or greater than 18 years in south Xinjiang, and to provide scientific evidence for prevention and control of viral hepatitis. Methods: Uyghur students in four towns and villages were selected by cluster random sampling from Feb to May, 2015, and Uyghur residents aged 18 to 69 years were selected by stratified cluster sampling from May to September, 2016. 4 507 middle and primary Uygur students and 4 833 Uyghur resides equal or greater than 18 years attended this survey. Self-designed questionnaire was used to collect the demographic information. And Elisa test was adopted to detect HAV-IgG, HBsAg, HBsAb and HCV-IgG. Chi-square test was used to calculate the difference on antibody positive rate of three types of hepatitis among the participants. Results: The overall HAV-IgG positive rate was 99.45% (9 289/9 340). The positive rates were 99.70% (4 006/4 018) in male and 99.27% (5 283/5 322) in female (χ(2)=7.95, P=0.005). The HAV-IgG positive rate among people aged 10 to 14 years was the highest (99.91%, 2 233/2 235), and the difference between the age specific HAV-IgG positive rates was statistical significant (χ(2)=38.21, P<0.001). The overall HBsAg positive rate was 4.11% (384 cases), with 4.55% (183 cases) for male and 3.78% (201 cases) for female. The HBsAg positive rate among participants 19 to 24 years old was the highest (9.46%, 21/222) and the differences between the age specific HBsAg was statistically significant (χ(2)=116.22, P<0.001). The HBsAb positive rate was 35.03% (3 272 cases), with 35.59% (1 430 cases) for male and 34.61% (1 842 cases) for female, and the HBsAb positive rate among participants aged 15 to 18 years was the highest, which was 69.12% (696/1 007). The differences between the age specific HBsAb rates appeared statistically significant (χ(2)=671.80, P<0.001). The overall HCV-IgG positive rate was 0.65%(61 cases). The HCV-IgG positive rate in female was 0.86% (46 cases) and 0.37% (15 cases) in male (χ(2)=8.51, P=0.004).The HCV-IgG positive rate among participants aged over 70 years was the highest (3.78%,9/238) , and the difference between the age specific HCV-IgG positive rates had statistic significance (χ(2)=70.30, P<0.001). The HAV-IgG positive rate in hepatitis A vaccinees (100%, 876/876) was higher than that among the non-vaccinees (99.40%, 8 413/8 464) (χ(2)=4.26, P=0.039). The HBsAb positive rate in hepatitis B vaccinees was 39.32% (1 816/4 619) which was higher than that among the non-vaccinees (30.84%, 1 456/4 721) (χ(2)=73.68, P<0.001). Conclusion: The positive rate of overall HAV-IgG was high, male and participants aged between 10 to 14 had higher probability to be infected. But the infection rates of hepatitis B and C were low, with the low vaccination rate and the poor protective effectiveness of hepatitis B.

[Prevalence of dyslipidemia and normal blood lipids level in Uygur population in Kashgar area of Xinjiang Uygur Autonomous Region].

Objective: To understand the prevalence of dyslipidemia and normal blood lipids level in Uygur diabetes patients in Kashgar prefecture in southern area of Xinjiang. Methods: A total of 5 078 local residents aged ≥18 years (42.56% were men) selected through cluster random sampling in Kashgar were surveyed by means of questionnaire survey, physical examination and laboratory test, and 521 diabetes patients were screened. Results: The overall prevalence of dyslipidemia in diabetes patients was 59.50% (310/521) with adjusted rate as 49.39%. Age ≥65 years, overweight, obesity and abdominal obesity increased the risk for dyslipidemia by 0.771 times (95% CI: 1.015-3.088), 1.132 times (95% CI: 1.290-3.523), 1.688 times (95% CI: 1.573-4.592) and 0.801 times (95% CI: 1.028-3.155) respectively. Compared with males, female was a protective factor for dyslipidemia (OR=0.507, 95%CI: 0.334-0.769). The overall normal rate of blood lipids level including total cholesterol (TC), triglycerides (TG), high-density lipoprotein cholesterol (HDL-C) and low-density lipoprotein cholesterol (LDL-C) for type 2 diabetes patients was 11.13%. Female, higher BMI and abdominal obesity were the factors influencing the overall normal blood lipids level. The normal rate of LDL-C level decreased with increase of age, BMI and waist circumferences (trend test χ(2)=18.049, P<0.001; trend test χ(2)=10.582, P=0.001; χ(2)=19.081, P<0.001), but increased with educational level (trend test χ(2)=9.764, P=0.002). Conclusion: The prevalence of dyslipidemia in Uygur diabetes patients in Kashgar was high, however, the overall normal rate of blood lipid level was relatively low. Obesity was the most important risk factor for dyslipidemia in this area. More attention should be paid to dyslipidemia prevention in women.

[Prevalence of diabetes mellitus and associated risk factors in Uygur population in Kashgar area of Xinjiang Uygur Autonomous Region].

Objective: To investigate the epidemiologic characteristics of diabetes mellitus (DM) in Uygur residents in Kashgar of Xinjiang. Methods: The survey was conducted among the Uygur residents aged ≥18 years selected through stratified cluster sampling in Kashgar by means of questionnaire survey, physical examination and basic laboratory test. The prevalence of different groups were calculated and risk factors of DM was analyzed by logistic vegression model. Results: A total of 4 608 adults were surveyed. The prevalence of DM was 11.31% (standardized prevalence: 10.59%) and the prevalence was 13.65% (standardized prevalence: 12.34%) in males and 10.04% (standardized prevalence: 9.83%) in females. The prevalence increased with age. The prevalence of DM was higher than the prevalence of impaired fasting glucose (IFG) in people aged >60 years, especially in females. The rates of awareness, treatment and control of DM were 28.02%, 21.31% and 5.57%, respectively. Multivariate logistic regression analysis indicated that people aged 45-55, 55-65 and >65 years had higher risk of DM and the odds ratio were 2.08 (95%CI: 1.24-3.48), 2.73 (95%CI: 1.63-4.56) and 3.90 (95%CI: 2.24-6.78) for men and 2.63 (95% CI: 1.71-4.02), 3.14 (95%CI: 2.00-4.94) and 5.56 (95%CI: 3.47-8.92) for woman, respectively. Family history of DM (OR=2.88 for men, 95% CI: 1.45-5.72; OR=2.52 for women, 95% CI: 1.49-4.26) and BMI≥28.0 kg/m(2) (OR=1.77 for men, 95% CI: 1.19-2.64, OR=1.80 for women, 95% CI: 1.30-2.50) were also risk factors for DM. Conclusion: The prevalence of DM was high in Uygur residents in Kashgar, but the rate of awareness, treatment and control of DM were low. It is necessary to improve the detection rate of DM and conduct targeted prevention and control of DM.

[Prevalence of hypertension and risk factors in Uygur population in Kashgar area of Xinjiang Uygur Autonomous Region].

Objective: To investigate the prevalence of hypertension and risk factors in Uygur adults in Kashgar of Xinjiang. Methods: A total of 4 748 Uygur adults aged ≥18 years selected through cluster random sampling in Shufu county of Kashgar prefecture were surveyed by means of questionnaire survey, physical examination and laboratory test. The prevalence, awareness, treatment and control rate of hypertension of different groups were calculated and risk factors of hypertension was analyzed by using non-conditional logistic regression model. Results: The overall prevalence of hypertension was 15.73% (age-adjusted prevalence was 13.75%). The prevalence rates of hypertension in men and women were 16.36% (age-adjusted prevalence was 12.96%), 15.39% (age-adjusted prevalence was 14.34%), respectively. The rates of awareness, treatment and control of hypertension were 59.57%, 52.74%, 21.29%, respectively. The prevalence of hypertension increased with age. Compared with age group 18-34 years, the age groups 55-64, ≥65 years had higher risk of hypertension and the OR values were 10.53, 20.96 for men and 16.27, 33.20 for women. The overweight (OR=1.47 for men, OR=1.82 for women, P<0.05) and obesity (OR=1.88 for men, OR=2.66 for women, P<0.05) also increased the risk of hypertension. The groups with family history of hypertension (OR=3.85 for men, OR=2.34 for women, P<0.05) also had higher risk of hypertension. Hypertriglyceridemia was positively correlated with the prevalence of hypertension in men (OR=1.62, 95%CI: 1.09-2.41). Conclusions: The prevalence of hypertension in Uygur adults in Kashgar area of Xinjiang was at relatively low level. The related risk factors were age, overweight, obesity, family history and hypertriglyceridemia in men and the risk factors were similar in women except hypertriglyceridemia.

Revealing extraordinary tensile plasticity in layered Ti-Al metal composite.

Layered Ti-Al metal composite (LMC) fabricated by hot-pressing and hot-rolling process displays higher ductility than that of both components. In this paper, a combination of digital image correlation (DIC) and X-ray tomography revealed that strain delocalization and constrained crack distribution are the origin of extraordinary tensile ductility. Strain delocalization was derived from the transfer of strain partitioning between Ti and Al layer, which relieved effectively the strain localization of LMC. Furthermore, the extensive cracks of LMC were restricted in the interface due to constraint effect. Layered architecture constrained the distribution of cracks and significantly relieved the strain localization. Meanwhile, the transfer of strain partitioning and constrained crack distribution were believed to inhibit the strain localization of Ti and change the deformation mechanisms of Ti. Our finding enriches current understanding about simultaneously improving the strength and ductility by structural design.

The comparative, long-term effect of the Salter osteotomy and Pemberton acetabuloplasty on pelvic height, scoliosis and functional outcome.

AIMS: This study compared the long-term results following Salter osteotomy and Pemberton acetabuloplasty in children with developmental dysplasia of the hip (DDH). We assessed if there was a greater increase in pelvic height following the Salter osteotomy, and if this had a continued effect on pelvic tilt, lumbar curvature or functional outcomes. PATIENTS AND METHODS: We reviewed 42 children at more than ten years post-operatively following a unilateral Salter osteotomy or Pemberton acetabuloplasty. We measured the increase in pelvic height and the iliac crest tilt and sacral tilt at the most recent review and at an earlier review point in the first decade of follow-up. We measured the lumbar Cobb angle and the Short Form-36 (SF-36) and Harris hip scores were collected at the most recent review. RESULTS: During the first decade of follow-up, there was a greater increase in pelvic height in the children who had a Salter osteotomy (Salter, 10.1%; Pemberton, 4.3%, p < 0.001). The difference in the increase in pelvic height was insignificant at the most recent review (Salter, 4.4%; Pemberton, 3.1%, p = 0.249). There was no significant difference between the two groups for the lumbar Cobb angle, (Salter, 3.1°; Pemberton, 3.3°, p = 0.906). A coronal lumbar curve was seen in 41 children (97%), 30 of these had a compensatory curve. Sacral tilt was the radiographic parameter for pelvic imbalance that correlated most with the lumbar Cobb angle (Pearson correlation co-efficient 0.59). The Harris hip score and SF-36 were good and showed no differences between the two groups. CONCLUSION: In the long-term, we found no difference in the functional results or pelvic imbalance between Salter osteotomy and Pemberton acetabuloplasty in the management of children with DDH. Cite this article: Bone Joint J 2016;98-B:1145-50.

Mid-infrared photodetectors operating over an extended wavelength range up to 90 K.

We report a wavelength threshold extension, from the designed value of 3.1 to 8.9 µm, in a p-type heterostructure photodetector. This is associated with the use of a graded barrier and barrier offset, and arises from hole-hole interactions in the detector absorber. Experiments show that using long-pass filters to tune the energies of incident photons gives rise to changes in the intensity of the response. This demonstrates an alternative approach to achieving tuning of the photodetector response without the need to adjust the characteristic energy that is determined by the band structure.

Serum nerve growth factor level indicates therapeutic efficacy of 125I seed implantation in advanced pancreatic adenocarcinoma.

OBJECTIVE: To evaluate serum nerve growth factor (NGF) as a marker in predicting effectiveness of 125I seed implantation in advanced pancreatic carcinoma. PATIENTS AND METHODS: A total of 45 patients (30 males/15 females with mean age of 52.07±8.43 years) diagnosed with advanced pancreatic adenocarcinoma (PCa) between January 2011 to May 2014 were enrolled as PCa group in this study. Tumors were categorized as at least stage III with unresectionable condition by the TNM standard. The average tumour shortest diameter was 37.54±13.84 mm (18.50-71.20 mm). NGF level in serum before 125I seed implantation and in tumor tissue resected during surgery was measured by ELISA. After treatment, CT Scan was used to serially monitor the diameters of the tumour monthly for 6-month follow-up. RECIST was applied to evaluate the efficacy. Predictive value of serum and tumour derived NGF was evaluated based on ROC curve chart. RESULTS: We found that the serum NGF level was significantly increased in PCa patients (775.60 ± 250.97 pg/ml) compared to the healthy control group (35.03 ± 25.36 pg/ml), after age and gender adjustment. In the PCa group, the serum NGF level positively correlated with that from loci tumor tissue (r=0.487). The serum NGF level was compared between the effective group (537.42 ± 122.61 pg/ml) and noneffective group (883.17 ± 217.79 pg/ml), and significant difference was detected (p<0.0001). Patients with lower serum NGF level had good response to the 125I seeds implantation. Taking cut-off at 649.59 pg/ml, 85.70% specificity and 90.30% sensitivity were achieved by ROC. Area under the Curve of serum NGF was 0.945, standard deviation was 0.032, 95% confidence interval was 0.882-1.000. CONCLUSIONS: The level of serum NGF could be a referential index to predict the therapeutic efficacy of 125I seed implantation treatments in advanced pancreatic adenocarcinoma.

IFI27, a novel epidermal growth factor-stabilized protein, is functionally involved in proliferation and cell cycling of human epidermal keratinocytes.

OBJECTIVES: IFI27 is highly expressed in psoriatic lesions but its function has not been known. The present study aimed to explore its role in proliferation of epidermal keratinocytes. MATERIALS AND METHODS: IFI27 knockdown and over-expression in keratinocytes were used to compare their proliferation, by MTT assay, apoptosis (by annexin V binding) and cell cycle progression by flow cytometry. Formation of cyclin A/CDK1 complex was examined by a co-immunoprecipitaion method. Anti-proliferation effects of IFI27 were also examined in vivo by topical application of IFI27 siRNA on imiquimod-induced psoriatic lesions, in a mouse model. RESULTS: Epidermal growth factor was demonstrated to increase IFI27 expression by prolonging half-life of IFI27 protein. The IFI27 knockdown in keratinocytes reduced the proliferation rate, but had no effect on apoptosis nor on apoptosis-related genes. Interestingly, IFI27 knockdown resulted in S-phase arrest that was found to be associated with increased Tyr15 phosphorylation of CDK1, reduced CDC25B and reduced formation of cyclin A/CDK1 complex. In addition, IFI27 knockdown was also shown to activate p53 by Ser15 phosphorylation and increase p21 expression. Topical application of IFI27 siRNA on imiquimod-induced psoriatic lesion in a mouse model reduced epidermal thickness, formation of rete ridges and PCNA expression. CONCLUSIONS: Our study demonstrates for the first time, that cell function of IFI27 is involved in proliferation of skin keratinocytes both in vitro and in vivo. It suggests that IFI27 might be a suitable target for development of a novel anti-psoriasis therapy.

CFD based investigation on the impact acceleration when a gannet impacts with water during plunge diving.

Plunge diving is the most commonly used feeding method of a gannet, which can make the gannet transit from air to water rapidly and successfully. A large impact acceleration can be generated due to the air-to-water transition. However, the impact acceleration experienced by the gannet during plunge diving has not been studied. In this paper, this issue is investigated by using the CFD method. The effect of the dropping height and the water-entry inclination angle on the impact acceleration is considered. The results reveal that the impact acceleration along the longitudinal body axis increases with either of the two parameters. The peak time decreases with the dropping height. A quadratic relation is found between the peak impact acceleration and the initial water-entry velocity. According to the computation, when the dropping height is 30 m (most of gannets plunge from about this height), the peak impact acceleration can reach about 23 times the gravitational acceleration, which will exert a considerable force on the gannet body. Furthermore, the pressure distribution of different water-entry inclination angles indicates that the large pressure asymmetry caused by a small oblique angle may lead to a large impact acceleration in the direction perpendicular to the longitudinal body axis and cause damage to the neck of the gannet, which partly explains the reason why a gannet performing a high plunge diving in nature enters water with a large oblique angle from the perspective of impact mechanics. The investigation on the plunge-diving behavior in this paper will inspire and promote the development of a biomimetic amphibious robot that transits from air to water with the plunge-diving mode.

Hydrodynamic investigation of a self-propelled robotic fish based on a force-feedback control method.

We implement a mackerel (Scomber scombrus) body-shaped robot, programmed to display the three most typical body/caudal fin undulatory kinematics (i.e. anguilliform, carangiform and thunniform), in order to biomimetically investigate hydrodynamic issues not easily tackled experimentally with live fish. The robotic mackerel, mounted on a servo towing system and initially at rest, can determine its self-propelled speed by measuring the external force acting upon it and allowing for the simultaneous measurement of power, flow field and self-propelled speed. Experimental results showed that the robotic swimmer with thunniform kinematics achieved a faster final swimming speed (St = 0.424) relative to those with carangiform (St = 0.43) and anguilliform kinematics (St = 0.55). The thrust efficiency, estimated from a digital particle image velocimetry (DPIV) flow field, showed that the robotic swimmer with thunniform kinematics is more efficient (47.3%) than those with carangiform (31.4%) and anguilliform kinematics (26.6%). Furthermore, the DPIV measurements illustrate that the large-scale characteristics of the flow pattern generated by the robotic swimmer with both anguilliform and carangiform kinematics were wedge-like, double-row wake structures. Additionally, a typical single-row reverse Karman vortex was produced by the robotic swimmer using thunniform kinematics. Finally, we discuss this novel force-feedback-controlled experimental method, and review the relative self-propelled hydrodynamic results of the robot when utilizing the three types of undulatory kinematics.

Effect of triethylene glycol dimethacrylate on the cytotoxicity, cyclooxygenase-2 expression and prostanoids production in human dental pulp cells.

AIM: To evaluate the effect of TEGDMA on cell cycle progression as well as alterations of cell cycle-related gene and protein expression. METHODOLOGY: Human dental pulp cells were exposed to 0-5 mmol L(-1) TEGDMA for 24 h. Cytotoxicity was evaluated by 3-(4, 5-dimethyl-thiazol-2-yl)-2,5-diphenyl-tetrazolium bromide assay. Cell cycle progression was analysed by propidium iodide (PI) flow cytometry. Cell death pathway was surveyed by annexin V/PI dual-staining flow cytometry. The mRNA expression of cell cycle-related genes (cdc2, cyclinB1 and p21) and COX-2 was evaluated by reverse transcriptase-polymerase chain reaction, and their protein expression was evaluated by Western blotting. The production of PGE(2) and PGF(2α) in the culture medium was determined by enzyme-linked immunosorbent assay. RESULTS: Triethylene glycol dimethacrylate inhibited cellular growth and induced cell cycle deregulation in dental pulp cells. High-dose exposure provoked both necrotic and apoptotic cell death. The gene and protein expression of cdc2, cyclin B1 and cdc25C declined obviously whilst cells treated with 2.5 mmol L(-1) TEGDMA concurrent with the elevated expression of p21. The mRNA and protein expression of COX-2, along with production of PGE(2) and PGF(2α), are drastically raised by 2.5-5 mmol L(-1) TEGDMA. CONCLUSIONS: Triethylene glycol dimethacrylate induced cytotoxicity, cell cycle arrest and apoptosis in dental pulp cells, which was associated with the decline of cdc2, cyclin B1, cdc25C expression and elevation of p21 expression. Concomitantly, COX-2 expression, PGE(2) and PGF(2α) production increased. These effects may contribute to explain the pulpal damage and inflammation induced by TEGDMA after operative procedures.

Carboxylesterase expression in human dental pulp cells: role in regulation of BisGMA-induced prostanoid production and cytotoxicity.

Biocompatibility of dentin bonding agents (DBA) and composite resin may affect the treatment outcome (e.g., healthy pulp, pulpal inflammation, pulp necrosis) after operative restoration. Bisphenol-glycidyl methacrylate (BisGMA) is one of the major monomers present in DBA and resin. Prior studies focused on salivary esterase for metabolism and degradation of resin monomers clinically. This study found that human dental pulp cells expressed mainly carboxylesterase-2 (CES2) and smaller amounts of CES1A1 and CES3 isoforms. Exposure to BisGMA stimulated CES isoforms expression of pulp cells, and this event was inhibited by catalase. Exogenous addition of porcine esterase prevented BisGMA- and DBA-induced cytotoxicity. Interestingly, inhibition of CES by bis(p-nitrophenyl) phosphate (BNPP) and CES2 by loperamide enhanced the cytotoxicity of BisGMA and DBA. Addition of porcine esterase or N-acetyl-l-cysteine prevented BisGMA-induced prostaglandin E(2) (PGE(2)) and PGF(2α) production. In contrast, addition of BNPP and loperamide, but not mevastatin, enhanced BisGMA-induced PGE(2) and PGF(2α) production in dental pulp cells. These results suggest that BisGMA may induce the cytotoxicity and prostanoid production of pulp cells, leading to pulpal inflammation or necrosis via reactive oxygen species production. Expression of CES, especially CES2, in dental pulp cells can be an adaptive response to protect dental pulp against BisGMA-induced cytotoxicity and prostanoid release. Resin monomers are the main toxic components in DBA, and the ester group is crucial for monomer toxicity.

Prostaglandin F(2alpha) stimulates MEK-ERK signalling but decreases the expression of alkaline phosphatase in dental pulp cells.

AIM: To study prostaglandin F(2alpha) (PGF(2alpha)) receptor expression and downstream signalling in cultured human dental pulp cells and the effect of PGF(2alpha) on the alkaline phosphatase (ALP) activity of dental pulp cells. METHODOLOGY: Human dental pulp cells were cultured and exposed to PGF(2alpha). The expression of PGF(2alpha) (FP) receptors was analysed by reverse transcriptase polymerase chain reaction (RT-PCR) and Western blotting. The activation of extracellular regulated kinase (ERK) and cAMP responsive element binding protein/activating transcription factor-1 (CREB/ATF-1) signalling was determined by Western blotting. The expression of ALP in pulp cells after exposure to PGF(2alpha) was evaluated by ALP staining and PCR. RESULTS: Dental pulp cells expressed FP receptor mRNA and protein. Exposure to PGF(2alpha) revealed little cytotoxicity to pulp cells. PGF(2alpha) induced both ERK and CREB/ATF-1 phosphorylation in pulp cells. Exposure to PGF(2alpha) (>1 micromol L(-1)) further decreased the ALP activity and mRNA expression. However, U0126 (an inhibitor of MEK1) showed little preventive effect on the decline of ALP activity in dental pulp cells by PGF(2alpha). CONCLUSION: PGF(2alpha) may potentially activate FP receptors leading to ERK/CREB-ATF-1 activation during its production in inflamed dental pulp. PGF(2alpha) attenuated the ALP activity of pulp cells possibly via pathways not solely by MEK/ERK activation. PGF(2alpha) is a contributing factor of pulpal inflammation by regulating the activities of pulp cells.

Utility of PDL progenitors for in vivo tissue regeneration: a report of 3 cases.

OBJECTIVE: Periodontal disease is an inflammatory disorder with widespread morbidities involving both oral and systemic health. The primary goal of periodontal treatment is the regeneration of the lost or diseased periodontium. In this study, we retrospectively examined feasibility and safety of reconstructing the periodontal intrabony defects with autologous periodontal ligament progenitor (PDLP) implantation in three patients. MATERIALS AND METHODS: In this retrospective pilot study, we treated 16 teeth with at least one deep intrabony defect of probing depth (PD) > OR = 6 mm with PDLP transplantation and evaluated clinical outcome measures in terms of probing depth, gingival recession and attachment gain for a duration of 32-72 months. Furthermore, we compare PDLPs with standard PDL stem cells (PDLSCs) and confirmed that PDLPs possessed progenitor characters. RESULTS: Clinical examination indicated that transplantationof PDLPs may provide therapeutic benefit for the periodontal defects. All treated patients showed no adverse effects during the entire course of follow up. We also found that PDLPs were analogous to PDLSCs in terms of high proliferation, expression of mesenchymal surface molecules, multipotent differentiation, and in vivo tissue regain. However, PDLPs failed to express scleraxis, a marker of tendon, as seen in PDLSCs. CONCLUSIONS: This study demonstrated clinical and experimental evidences supporting a potential efficacy and safety of utilizing autologous PDL cells in the treatment of human periodontitis.