[Research progress in immunomodulation in orthodontic tooth movement].

In the process of orthodontic tooth movement, the secretion of cytokines by immune cells or cell-cell interaction affects the regulation of osteoclast and osteoblast differentiation. Increasingly, studies have focused on the role in the immune system in orthodontic bone remodeling. Based on the biological role of different immune cells or cytokines, this article briefly presents the research progress of immunomodulation in orthodontic tooth movement and future perspective, hopefully providing a deeper and more comprehensive understanding of the biological mechanism in orthodontic tooth movement.

Vitamin D levels in the assessment of Crohn's disease activity and their relation to nutritional status and inflammation.

BACKGROUND: Crohn's disease (CD) is frequently associated with malnutrition, inflammation and a deficiency of vitamin D (VD) with the relationships between these symptoms being poorly defined. VD is a modulator of the immune system and is associated with the onset of CD and disease activity. The level of serum VD may have potential in the assessment of CD activity. This study aimed to evaluate the relationships between VD, nutritional status and inflammation, and to identify more accurate VD thresholds. METHODS: The study included 76 outpatients with CD diagnosed between October 2018 and October 2020 and 76 healthy volunteers. Levels of serum 25(OH)D and nutritional indicators, as well as biochemical and disease activity assessments, were conducted. RESULTS: Patients with CD and healthy participants were found to differ significantly in their 25(OH)D levels as well in levels of nutritional and inflammatory indicators. The optimal VD cut-off value was found to be 46.81 nmol/L for CD development and 35.32 nmol/L for disease activity. Levels of 25(OH)D were correlated with both nutritional status and inflammation. CONCLUSIONS: The VD level is likely to be a useful additional tool in the evaluation of CD patients and predicting the disease activity and clinical response. The VD level may relate both to the nutritional status and levels of inflammation in CD patients, and disease progression.

[Efficacy observation and compliance analysis of pollen allergen drops in seasonal allergic rhinitis].

To study the efficacy and compliance analysis of pollen allergen drops in the treatment of allergic rhinitis. The method of single-center controlled was used to analyze the dates' results. From July 2021 to September 2021, 80 patients with seasonal allergic rhinitis were referred to the clinic of otorhinolaryngology in First Hospital of Shanxi Medical University.40 patients received sublingual immunotherapy (SLIT group), and the other 40 patients received symptomatic drug treatment as the control group. The total rhinoconjunctivitis symptom score (TRSS), the visual analogue scale(VAS), total medication score (TMS) and combined scores of medication and rhinoconjunctivitis symptoms (CSMRS) of the patient before the start of the treatment and after the first year of the treatment were compared to assess the efficacy of sublingual immunotherapy of Artemisia pollen. Follow the shedding during the study, the safety of the drug and the causes for compliance analysis were analyzed and recorded. The results of comparison with TRSS, VAS, TMS and CSMRS in two groups in the period of pretherapy were as follows: TRSS(12.393±3.023, 12.450±3.029, t=-0.077, P=0.939), VAS(8.357±1.026, 8.400±0.982, t=-0.173, P=0.862), TMS(3.214±0.568, 3.175±0.501, t=0.301, P=0.764), CSMRS (5.286±0.680, 5.253±0.677, t=0.199, P=0.843), there was no significant difference (P>0.05); lower observed symptom scores were got in the post-treatment pollen peak SLIT group compared to the control group, TRSS(3.964±1.551, 7.750±2.169, t=-7.918, P<0.05), VAS(2.893±0.956, 5.175±1.481, t=-8.286, P<0.05), TMS (1.821±0.863, 3.175±0.501, t=-8.163, P<0.05), CSMRS (2.489±0.921, 4.468±0.601, t=-10.723, P<0.05), and the differences between the groups were statistically significant (P<0.05); the SLIT group significantly reduced all symptom scores at the first peak compared to the starting, TRSS(12.393±3.023, 3.964±1.551, t=20.576, P<0.05), VAS (8.357±1.026, 2.893±0.956, t=30.070, P<0.05), TMS (3.214±0.568, 1.821±0.863, t=7.151, P<0.05), CSMRS(5.286±0.680, 2.489±0.921, t=14.533, P<0.05) and there was statistical difference (P<0.05). No significant adverse reactions occured during medication in the SLIT group. A total of 12 cases were shed in the SLIT group, so the compliance rate was 70%. The four reasons were that patients considered the course was long (4 cases, 33%); the drugs were expensive (3 cases, 25%); patients were busy with their work and life (3 cases, 25%); patients were affected by the outbreak (2 cases, 17%). In summary, Artemisia pollen sublingual drops may improve the symptoms of the patients who got allergic rhinitis caused by Artemisia pollen after the treatment for one year. However, due to the lack of sufficient understanding of immunotherapy or the difficulty in adhering to standardized medication, the compliance with sublingual immunotherapy is still poor, the compliance with sublingual immunotherapy needs to be further improved through patient education.

Targeting TGF-ß1 and AKT signal on growth and metastasis of anaplastic thyroid cancer cell in vivo.

The article "Targeting TGF-ß1 and AKT signal on growth and metastasis of anaplastic thyroid cancer cell in vivo, by Y. Li, D. Chen, F.-Y. Hao, K.-J. Zhang, published in Eur Rev Med Pharmacol Sci 2016; 20 (12): 2581-2587. PMID: 27383308" has been withdrawn from the authors. The Publisher apologizes for any inconvenience this may cause. https://www.europeanreview.org/article/11013.

The long non-coding RNA AK001796 contributes to poor prognosis and tumor progression in hepatocellular carcinoma.

OBJECTIVE: Increasing studies have indicated the important functions of long non-coding RNAs (lncRNAs) in tumorigenesis and progression including hepatocellular carcinoma (HCC). The study aims to explore the role of long non-coding RNA AK001796 in HCC progression. PATIENTS AND METHODS: Quantitative Real-time polymerase chain reaction (QRT-PCR) analysis was performed to examine the lncRNA AK001796 expression in 73 cases of human HCC tissue samples and matched adjacent normal tissues. Besides, the relationship between lncRNA AK001796 expression and clinicopathologic characteristics was analyzed. Overall survival (OS) curves of patients were constructed by the Kaplan-Meier methods. Multivariate Cox regression analysis was used to evaluate independent risk factors affecting HCC prognosis. Cell proliferation and invasion abilities are analyzed by cell counting kit-8 (CCK-8) and transwell invasion assays. RESULTS: We showed that the lncRNA AK001796 expression was significantly up-regulated in HCC tissues and cell lines, compared to their controls, respectively. Higher lncRNA AK001796 expression closely correlated with tumor size (p<0.05), TNM stage (p<0.05) and the poor overall survival (OS) rate of HCC patients (p<0.05). Besides, multivariate Cox regression analysis found that lncRNA AK001796 expression was identified as an independent risk factor for HCC prognosis. In vitro, we showed that lncRNA AK001796 knockdown markedly suppressed cell proliferation and cell invasion abilities. CONCLUSIONS: Our results suggested that lncRNA AK001796 acts as a predictor of HCC prognosis and may provide an important clinical value for HCC treatment.

[Analysis on the spatial-temporal characteristics of hand-foot-mouth disease in Shaanxi province, 2009-2013].

Objective: To study the spatial-temporal dynamical features of hand-foot-mouth disease (HFMD) in Shaanxi Province, so as to provide evidence for the development of relative prevention and control programs on HFMD. Methods: Surveillance data of HFMD was collected from the China Information System for Diseases Control and Prevention from 2009 to 2013. Related data on population and gross domestic product (GDP) was obtained from Shaanxi Statistical Yearbook. Statistical tools as R3.4.1, ArcGIS 10.2 and SaTScan 9.2 software were used to describe the spatial-temporal distribution of the disease. Power-law method on spatial-temporal-multicomponent model was used to analyze the spatial-temporal evolution of the HFMD epidemics in Shaanxi Province. Results: A total of 229 904 cases of HFMD were reported in Shaanxi Province from 2009 to 2013, with an average annual incidence as 122.50 per 100 000. Obvious seasonal characteristics were noticed, with 71.71% of the total cases identified between April and July. Counties with high incidence were mainly distributed in the mid-and east parts of Guanzhong area. Through temporal and spatial scan statistics, we identified that ClassⅠ clustering area was fixed to the central and southeast regions of Shaanxi province which were around Xi'an City between 2009 and 2013, with the relative risk (RR) as 2.24, ranging from 2.18 to 3.08. Results from Power-law analysis showed that the continuous follow-up impact from the previous HFMD epidemics appeared strong in Tongguan, Pucheng districts of Weinan City and Weiyang district of Xi'an, with autoregressive components as 1.14, 0.97 and 0.89, respectively. The risk of HFMD seemed high in Huayin city, Changan and Yanta districts and with the endemic components as 5.08, 4.12 and 4.08, respectively. Impact of the epidemics on nearby districts was largely seen in Lianhu district of Xi'an, Wugong district of Xianyang and Gaoling district of Xi'an with epidemic components as 2.12, 2.08 and 1.77, respectively. The etiological constituents of HFMD were mainly Enterovirus 71 between 2009 and 2012, while HFMD was mainly caused by other entero-viruses, in 2013. Conclusion: Significant spatial-temporal heterogeneity of HFMD was seen in Shaanxi province, which called for specific strategies to be developed in the highly endemic areas.

Coupling of Surface Plasmon Modes and Refractive Index Sensitivity of Hollow Silver Nanoprism.

Localized surface plasmon (LSP) modes depend strongly on the morphology of nanoparticle and the surrounding dielectric medium. The hollow nanostructure provides a new way to modulate the surface plasmon modes due to the additional cavity surface. In this work, we study systematically the multipolar surface plasmon modes of hollow silver nanoprism (HSN) by simulation of electron energy loss spectroscopy (EELS) spectra based on the boundary element method (BEM). Herein the effects of the cavity size and position are taken into account. The LSP modes of HSNs are compared with those of perfect silver nanoprism (SN). The red-shift behaviors of multipolar modes can be found as increasing the cavity size. Modes A and C have similar red-shift tendency and obey the plasmon ruler equation, which can be explained by dipole-dipole coupling mode. Meanwhile, the degenerate modes will be split by changing the cavity position, and opposite shift tendencies of split degenerate states are observed. These are caused by different coupling nature of degenerate modes. Moreover, high refractive index sensitivity (RIS) can be obtained for HSN by changing the cavity size and position.

Propofol induces apoptosis of non-small cell lung cancer cells via ERK1/2-dependent upregulation of PUMA.

OBJECTIVE: Propofol is one of the most commonly used intravenous anesthetic agents used in cancer resections, but the effect of propofol on non-small cell lung cancer (NSCLC) remains unclear. Previous researches have reported that propofol can inhibit extracellular signal-regulated kinase (ERK) 1/2 phosphorylation or activate p53-upregulated modulator of apoptosis (PUMA) signaling, resulting in apoptosis. In addition, PUMA is negatively regulated by ERK1/2 activation. In the present work, we determined the effect of propofol on NSCLC A549 cells and explored its signaling pathway. MATERIALS AND METHODS: A549 cells were treated with different concentrations of propofol (1-10 µg/mL) for 6 h. After washing, cells were cultured in Dulbecco's Modified Eagle Medium supplemented with 10% fetal bovine serum and antibiotics for another 72 h. Cell survival and apoptosis were determined by MTT, flow cytometry, and TUNEL analyses. To assess whether propofol functions via ERK1/2 and PUMA signaling pathways, A549 cells were transfected with small interfering RNA (siRNA) to target PUMA, or treated with human recombinant ERK1/2 (hrERK1/2) to activate ERK1/2. RESULTS: Propofol treatment inhibited viability and induced apoptosis of A549 cells in a dose-dependent manner in vitro. Propofol inhibited phosphorylation of ERK1/2 (pERK1/2) and increased ERK1/2-dependent PUMA expression. Knockdown of PUMA by siRNA or treatment with hrERK1/2 to activate ERK1/2 blocked propofol-induced apoptosis and cell viability. Upregulation of PUMA expression by propofol requires pERK1/2 inactivation. CONCLUSIONS: Propofol inhibits viability and induces apoptosis of A549 cells via an ERK1/2-dependent PUMA signaling.

[Analysis on the factors related to the immediate success rate of radiofrequency catheter ablation on patients with idiopathic right ventricular outflow tract ventricular arrhythmia].

Objective: To analyze the clinical characteristics of patients with idiopathic right ventricular outflow tract (RVOT) ventricular arrhythmias (VA) and factors related to the immediate success rate of radiofrequency ablation. Methods: Patients diagnosed as idiopathic RVOT arrhythmia in Fuwai Hospital from February 2009 to January 2013 were retrospectively screened. Patients with structural heart disease or inherited arrhythmia were excluded. All patients underwent endocardial electrophysiological study and radiofrequency catheter ablation. Baseline clinical and operation records were collected and analyzed. Immediate success rate was defined as no inducible ventricular arrhythmia by isoprinosine and electrophysiological induction at the end of ablation. The origins of idiopathic RVOT were classified as septal, anterior, posterior, free wall site, epicardial and RVOT-aorta root site. Results: A total of 468 patients were finally included, and the age was (40.4±13.3) years old and 60.5%(283/468) patients were female. Immediate radiofrequency success rate was 89.3%(418/468). Patients were divided into ablation success group (n=418) and ablation failure group (n=50). Percent of female patients and patients with interventricular septal origin was significantly higher in the ablation success group than in ablation failure group (261(62.4%) vs. 22 (44.0%) , P=0.01, and 233(55.7%) vs. 18(36.0%), P=0.005), while percent of patients with epicardial origin was significantly lower in the ablation success group than in ablation failure group (17(4.1%) vs. 11(22.0%), P<0.001). Immediate success rate was the highest for patients with the septal origin and the lowest for patients with epicardial origin (92.8%(233/251) vs. 60.7%(17/28), P<0.05). Multivariate analysis showed that the origin site of VAs was the most important independent factor related to the success rate of ablation. Compared with the septal origin patients, patients with RVOT-aorta root and epicardial origin VAs faced with 1.82-fold and 8.26-fold increased risk of failed ablation, respectively (OR=2.82, 95%CI 1.05-7.57, and OR=9.26, 95%CI 3.60-23.86). Sex category was not the independent risk factor for failed ablation(OR=1.76, 95%CI 0.93-3.33, P=0.08) . Conclusions: The immediate success rate of radiofrequency catheter ablation for idiopathic RVOT ventricular arrhythmia is relative high, however, immediate success rate of radiofrequency catheter ablation is relatively low for patients with epicardial and RVOT-aorta root origin arrhythmia and VAs origin is an independent risk factor of immediate ablation success rate.

Effect of asymmetric morphology on coupling surface plasmon modes and generalized plasmon ruler.

Plasmon coupling in aggregated noble metal systems can provide a path to manipulate the optical response purposefully and possesses a wide range of application. Previously, most studies focused on the coupling behavior of Ag-Ag dimers with the same shape. However, plasmon coupling between nanoparticles at different morphologies can provide a new way to modulate optical properties due to broken of symmetry. In this work, we investigate systematically the coupling modes of asymmetric Ag-Ag heterodimers consisting of different morphologies by the boundary element method (BEM). Herein nanoparticles with different surface curvatures (modified by rounding parameter e) are constructed and combined as asymmetric Ag-Ag heterodimers. Simulated electron energy loss spectroscopy (EELS) spectra and eigenmodes are combined to analyze the evolution of coupling modes. The mode energy degeneracy and degeneracy breaking phenomena are found, while the charge states are always not degenerate, for the first time by modulating symmetry of the morphology. It is also found that coupling gap mode G2 can only be excited for Ag-Ag heterodimers with quite small separation distance, and will be greatly influenced by nanogap morphology. The rounded effect can also cause distinct blue shift of bounding dipolar modes. These results provide the possibility to modulate optical response by using different asymmetric dimers effectively. In contrast, optical response of high-order coupling modes is less sensitive to topographic effect than that of low-order coupling modes. Moreover, plasmon ruler for asymmetric Ag-Ag heterodimers is investigated and we demonstrate that a generalized plasmon ruler is applicable to predict the relative shift of coupling dipolar due to change of separation distance.

[Allergic rhinitis management:environment control and patient education].

Objective:To observe the auxiliary curative effect of combined clostridium and bifidobacterium capsules, live (also called Changlekang) in the treatment of allergic rhinitis by comparing IL-10, transforming growth factor-ß1(TGF-ß1), the quality of life score and symptom score before and after oral Changlekang.Method:Twenty qualified patients in the study group and 20 qualified patients in the control group were enrolled.The study group was given changlekang, desloratadine citrate disodium tablets and mometasone furoate nasal spray for treatment. After 2 weeks of treatment, Changlekang was still given for maintenance therapy for 6 weeks, and no other two kinds of drugs. The control group was given the desloratadine citrate disodium tablets and mometasone furoate nasal spray for 2 weeks and then quited the clinical trials. The changes of symptom score, quality of life score, serum IL-10, serum TGF-ß1 would be statistically analyzed during the treatment.Result:①Before treatment, serum TGF-ß1 and IL-10 of normal group was significantly different from the study group and the control group (P< 0.001), and the study group and the control group's were significantly lower than the normal group.②With the increase of treatment time, serum IL-10, TGF-ß1 levels of patients in the study group increased gradually. Four point method ocular symptoms score, VAS ocular symptoms score and total score of RQLQ decreased gradually; ③patients in the control group after 2 weeks'treatment, serum IL-10, TGF-ß1 was higher than that before treatment (P< 0.001), at the same time all symptom scores, total score of RQLQ were lower than those before treatment (P< 0.001). ④After 2 weeks' treatment, patients in the study group, the serum IL-10 is higher than that of control group (P< 0.001); ⑤Before treatment serum IL-10, TGF-ß1 of AR patients might have little correlation with symptom scores, total score of RQLQ on linear (P> 0.05).Conclusion:①serum IL-10, TGF-ß1 levels of AR patients may be lower thannormal, and IL-10, TGF-ß1 may be involved in the pathogenesis of AR. ②Changlekang may increase the production of serum IL-10, TGF-ß1 in AR patients. ③AR patients with desloratadine citrate and mometasone furoate nasal spray treatment combined with Canglekang may promote higher serum IL-10 production than conventional two combination therapy, but there is no more significant improvement in symptoms score and quality of life score. ④Changlekang may improve ocular symptoms and the quality of life in AR patients. ⑤Before treatment serum IL-10, TGF-ß1 of AR patients may have little correlation with symptom scores, total score of RQLQ, as a result the level of serum IL-10 and TGF-ß1 can not be used to evaluate the severity of AR for the time being.

Targeting TGF-ß1 and AKT signal on growth and metastasis of anaplastic thyroid cancer cell in vivo.

OBJECTIVE: We have recently reported that therapies targeting TGF-ß1 signaling were effective to prevent the anaplastic thyroid cancer (ATC) cell growth, but not the invasion. Phosphatidylinositol 3-kinase (PI3K)/AKT signaling are activated in ATC and play a major role in ATC invasion. Herein, we examined the effects of targeting TGF-ß1 by shRNA in combination with pan-AKT inhibitor, MK-2206 on growth and metastasis of ATC xenografts implanted in severe combined immunodeficient mice. MATERIALS AND METHODS: 8505C cells or 8505C/shRNA cells or 8505C/TGF-ß1 shRNA cells were implanted sc in 5-week-old female nude mice. Upon establishment of palpable tumours, MK-2206 was administered at 60 mg/kg, orally, three times a week for 6 weeks. RESULTS: The results showed that TGF-ß1/shRNA alone only prevents anaplastic thyroid cancer (ATC) tumor formation, but not lung metastasis. MK-2206 alone only inhibits lung metastasis, but not tumor formation. The combined treatment with TGF-ß1/shRNA and MK-2206 led to an approximately 71% growth inhibition compared with TGF-ß1/shRNA (44%) and MK-2206 (15%). The combined treatment with TGF-ß1/shRNA and MK-2206 significantly inhibits lung metastasis. CONCLUSIONS: These findings demonstrated that targeting TGF-ß1 in combination with MK-2206 was the effective method for treatment of ATC.

Association of TUSC3 gene polymorphisms with non-syndromic mental retardation based on nuclear families in the Qinba mountain area of China.

TUSC3 interacts with the protein phosphatase 1 and magnesium ion transport system, which plays an important role in learning and memory. Abnormal conditions of learning and memory are common clinical characteristics of mental retardation (MR). However, the association of TUSC3 genetic polymorphisms with MR remains unknown. A total of 456 DNA samples including 174 nuclear families containing MR were collected in the Qinba mountain area of China. The genotypes of eight tag single nucleotide polymorphisms of TUSC3 were evaluated with traditional genetic methods. Family-based association tests, transmission disequilibrium tests (TDTs), and haplotype relative risk (HRR) analyses were performed to investigate the association between genetic variants of the TUSC3 gene and MR. The genetic polymorphisms rs10093881, rs6530893, and rs6994908 were associated with MR (all P values <0.05) based upon the results of single-site TDT and HRR analyses. The haplotype block consisting of rs6530893 and rs6994908, harboring the sixth exon of TUSC3, was also associated with MR (all P values <0.05). This study demonstrated an association between genetic polymorphisms of the TUSC3 gene and MR in the Qinba mountain area, the sixth exon of which might contribute to the risk of MR. However, further studies are needed on the causal mechanisms in this association.

VEGF Trapon inhibits tumor growth in papillary thyroid carcinoma.

OBJECTIVE: Vascular endothelial growth factor (VEGF) is the most potent inducer of neovasculature, and its increased expression has been related to a worse clinical outcome in many disease. Angiogenesis from thyroid cancer cell plays the important roles in post-surgical persistent, recurrent, and metastatic papillary thyroid cancer (PTC). Vascular endothelial growth factor (VEGF) Trapon is a newly developed VEGF-blocking agent with stronger affinity and broader activity than the anti-VEGF antibody bevacizumab. In this study, we tested the activity of VEGF Trapon on a PTC model in vivo. MATERIALS AND METHODS: BC-PAP (derived from papillary carcinomas) transfected with a luciferase-expressing vector were injected into the back to mice. I.p. treatment with VEGF Trapon or control protein (25 mg/kg twice weekly) was started shortly after tumor injection to prevent tumor development (prevention model) or after established tumors were formed to inhibit tumor growth and metastasis formation (intervention model). RESULTS: In the prevention model, VEGF Trapon inhibited tumor growth by 73 ± 12% compared with control (p = 0.014) and significantly prolonged survival. In the intervention model, VEGF Trapon inhibited tumor growth by 68 ± 7% (p < 0.01). Microvascular density was reduced by 56% due to VEGF Trapon treatment (p < 0.01). CONCLUSIONS: VEGF Trapon is a potent inhibitor of BC-PAP tumor growth, angiogenesis and blocks the biological function of VEGF in vivo. These results support further clinical development of VEGF Trapon for PTC and other cancer types.

Phospholipases A-II (PLA2-II) induces acute pancreatitis through activation of the transcription factor NF-kappaB.

OBJECTIVES: Acute pancreatitis (AP) is an inflammatory disease of the pancreas characterized by local inflammation. Secretory phospholipases A-II (sPLA2-II) have been implicated in triggering AP, but their exact role to evoke AP is largely unknown. NF-kB activation has previously been shown to induce acute pancreatitis. The aim of this study is to explore that PLA2-II triggers AP by activation of NF-kB and the expression of inducible inflammatory mediators. MATERIALS AND METHODS: Acute pancreatitis in vivo was induced in Wistar rats by retrograde infusion of 4% sodium taurocholate (TAC) into the pancreatic duct. Then the Wistar rats were devided into 2 groups: (1) PLA2 II-specific siRNA was subsequently administrated subcapsularly after infusion of TAC. (2) One hour before the intraductal injection of TCA, the rats were treated with PDTC 100 mg/kg twice i.p. in 1 h interval. Induction of pancreatitis was confirmed by histopathology, NF-kB activity and expression in pancreas was detected by EMSA and immunohistochemistry. Inflammatory mediators such as the tumor necrosis factor-alpha (TNF-α), interleukin (IL)-1beta, intercellular adhesion molecule-1 (ICAM-1), IL-6 and IL-8 in blood was detected by ELISA. The severity of the disease and the mortality were observed. RESULTS: We demonstrated that TAC specifically induces pancreatitis, induces PLA2-II expression and activates NF-kappaB and proinflammatory cytokine synthesis in the pancreas of rats. sPLA2-II siRNA transfection blocked NF-kappaB activation and proinflammatory cytokine expression and relieved pancreatitis severity. PDTC treatment blocked NF-kappaB activation and proinflammatory cytokine expression. Pretreatment with PDTC or PLA2 II-specific siRNA transfection improved the survival of the rats. CONCLUSIONS: These findings suggest that PLA2-II induces acute pancreatitis through activation of the transcription factor NF-kappaB. siRNA mediated gene knockdown of PLA2-II relieves pancreatitis severity at least partly mediated by the inhibition of NF-kappaB activation and proinflammatory cytokine synthesis.

Clinical significance of serum matrix metalloproteinase-13 levels in patients with esophageal squamous cell carcinoma (ESCC).

OBJECTIVES: Matrix metalloproteinase-13 (MMP13) is a highly regulated zinc-dependent endopeptidase and has been reported to be associated with vascular invasion and lymph node metastasis and predicts poor outcome for relatively early stage in esophageal squamous cell carcinoma (ESCC) patients. However, the role of the serum MMP-13 levels in ESCC is still unknown. In the present study, we investigate the clinical significance of MMP-13 levels in patients with ESCC. PATIENTS AND METHODS: The serum level of MMP-13 was measured with commercially available ELISA kit in 112 healthy controls and 141 ESCC patients prior to surgical resection. Statistical associations between clinicopathological observations and MMP-13 levels were determined using the Mann-Whitney U test. The clinical value of MMP-13 level as a prognostic parameter was evaluated using the Cox's proportional hazards model. RESULTS: The results showed compared with the healthy control group (74.5±12.3 ng/ml), ESCC patients tended to have significantly higher serum MMP-13 concentrations (86.2 ± 14.6 ng/ml) (p < 0.05). Elevation of MMP-13 levels (≥ 76.4 ng/ml) was observed in 61.7% (87/141) of patients with ESCC, and 18.4% (26/141) in healthy controls. MMP-13 levels were associated with lymph node metastasis (p < 0.001), distant metastasis (p < 0.001), histological differentiation (p = 0.026), T classification (p < 0.005), but not with the tumor size, clinical stage, age and gender of the patients or tumor location. Multivariate analysis revealed that patients with an elevated level of MMP-13 (≥ 76.4 ng/ml) had significantly lower 5 year survival rate than those with non-elevated MMP-13 (< 76.4 ng/ml, log-rank p < 0.001). CONCLUSIONS: It is suggested that the elevated level of preoperative MMP-13 was found to associate with tumor progression and poor survival in patients with ESCC.

No association between FGD1 gene polymorphisms and intellectual developmental disability in the Qinba mountain area.

FGD1 encoding a guanine nucleotide exchange factor, specifically activates Rho GTPase cell division cycle 42 (Cdc42). Dysfunction of FGD1 causes Aarskog-Scott syndrome (MIM #305400), an X-linked disorder that may affect bone and intellectual development. However, the relationship between FGD1 and intellectual developmental disorders (IDD) remains unclear. The purpose of this study was to investigate the genetic association between the FGD1 polymorphism and IDD. Working with families from the Qinba mountain area where the occurrence of IDD is higher than the average in China, we analyzed 456 samples from 130 nuclear families, effectively controlling for stratification and environmental factors. Five SNP loci (rs2230265, rs7881608, rs2239809, rs6614244, and rs2284710) were selected that were well distributed within the FGD1 gene. Genotyping was performed through single-strand conformation polymorphism and restriction fragment length polymorphism. The data were analyzed with transmission disequilibrium tests. In the Qinba mountain area, no significant association was observed between IDD and allele or genotype frequencies, or the haplotype of the 5 SNP loci of the FGD1 gene. The results indicate that FGD1 may not be a monogenetic X-linked factor in IDD. Further studies are required to investigate its role in intellectual development based on its specific interactions with Cdc42 or other partner proteins contributing to IDD.

Molecular cloning and characterization of the pseudorabies virus US1 gene.

Using polymerase chain reaction, a 1050-bp sequence of the US1 gene was amplified from the pseudorabies virus (PRV) Becker strain genome; identification of the US1 gene was confirmed by further cloning and sequencing. Bioinformatics analysis indicated that the PRV US1 gene encodes a putative polypeptide with 349 amino acids. The encoded protein, designated PICP22, had a conserved Herpes_IE68 domain, which was found to be closely related with the herpes virus immediate early regulatory protein family and is highly conserved among the counterparts encoded by Herpes_IE68 genes. Multiple nucleic acid sequence and amino acid sequence alignments suggested that the product of PRV US1 has a relatively higher homology with ICP22-like proteins of genus Varicellovirus than with those of other genera of Alphaherpesvirinae. In addition, phylogenetic analysis showed that PRV US1 has a close evolutionary relationship with members of the genus Varicellovirus, especially Equid herpes virus 1 (EHV-1), EHV-4 and EHV-9. Antigen prediction indicated that several potential B-cell epitopes are located in PICP22. Also, subcellular localization analysis demonstrated that PICP22 is predominantly located in the cytoplasm, suggesting that it might function as a cytoplasmic-targeted protein.