Brasilicardin A, a diterpene glycoside isolated from pathogenic actinomycete Nocardia brasiliensis IFM 0406, has become a novel immunosuppressant candidate due to its significant immunosuppressive activity, low toxicity and unique mechanism of action. However, brasilicardin A and its analogues have become a research hotspot to the development of this promising immunosuppressant because of the low-yield production in the natural pathogenic producer and the synthetically challenging skeleton. According to the reported biosynthetic pathway of brasilicardin A, the function of involved diterpene synthase was analyzed by bioinformatics. Then the genes bra1-5 that synthesize the brasilicardin A skeleton were directionally amplified from the pathogenic strain N. brasiliensis IFM 0406, and heterologous expression was achieved successfully in Streptomyces albus R1. The compounds were isolated and purified by using various column chromatographies including silica gel column chromatography and semi-preparative HPLC. Six new brasilicardins were established and named brasilicardin H-M. The activity of brasilicardins was screened using lipopolysaccharide (LPS)-activated mouse primary macrophage inflammation model. Brasilicardin H-M exhibited good inhibitory activity on nitric oxide (NO) release with IC₅₀ values of 28.24 ± 3.70, 37.44 ± 2.00, 39.85 ± 4.02, 26.77 ± 4.40, 65.25 ± 1.48 and 15.24 ± 2.72 μmol·L^-1, respectively (indomethacin as the positive control with IC₅₀ value of 34.28 ± 4.10 μmol·L^-1). The results indicated that six compounds had potential anti-inflammatory activity. This study laid a foundation for the elucidation of the brasilicardin A biosynthetic pathway and evaluation of the structure-activity relationship as well as new drug developments.

Non-alcoholic fatty liver disease (NAFLD) incidence is rapidly increasing and become the most common chronic liver disease globally. NAFLD also possesses a risk of developing cardiovascular, kidney, and other diseases. To date, NAFLD still faces difficulties in early diagnosis and treatment options. Thus, early detection, prevention, optimally individualized treatment selections, and prediction of prognosis all are the keys in clinical NAFLD control. Although there are assessment tools available for NAFLD severity appraisal using different clinical parameters, it becomes a hot topic of research in the field for how to optimize non-invasive assessment methodologies. Artificial intelligence (AI) and machine learning are increasingly being used in healthcare, especially in assessment and analysis of chronic liver disease, including NAFLD. This review summarized and discussed the most recent progress of AI and machine learning in differential diagnosis of NAFLD and evaluation of NAFLD severity, in order to provide treatment selections, i.e., the novel AI diagnosis models based on the electronic health records and laboratory tests, ultrasound and radiographic imaging, and liver histopathology data. The therapeutic models discussed the personalized lifestyle changes and NAFLD drug development. The NAFLD prognosis model reviewed and predicted how NAFLD-changed liver metabolisms affect prognosis of patients. This review also speculated future prospective research hot spots and development in the filed for how to utilize the existing AI models to distinguish NAFLD and non-alcoholic steatohepatitis (NASH) and assess NAFLD fibrosis status.

Objective: The relationship between outdoor temperature and blood pressure (BP) has been inconclusive. We analyzed data from a prospective cohort study in northwestern China to investigate the effect of outdoor temperature on BP and effect modification by season. Methods: A total of 32,710 individuals who participated in both the baseline survey and the first follow-up in 2011-2015 were included in the study. A linear mixed-effect model and generalized additive mixed model (GAMM) were applied to estimate the association between outdoor temperature and BP after adjusting for confounding variables. Results: The mean differences in systolic blood pressure (SBP) and diastolic blood pressure (DBP) between summer and winter were 3.5 mmHg and 2.75 mmHg, respectively. After adjusting for individual characteristics, meteorological factors and air pollutants, a significant increase in SBP and DBP was observed for lag 06 day and lag 04 day, a 0.28 mmHg (95% Conclusions This study demonstrated a significant negative association between outdoor temperature and BP in a high-altitude environment of northwest China. Moreover, BP showed a significant seasonal variation. The association between BP and temperature differed by season and individuals' demographic characteristics (age, gender, BMI), unhealthy behaviors (smoking and alcohol consumption), and chronic disease status (CVDs, hypertension, and diabetes).
Adult ; Blood Pressure/physiology* ; China/epidemiology* ; Environmental Exposure/statistics & numerical data* ; Female ; Humans ; Male ; Middle Aged ; Prospective Studies ; Risk Factors ; Seasons ; Temperature

OBJECTIVE: To test the reliability and validity of the Chinese version of parenting sense of competence scale (PSOC) in Chinese mothers of preschool children, and to explore the perception of preschool children's mothers on their own parenting skills and their comfort of being a parent in Yanqing District of Beijing. METHODS: A cross-sectional survey was conducted using a convenience sample in 1 384 preschool children's mothers in Yanqing District of Beijing. SPSS 21.0 and Mplus 7.4 software were used for statistical analysis to test the structural validity, criterion related validity, internal consistency and split half reliability of the scale, and to analyze the score of the scale and its influencing factors. RESULTS: The PSOC had good reliability and validity. Exploratory factor analysis showed that each item of the PSOC had more than 0.4 factor loading in efficacy factor or satisfaction factor, and there was no double load phenomenon. Confirmatory factor analysis showed that the factor loadings ranged from 0.212 to 0.843 in efficacy factor and satisfaction factor, respectively. The goodness of fit test showed that all the fitting indexes were within the acceptable range, and the correlation between the effectiveness subscale and the satisfaction subscale was high. The Cronbach's α coefficient of the whole scale, the efficacy subscale and the satisfaction subscale were 0.872, 0.802, and 0.874, respectively. The Spearman-Brown coefficient of PSOC was 0.851. The average score of the whole scale, the efficacy subscale, and the satisfaction subscale were 72.33±11.31, 35.54±5.91, and 36.79±7.11, respectively, and the score of parenting competence in Chinese mothers of preschool children was influenced by the mother's educational level and the annual income of her family. CONCLUSION The PSOC has satisfactory reliability and validity in Chinese mothers of preschool children. It can be used as an evaluation instrument for measuring the parenting competency, self perceived efficacy and satisfaction in the mainland Chinese mothers of preschool children. The competency of preschool children's mothers in Yanqing District of Beijing is very good, which may be related to the higher education level of the mothers and the higher annual income of their families in this study.
Beijing ; Child, Preschool ; China ; Cross-Sectional Studies ; Female ; Humans ; Mothers ; Parenting ; Psychometrics ; Reproducibility of Results ; Surveys and Questionnaires

Knee osteoarthritis is the most common type of arthritis, which is manifested by the deformation and degeneration of articular cartilage and the discomfort of patients with joint pain, which affects the quality of life of patients and aggravates the medical burden of society. The pathogenesis of knee osteoarthritis is very complex. This paper reviews the inflammatory factors and signal pathways involved in knee osteoarthritis. It is found that most of the inflammatory factors involved are interleukin, such as IL-1 β, IL-6, IL-15, IL-17, IL-18, and tumor necrosis factors, such as TNF-α. These inflammatory factors aggravate knee osteoarthritisby activating corresponding pathways and promoting the release of inflammatory mediators. The inflammatory signaling pathways involved in knee osteoarthritis are complex. Notch pathway, Wnt pathway, SDF-1 / CXCR4 pathway, TLRs pathway, MAPKs pathway, hippo Yap pathway, OPG-RANK-RANKL pathway and TGF-β pathway are all involved in the regulation of knee osteoarthritis, and the pathways related to inflammatory mechanism are mainly MAPKs pathway and TLRs pathway. Different signaling pathways can cause the destruction of articular cartilage, promote the apoptosis of chondrocytes, and finally lead to the further imbalance of homeostasis in the knee joint. At the same time, the activation of signal pathway can promote the release of inflammatory factors, so under the cascade reaction of inflammatory factors and signal pathway, knee osteoarthritis is aggravating.
Cartilage, Articular ; Chondrocytes ; Humans ; Interleukin-1beta ; Osteoarthritis, Knee ; Quality of Life ; Signal Transduction

Background: This study aims to investigate the effect of integrin β1 on wound healing induced by adipose-derived stem cells (ADSCs), as well as the corresponding mechanism. Methods: Integrin β1 was overexpressed in ADSCs. Thereafter, flow cytometry and transwell chambers technology were used to measure the endothelial-like differentiation (CD31 as a biomarker of endothelial cell) and cell migration, respectively. Western blot was used to detect the activation of PI3K/AKT, NF-κB and ERK signaling pathways. The effects of integrin β1 overexpression on healing time, healing rate and fibroblast number were further evaluated in the rat models of chronic refractory wound. Results: The overexpression of integrin β1 increased CD31+ endothelial-like cells (about 3.6-fold), promoted cell migration (about 1.9-fold) and enhanced the activation of PI3K (p-PI3K; about 2.1-fold) and AKT (p-AKT; about 2.2-fold). These effects were all weakened when PI3K/AKT pathway was inhibited by LY294002 treatment. In addition, the experiments in rat wound models showed that integrin β1 overexpression obviously shortened healing time (approximately 0.41-fold), increased healing rate (about 2.7-fold, 2.8-fold and 1.6-fold at day 7, 14 and 21) and increased the number of fibroblasts (approximately 3.1-fold at day 21). All of the above differences were statistically significant (p < 0.05). Conclusion Integrin β1 can promote the migration and endothelial-like differentiation of ADSCs by activating PI3K/AKT pathway and then enhance the function of ADSCs in promoting wound healing.

Purpose: Hepatocellular carcinoma (HCC) patients with major portal vein tumor thrombosis (mPVTT) complications were generally characterized by extremely poor prognoses. The aim of this study was to explore the role of 18F-fluorodeoxyglucose (18F-FDG) PET/CT imaging in predicting HCC complicated by mPVTT. Methods: Five hundred one HCC patients received surgery in our hospital during November 2008 to December 2014, among which 32 patients (6.4%) were diagnosed as HCC complicated by mPVTT. Six cases were excluded for reasons of complex medical conditions, including 2 cases of salvage liver transplantation, 2 cases of re-resection, 1 case of mPVTT combined with inferior vina cava tumor thrombosis, and 1 case of residual portal vein tumor thrombosis. Ultimately, 26 cases were enrolled in this study. The maximal tumor standardized uptake value (SUVmax) was identified as a predictive factor and detected. The univariate and multivariate regression analyses were performed to identify the prognostic factors for recurrence-free survival (RFS) and overall survival (OS) of HCC patients complicated by mPVTT. Results: Our results showed that the median OS was 16 months. The 1-, 3-, and 5-year cumulative OS was 55.6%, 31.7%, and 31.7%, respectively. The multivariate regression analysis revealed that SUVmax ≥ 4.65 was the only independent risk factor for RFS and OS. Conclusion SUVmax was an independent predictor for RFS and OS of patients suffering from both HCC and mPVTT. L ow SUVmax could serve as an effective factor for selecting candidates with low recurrence risks and for helping with improving patient survival after surgical resection.

Objective:To investigate the clinicopathological features, immunophenotype, molecular characteristics and differential diagnosis of primary skull base chondrosarcoma.Methods:Nine cases of primary skull base chondrosarcoma were collected at the First Affiliated Hospital of Fujian Medical University, from January 2006 to June 2019, reviewed for the clinical and radiologic data and morphologic features, immunophenotype and molecular characteristics.Results:Among all the 9 cases, six were male, three were frmale, with average age 47 years, and median age 47 years; five cases were WHO gradeⅠ, and four were WHO grade Ⅱ. Microscopically, the tumor showed lobulated growth pattern with low-medium cellularity within a chondroid or mucoid background. The tumor cells showed mild-moderate atypia, with binucleated forms, and mitosis was rare or occasional. Immunohistochemistry (IHC) showed tumor cells were positive for S-100 protein, vimentin, SOX-9 and D2-40, and negative for Brachyury, CK, EMA and CK8/18; the Ki-67 index was low (1% to 5%). Molecular analysis showed IDH1 R132C mutation in four cases.Conclusions:Skull base chondrosarcoma is a rare cartilaginous malignant tumor with a good prognosis. Its characteristic morphologies, combined with IHC and molecular detection are helpful for the differential diagnosis.

Objective To understand the epidemiological characteristics of recent brucellosis in Hohhot.Methods Clinical data of patients with brucellosis in Hohhot City were retrospectively analyzed,and the patients were diagnosed in the outpatient clinic of Comprehensive Center for Disease Prevention and Control of Inner Mongolia Autonomous Region from 2014 to 2017.To analyze the patient's area,age,gender,occupation and time distribution of the disease.Results A total of 1 940 patients with brucellosis were diagnosed in Hohhot from 2014 to 2017,with an average age of 50.8 years old.There were 1 464 males with an average age of 50.4 years old and 476 females with an average age of 51.9 years old;the male-female ratio was 3:1.The number of cases of brucellosis in 2014-2017 was 612,649,402,and 277,respectively.Brucellosis was mainly distributed in three districts including Horinger County (937 cases),Tumd Left Banner (236 cases) and Tuoketuo County (191 cases),accounting for 70.31％ (1 364/1 940) of the total number of cases in the city.The age of onset was at least 1 year old,the oldest age was 86 years old,and most cases were in the 45-＜ 65 age group,the total number of cases was 1 046,accounting for 53.92％ (1 046/1 940) of the total number of cases in the city;the occupational distribution was mainly farmers (1 795 cases),herders (13 cases) and veterinarians (17 cases),with a total of 1 825 cases,accounting for 94.07％ (1 825/1 940).The time distribution was mainly concentrated in March-July,and the number of cases was 1 157 cases.Conclusions The number of brucellosis cases in Hohhot area of Inner Mongolia is mainly from Horinger County,Tumd Left Banner and Tuoketuo County;the cases occur frequently in Spring and Summer;the age of onset is mainly between 45-＜ 65 years old,they are mainly male farmers.

Objective To explore the influencing factors of the vaginal birth after cesarean section (VBAC), and establish a model for predicting the risk of trial of the trial of labor after cesarean section (TOLAC). Methods From January 2016 to December 2018, total 694 pregnant women who underwent TOLAC in Northwest Women's and Children's Hospital were retrospectively analyzed. Those cases were divided into two groups according to the mode of delivery: the VBAC group and the failed TOLAC group. At the same time, 700 cases in the elective repeat cesarean section (ERCS) group were randomly selected as control group. The influencing factors of VBAC were analyzed by univariate and multivariate logistic regression, and the pregnancy outcomes between the three groups were compared. Results (1) The VBAC rate was 76.1% (528/694) and 166 women underwent the failed TOLAC (23.9%, 166/694). (2) Univariate analysis found that, the pre-pregnancy body mass index (BMI) [(22.0±3.0),(23.3±2.7) kg/m2], the previous vaginal delivery history [10.4%(55/528),3.6%(6/166)], the cervical score (5.2±1.9,4.3±1.6) and the neonatal birth weight [(3 315 ± 468), (3 484 ± 274) g] of the VBAC group were significantly different from the failed TOLAC group (P<0.05). (3) The comparison of pregnancy outcomes: the neonatal birth weight was (3 315± 468) g, and the intrapartum hemorrhage volume was (255 ± 121) ml in the VBAC group, which were significantly lower than those in the failed TOLAC group [intrapartum hemorrhage (325 ± 173) ml] and the ERCS group [(3 572±344) g, (281±125) ml], there were statistically significant differences in the comparison among the three groups (all P<0.05). Two cases of bladder injury occurred during cesarean section in the TOLAC failure group (1.2%,2/166). The rates of the blood transfusion, puerperal infection, 5-minute Apgar score and neonatal ICU admission among the three groups were no statistically significantly different (all P>0.05). There was no maternal or perinatal death. (4) Multivariate logistic regression analysis showed that the delivery age of pregnant women ( OR=0.92, 95% CI : 0.87-0.98), pre-pregnancy BMI ( OR=0.92, 95% CI :0.86-0.98), vaginal delivery history ( OR=3.31, 95% CI : 1.35-8.01), cervical score ( OR=1.29, 95% CI :1.13-1.42) and the birth weight of the neonates <3 300 g ( OR=3.15, 95% CI : 2.02-4.90) were independent influencing factors for VBAC. The area under curve of the receiver operating characteristic curve was 0.74. Conclusions The influencing factors of VBAC are delivery age, pre-pregnancy BMI, vaginal delivery history, cervical score and neonatal birth weight <3 300 g. The adequate individualized management and assessment of the TOLAC may be helpful to improve the VBAC rate.