Two new flavonoid glycosides from Diphylleia sinensi / 药学学报

Five flavonoid glycosides were isolated from the methanol and ethyl acetate fractions of the ethanol extract of Diphylleia sinensi by using various chromatographic methods, including silica gel, MCI gel, Sephadex LH-20, ODS and semi-preparative HPLC. The structures of the isolated compounds were identified as diphyflavonoid A (1), diphyflavonoid B (2), quercetin-3-O-β-D-glucopyranoside (3), kaempferol-3-O-β-D-glucopyranoside (4), kaempferol-3-O-(6″-O-acetyl)-β-D-glucopyranoside (5) by spectroscopy methods (1D NMR, 2D NMR, UV, IR, and MS). Compounds 1 and 2 were two new flavonoid glycosides, and compounds 3 and 5 were isolated from the genus Diphylleia for the first time.

Analysis of clinicopathological and molecular abnormalities of angioimmunoblastic T-cell lymphoma / 北京大学学报(医学版)

OBJECTIVE@#To analyze the clinicopathological features, molecular changes and prognostic factors in angioimmunoblastic T-cell lymphoma (AITL).@*METHODS@#Sixty-one cases AITL diagnosed by Department of Pathology of Peking University Cancer Hospital were collected with their clinical data. Morphologically, they were classified as typeⅠ[lymphoid tissue reactive hyperplasia (LRH) like]; typeⅡ[marginal zone lymphoma(MZL)like] and type Ⅲ [peripheral T-cell lymphoma, not specified (PTCL-NOS) like]. Immunohistochemical staining was used to evaluate the presence of follicular helper T-cell (TFH) phenotype, proliferation of extra germinal center (GC) follicular dendritic cells (FDCs), presence of Hodgkin and Reed-Sternberg (HRS)-like cells and large B transformation. The density of Epstein-Barr virus (EBV) + cells was counted with slides stained by Epstein-Barr virus encoded RNA (EBER) in situ hybridization on high power field (HPF). T-cell receptor / immunoglobulin gene (TCR/IG) clonality and targeted exome sequencing (TES) test were performed when necessary. SPSS 22.0 software was used for statistical analysis.@*RESULTS@#Morphological subtype (%): 11.4% (7/61) cases were classified as type Ⅰ; 50.8% (31/61) as type Ⅱ; 37.8% (23/61) as type Ⅲ. 83.6% (51/61) cases showed classical TFH immunophenotype. With variable extra-GC FDC meshwork proliferation (median 20.0%); 23.0% (14/61) had HRS-like cells; 11.5% (7/61) with large B transformation. 42.6% (26/61) of cases with high counts of EBV. 57.9% (11/19) TCR+/IG-, 26.3% (5/19) TCR+/IG+, 10.5% (2/19) were TCR－/IG－, and 5.3% (1/19) TCR－/IG+. Mutation frequencies by TES were 66.7% (20/30) for RHOA, 23.3% (7/30) for IDH2 mutation, 80.0% (24/30) for TET2 mutation, and 33.3% (10/30) DNMT3A mutation. Integrated analysis divided into four groups: (1) IDH2 and RHOA co-mutation group (7 cases): 6 cases were type Ⅱ, 1 case was type Ⅲ; all with typical TFH phenotype; HRS-like cells and large B transformation were not found; (2) RHOA single mutation group (13 cases): 1 case was type Ⅰ, 6 cases were type Ⅱ, 6 cases were type Ⅲ; 5 cases without typical TFH phenotype; 6 cases had HRS-like cells, and 2 cases with large B transformation. Atypically, 1 case showed TCR－/IG－, 1 case with TCR－/IG+, and 1 case with TCR+/IG+; (3) TET2 and/or DNMT3A mutation alone group (7 cases): 3 cases were type Ⅱ, 4 cases were type Ⅲ, all cases were found with typical TFH phenotype; 2 cases had HRS-like cells, 2 cases with large B transformation, and atypically; (4) non-mutation group (3 cases), all were type Ⅱ, with typical TFH phenotype, with significant extra-GC FDC proliferation, without HRS-like cells and large B transformation. Atypically, 1 case was TCR－/IG－. Univariate analysis confirmed that higher density of EBV positive cell was independent adverse prognostic factors for both overall survival (OS) and progression free survival(PFS), (P=0.017 and P=0.046).@*CONCLUSION@#Pathological diagnoses of ALTL cases with HRS-like cells, large B transformation or type Ⅰ are difficult. Although TCR/IG gene rearrangement test is helpful but still with limitation. TES involving RHOA, IDH2, TET2, DNMT3A can robustly assist in the differential diagnosis of those difficult cases. Higher density of EBV positive cells counts in tumor tissue might be an indicator for poor survival.

Mechanism of advanced glycation end products inhibiting the proliferation of peripheral blood mononuclear cells and osteoblasts in rats / 北京大学学报(医学版)

OBJECTIVE@#To explore the mechanism of nuclear factor-kappa B (NF-κB), phosphatidylinositol 3-kinase (PI3K)/protein kinase B(PKB/Akt) and mitogen-activated protein kinase (MAPK) signaling pathways after intervention of advanced glycosylation end products (AGEs) in peripheral blood mononuclear cells (PBMCs) and osteoblasts (OB) in rats, so as to provide certain experimental basis and theoretical basis for further research on the clinical treatment of periodontal tissue inflammation caused by diabetes mellitus.@*METHODS@#AGEs were prepared, PBMCs and OB were isolated and cultured in vitro. CCK-8 was used to detect the cell viability intervened by different concentrations and time of AGEs. Western blot and qRT-PCR were used to detect the expression changes of genes related to NF-κB, PI3K/PKB and MAPK signaling pathways.@*RESULTS@#OB and PBMCs were successfully isolated and cultured in vitro. The activity of PBMCs and OB cells was significantly correlated with the concentration, time and interaction of AGEs. With the increase of AGEs concentration and time, the activity of PBMCs and OB cells significantly decreased (P < 0.001). AGEs stimulation significantly increased the expression of NF-κB in PBMCs and the contents of tumor necrosis factor α(TNF-α), interleukin-1β(IL-1β) (P < 0.01). TNF-α, IL-1β levels were significantly reduced after inhibition of NF-κB pathway (P < 0.01). NF-κB p65, JNK, and p38 phosphorylated and non-phosphorylated proteins increased significantly after AGEs stimulation of OB (P < 0.05). The phosphorylated protein expression of IκB was significantly increased, while the expression of non-phosphorylated protein was decreased (P < 0.01).The expressions of NF-κB p65, JNK, and IκB were significantly increased at the mRNA levels, and the expressions of IκB mRNA were significantly decreased (P < 0.05). There was no difference in the expression of Akt in either phosphorylated or non-phosphorylated proteins or at the mRNA level (P>0.05). With the addition of MAPK signaling pathway inhibitors, the phosphorylation and non-phosphorylated protein expressions of NF-κB p65, p38 and JNK were significantly reduced, and the phosphorylated protein of IκB was significantly decreased and the non-phosphorylated protein was significantly increased compared with the group with AGEs alone (P < 0.05). The results of qRT-PCR showed that the expression of IκB increased significantly after the addition of the JNK pathway blocker (P < 0.05), and the expression of NF-κB p65, p38 and JNK decreased, but the difference was not significant (P>0.05). While NF-κB p65, p38 and JNK were significantly decreased and IκB was significantly increased in the AGEs group after the addition of the p38 pathway blocker (P < 0.05). At this time, there was still no significant change in the expression of Akt at the protein level and mRNA level (P>0.05).@*CONCLUSION@#AGEs inhibit the proliferation of PBMCs and OB, and the NF-κB and MAPK pathways are likely involved in regulating this process, but not the PI3K/PKB pathway.

Associations of distribution of time spent in physical activity and sedentary behavior with obesity / 北京大学学报(医学版)

OBJECTIVE@#To explore associations of distribution of time spent in physical activity (PA) and sedentary behavior (SB) with obesity with taking account that time is finite during the day of adult residents in Wuhai City.@*METHODS@#A cross-sectional study was undertaken in Wuhai City, and we carried out a sampling of local residents aged 18-79 by using multiple stratified cluster sampling method. Data about social demographic characteristics, time spent in PA and SB, diet intake, controlling situation of chronic disease and other covariates were obtained by qualified investigators for face-to-face questionnaire survey. Data about height, weight, and waist circumstance, were obtained by doctors in a secondary hospital or above for body measurements. The statistical method used in our study was known as compositional data analysis, which had been used to process compositional data in many fields. Liner regression analysis with compositional data was used to synthetically analyze the associations of distribution of time spent in PA and SB with obesity,and to investigate the effect of re-allocating time from one behavior to another one whilst the remaining one was kept stable.@*RESULTS@#The investigation revealed the special advantage of compositional data analysis in processing time-use data. The result of liner regression analysis with the compositional data showed that after controlling the potential confounding factors, the associations of distribution of time spent in PA and SB was significantly associated with body mass index (BMI, P<0.001) and the negative natural logarithm of waist to height ratio (-lnWHtR, P<0.001). Among them, in professional population, the proportion of time spent in moderate-to-vigorous physical activity (MVPA) was negatively correlated with -lnWHtR (β=-0.008, P=0.022), while the proportion of time spent in SB was positively correlated with BMI and -lnWHtR (β=0.117, P=0.003; β=0.007, P=0.005). However, in nonprofessional population, the proportion of time spent in MVPA was only negatively correlated with BMI (β=-0.079, P=0.041). Nevertheless, the proportion of time spent in low-intensity physical activity (LIPA) was not significantly associated with BMI and -lnWHtR in both professional and nonprofessional population. In addition, the effects of MVPA replacing another behavior and of MVPA being displaced by another behavior were not symmetrical, and 10 minutes of MVPA replacing LIPA or SB had a greater influence on intervention and prevention of obesity than 10 minutes MVPA being replaced by LIPA or SB.@*CONCLUSION@#The research has resulted in a solution of the associations of the distribution of time spent in PA, SB with health risk. Our results suggest that public health messages should target the health effects of the distribution of time of PA and SB synergistically in developing PA guidelines and health management practice, rather than simply increasing or decreasing the absolute time of PA or SB, so that we can provide scientific suggestions to make people get a profounder healthy effect.

Analysis on monitoring results of iodine deficiency disorders of children aged from 8 to 10 years and pregnant women in Wuhai City in 2017 / 中华疾病控制杂志

Objective To explore current situation of iodine deficiency disorders(IDD) and iodine nutrient level by analyzing monitoring data of IDD from children aged from 8 to 10 and pregnant women in Wuhai City in 2017,so as to provide basis for the prevention and control of IDD. Methods Our surveillance points were located in Haibowan District, Wuda District, Hainan District of Wuhai City. Samples of salt and human urine were collected from 200 children aged 8 to 10 and 100 pregnant women at random. Urine iodine concentration and salt iodine concentration were measured. Thyroid volume was determined by B-ultrasound. Results There were 10 children diagnosed as thyroid goiter. Children’s Goiter rate in this area was 1.67%.The averaged covering rate of eating iodine among children reached 99.56%, their acceptance rate of iodized salt was 12.7%. Median of salt-iodine was 21.7 mg/kg. Median of urinary iodine(MUI) for children was 204.5 μg/L. The percentage of children whose urinary iodine was less than 100 μg/L and 50 μg/L was 12.7% and 2.2%, respectively. Median of urinary iodine in boys was 224.0 μg/L, which was higher than in girls(191.5 μg/L), the difference was statistically significant(P=0.004). Median of urinary iodine in pregnant women was 145.8 μg/L. Pregnant women whose urine iodine below 150 μg/L accounted for 51.7%. The MUI in pregnant women during the first trimester was 115.5 μg/L. Pregnant women during the first trimester whose urine iodine below 150 μg/L accounted for 62.0%. Conclusions The iodine nutrition condition in children is basically normal, while iodine nutrition deficiency exist in pregnant women in this area. We should particularly enhance monitoring urinary iodine for pregnant women during the first trimester to reduce iodine deficiency.

Broussonin E suppresses LPS-induced inflammatory response in macrophages via inhibiting MAPK pathway and enhancing JAK2-STAT3 pathway / 中国天然药物

Macrophages play an important role in inflammation, and excessive and chronic activation of macrophages leads to systemic inflammatory diseases, such as atherosclerosis and rheumatoid arthritis. In this paper, we explored the anti-inflammatory effect of broussonin E, a novel phenolic compound isolated from the barks ofBroussonetia kanzinoki, and its underlying molecular mechanisms. We discovered that Broussonin E could suppress the LPS-induced pro-inflammatory production in RAW264.7 cells, involving TNF-α, IL-1β, IL-6, COX-2 and iNOS. And broussonin E enhanced the expressions of anti-inflammatory mediators such as IL-10, CD206 and arginase-1 (Arg-1) in LPS-stimulated RAW264.7 cells. Further, we demonstrated that broussonin E inhibited the LPS-stimulated phosphorylation of ERK and p38 MAPK. Moreover, we found that broussonin E could activate janus kinase (JAK) 2, signal transducer and activator of transcription (STAT) 3. Downregulated pro-inflammatory cytokines and upregulated anti-inflammatory factors by broussonin E were abolished by using the inhibitor of JAK2-STAT3 pathway, WP1066. Taken together, our results showed that broussonin E could suppress inflammation by modulating macrophages activation statevia inhibiting the ERK and p38 MAPK and enhancing JAK2-STAT3 signaling pathway, and can be further developed as a promising drug for the treatment of inflammation-related diseases such as atherosclerosis.

Relationship between sugary drinks and diabetes of adults in Wuhai city / 北京大学学报(医学版)

OBJECTIVE@#To explore the relationship between sugary drinks and diabetes of adults in Wuhai city.@*METHODS@#A multiple stage stratified cluster sampling was conducted on 8 131 residents who were between 35 and 79 years by cross-sectional study in Wuhai city. Questionnaires, physical measurements and laboratory tests were used to collect information on demographic information, dietary behavior, health status, blood glucose indicators. Besides, other covariate information was also collected by these ways. The analysis was carried out by chi-square test, trend chi-square test and multifactor Logistic regression.@*RESULTS@#The detection rates of impaired fasting glucose and diabetes of people who were 35 years old and above in Wuhai city were 6.0% and 18.4%, respectively, and they both increased with age (P<0.01, P< 0.01). The detection rates of impaired fasting glucose and diabetes of the men were both far higher than the women (P< 0.01, P< 0.01). For the men, the detection rate of diabetes increased with age (Ptrend<0.01), but for the women, and the detection rate of impaired fasting glucose and diabetes both increased with age (Ptrend<0.01, Ptrend<0.01). The consumption rate of sugary drinks of the people who were 35 years old and above in Wuhai city was 30.2%. And after all the subjects were classified into three groups, A (0- mL/d), B (16- mL/d), and C (237- mL/d) according to the daily different drinking quantities, statistical results found that group A accounted for 75.4%, group B for 21.5%, and group C for 3.1%. In group A, for comparison, the impaired fasting glucose OR values of group B and group C were 1.4 and 2.2, respectively. And diabetes OR values of group B and group C were 1.2 and 2.1 respectively compared with group A, and the trend of OR values increased both had statistical significance (Ptrend <0.01, Ptrend < 0.01). Also, after adjusting for other covariates in multifactor Logistic regression, the OR values of impaired fasting glucose in group B and group C were 1.6 and 3.8 respectively, and the OR values of diabetes were 1.9 and 4.9 respectively, compared with group A, and besides, the trend of OR values increased both still had statistical significance (Ptrend <0.01, Ptrend < 0.01).@*CONCLUSION@#Increased consumption of sugary drinks will increase the risk of impaired fasting glucose and diabetes. Residents in Wuhai city should control their consumption of sugary drinks.

Application of bronchofiberscope combined with ultrasonic positioning laryngeal mask in airway management of aged patients under general anesthesia / 中国内镜杂志

Objective To compare the clinical effects of visual technological intubation with positioning laryngeal mask and tracheal intubation for the patients under general anesthesia. Method This test contains 80 aged patients under general anesthesia, with ASA I~III, randomly divided into two groups, 40 patients in A group named tracheal intubation group, and the other 40 patients in B group named laryngeal mask group. Relatively record the MAP and HR changes when 5 minutes after enter in operating room and keep quiet (T0), before immediate insert into (laryngeal mask) with tracheal catheter (T1), immediate insert (T2), 3 minutes after insert (T3), removing time (T4), immediate time after remove (T5), 3 minutes after remove (T6), and the occurrence rate of postoperative complications like pharyngalgia etc. Then observe and record the complications like bucking during emergence period, nausea, vomiting, pharyngalgia and hoarseness etc in the early postoperative period and make comparison. Result The patients in A Group and B Group all accept safe operations, there is no obvious changes about MAP and HR before and after the insert and remove laryngeal mask in B Group (P > 0.05); and there is obvious changes about MAP and HR before and after remove tracheal catheter in A Group (P < 0.05), and obviously increased than B Group (P < 0.05). In B Group, the occurrence rate of bucking, nausea, vomiting, and pharyngalgia after operation is obvious less than that in A Group (P < 0.05). Conclusion The application of ultrasonic combined with bronchofiberscope positioning laryngeal mask in airway management of aged patients under general anesthesia is safety and workable. And comparing with tracheal intubation, it has simple operation, smooth and steady hemodynamics and less complications, which is fit for the application of aged patients' airway management under general anesthesia.