Human with bi-allelic WNT10A mutations and epithelial Wnt10a knockout mice present enlarged pulp chamber and apical displacement of the root furcation of multi-rooted teeth,known as taurodontism;thus,indicating the critical role of Wnt10a in tooth root morphogenesis.However,the endogenous mechanism by which epithelial Wnt10a regulates Hertwig's epithelial root sheath(HERS)cellular behaviors and contributes to root furcation patterning remains unclear.In this study,we found that HERS in the presumptive root furcating region failed to elongate at an appropriate horizontal level in K14-Cre;Wnt10afl/flmice from post-natal day 0.5(PN0.5)to PN4.5.EdU assays and immunofluorescent staining of cyclin D1 revealed significantly decreased proliferation activity of inner enamel epithelial(IEE)cells of HERS in K14-Cre;Wnt10afl/flmice at PN2.5 and PN3.5.Immunofluorescent staining of E-Cadherin and acetyl-α-Tubulin demonstrated that the IEE cells of HERS tended to divide perpendicularly to the horizontal plane,which impaired the horizontal extension of HERS in the presumptive root furcating region of K14-Cre;Wnt10afl/flmice.RNA-seq and immunofluorescence showed that the expressions of Jag1 and Notch2 were downregulated in IEE cells of HERS in K14-Cre;Wnt10afl/fl mice.Furthermore,after activation of Notch signaling in K14-Cre;Wnt10afl/flmolars by Notch2 adenovirus and kidney capsule grafts,the root furcation defect was partially rescued.Taken together,our study demonstrates that an epithelial Wnt10a-Notch signaling axis is crucial for modulating HERS cell proper proliferation and horizontal-oriented division during tooth root furcation morphogenesis.

Collaborative development among medical practice, education and research is a strategic decision of the country in disciplinary development guided by the innovation-driven strategy. In October 2017, Beijing Hospitals Authority organized 18 tertiary hospitals with pediatrics discipline and founded a collaborative development center for pediatrics. This center operated in a model featuring both leadership of due authorities and autonomous administration. Two of the specialized pediatrics hospitals work as leading units, and existing high quality pediatrics resources of the member hospitals were pooled to establish an academics committee and an executive committee. A development system was established with disciplinary construction as the focus, collaborative development as the goal and horizontal collaboration as the means. It was designed to explore a new model featuring overall planning and standardized management of the discipline, building of a shared platform for clinical capacity development, joint development of continued medical education and talent cultivation, as well as diversified and multi-centered research and platform resources sharing. This model can effectively promote the overall development level of pediatrics in Beijing municipal hospitals.

Objective:To investigate the effects of Clostridium butyricum on colitis and intestinal microbiota in mice with or without antibiotic pretreatment. Methods:Thirty specific pathogen free BALB/c mice were randomly divided into the blank control group, dextran sulfate sodium (DSS) group, antibiotic + DSS group, Clostridium butyricum + DSS group and antibiotic+ Clostridium butyricum + DSS group, with 6 mice in each group. After the mice were pretreated with quadruple antibiotics (ampicillin 1 g/L, neomycin 1 g/L, metronidazole 1 g/L, and vancomycin 0.5 g/L) in normal drinking water for 30 d, the mice colitis model was induced with DSS. At the same time, the mice in Clostridium butyricum + DSS group and antibiotics+ Clostridium butyricum + DSS group were given 1×10 6colony-forming unit (CFU) Clostridium butyricum by gavage. The effect of Clostridium butyricum on mice with colitis was evaluated by disease activity index (DAI), colon length and histopathological score. The level of serum inflammatory factors was detected by enxyme linked immunosorbent assay, and the effect of Clostridium butyricum on gut microbita in mice was determined by fecal 16S rRNA sequencing. Results:The general condition of mice of the blank control group were good, and their DAI scores fluctuated around 0. Since the fourth day after DSS drinking water was given, the mice of the DSS group showed signs of colitis such as weight loss, unformed stools and bloody stools. On the fourth day after intervention, the DAI score of Clostridium butyricum + DSS group was lower than that of DSS group (0.000±0.000 vs. 0.444±0.111), and the difference was statistically significant ( t=4.000, P=0.016 1). On the tenth and twelfth day after the intervention, the DAI scores of antibiotic+ Clostridium butyricum + DSS group were both lower than those of antibiotic+ DSS group (0.000±0.000 vs. 1.111±0.222, 0.667±0.000 vs. 1.889±0.222), and the differences were statistically significant ( t=5.000 and 5.500, both P<0.05). The histopathological score of mice colon tissue of Clostridium butyricum + DSS group was lower than that of DSS group (2.50±1.73 vs. 5.50±1.00), and the histopathological score of mice colon tissue of antibiotic+ Clostridium butyricum+ DSS group was lower than that of antibiotic+ DSS group (1.25±0.96 vs. 5.00±0.82), and the differences were statistically significant ( t=3.000 and 5.960, both P<0.05). The serum level of interleukin (IL)-1β Clostridium butyricum+ DSS group was higher than that of blank control group ((4.464±0.075) ng/L vs. (3.907±0.080) ng/L), the serum levels of tumor necrosis factor-α, IL-6 and IL-1β of Clostridium butyricum+ DSS group and antibiotic+ Clostridium butyricum + DSS group were all lower than those of DSS group ((2.402±0.383) ng/L , (1.845±0.345) ng/L vs. (6.958±1.084) ng/L, (1.752±0.146) ng/L, (1.307±0.048) ng/L vs. (3.537±0.608) ng/L, (4.464±0.075) ng/L, (4.066±0.190) ng/L vs. (7.477±0.339) ng/L), and the differences were statistically significant ( t=5.005, 3.964, 4.495, 4.693, 6.294, 8.674 and 8.774 , all P<0.05). The results of 16S rRNA sequencing showed that there were a significantly large number of anti-inflammatory or short-chain fatty acid producing bacteria in the gut microbiota of mice intervened by Clostridium butyricum, among which the dominant bacteria genus in Clostridium butyricum + DSS group and antibiotic+ Colstridium butyicum+ DSS group were Mucispirillum (linear discriminant analysis (LDA)=3.667 log10, P=0.004) and Stenotrophomonas (LDA=2.778 log10, P=0.044). In the antibiotic+ Clostridium butyricum+ DSS group, the dominant bacteria genus were Peptococcus (LDA=2.685 log10, P=0.018), Butyricimonas (LDA=2.712 log10, P=0.011), Bilophila (LDA=3.204 log10, P=0.014), Intestinimonas (LDA=3.346 log10, P=0.010), Candidatus- Saccharimonas (LDA=3.363 log10, P=0.029), Desulfovibrio (LDA=3.402 log10, P=0.025), Oscillibacter (LDA=2.870 log10, P=0.019) and Akkermansia (LDA=4.031 log10, P=0.005). Conclusions:Clostridium butyricum can effectively improve colitis in mice and regulate the intestinal microbial structure of mice, whlie antibiotic pretreatment can strengthen its regulation of intestinal microbiota to and enhance the efficacy of Clostridium butyricum.

Objective:To explore the effects of maternal pre-pregnancy body mass index (BMI) and gestational weight gain and its subtypes on the risk of preeclampsia.Methods:Pregnant women delivered in the Department of Obstetrics and Gynecology of the First Affiliated Hospital of Shanxi Medical University from March 2012 to September 2016 were selected as the research subjects. According to the inclusion and exclusion criteria, 9 274 pregnant women were included. 901 preeclampsia pregnant women were selected as the case group, and 8 373 non-preeclampsia pregnant women were selected as the control group. General demographic characteristics, pre-pregnancy weight, height, lifestyle during pregnancy, reproductive history, and disease history of pregnant women were collected, and pre-pregnancy BMI and gestational weight gain were calculated. Unconditional logistic regression was used to analyze the relationship between pre-pregnancy BMI and weight gain during pregnancy and PE and its clinical subtypes.Results:Among the 901 preeclampsia after inclusion and exclusion, 401 cases were diagnosed as early-onset PE (EOPE), 500 cases were late-onset PE (LOPE), 178 cases were Mild PE (MPE), and 723 cases were severe PE (SPE). There were statistically significant differences between PE and non-PE pregnant women in terms of maternal age, residence, parity, family history of gestational diabetes and hypertension ( P<0.05). After adjusting for the above factors, the logistic regression analysis results showed that pre-pregnancy BMI<18.5 kg/m 2 and inadequate gestational weight gain were protective factors for PE ( OR=0.74, 95% CI: 0.56-0.98; OR=0.78, 95% CI: 0.62-0.99), while pre-pregnancy BMI≥24.0 kg/m 2 and excessive gestational weight gain were risk factors for PE ( OR=1.82, 95% CI: 1.54-2.14; OR=1.82, 95% CI: 1.54-2.15). After subtype analysis on PE, the results showed that pre-pregnancy BMI<18.5 kg/m 2 was a protective factor for EOPE and MPE ( OR=0.52, 95% CI: 0.32-0.83; OR=0.47, 95% CI: 0.23-0.97), while pre-pregnancy BMI≥24.0 kg/m 2 and excessive gestational weight gain were risk factors for clinical subtypes of PE. After stratification according to pre-pregnancy BMI, excessive gestational weight gain was the risk factor for PE ( OR=1.86, 95% CI: 1.51-2.30; OR=1.90, 95% CI: 1.39-2.60) in pregnant women 18.5 kg/m 2≤BMI<24.0 kg/m 2 and ≥24.0 kg/m 2. Inadequate gestational weight gain ( OR=0.55, 95% CI: 0.34-0.89) was a protective factor for PE in pregnant women with pre-pregnancy BMI≥24.0 kg/m 2. Excessive gestational weight gain ( OR=4.05, 95% CI: 1.20-13.69) was a risk factor for EOPE in pregnant women with pre-pregnancy BMI<18.5 kg/m 2. Excessive gestational weight gain was a risk factor for the clinical subtype of PE in pregnant women 18.5 kg/m 2≤BMI<24.0 kg/m 2 before pregnancy. Inadequate gestational weight gain was a protective factor for EOPE and MPE ( OR=0.39, 95% CI: 0.19-0.80; OR=0.29, 95% CI: 0.11-0.77) in pregnant women with pre-pregnancy BMI≥24.0 kg/m 2. Excessive weight gain was a risk factor for EOPE, LOPE and SPE ( OR=1.60, 95% CI: 1.06-2.42; OR=2.20, 95% CI: 1.44-3.37; OR=2.28, 95% CI: 1.58-3.29). Conclusions:Pre-pregnancy BMI and gestational weight gain affect the risk of preeclampsia and its clinical subtypes. In contrast, the influence of gestational weight gain on preeclampsia varies among different pre-pregnancy BMI groups. Therefore, it is recommended to pay attention to the changes in pre-pregnancy BMI and gestational weight gain simultaneously to reduce preeclampsia.

Objective:To investigate the expression of circ0008234 and miR-1205 in breast cancer and the oncology characteristics of CT.Methods:40 patients with breast cancer were collected as observational objects from Jan.2018 to Dec.2018 and 40 patients without breast cancer were selected as the control group. The expression levels of circ0008234 and miR-1205 of all patients were estimated by quantitative real-time polymerase chain reaction. Bioinformatics was used for the predictions of circ0008234 target miRNA. A dual-luciferase reporter assay was used to confirm the interaction between circ0008234 and miR-1205. All patients of the observation group were examined by multi-slice CT. CT images were analyzed through observing tumor size, shape, calcification area, lymph node metastasis and margin. The correlation between CT signs and the expression of circ0008234 and miR-1205 was further analyzed.Results:The levels of circ0008234 of observation group were significantly higher than those of the control group (2.23±0.86, 1.07±0.37, P=0.00) , but the expression levels of miR-1205 were lower than the control group (0.76±0.29, 1.04±0.29, P=0.00) . In the observation group, there were no significant differences in the expression of circ0008234 and miR-1205 among patients with different tumor marginal morphology and micro calcifications. However the expression of circ0008234 in patients with regular lump form were significantly higher than those in patients with inregular form (2.52±0.88, 1.91±0.74, P=0.025) , and the expression of miR-1205 were lower than those in patients with inregular form (0.66±0.30, 0.86±0.25, P=0.025) . In the observation group, the expression of circ0008234 in patients with mass diameter≥2 cm were significantly higher than those in patients with mass diameter<2 cm (2.59±0.95, 1.69±0.17, P=0.001) , but the expression of miR-1205 were lower than those in patients with mass diameter<2 cm (0.65±0.21, 0.92±0.33, P=0.003) . In the observation group, the expression of circ0008234 in patients with lymph node metastasis were higher than those without lymph node metastasis (2.55±1.09, 1.94±0.44, P=0.022) , but the expression of miR-1205 in patients with lymph node metastasis were lower than those without lymph node metastasis (0.65±0.26, 0.85±0.30, P=0.027) . miR-1205 was verified as a direct target of circ0008234 by luciferase assay. circ0008234 could negatively regulate the expression of miR-1205. Conclusion:There is a correlation between CT imaging signs and the expression of circ0008234 and miR-1205 in patients with breast cancer, which can provide more reference for the judgment of malignant degree and prognosis of patients with breast cancer.

OBJECTIVE: To investigate the correlation between plasma cytokine levels and liver functions in patients with occupational medicamentosa-like dermatitis due to trichloroethylene(OMDT). METHODS: A total of 22 OMDT patients were selected as research subjects using judgment sampling method. Blood samples were collected from patients on the 1 st, 2 nd, 3 rd, 4 th, and 5 th week of admission and the day of hospital discharge. The automatic biochemical instrument was used for detecting the index of serum liver function. The levels of cytokines including tumor necrosis factor-α(TNF-α), interferon-γ(IFN-γ), interleukin(IL)-5, IL-6, and IL-10 in plasma were measured by enzyme-linked immunosorbent assay. The Spearman correlation analysis was performed to analyze the correlation between cytokines and liver function in 15 patients with exfoliative dermatitis. RESULTS: The levels of alanine aminotransferase(ALT), aspartate aminotransferase(AST), total bilirubin(TBIL), direct bilirubin(DBIL), glutamyl transpeptidase(GGT), and total bile acid(TBA) of OMDT patients on the 1 st week of admission increased(P<0.05), while total protein(TP) and albumin(ALB) decreased(P<0.05) compared with the results at discharge(a stage of recovery). The correlation analysis results of patients with exfoliative dermatitis showed that: the levels of TNF-α, IFN-γ and IL-6 were negatively correlated with the levels of TP and ALB respectively(P<0.05), the level of IL-5 was negatively correlated with TBIL(P<0.05), and the level of IL-10 was negatively correlated with ALB(P<0.05) in the 1 st week. The level of IL-6 was positively correlated with ALT(P<0.05) in the 2 nd week. The level of TNF-α was positively correlated with TBIL(P<0.05), the level of IL-10 was positively correlated with AST(P<0.05) in the 3 rd week. The levels of TNF-α and IL-10 were positively correlated with AST and ALT respectively(P<0.05), the level of IFN-γ was positively correlated with AST(P<0.05) in the 4 th week. The levels of IL-6 and IL-10 were positively correlated with ALT and GGT(P<0.05), and the levels of TNF-α and IFN-γ were positively correlated with AST(P<0.05) in the 5 th week. The level of TNF-α was negatively correlated with DBIL(P<0.05) and was positively correlated with TBA(P<0.05) at discharge.CONCLUSION:s Patients with OMDT are frequently accompanied with severe liver function damage at the early stage. The level of plasma cytokines(TNF-α, IFN-γ, IL-6 and IL-10) might correlate with the severity of liver dysfunction.

OBJECTIVE: To observe the pathological changes of rat silicosis model at different time points. METHODS: The specific pathogen free SD rats were randomly divided into control group and 7, 15, 21, 30, 45, 60, 75 and 90 day model groups based on their body weight, with 5 rats in each group. Non-exposed endotracheal intubation was performed. Silicosis rat model was established by intratracheal instillation of 250 g/L silica suspension in each rat, and 0.9% sodium chloride solution was perfused into the trachea of rats in the control group. The rats in the control group were sacrificed on the 90 th day after exposure, and the model rats in the other 8 groups were sacrificed on the 7 th, 15 th, 21 st, 30 th, 45 th, 60 th, 75 th and 90 th days after the end of exposure. The gross appearance of the lung tissue of rats was observed. The rat lung tissues were stained with hematoxylin-eosin and Masson staining to observe the pathological changes, and Ashcroft score was evaluated. RESULTS: The gross observation showed that the lungs of rats in the model groups had varying degree of gray changes, hardened texture, and spots and nodules on the surface of the lobes. These changes were aggravated with the increase of time after dust exposure. The results of histopathological examination of the lungs showed that the rats developed acute alveolar inflammation, and a large number of macrophages and neutrophils were seen in the lung tissues in the 7 th and 15 th day model groups. Cellular nodules appeared in the lung tissue, and fibrosis appeared in the center of the nodule in the rats of 21 st, 30 th, and the 45 th day model groups; the silicosis nodules appeared in the lung tissues of rats in the 60 th, 75 th, and 90 th day model groups, and the small nodules gradually merged into larger ones. Simultaneously, with the increase of time after dust exposure, the lung tissue of rats gradually showed severe pulmonary fibrosis. The lung organ coefficient and Aschcroft score of rats increased with the increase of time after dust exposure(P<0.01). CONCLUSION: The rat lung changes after dust exposure. Acute alveolar inflammation occurs on the 7 th to 15 th day after dust exposure; cellular nodules develop on the 21 st to 45 th day after dust exposure; silicosis nodules develop on the 60 th to 90 th day after dust exposure. The severity of lung fibrosis after dust exposure showed a time-effect relationship in rats.

OBJECTIVE: To analysis the dynamic change of cytokines in patients with occupational trichloroethylene-induced medicamentosa-like dermatitis(OMDT) at the initial stage of treatment. METHODS: Twenty-two cases of early onset OMDT with no glucocorticoid treatment history were selected as the research subjects by judgment sampling method. Blood samples were collected on the 1 st, 2 nd, 3 rd, 4 th and 5 th weeks after admission and on the day of hospital discharge. The levels of tumor necrosis factor-α(TNF-α), interferon-γ(IFN-γ), interleukin(IL)-5, IL-6 and IL-10 in plasma samples were measured by the enzyme linked immunosorbent assay. RESULTS: The five cytokines in patients with exfoliative dermatitis showed an increasing trend at the initial stage of treatment. Among them, the levels of TNF-α, IL-5 and IL-10 reached a peak and then dropped rapidly to form a plateau, and the levels of IFN-γ and IL-6 were slightly increased and the duration of increase was shorter than that of other cytokines. The levels of TNF-α, IFN-γ, IL-5 and IL-6 in patients with erythema multiforme remained within the detection limits in the detection process. Only a few patients showed a short-term increase, the IL-10 level showed a slight increase at the initial stage and then decreased to the plateau stage. The levels of TNF-α, IFN-γ and IL-6 in patients with bullous epidermal necrolysis increased rapidly at the initial detection stage for a short period of time, and then decreased sharply. The level of IL-5 remained at the detection limit, and the IL-10 level showed alternative rising and falling pattern. Part of the dynamic change of cytokines in patients with exfoliative dermatitis and bullous epidermal necrolysis was similar. CONCLUSION: The levels of TNF-α, IFN-γ, IL-5, IL-6, and IL-10 in OMDT patients changed with the progression of the disease at the early treatment stage, and the degree of change was related to the type of rash. Among them, the levels of TNF-α and IL-10 showed dynamic changes due to the progression of the disease, which could be considered as effect biomarkers to evaluate the severity and progression of the disease, and provide a reference for the rational treatment of patients.

Neonatal hypoxic-ischemic encephalopathy (HIE) is a major cause of neonatal mortality and neurologic sequelae. Current evidence showed that the brain-derived neurotrophic factor (BDNF) could be considered as a specific biomarker of brain injury, which could help to assess the severity and prognosis of neonatal HIE. Also, BDNF may be widely applied in clinical practice to monitor the treatment of neonatal HIE due to its important role in neuronal survival and growth. This paper summarizes the possible role of BDNF in the management of HIE from these aspects.

Objective:To investigate the effects of highly active anti-retroviral therapy (HAART) on the activation of T lymphocytes and expression of CD4 + CD45RA + T cell subsets in HIV/AIDS patients. Methods:This study prospectively analyzed 105 HIV/AIDS patients undergoing HAART and 35 HIV-1-negative cases (healthy controls). Flow cytometry was used to detect the activation of T lymphocytes and the percentages of CD4 + CD45RA + T cell subsets in whole blood samples taken from healthy controls and HIV/AIDS patients before and after therapy. Results:The activation of T lymphocytes was significantly enhanced in the 105 HIV/AIDS patients than in the healthy controls before treatment ( P<0.01). The activated T lymphocytes gradually decreased after HAART. Firstly, CD4 + CD38 + HLA-DR + , CD8 + CD38 + and CD8 + HLA-DR + T lymphocytes decreased one month after therapy ( P<0.05). Then, four indicators of T lymphocyte activation including the expression of CD8 + CD38 + HLA-DR + T lymphocytes decreased significantly six months after therapy ( P<0.01). The percentage of CD8 + CD38 + HLA-DR + T lymphocytes detected 12 months after therapy was significantly lower than that analyzed six months after therapy ( P<0.01). No significant difference was found in the expression of the other three indicators for activation ( P>0.05). Twelve months after therapy, the four indicators for T lymphocyte activation in HIV/AIDS patients were still significantly higher than those of the control group ( P<0.01). The percentages of CD4 + CD45RA + T lymphocytes in HIV/AIDS patients were significantly lower than those in healthy controls before and 12 months after treatment ( P>0.05). Conclusions:HAART could reduce immune activation after six months of treatment, but could not reverse the activation nor restore the expression of CD4 + CD45RA + T lymphocytes in HIV/AIDS patients.