Entinostat, a class I selective histone deacetylase inhibitor, plus exemestane for Chinese patients with hormone receptor-positive advanced breast cancer: A multicenter, randomized, double-blind, placebo-controlled, phase 3 trial

Entinostat plus exemestane in hormone receptor-positive (HR+) advanced breast cancer (ABC) previously showed encouraging outcomes. This multicenter phase 3 trial evaluated the efficacy and safety of entinostat plus exemestane in Chinese patients with HR + ABC that relapsed/progressed after ≥1 endocrine therapy. Patients were randomized (2:1) to oral exemestane 25 mg/day plus entinostat (n = 235) or placebo (n = 119) 5 mg/week in 28-day cycles. The primary endpoint was the independent radiographic committee (IRC)-assessed progression-free survival (PFS). The median age was 52 (range, 28-75) years and 222 (62.7%) patients were postmenopausal. CDK4/6 inhibitors and fulvestrant were previously used in 23 (6.5%) and 92 (26.0%) patients, respectively. The baseline characteristics were comparable between the entinostat and placebo groups. The median PFS was 6.32 (95% CI, 5.30-9.11) and 3.72 (95% CI, 1.91-5.49) months in the entinostat and placebo groups (HR, 0.76; 95% CI, 0.58-0.98; P = 0.046), respectively. Grade ≥3 adverse events (AEs) occurred in 154 (65.5%) patients in the entinostat group versus 23 (19.3%) in the placebo group, and the most common grade ≥3 treatment-related AEs were neutropenia [103 (43.8%)], thrombocytopenia [20 (8.5%)], and leucopenia [15 (6.4%)]. Entinostat plus exemestane significantly improved PFS compared with exemestane, with generally manageable toxicities in HR + ABC (ClinicalTrials.gov #NCT03538171).

Research and application of leek roots in medicinal field / 中草药·英文版

Some Chinese herbs have been used to prevent and treat diseases, and are also used as common food ingredients. These Chinese herbs are potential resource for research and development of new drugs. Leek roots is a typical medicine of food and medicine continuum. It has a long history of medicinal applications and edible food in China. In this paper, the origin, biological active components, pharmacological action and clinical application of leek roots were introduced. We hope that this review will contribute to the development of leek roots for pharmaceutical research and clinical applications, as well as related health products.

Measurement of the Thermic Effect of Food in a Chinese Mixed Diet in Young People / 生物医学与环境科学（英文）

OBJECTIVE@#To determine the thermic effect of food (TEF) in a Chinese mixed diet in young people.@*METHODS@#During the study, the participants were weighed and examined for body composition every morning. The total energy expenditure (TEE) of the participants was measured by the doubly labeled water method for 7 days, and during this period, basal energy expenditure was measured by indirect calorimetry and physical activity energy expenditure was measured by an accelerometer. The value obtained by subtracting basal energy expenditure and physical activity energy expenditure from TEE was used to calculate TEF.@*RESULTS@#Twenty healthy young students (18-30 years; 10 male) participated in the study. The energy intake of the participants was not significantly different from the Chinese Dietary Reference Intake of energy ( P > 0.05). The percentage of energy from protein, fat and carbohydrate were all in the normal range. The intakes of fruits, milk and dietary fiber of the participants were significantly lower than those in the Chinese Dietary Guidelines ( P < 0.05). There was no significant difference in the body weight of the participants during the experiment ( P > 0.05). When adjusted for body weight, there was no significant difference in either TEE or basal energy expenditure between the male and female participants ( P > 0.05). In addition, there was no significant difference in physical activity energy expenditure and TEF between the male and female participants ( P > 0.05). The percentage of TEF in TEE was 8.73%.@*CONCLUSION@#The percentage of TEF in TEE in a Chinese mixed diet in young people was significantly lower than 10% ( P < 0.001). A value of 10% is usually considered to be the TEF in mixed diets as a percentage of TEE.

Levels and health risks of exposure to neonicotinoid insecticides among 5-year-old children: Based on Laizhou Wan Birth Cohort in Shandong Province / 环境与职业医学

Background Neonicotinoid insecticides (NEOs) are emerging synthetic insecticides that have been used in various pest management regimens worldwide as alternatives to conventional insecticides. Recently, several studies have indicated that humans are widely exposed to NEOs, but limited is known about the levels and associated health risks of NEOs exposure among children. Objective To estimate exposure levels of four kinds of NEOs in urine samples among 5-year-old children from Laizhou Wan, Shandong Province, and to evaluate health risks of single and cumulative exposure to NEOs among children in this area. Methods A total of 205 children who participated in the 5-year-old follow-up in Laizhou Wan Birth Cohort (LWBC) were included. Urinary concentrations of four NEOs [imidacloprid (IMI), acetamiprid (ACE), clothianidin (CLO), and thiamethoxam (THM)] were measured by high-performance liquid chromatography coupled with triple quadrupole mass spectrometry. Based on the detected NEOs concentrations, estimated daily intake (EDI) was calculated, and the health risk of exposure to single NEO was assessed using hazard quotient (HQ, risk threshold=1). A relative potency factor (RPF) approach was used to standardize the concentrations of the four NEOs by IMI to calculate their cumulative concentrations. Then, the health risk of cumulative exposure to the four NEOs was further evaluated based on the HQ method. Results The detection rates of the four NEOs in the 5-year-old children were all above 90%, and their median creatinine-adjusted urinary concentrations were in the order from high to low as follows: CLO (1.373 μg·g−1) > THM (0.628 μg·g−1) > IMI (0.310 μg·g−1) > ACE (0.073 μg·g−1). Of the four NEOs, the median EDI of IMI was 0.035 µg·kg−1·d−1, higher than those of CLO (0.032 µg·kg−1·d−1), THM (0.012 µg·kg−1·d−1), and ACE (0.002 µg·kg−1·d−1). The maximum HQ values of IMI, CLO, THM, and ACE were 0.168, 0.152, 0.055, and 0.022, respectively, which were all far lower than the risk threshold of 1. The median concentration of cumulative exposure to the four NEOs standardized by IMI was 21.241 μg·g−1, and its median EDI was 2.370 µg·kg−1·d−1. The maximum HQ of cumulative exposure to the four NEOs was only 0.694, which also did not exceed the risk threshold of 1. Conclusion NEOs exposure is common among the 5-year-old children in Laizhou Wan, Shandong. Although there is no obvious health risk associated with single and cumulative exposure to NEOs in the children in this area, their exposure levels of NEOs are higher than those in some foreign areas. The adverse health effects of long-term exposure to low dose of NEOs deserve our extensive attention.

Design, synthesis and evaluation of phenoxyacetic acid-based PTP1B inhibitors / 药学学报

Protein tyrosine phosphatase (PTP) 1B is a potential therapeutic target for type 2 diabetes. Phosphotyrosine (pTyr) mimetics still dominate the currently available PTP1B inhibitors. The phenoxyacetic acid moiety was taken as a pTyr mimetic herein and phenoxyacetic acid-based compounds 2a-2g and 3a-3c were designed. Among them, compounds 2a-2g exhibited potent inhibition against PTP1B, and compound 2g showed an IC50 of 0.42 μmol·L-1 against PTP1B. Compound 2f exhibited pharmacological profiles similar to that of rosiglitazone, and could improve the insulin sensitivity and the serum total cholesterol level. The results suggest that PTP1B inhibitors might be effective in treating type 2 diabetes as well as associated metabolic syndromes.

Establishment and application of activity determining methods for different subtypes of xanthine oxidoreductase / 药学学报

Xanthine oxidoreductase (XOR), the key enzyme catalyzing purine to produce uric acid, including two subtypes, xanthine dehydrogenase (XDH) and xanthine oxidase (XO), respectively, in vivo. Usually, XDH and XO can transform to each other. In this study, based on the principle that the subtype XO or XDH uses different electron acceptors, the methods for the measuring the activities of bovine milk XOR (pure enzyme) and its subtypes were established. The optimal concentrations of substrate xanthine (50 μmol·L-1) and electron acceptor NAD+ (50 μmol·L-1), pH value (7.80) were investigated. The ranges of the XOR, XO, XDH activity which could be determined were 0.97-17.5 U·L-1, 1-9 U·L-1, and 66-1 191 mU·L-1, respectively. Furthermore, the methods for determining the activities of XOR and its subtypes in mouse liver were established. The preparation of liver samples, the optimal concentrations of xanthine (100 μmol·L-1) and NAD+ (100 μmol·L-1) were researched. And the activity ranges of XOR, XO and XDH in mouse liver which could be determined were 0.67-3.98, 0.19-1.08, and 0.52-3.55 U·gprot-1, respectively. With the methods above, the effects of classic XOR inhibitor allopurinal (Allo) on XOR, XO and XDH from both milk and mouse liver were determined. All animal experiments have been approved by the Animal Experimental Center, Institute of Materia Medica, Chinese Academy of Medical Science and Peking Union Medical College (00003346). This study established new methods for the determination of XOR and its subtypes activity in pure enzyme system and in mouse liver, respectively, which were accurate and convenient. It laid the experimental foundation for exploring the different pathophysiological effects of XOR in the body and developing new XOR inhibitors.

Exploration of undergraduate practice teaching method for nursing internal medicine based on BOPPPS teaching model / 中华医学教育探索杂志

Objective:To explore the feasibility of applying BOPPPS (B-bridge in, O-objective, P-pre-assessment, P-participatory learning, P-post-assessment, S-summary) course design mode in the teaching of internal medicine practice for nursing undergraduates.Methods:A total of 73 nursing interns of Kunming Medical University were selected as subjects and divided into the experimental group ( n=30) and the control group ( n=43). The experimental group adopted the practice teaching method based on BOPPPS model, while the control group adopted the traditional teaching method. Students' evaluation was collected by questionnaire. The students' comprehensive reasoning ability, holistic nursing skills ability and clinical nursing evaluation ability were evaluated by taking out questions from the question bank. And the results of teachers' evaluation on the participation of case study and problem solving in the process of students' internship were collected. SPSS 20.0 was used for t-test. Results:The students' evaluation of the practice process in the experimental group (86.81±2.85) was significantly better than that in the control group (82.61±3.82) ( P<0.001). The experimental group was significantly better than the control group in comprehensive reasoning of clinical thinking and assessment of holistic nursing ability ( P <0.001). Teachers' evaluation in the experimental group was better than that in the control group ( P <0.05). The overall effect of the experimental group (20.60±1.73) was significantly better than that of the control group (17.84±1.70) ( P <0.001). Conclusion:BOPPPS mode is helpful for teachers to carry out and demonstrate holistic nursing teaching with symptoms as the core according to the overall teaching objectives of nursing internal medicine, optimize the time arrangement and knowledge structure, improve the practice efficiency, and promote the establishment of holistic nursing thinking mode of students.

Effects of Gongyanping Capsule on genital tract infected by ureaplasma urealyticum and fertility of mice / 国际中医中药杂志

Objective:To observe the effect of Gongyanping Capsule on genital tract infected by ureaplasma urealyticum and fertility of mice, and to explore its mechanism.Methods:One hundred female ICR mice were divided into normal control group, model control group, azithromycin group, the low and high-dose group of Gongyanping Capsule according to random number table method. Except for the normal control group, the other groups were infected with ureaplasma urealyticum to establish the reproductive tract inflammation model. The azithromycin group was given 40 mg/kg of azithromycin, the low and high-dose groups were given 50 and 100 mg/kg of Gongyanping Capsule respectively, the normal control group and model control group were given equal volume of normal saline, once a day, for 4 consecutive weeks. The fertility status of each group was recorded. HE staining was used to observe the pathological changes of the vaginal tissues of the mice in each group, and the content of monocyte chemoattractant protein 1 (MCP-1), IL-4, IL-12, TNF-α myeloperoxidase (MPO) and GSH-Px of the mice in each group were determined; RT-PCR and Western blot were used to determine the vagina level of mRNA and protein expressions of TLR4 and NF-κB.Results:Compared with the model control group, the birth time and the number of dead mice in the azithromycin group and the low and high dose groups of Gongyanping Capsule decreased ( P<0.05), and the number of born mice increased ( P<0.05). The level of MCP-1, MPO, IL-4, IL-12, TNF-α decreased ( P<0.05), the level of GSH-Px increased ( P<0.05), the expression of TLR4 mRNA (1.25±0.33, 2.97±0.92, 2.32±0.72 vs. 3.69±1.32), NF-κB mRNA (1.48±0.42, 2.91±0.99, 2.13±0.70 vs. 3.83±1.41) decreased ( P<0.05), the expression of TLR4 (0.63±0.13, 1.32 ± 0.34, 1.04 ± 0.33 vs. 1.63 ± 0.41), NF-κB (0.63 ± 0.14, 1.36 ± 0.32, 1.03 ± 0.30 vs. 1.94 ± 0.58) decreased ( P<0.05), and had a certain dose-dependence. Conclusion:Gongyanping Capsule has obvious therapeutic effect on genital tract mice infected by ureaplasma urealyticum, and can significantly improve the fertility of mice; the mechanism may be related to that Gongyanping Capsule could inhibit the vaginal TLR4/NF-κB pathway in mice.

Effects of maternal exercise during pregnancy on neonatal weight and subcutaneous fat thickness / 环境与职业医学

Background Exercise during pregnancy is closely related to maternal and infant health. Previous studies in developed countries have linked maternal exercise during pregnancy with newborn body weight as well as subcutaneous fat thickness. However, the relevant studies in China are limited, and the conclusions remain inconsistent. Objective To investigate the effects of maternal exercise during pregnancy on neonatal weight and subcutaneous fat thickness. Methods Based on the Shanghai Birth Cohort, 959 maternal-infant pairs were included in this study. The International Physical Activity Questionnaire was used to collect average weekly frequency and daily minutes of walking in the first and second trimesters, and entropy weight method was used to calculate the cumulative exercise index in the two trimesters. Birth weight was measured using a calibrated weigh scale. Subcutaneous fat thickness was measured at abdomen, scapula, and triceps with a Harpenden skinfold caliper for all newborns and the sum of the thickness for the three sites was then calculated. A multiple linear regression model was employed to estimate the relationships of cumulative exercise index during pregnancy with neonatal body weight and subcutaneous fat thickness. Subgroup analyses stratified by pre-pregnancy body mass index (BMI) and sex of newborns were also performed. Results The mean age of pregnant women was (28.5±3.8) years, and the pre-pregnancy BMI was (21.4±3.0) kg·m−2. Newborn boys were slightly more than newborn girls (54.3% vs 45.7%), and the neonatal weight was (3374.0±427.5) g. The means of newborns' abdominal, scapular, and triceps subcutaneous fat thickness were (4.4±1.3), (5.4±1.4), and (6.0±1.5) mm, respectively, and the sum of subcutaneous fat thickness was (15.8±3.9) mm. In the first and second trimesters, 77.3% and 88.7% of pregnant women walked 4 d per week and more, respectively; the daily minutes of walking was (36.9±27.2) min and (43.3±26.3) min, respectively; the cumulative exercise index was 25.6±17.7 and 35.9±21.1, respectively. The results of multiple linear regression analysis showed that the cumulative exercise index in the second trimester was negatively associated with newborns' abdominal (b=−0.006, 95%CI: −0.010-−0.003), scapular (b=−0.005, 95%CI: −0.009-−0.002), triceps (b=−0.006, 95%CI: −0.010-−0.002), and their sum of (b=−0.018, 95%CI: −0.028-−0.007) subcutaneous fat thickness (P<0.05); in the first and second trimesters, however, the relationship between maternal cumulative exercise and newborns' body weight was not significant. The results of stratified analyses showed that the negative associations between maternal cumulative exercise index and newborns' subcutaneous fat thickness for the second trimester remained significant in the subgroups of boys and neonates whose mothers had normal pre-pregnancy BMI (P<0.05). Conclusion Cumulative exercise index in the second trimester is negatively correlated with the neonatal thickness of subcutaneous fat, and the association may be altered by neonatal sexes and maternal pre-pregnancy BMI levels.

Possible mechanisms of nutritional components ameliorating adverse health effects caused by environmental pollutants / 环境与职业医学

Exposure to environmental pollutants imposes important health risks to human beings. In recent years, emerging evidence has suggested that nutritional components may ameliorate the adverse health effects of environmental pollutants. Therefore, it raises great public health interests in protecting human health from environmental pollutants by nutrition interventions. Considering in vivo and in vitro experimental evidence, as well as epidemiological studies, this paper reviewed the possible mechanisms underlying how nutritional components counteract the adverse health impacts of environmental pollutants, which can provide directions for further studies on health risk assessment and nutrition intervention associated with environmental pollutant exposure.

Advances on immunotoxicities induced by per- and polyfluoroalkylated substances / 环境与职业医学

Per-and polyfluoroalkylated substances (PFASs) are a group of persistent organic pollutants that are widespread in the environment and organisms. Given their unique hydrophobicity, oil-repellence, and chemical stability, PFASs are widely used in various industrial and commercial products. PFASs can accumulate and be biomagnified through the food chain, and its toxic effects have posed a certain threat to human health. The response of the immune system to PFASs exposure is one of the most sensitive human health effects, and has attracted remarkable attention from related scientists and organizations. We summarized international and domestic epidemiological studies on the associations between exposure to PFASs and immune system, including immunosuppression and immunoenhancement. We also reviewed experimental evidence of PFASs on immune system from perspectives of immune organs, immune cells, and cytokines. Furthermore, the possible mechanisms of peroxisome proliferator-activated receptor-α (PPAR-α)-dependent, nuclear factor-κB (NF-κB)-activated, and mitochondrial apoptosis pathways were summarized. While the relationships between PFASs and immune-related diseases in human are not yet conclusive, accumulative epidemiological studies provide evidence for associations between PFASs and reduced immune response to vaccination in children. In addition, previous studies mainly focus on the immunotoxicity of traditional PFASs, and our understanding of the molecular mechanism of the effects of PFASs on immune system is still in its infancy. Therefore, it is necessary to further explore the immunotoxicity of new PFASs and associated mechanism.

Association between heavy metal exposure level and physical development indicators among school-age children / 环境与职业医学

Background Heavy metals are widely present in the environment, difficult to degrade, and bioaccumulative. Children's physical development are not mature, and exposure to heavy metals which may cause irreversible harm to them. However, the current research conclusions are still inconsistent. Therefore, it is very important to pay attention to the impact of heavy metal pollutants on physical development. Objective To detect the level of heavy metal exposure of school-age children in Laizhou Wan, Shandong Province, and to explore the relationship between heavy metal exposure level and physical development indexes of school-age children. Methods The subjects of this study were 318 children born to pregnant women recruited from Laizhou Wan Birth Cohort in Shandong Province from September 2010 to December 2013. The school-age children at age 7 were followed up from July to September 2019. Their urine samples were collected and the levels of arsenic (As), cadmium (Cd), lead (Pb), and mercury (Hg) in urine were detected by inductively coupled plasma mass spectrometry (ICP-MS). At the same time, the height, weight, body mass index (BMI), waist circumference, and body fat percentage of the children were evaluate to analyze the relationship between the four heavy metals in children's urine and the indicators related to children's physical development. Results Among the 318 school-age children with an age (\begin{document}$\bar x \pm s $\end{document}) of (7.77±0.67) years, the median (P25, P75) levels of As, Cd, Pb, and Hg in urine were 73.98 (44.81, 124.61), 0.40 (0.27, 0.58), 1.20 (0.71, 1.72), and 2.38 (1.32, 4.80) µg·g−1 (of creatinine), respectively. The children’s urinary Cd level was positively correlated with their weight, BMI, and waist circumference (P<0.05), and corresponding regression coefficients (b) and its 95% confidence intervals (CI) were 0.99 (0.14-1.83), 0.43 (0.06-0.81), and 1.35 (0.27-2.42), respectively; while the other heavy metals were not related to the above physical development indicators (P>0.05). After sex stratification, it was found that boys’ urinary Cd level was positively correlated with their height, weight, BMI, and waist circumference (P <0.05) with associated b (95%CI) of 1.73 (0.53-2.93), 2.03 (0.60-3.47), 0.75 (0.11-1.38), and 2.66 (0.85-4.47), respectively; such associations were not found in girls. After further stratification of boys’ BMI according to normal, overweight, and obesity, it was found that a higher urinary Cd level was correlated with an increased risk of obesity in boys (P<0.05), and the associated b (95%CI) was 2.34 (1.02-5.36). Conclusion The level of urinary Cd exposure of boys in Laizhou Wan, Shandong Province is positively correlated with their height, weight, BMI, and waist circumference, and may be related to obesity in boys.

Metagenomic data-analysis reveals enrichment of lipopolysaccharide synthesis in the gut microbiota of atrial fibrillation patients / 中华心血管病杂志

Objective: To investigate the functional changes of key gut microbiota (GM) that produce lipopolysaccharide (LPS) in atrial fibrillation (AF) patients and to explore their potential role in the pathogenesis of AF. Methods: This was a prospective cross-sectional study. Patients with AF admitted to Beijing Chaoyang Hospital of Capital Medical University were enrolled from March 2016 to December 2018. Subjects with matched genetic backgrounds undergoing physical examination during the same period were selected as controls. Clinical baseline data and fecal samples were collected. Bacterial DNA was extracted and metagenomic sequencing was performed by using Illumina Novaseq. Based on metagenomic data, the relative abundances of KEGG Orthology (KO), enzymatic genes and species that harbored enzymatic genes were acquired. The key features were selected via the least absolute shrinkage and selection operator (LASSO) analysis. The role of GM-derived LPS biosynthetic feature in the development of AF was assessed by receiver operating characteristic (ROC) curve, partial least squares structural equation modeling (PLS-SEM) and logistic regression analysis. Results: Fifty nonvalvular AF patients (mean age: 66.0 (57.0, 71.3), 32 males(64%)) were enrolled as AF group. Fifty individuals (mean age 55.0 (50.5, 57.5), 41 males(82%)) were recruited as controls. Compared with the controls, AF patients showed a marked difference in the GM genes underlying LPS-biosynthesis, including 20 potential LPS-synthesis KO, 7 LPS-biosynthesis enzymatic genes and 89 species that were assigned as taxa harbored nine LPS-enzymatic genes. LASSO regression analysis showed that 5 KO, 3 enzymatic genes and 9 species could be selected to construct the KO, enzyme and species scoring system. Genes enriched in AF group included 2 KO (K02851 and K00972), 3 enzymatic genes (LpxH, LpxC and LpxK) and 7 species (Intestinibacter bartlettii、Ruminococcus sp. JC304、Coprococcus catus、uncultured Eubacterium sp.、Eubacterium sp. CAG:251、Anaerostipes hadrus、Dorea longicatena). ROC curve analysis revealed the predictive capacity of differential GM-derived LPS signatures to distinguish AF patients in terms of above KO, enzymatic and species scores: area under curve (AUC)=0.957, 95%CI: 0.918-0.995, AUC=0.940, 95%CI 0.889-0.991, AUC=0.972, 95%CI 0.948-0.997. PLS-SEM showed that changes in lipopolysaccharide-producing bacteria could be involved in the pathogenesis of AF. The key KO mediated 35.17% of the total effect of key bacteria on AF. After incorporating the clinical factors of AF, the KO score was positively associated with the significantly increased risk of AF (OR<0.001, 95%CI:<0.001-0.021, P<0.001). Conclusion: Microbes involved in LPS synthesis are enriched in the gut of AF patients, accompanied with up-regulated LPS synthesis function by encoding the LPS-enzymatic biosynthesis gene.

Mechanism of Cancer Drug Resistance and Reversal Effect of Chinese Medicine： A Review / 中国实验方剂学杂志

Malignant tumor is a serious threat to human life and health. The prevalence and mortality of malignancies in China are increasing year by year. Conquering cancer has become a difficult problem for human beings. Chemical drug therapy combined with molecular targeted therapy is a general and preferred anti-tumor clinical scheme， but the side effects and the drug resistance of cancer cells often hinder the efficacy. Therefore， it is of great significance to study the mechanism of drug resistance and the methods to reverse drug resistance. Chinese medicine has the characteristics of complex components， multiple targets， low toxicity， etc. A large number of experimental studies have demonstrated that the effective components or extracts of Chinese medicine can inhibit the proliferation， migration， and invasion of cancer cells， and induce apoptosis， autophagy， differentiation， and senescence. In clinical practice， Chinese medicine has been applied to the protection against ttumor， adjuvant treatment， and later consolidation. The research on Chinese medicine is expected to promote drug resistance reversal and cancer therapy. Studies have shown that the combination of Chinese medicine and chemotherapy can reverse drug resistance and increase efficacy， which has become the mainstream trend of cancer treatment. This study reviewed the mechanisms of the drug resistance of cancer cells induced by self-protective autophagy， gene mutation， high expression of enzymes， abnormal signaling pathways， and abnormal expression of RNA and protein， and summarized how compounds isolated from Chinese medicine， single drug and its extract， and classic anti-cancer prescription reversed the drug resistance to lay a solid foundation for the further investigation of the anti-tumor effect of Chinese medicine.

Anti-tumor Effect of Draconis Sanguis Petroleum Ether Fraction on Human Gastric Cancer HGC-27 and MGC-803 Cells / 中国实验方剂学杂志

ObjectiveTo investigate the effect of Draconis Sanguis petroleum ether fraction （DSPEF） on the proliferation， apoptosis， migration， and autophagy of human gastric cancer HGC-27 and MGC-803 cells， and preliminarily elucidate its molecular mechanism. MethodCell counting kit-8 （CCK-8） assay was used to detect the effect of DSPEF at different concentrations （0， 20， 40， 60， 80 mg·L-1） on the proliferation of HGC-27 and MGC-803 cells after 24， 48， 72 h. Hoechst staining and flow cytometry were used to explore the effects of DSPEF at different concentrations on the apoptosis and apoptosis rate of HGC-27 and MGC-803 cells after 48 h treatment， respectively. The wound healing assay and acridine orange staining were used to investigate the effects of DSPEF on the migration and autophagy of HGC-27 and MGC-803 cells， respectively. Western blot was used to detect the expression levels of signaling pathway-related proteins in HGC-27 and MGC-803 cells treated with DSPEF for 48 h. ResultCompared with the control group， DSPEF（30 mg·L-1） inhibited the proliferation and migration of HGC-27 and MGC-803 cells in a concentration- and time-dependent manner （P<0.05）， and induced the apoptosis （P<0.01） and autophagy of HGC-27 and MGC-803 cells. DSPEF （60 mg·L-1） down-regulated the protein levels of phosphorylated mammalian target of rapamycin （p-mTOR） （P<0.05， P<0.01） and down-regulated phospho-signal transducer and activator of transcription 3 （p-STAT3） in HGC-27 and MGC-803 cells （P<0.01）， suggesting that DSPEF presumedly inhibited the proliferation and migration of human gastric cancer HGC-27 and MGC-803 cells and induced their apoptosis and autophagy by inhibiting the mTOR/STAT3 signaling pathway. ConclusionThe down-regulation of the mTOR/STAT3 signaling pathway may be involved in the anti-gastric cancer effect of DSPEF. This study is expected to provide a reference for the investigation of the anti-tumor effect of Draconis Sanguis.

Effect of indoor and outdoor environmental factors on allergic and infectious diseases in children / 上海预防医学

Objective To investigate the prevalence of allergic and infectious diseases in children， and to assess the influence of indoor and outdoor environmental factors on these two common diseases in children. Methods A questionnaire was used to investigate the prevalence of allergic and infectious diseases in 140 children of 7 years old in Laizhou Bay， Shandong Province. Logistic regression was used to analyze the associations between indoor and outdoor environmental factors and children’s allergic and infectious diseases， respectively. Results The prevalence of previous eczema and other allergic diseases for the past year in children was 37.9% and 15.0%， respectively， and the prevalence of infectious diseases for the past year was 35.7%. As for allergic diseases， eye irritation due to outdoor air （ OR =2.977； 95% CI ： 1.407‒6.296） and nose irritation due to outdoor air （ OR =5.147； 95% CI ： 1.272‒20.827） were the risk factors for previous eczema in children. Indoor musty taste increased the risks of urticaria （ OR =4.306； 95% CI ： 1.062‒17.454） and previous eczema （ OR =3.853； 95% CI ： 1.080‒13.743）. The use of cockroach killers indoors increased the risk of rhinitis （ OR =6.102； 95% CI ：1.297‒28.697）. As for infectious diseases， having outdoor pollution sources increased the risk of gastrointestinal infection （ OR =4.937； 95% CI ： 1.050‒23.216）， and the use of mosquito coils and clothing mothproofing agents increased the risks of respiratory （ OR =6.333； 95% CI ： 1.397‒28.714） and gastrointestinal infections （ OR =3.218； 95% CI ： 1.074‒9.644）， respectively. However， we did not find associations between indoor passive smoking and allergic or infectious diseases. Conclusion Except outdoor passive smoking， all the other indoor and outdoor environmental factors increase the risks of children’s allergies and infectious diseases.

Effect of indoor and outdoor environmental factors on allergic and infectious diseases in children / 上海预防医学

Objective To investigate the prevalence of allergic and infectious diseases in children， and to assess the influence of indoor and outdoor environmental factors on these two common diseases in children. Methods A questionnaire was used to investigate the prevalence of allergic and infectious diseases in 140 children of 7 years old in Laizhou Bay， Shandong Province. Logistic regression was used to analyze the associations between indoor and outdoor environmental factors and children’s allergic and infectious diseases， respectively. Results The prevalence of previous eczema and other allergic diseases for the past year in children was 37.9% and 15.0%， respectively， and the prevalence of infectious diseases for the past year was 35.7%. As for allergic diseases， eye irritation due to outdoor air （ OR =2.977； 95% CI ： 1.407‒6.296） and nose irritation due to outdoor air （ OR =5.147； 95% CI ： 1.272‒20.827） were the risk factors for previous eczema in children. Indoor musty taste increased the risks of urticaria （ OR =4.306； 95% CI ： 1.062‒17.454） and previous eczema （ OR =3.853； 95% CI ： 1.080‒13.743）. The use of cockroach killers indoors increased the risk of rhinitis （ OR =6.102； 95% CI ：1.297‒28.697）. As for infectious diseases， having outdoor pollution sources increased the risk of gastrointestinal infection （ OR =4.937； 95% CI ： 1.050‒23.216）， and the use of mosquito coils and clothing mothproofing agents increased the risks of respiratory （ OR =6.333； 95% CI ： 1.397‒28.714） and gastrointestinal infections （ OR =3.218； 95% CI ： 1.074‒9.644）， respectively. However， we did not find associations between indoor passive smoking and allergic or infectious diseases. Conclusion Except outdoor passive smoking， all the other indoor and outdoor environmental factors increase the risks of children’s allergies and infectious diseases.

Evaluation of methodological and reporting quality of domestic clinical guidelines for hyperuricemia / 中国中药杂志

This study aims to evaluate the methodological and reporting quality of diagnosis and treatment guidelines for hyperuricemia as well as the expert consensuses and promote the understanding and application of the diagnosis and treatment guidelines for hyperuricemia. With "hyperuricemia" "guidelines" "consensus" "recommendations" as the key words in titles, the authors searched for the published clinical guidelines on hyperuricemia in Chinese against CNKI, Wanfang, VIP, Medlive and the official website of the industry association. The retrieval time limit was until May 31, 2021. The appraisal of guidelines for research and evaluation Ⅱ(AGREEⅡ) and the reporting items for practice guidelines in health care(RIGHT) were employed to evaluate the methodological quality and reporting quality of 14 guidelines/consensuses included. The average scores of the guidelines/consensuses were 80.85%(48.61%-98.61%) for the domain of scope and purpose, 34.52%(0-69.44%) for the domain of stakeholder involvement, 35.53%(6.25%-92.19%) for the domain of rigor of development, 55.85%(23.61%-86.11%) for the domain of clarity of presentation, 26.19%(0-76.04%) for the domain of applicability, and 21.42%(0-50.00%) for the domain of editorial independence. Nine guidelines/consensuses were of medium overall quality with grade B recommendation, and five guidelines/consensuses were of poor quality with grade C recommendation. The RIGHT classified the fourteen guidelines/consensuses into one of high reporting quality, three of medium reporting quality, and ten of low reporting quality. The results of this study indicate that the standardization and rigor of the methodological quality and the reporting quality of the clinical guidelines/consensuses for hyperuricemia in China remain to be strengthened.

Prognostication of early-onset endometrioid endometrial cancer based on genome-wide DNA methylation profiles / 부인종양

Objective@#The aim of this study was to establish criteria that would indicate whether fertility preservation therapy would likely be safe for patients aged 40 years or less with endometrioid endometrial cancer based on their DNA methylation profile. @*Methods@#Forty-nine fresh-frozen tissue samples from patients with endometrial cancer from an initial cohort and 31 formalin-fixed paraffin-embedded tissue samples from a second cohort were subjected to genome-wide DNA methylation analysis using the Infinium MethylationEPIC BeadChip. @*Results@#Epigenomic clustering of early-onset endometrial cancer was correlated with the widely used recurrence risk classification. Genes showing differences in DNA methylation levels between the low-recurrence-risk category and intermediate- and high-risk categories were accumulated in pathways related to fibroblast growth factor and nuclear factor-κB signaling. DNA hypomethylation and overexpression of ZBTB38 were frequently observed in the low-risk category. Eight hundred thirty-one marker CpG probes showed area under the curve values of >0.7 on the receiver operating characteristic curve for discrimination of patients belonging to the low-risk category. By combining marker CpG sites, seven panels for placing patients into the low-risk category with 91.3% or more sensitivity and specificity in both the initial and second cohorts were established. @*Conclusions@#DNA methylation diagnostics criteria using up to 6 of 8 CpG sites for LPP, FOXO1, RNF4, EXOC6B, CCPG1, RREB1 and ZBTB38 may be applicable to recurrence risk estimation for patients aged 40 years or less with endometrial cancer, regardless of tumor cell content, even if formalin-fixed paraffin-embedded biopsy or curettage materials are used.

Effect of para-nitrophenol concentration in urine of healthy adults on thyroid function based on US NHANES / 环境与职业医学

Background Parathion and methyl parathion are typical organophosphorus insecticides and para−nitrophenol (PNP) is their main specific metabolite. Previous studies have shown that parathion and methyl parathion may play a role as endocrine disrupting chemicals, but the evidence is limited. Objective Our aim is to evaluate association between urinary PNP concentration and thyroid function among healthy adults and whether this association has gender differences. Methods The study was based on the 2007—2008 US National Health and Nutrition ExaminationSurvey (NHANES). A total of 1071 subjects aging from 20 to 64 years with data on both urinary PNP and serum thyroid function indicators were finally enrolled. Thyroid function was evaluated by measuring serum thyroid stimulating hormone (TSH), free triiodothyronine (FT3), free thyroxine (FT4), total triiodothyronine (TT3), total thyroxine (TT4), thyroglobulin (TG), and thyroglobulin antibody (TG-Ab). A generalized linear model was used to analyze the relationship between urinary PNP and serum thyroid function indicators and the dose-response relationship. Gender differences were also explored. Results In the total population, the positive rate of PNP was 92.5%, and the median urinary PNP concentration adjusted for urinary creatinine was 0.62 μg·g−1. The median creatinine-adjusted urinary PNP concentrations in the male and female populations were 0.60 and 0.66 µg·g−1 respectively. The median activities or concentrations of serum thyroid function indicators TSH, FT3, FT4, TT3, and TT4 in the total population were 1500.00 μIU·L−1, 3200.00 pg·L−1, 8.00 ng·L−1, 1140.00 ng·L−1, and 76.00 μg·L−1 respectively. In the total population, a logarithmic unit increase of urinary PNP was associated with 1050.00 pg·L−1 decrease in serum FT3 levels (b=−0.02, 95%CI: −0.02-−0.01), 10.50 ng·L−1 decrease in FT4 levels (b=−0.02, 95%CI: −0.03-−0.01), and 10.50 ng·L−1 decrease in TT3 levels (b=−0.02, 95%CI: −0.03-−0.01), all in a dose-response manner (all Ptrend<0.05). After sex stratification, for every logarithmic unit increase of urinary PNP, the serum TG-Ab level was increased by 1100.00 IU·L−1 (b=0.04, 95%CI: 0.00-0.08) and the serum FT3 level was reduced by 1020.00 pg·L−1 (b=−0.01, 95%CI: −0.02-0.00) among males, and both showed dose-response relationships (both Ptrend<0.05); every logarithmic unit increase of urinary PNP was associated with 1050.00 pg·L−1 decrease in FT3 levels (b=−0.02, 95%CI: −0.03-−0.01), 10.50 ng·L−1decrease in FT4 levels (b=−0.02, 95%CI: −0.03-0.00), 10.70 ng·L−1 decrease in TT3 levels (b=−0.03, 95%CI: −0.05-−0.01), and 10.50 μg·L−1 decrease in TT4 levels (b=−0.02, 95%CI: −0.04-0.00) among females, and there were dose-response relationships of urinary PNP concentration with serum FT3 and TT3 levels (both Ptrend<0.001). Conclusion Changes in the concentration of PNP in urine are associated with changes in serum FT4, FT3, and TT3 levels and the results also show gender differences.