Objective:To preliminarily explore therapeutic effects and possible molecular mechanisms of sinomenine on atopic dermatitis (AD) -like mouse models.Methods:Thirty female BALB/c mice (6 - 8 weeks old) were randomly divided into 5 groups: blank control group, model group, positive control group, topical sinomenine group, and oral sinomenine group. Except for the blank control group, all groups were subjected to repeated topical stimulation with 2,4-dinitrochlorobenzene (DNCB) on the dorsal skin to establish an AD-like mouse model. After modeling, no special treatment was given to the blank control group, the positive control group was topically treated with 100 μg of 0.1% mometasone furoate cream twice daily on the lesions, the topical sinomenine group was topically treated with 100 μl of 10 mg/ml sinomenine solution twice daily on the lesions, and the oral sinomenine group was gavaged with sinomenine solution at a dose of 100 mg·kg -1·d -1 (100 μl per dose, twice daily) . Treatments lasted for 14 days. Twelve hours after the final treatment, the severity of skin lesions in each group was assessed. Blood samples were collected via enucleation, and serum levels of interleukin (IL) -1β, IL-6, and immunoglobulin E (IgE) were measured using enzyme-linked immunosorbent assay (ELISA) . Histopathological changes in dorsal skin lesions were observed, and immunohistochemical study was performed to detect the expression levels of p38 mitogen-activated protein kinase (MAPK) and nuclear factor (NF) -κB p65 in skin tissues, expressed as the percentage of the immunopositive area. One-way analysis of variance was used for multiple group comparisons, while Tukey′s test or the Games-Howell test was applied for post-hoc comparisons between groups. Results:Compared with the blank control group, the model group exhibited epidermal hyperkeratosis with parakeratosis, thickening of the spinous layer, spongiosis, significant inflammatory cell infiltration, and prominent angiogenesis. In contrast, the positive control group, topical sinomenine group, and oral sinomenine group showed reduced spinous layer thicknesses, decreased inflammatory cell infiltration, and less pronounced angiogenesis compared to the model group. In the blank control group, model group, positive control group, topical sinomenine group, and oral sinomenine group, the severity scores of skin lesions were 0, 8.83 ± 0.75, 4.33 ± 1.08, 2.58 ± 0.49, 2.83 ± 0.93 respectively, the serum levels of IL-1β were 52.58 ± 1.72, 168.40 ± 7.23, 57.07 ± 6.39, 85.74 ± 4.15, 100.30 ± 11.55 pg/ml respectively, IL-6 levels were 86.88 ± 4.60, 215.00 ± 5.02, 79.34 ± 4.91, 127.20 ± 1.06, 149.00 ± 6.21 pg/ml respectively, IgE levels were 2 159.00 ± 176.00, 3 493.00 ± 89.61, 2 294.00 ± 158.10, 2 550.00 ± 214.70, 2 814.00 ± 119.70 μg/ml respectively, the expression levels of p38 MAPK in skin tissues were 3.03% ± 3.38%, 12.95% ± 6.89%, 2.14% ± 1.28%, 5.28% ± 3.71%, 3.85% ± 2.26% respectively, and NF-κB p65 expression levels were 0.61% ± 0.49%, 18.92% ± 6.96%, 3.77% ± 1.90%, 5.66% ± 2.28%, 6.25% ± 3.14% respectively; the differences in all the above parameters were statistically significant among groups (all P < 0.05) . Compared with the blank control group, the model group had significantly increased skin lesion severity scores, serum IL-1β, IL-6, and IgE levels, as well as elevated expression of p38 MAPK and NF-κB p65 in skin tissues (all P < 0.01) . Compared with the model group, the positive control group, topical sinomenine group, and oral sinomenine group showed significantly reduced skin lesion severity scores, decreased serum IL-1β, IL-6, and IgE levels, and lower expression of p38 MAPK and NF-κB p65 in skin tissues (all P < 0.05) . Compared with the positive control group, the topical and oral sinomenine groups exhibited further reductions in skin lesion severity scores (both P < 0.05) . Additionally, the topical sinomenine group showed significantly lower serum levels of IL-1β and IL-6 compared with the oral sinomenine group (both P < 0.05) . Conclusion:Sinomenine solution could obviously alleviate the severity of skin lesions in AD-like mouse models, likely by down-regulating the expression of IL-1β, IL-6 and IgE, inhibiting the MAPK/NF-κB signaling pathway, and thus reducing the degree of inflammation.

Objective:To preliminarily explore therapeutic effects and possible molecular mechanisms of sinomenine on atopic dermatitis (AD) -like mouse models.Methods:Thirty female BALB/c mice (6 - 8 weeks old) were randomly divided into 5 groups: blank control group, model group, positive control group, topical sinomenine group, and oral sinomenine group. Except for the blank control group, all groups were subjected to repeated topical stimulation with 2,4-dinitrochlorobenzene (DNCB) on the dorsal skin to establish an AD-like mouse model. After modeling, no special treatment was given to the blank control group, the positive control group was topically treated with 100 μg of 0.1% mometasone furoate cream twice daily on the lesions, the topical sinomenine group was topically treated with 100 μl of 10 mg/ml sinomenine solution twice daily on the lesions, and the oral sinomenine group was gavaged with sinomenine solution at a dose of 100 mg·kg -1·d -1 (100 μl per dose, twice daily) . Treatments lasted for 14 days. Twelve hours after the final treatment, the severity of skin lesions in each group was assessed. Blood samples were collected via enucleation, and serum levels of interleukin (IL) -1β, IL-6, and immunoglobulin E (IgE) were measured using enzyme-linked immunosorbent assay (ELISA) . Histopathological changes in dorsal skin lesions were observed, and immunohistochemical study was performed to detect the expression levels of p38 mitogen-activated protein kinase (MAPK) and nuclear factor (NF) -κB p65 in skin tissues, expressed as the percentage of the immunopositive area. One-way analysis of variance was used for multiple group comparisons, while Tukey′s test or the Games-Howell test was applied for post-hoc comparisons between groups. Results:Compared with the blank control group, the model group exhibited epidermal hyperkeratosis with parakeratosis, thickening of the spinous layer, spongiosis, significant inflammatory cell infiltration, and prominent angiogenesis. In contrast, the positive control group, topical sinomenine group, and oral sinomenine group showed reduced spinous layer thicknesses, decreased inflammatory cell infiltration, and less pronounced angiogenesis compared to the model group. In the blank control group, model group, positive control group, topical sinomenine group, and oral sinomenine group, the severity scores of skin lesions were 0, 8.83 ± 0.75, 4.33 ± 1.08, 2.58 ± 0.49, 2.83 ± 0.93 respectively, the serum levels of IL-1β were 52.58 ± 1.72, 168.40 ± 7.23, 57.07 ± 6.39, 85.74 ± 4.15, 100.30 ± 11.55 pg/ml respectively, IL-6 levels were 86.88 ± 4.60, 215.00 ± 5.02, 79.34 ± 4.91, 127.20 ± 1.06, 149.00 ± 6.21 pg/ml respectively, IgE levels were 2 159.00 ± 176.00, 3 493.00 ± 89.61, 2 294.00 ± 158.10, 2 550.00 ± 214.70, 2 814.00 ± 119.70 μg/ml respectively, the expression levels of p38 MAPK in skin tissues were 3.03% ± 3.38%, 12.95% ± 6.89%, 2.14% ± 1.28%, 5.28% ± 3.71%, 3.85% ± 2.26% respectively, and NF-κB p65 expression levels were 0.61% ± 0.49%, 18.92% ± 6.96%, 3.77% ± 1.90%, 5.66% ± 2.28%, 6.25% ± 3.14% respectively; the differences in all the above parameters were statistically significant among groups (all P < 0.05) . Compared with the blank control group, the model group had significantly increased skin lesion severity scores, serum IL-1β, IL-6, and IgE levels, as well as elevated expression of p38 MAPK and NF-κB p65 in skin tissues (all P < 0.01) . Compared with the model group, the positive control group, topical sinomenine group, and oral sinomenine group showed significantly reduced skin lesion severity scores, decreased serum IL-1β, IL-6, and IgE levels, and lower expression of p38 MAPK and NF-κB p65 in skin tissues (all P < 0.05) . Compared with the positive control group, the topical and oral sinomenine groups exhibited further reductions in skin lesion severity scores (both P < 0.05) . Additionally, the topical sinomenine group showed significantly lower serum levels of IL-1β and IL-6 compared with the oral sinomenine group (both P < 0.05) . Conclusion:Sinomenine solution could obviously alleviate the severity of skin lesions in AD-like mouse models, likely by down-regulating the expression of IL-1β, IL-6 and IgE, inhibiting the MAPK/NF-κB signaling pathway, and thus reducing the degree of inflammation.

Epstein-Barr virus (EBV) is a biological factor associated with gastric carcinoma. The prognosis of EBV-associated gastric car-cinoma (EBVaGC) is good because of its distinct clinicopathological features. The pathogenesis mechanism of EBVaGC is extensively in-vestigated at present. The development of molecular techniques has stimulated the research on the expression of EBV genes in EB-VaGC, thereby providing a theoretical foundation on the diagnosis, therapy, and prevention of EBVaGC. This article reviewed present research advances in EBV genes in EBVaGC.

Objective:To evaluate the efficacy of Epstein-Barr nuclear antigen 1/immunoglobulin A (EBNA1/IgA), BamH1 Z transactivator/IgA (Zta/IgA), capsid antigen/IgA (VCA/IgA), and Epstein-Barr virus deoxyribonucleic acid (EBV-DNA) in detecting different stages of na-sopharyngeal carcinoma (NPC). The relationship between the EBV markers and stages of NPC was also analyzed. Methods:Blood sam-ples of 152 untreated patients with NPC and 675 healthy subjects were collected.ELISA was used to detect the serum levels of EBNA1/IgA, Zta/IgA, and VCA/IgA. Fluorescence quantitative PCR (FQ-PCR) was used to detect the plasma levels of EBV-DNA. ROC and correla-tion analyses were employed to assess the detection assays for NPC diagnosis. The positive rates of EBV markers in NPC patients in dif-ferent stages were analyzed statistically. Results: The positive rates of EBNA1/IgA, Zta/IgA, VCA/IgA, and EBV-DNA in NPC patients were higher than those in the healthy individuals. The expression of EBNA1/IgA was relatively high in early NPC. The sensitivity of EB-NA1/IgA was 77.8%. In advanced NPC, the level of EBV-DNA was high, and the sensitivity of EBV-DNA was 88.8%. The specificity of EBV-DNA and EBNA1/IgA could reach more than 96%. The combination of EBV-DNA and EBNA1/IgA showed the best diagnostic value, with a sensitivity of 92.1%(early stage 82.5%, advanced stage 98.9%) and a specificity of 96.9%. The positive rates of EBV-DNA were positively associated with the NPC clinic stage and N stage. The positives rates of Zta/IgA were positively associated with the NPC N stage. Conclusion:The best single index for NPC screening in an asymptomatic population is EBNA1/IgA. EBV–DNA is an ideal index for auxiliary diagnostics of advanced NPC. The combination of EBV-DNA and EBNA1/IgA shows the best diagnostic value. EBV-DNA is an important index in the stage and illness monitoring of NPC. Zta/IgA can indirectly reflect the character of lymph node metastasis, and it may be useful in assessment of NPC surveillance.

Nasopharyngeal carcinoma (NPC) is prevalent in Southeast Asia, especially in the area of southern China. It is acknowl-edged that NPC is absolutely related to EBV infection. Nevertheless, there are just a few researches about the relationship between the level of EBV antibodies and the tumor stages and it hasn't come to conclusion. This review makes a summary on present research progress and would be valuable for the better understanding of the contribution of EBV antibodies to the tumor stages in NPC.

OBJECTIVETo investigate the relationship between changes in high-risk populations and screening detected nasopharyngeal carcinoma (NPC) during the three-year follow-up of high-risk and moderate-risk groups at initial EB virus serology screening.

METHODSWe tested EB virus VCA-IgA and EBNA1-IgA antibody to identify the probability of suffering from NPC of the crowd. The high-risk and moderate-risk groups at initial screening in one county during 2009 to 2010 were followed-up once a year with EB virus serology testing. All the high-risk people during initial screening and follow-up were conducted with nasopharyngeal fiber endoscopy. Through the follow-up of three years, we analyzed changes in the number of high-risk group, detection rate of NPC in high-risk group, and tumor staging. Firstly detected NPC by screening was defined as screening group, and detected by following-up was defined as following-up group.

RESULTSA total of 404 participants were at high-risk and 1 041 participants were at moderate-risk group, 1 445 persons were in the group. All 404 persons were at high-risk at initial screening, the number of high-risk people during follow-up decreased from 371 to 187, 853 people of the all high-risk group were conducted with nasopharyngeal fiber endoscopy, and 38 cases of NPC were detected. NPC detection rate of high-risk group was 6.2% (25/404), 3.2% (12/371), 0.5% (1/188) and 0 (0/187) during the initial screening and three years follow-up respectively. The cumulative incidence of NPC in the high-risk and moderate-risk group were 7.7% (31/404) ,0.8% (8/1 041) . The early diagnosis rate of NPC in screening group and following-up group was 80% (20/25)and 11/13, respectively. With the primary tumor, the rate of T1 in screening group was higher than following-up group (80% to 38%, 20/25 to 5/13; P = 0.028). However, compared with following-up group, the rate of regional lymph node metastasis in screening group was higher (19/25 to 5/13; P = 0.035 ).

CONCLUSIONAlong with the high detection rate of early staging NPC in screening group and following-up group, the detection of NPC in high risk people is mainly at initial screening and the first year following-up and NPC detection rate thereafter is dropping significantly.

Antibodies, Viral ; Antigens, Viral ; Capsid Proteins ; Carcinoma ; Early Detection of Cancer ; Epstein-Barr Virus Nuclear Antigens ; Follow-Up Studies ; Herpesvirus 4, Human ; Humans ; Nasopharyngeal Neoplasms ; Neoplasm Staging ; Risk Factors

BACKGROUND:As the pharmacological effect of eugenol constantly being discovered, its application in medical and food industry becomes wider. However, its toxicity studies have not established a complete database, especialy in the improvement of safety assessment of developmental toxicity and teratogenicity. OBJECTIVE:To establish a model of embryonic stem cel test to evaluate the embryotoxicity of eugenol. METHODS:Mouse fibroblasts (3T3) and mouse embryonic stem cels (E14TG2a) were culturedin vitro, and MTT test was performed to detect the cytotoxicity of 3T3 cels and E14TG2a cels with positive control 5-fluorouracil, negative control penicilin G and tested compound eugenol. The concentration of the tested compounds that inhibiting 50% viability of embryonic stem cels (IC50 E14TG2a) and 3T3 fibroblasts (IC50 3T3) was calculated. The hanging-suspension-adherent culture systems were used to induce embryonic stem cels into cardiomyocytes, and the concentration of tested compounds that caused 50% inhibition of differentiation of E14TG2a cels into cardiomyocytes (ID50 E14TG2a) was calculated. The embryotoxic potential of eugenol was classified by prediction model of the embryonic stem cel test. RESULTS AND CONCLUSION:The proliferations of E14TG2a and 3T3 cels were inhibited by eugenol, of which the IC50 3T3 and IC50 E14TG2a values were (3.613±0.192) and (1.799±0.131) mg/L. The differentiation of E14TG2a was also inhibited by eugenol, of which the ID50 E14TG2a was (3.501±0.158) mg/L. Eugenol was evaluated as a chemical compound with strong embryotoxicity by the model of embryonic stem cel test.

Background:Inflammatory bowel disease( IBD)is a group of chronic and non-specific intestinal inflammatory diseases of undetermined origin. Functional impairment of macrophages has been associated with the dysregulation of mucosal immunity in intestinal tract of patients with IBD. Aims:To investigate the correlation of serum levels of macrophage polarization-related cytokines with the development and disease activity of IBD. Methods:A total of 105 IBD patients admitted from May 2013 to May 2014 at Shanghai Ruijin Hospital were recruited,of them 65 were Crohn’s disease (CD)and 40 were ulcerative colitis( UC). Twenty-four patients with colonic polyps were served as controls. Serum samples were obtained and the levels of interleukin-1beta(IL-1β),IL-6,IL-10,IL-13,interferon-gamma(IFN-γ)and inducible nitric oxide synthase(iNOS)were determined by ELISA method. Results:Serum levels of IL-1β,IL-6,IL-10, IL-13 and IFN-γ were significantly higher in CD group than in control group(P < 0. 05),and serum levels of IL-10,IL-13 and IFN-γ were significantly higher in UC group than in control group(P < 0. 05). Logistic regression analysis revealed that serum IL-13(OR = 1. 009,P = 0. 005)and iNOS( OR = 0. 982,P = 0. 013)were correlated with CD,while Spearman correlation coefficient demonstrated a link between serum IL-10 and disease activity of CD(rs = - 0. 432,P =0. 014). No correlations were observed between serum levels of these cytokines and development and disease activity of UC (P > 0. 05). Conclusions:Serum levels of macrophage polarization-related cytokines increase to varying degrees in IBD patients,but these cytokines have no obvious correlations with IBD and its disease activity. Presumably,theses cytokines are only involved in but not the triggers in the development of IBD.

Objective To establish a model of embryonic stem cell test(EST)and utilize this model to evaluate the embryotoxici-ty of hydroquinone.Methods Mouse 3T3 fibroblasts and mouse embryonic stem(ES)cells(ES-E14TG2a)were cultured in vitro, and methyl thiazolyl tetrazolium(MTT)test was performed to detect the cytotoxicity of 3T3 cells and ES-E14TG2a cells induced by the positive control(5-fluorouracil),negative control(penicillin G)and tested compound(hydroquinone).The concentrations of the test compounds that inhibited 50% viability of ES-E14TG2a cells(IC50 ES)and 3T3 fibroblasts (IC50 3T3)were calculated.The hanging-suspension-adherent culture systems were used to induce embryonic stem cells into cardiomyocytes,and the concentrations of test compounds that caused 50% inhibition of differentiation of ES-E14TG2a cells into cardiomyocytes (ID50 ES)was calculated. The embryotoxic potential of hydroquinone was classified by prediction model of the embryonic stem cell test.Results The prolif-eration of ES-E14TG2a and 3T3 cells were inhibited by hydroquinone,of which the IC50 3T3 and IC50 ES values were (5.97±0.48) and (2.57±0.10)μg/mL respectively.The differentiation of ES-E14TG2a cells were also inhibited by hydroquinone,of which the ID50 ES was (3.77±0.31)μg/mL.Hydroquinone was evaluated as a strong embryotoxicity chemical by prediction model of EST. Conclusion Hydroquinone exhibits a strong embryotoxicity.

Objective:To observe the differences in the dynamic change of the EB virus antibody between general population and first-degree relatives (FDR) of nasopharyngeal carcinoma patients during follow-up study one year after initial screening and discuss the difference among the nasopharyngeal carcinoma detections. Methods: Serologic data of all subjects that participated in the fol-low-up study were collected. Changes in EB virus antibodies were investigated and correlation of these changes with gender and age level was analyzed. Differences in the nasopharyngeal cancer detection rate of different populations were also compared. Results:NA1/IgA negative conversion rate was higher in the family group than in the control group (χ2=20.28, P<0.001). This rate was also higher in both male and female family groups than in the male and female control groups (χ2=22.59, P<0.001;χ2=4.03, P<0.05, respectively). NA1/IgA positive conversion rate was lower in the family group than in the control group (χ2=7.79, P<0.05). Likewise, this rate was lower in both male and female family groups than in the male and female control groups (χ2=9.46, P<0.05;χ2=0.74, P=0.39, respective-ly). VCA/IgA negative conversion rate was higher in the family group than in the control group (χ2=1.90, P<0.001). This rate was also higher in the male and female family groups than in the male and female control groups (χ2=7.50, P<0.05; χ2=no expression, P=0.108, determined by Fish exact test, respectively). VCA/IgA positive conversion rate was higher in the family group than in the control group (χ2=0.10, P=0.70). This rate was again higher in both male and female family groups than in the male and female control groups (χ2=0.02, P=0.90,χ2=0.51, P=0.48, respectively). Ten cases from the control group manifested nasopharyngeal carcinoma;the same disease was not observed in the family group. Nasopharyngeal carcinoma detection rate was significantly higher in the control group than in the family group, but the difference was not statistically significant (χ2=1.05, P=0.31). Conclusion:a. Reactivation of the EB virus is not closely linked with genetic factors. b. The detection rate of NPC in FDR was lower compared with the general population after initial screening;thus, the rule of selective follow-up is not applicable for FDR.