Lycium barbarian seed oil activates Nrf2/ARE pathway to reduce oxidative damage in testis of subacute aging rats / 中国药理学通报

Aim To explore the effects of Lycium berry seed oil on Nrf2/ARE pathway and oxidative damage in testis of subacute aging rats. Methods Fifty out of 60 male SD rats, aged 8 weeks, were subcutaneously injected with 125 mg • kg"D-galactosidase in the neck for 8 weeks to establish a subacute senescent rat model. The presence of senescent cells was observed using P-galactosidase ((3-gal), while testicular morphology was examined using HE staining. Serum levels of testosterone (testosterone, T), follicle-stimulating hormone ( follicle stimulating hormone, FSH ) , luteinizing hormone ( luteinizing hormone, LH ) , superoxide dis-mutase ( superoxide dismutase, SOD ) , glutathione ( glutathione, GSH) and malondialdehyde ( malondial-dehyde, MDA) were measured through ELISA, and the expressions of factors related to aging, oxidative damage, and the Nrf2/ARE pathway were assessed via immunohistochemical analysis and Western blotting. Results After successfully identifying the model, the morphology of the testis was improved and the intervention of Lycium seed oil led to a down-regulation in the expression of [3-gal and -yH2AX. The serum levels of SOD, GSH, T, and FSH increased while MDA and LH decreased (P 0. 05) . Additionally, there was an up-regulated expression of Nrf2, GCLC, NQOl, and SOD2 proteins in testicular tissue ( P 0. 05 ) and nuclear expression of Nrf2 in sertoli cells. Conclusion Lycium barbarum seed oil may reduce oxidative damage in testes of subacute senescent rats by activating the Nrf2/ARE signaling pathway.

Associations between lifestyle and comorbid anxiety and depression in pregnant women / 环境与职业医学

Background Anxiety and depression are common perinatal mental health issues that often occur together and can have serious negative effects on both maternal and infant health. Objective To examine the relationships between lifestyle factors and comorbid anxiety and depression (CAD) among pregnant women in Shanghai. Methods The study estimated the prevalence of CAD during the first, second, and third trimesters of pregnancy using the Self-rating Anxiety Scale (SAS) and Center for Epidemiological Studies-Depression (CES-D) based on data from the China National Birth Cohort (CNBC) embryonic-derived diseases with assisted reproductive technology (ART) sub-cohort. Information on demographics, sleep status, nutritional intake, and exercise during each trimester was collected through self-made questionnaires, the Pittsburgh Sleep Quality Index (PSQI), and the Food Frequency Questionnaire (FFQ). Lifestyle factors (such as sleep status, nutritional intake, and exercise during each trimester) were analyzed using logistic regression and generalized linear mixed models (GLMM) to determine their impacts on the prevalence of CAD (yes or no) among pregnant women. Results A total of 2876 pregnant women were included in this study. The prevalence of CAD was 10.6% (305), 3.6% (103), and 5.5% (159) in the first, second, and third trimesters of pregnancy, respectively. The logistic regression analysis revealed that poor sleep quality throughout the entire pregnancy were statistically associated with an increased prevalence of CAD, and the odds ratios (OR) with 95% confidence intervals (CI) were 2.817 (1.845, 4.301), 2.840 (1.855, 4.347), and 9.316 (5.835, 14.876) for the first, second, and third trimesters, respectively, when compared to good sleep quality. Additionally, compared to an intake frequency of 7 times per week, the frequency of egg intake ≤3 times per week in the first trimester (OR=2.025, 95%CI: 1.197, 3.425) and the frequency of egg intake of 4–6 times per week (OR=1.896, 95%CI: 1.117, 3.216) or ≤3 times per week (OR=1.906, 95%CI: 1.082, 3.357) in the third trimester were associated with an increased risk of CAD (P<0.05). Moreover, when compared to a frequency of exercise >3 times per week, never or almost never exercising in the second trimester (OR=2.218, 95%CI: 1.220, 4.035) was associated with an increased risk of CAD (P<0.05). The GLMM analysis also demonstrated a significant association between poor sleep quality, lower exercise frequency, or lower intake frequency of vegetables, eggs, or milk and an increased risk of CAD (P<0.05). Conclusion The prevalence of CAD among pregnant women in Shanghai follows a U-shaped distribution, with the highest rate occurring in early pregnancy and the lowest rate in mid-pregnancy. Factors such as poor sleep quality, inadequate intake of vegetables, eggs, or milk, and lack of exercise during pregnancy may increase the risk of CAD. Implementing lifestyle interventions during pregnancy could potentially reduce the risk of mental health problems and improve the overall health of both mothers and babies.

Outcomes and care practices of extremely preterm infants at 22-25 weeks' gestation age from the Chinese Neonatal Network / 中华儿科杂志

Objective: To describe the current status and trends in the outcomes and care practices of extremely preterm infants at 22-25 weeks' gestation age from the Chinese Neonatal Network (CHNN) from 2019 to 2021. Methods: This cross-sectional study used data from the CHNN cohort of very preterm infants. All 963 extremely preterm infants with gestational age between 22-25 weeks who were admitted to neonatal intensive care units (NICU) of the CHNN from 2019 to 2021 were included. Infants admitted after 24 hours of life or transferred to non-CHNN hospitals were excluded. Perinatal care practices, survival rates, incidences of major morbidities, and NICU treatments were described according to different gestational age groups and admission years. Comparison among gestational age groups was conducted using χ2 and Kruskal-Wallis tests. Trends by year were evaluated by Cochran-Armitage and Jonckheere-Terpstra tests for trend. Results: Of the 963 extremely preterm infants enrolled, 588 extremely preterm infants (61.1%) were male. The gestational age was 25.0 (24.4, 25.6) weeks, with 29 extremely preterm infants (3.0%), 88 extremely preterm infants (9.1%), 264 extremely preterm infants (27.4%), and 582 extremely preterm infants (60.4%) at 22, 23, 24, and 25 weeks of gestation age, respectively. The birth weight was 770 (680, 840) g. From 2019 to 2021, the number of extremely preterm infants increased each year (285, 312, and 366 extremely preterm infants, respectively). Antenatal steroids and magnesium sulfate were administered to 67.7% (615/908) and 51.1% (453/886) mothers of extremely preterm infants. In the delivery room, 20.8% (200/963) and 69.5% (669/963) extremely preterm infants received noninvasive positive end-expiratory pressure support and endotracheal intubation. Delayed cord clamping and cord milking were performed in 19.0% (149/784) and 30.4% (241/794) extremely preterm infants. From 2019 to 2021, there were significant increases in the usage of antenatal steroids, antenatal magnesium sulfate, and delivery room noninvasive positive-end expiratory pressure support (all P<0.05). Overall, 349 extremely preterm infants (36.2%) did not receive complete care, 392 extremely preterm infants (40.7%) received complete care and survived to discharge, and 222 extremely preterm infants (23.1%) received complete care but died in hospital. The survival rates for extremely preterm infants at 22, 23, 24 and 25 weeks of gestation age were 10.3% (3/29), 23.9% (21/88), 33.0% (87/264) and 48.3% (281/582), respectively. From 2019 to 2021, there were no statistically significant trends in complete care, survival, and mortality rates (all P>0.05). Only 11.5% (45/392) extremely preterm infants survived without major morbidities. Moderate to severe bronchopulmonary dysplasia (67.3% (264/392)) and severe retinopathy of prematurity (61.5% (241/392)) were the most common morbidities among survivors. The incidences of severe intraventricular hemorrhage or periventricular leukomalacia, necrotizing enterocolitis, and sepsis were 15.3% (60/392), 5.9% (23/392) and 19.1% (75/392), respectively. Overall, 83.7% (328/392) survivors received invasive ventilation during hospitalization, with a duration of 22 (10, 42) days. The hospital stay for survivors was 97 (86, 116) days. Conclusions: With the increasing number of extremely preterm infants at 22-25 weeks' gestation admitted to CHNN NICU, the survival rate remained low, especially the rate of survival without major morbidities. Further quality improvement initiatives are needed to facilitate the implementation of evidence-based care practices.

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.

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.

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.

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.

Effects of berberine on colon dermal cell apoptosis in mice with ulcerative colitis based on JAK/STAT signaling pathway / 中国药理学通报

Aim To analyze the effects of berberine on the apoptosis of colon epithelial cells and polymorpho-nuclear neutrophils ( PMNs) in mice with ulcerative colitis ( UC ) by regulating JAK/STAT signaling pathway. Methods The UC mouse models were established by dextran sulfate sodium ( DSS) method and were randomly divided into control group, UC group, low-dose, middle-dose and high-dose berberine groups and positive drug group ( mesalazine enteric-coated tablet group) . In addition, the mice were randomly di¬vided into UC group, high-dose berberine group, AG490 group, and high-dose berberine + AG490 group. Levels of serum tumor necrosis factor a (TNF-α) and interleukin 6 (IL-6) and colon epithelial cell apoptosis and PMN apoptosis were compared among the groups. Western blot was used to detect the expres¬sions of colon tissue apoptosis-related and JAK/STAT signaling pathway-related proteins. Results The lev¬els of serum TNF-α and IL-6, apoptosis rate of colon epithelial cell and protein expressions of Fas, FasL, Bax, caspase-3, p-JAK2/JAK2 and p-STAT3/STAT3 in each dose berberine group and positive drug group were significantly lower than those in UC group (P < 0.05), and the above indicators in berberine groups were reduced gradually (P <0.05) . The PMN apoptosis rate and Bcl-2 protein expression were significantly higher in each dose berberine group and positive drug group than those in UC group (P <0. 05) , and the two indicators increased gradually in berberine groups ( P < 0.05). AG490 could reverse the above effects of berberine ( P < 0. 05 ). Conclusions Berberine can inhibit the apoptosis of colon epithelial cell and promote the apoptosis of PMN in UC mice by regulating the JAK/STAT signaling pathway, and then play a role in the treatment of UC.

Morin induces autophagy and apoptosis in hepatocellular carcinoma cells through Akt/mTOR/STAT3 pathway / 中国中药杂志

This study investigated the effect and mechanism of morin in inducing autophagy and apoptosis in hepatocellular carcinoma cells through the protein kinase B(Akt)/mammalian target of rapamycin(mTOR)/signal transducer and activator of transcription protein 3(STAT3) pathway. Human hepatocellular carcinoma SK-HEP-1 cells were stimulated with different concentrations of morin(0, 50, 100, 125, 200, and 250 μmol·L~(-1)). The effect of morin on the viability of SK-HEP-1 cells was detected by Cell Counting Kit-8(CCK-8). The effect of morin on the proliferation and apoptosis of SK-HEP-1 cells was investigated using colony formation assay, flow cytometry, and BeyoClick~(TM) EdU-488 with different concentrations of morin(0, 125, and 250 μmol·L~(-1)). The changes in the autophagy level of cells treated with morin were examined by transmission electron microscopy and autophagy inhibitors. The impact of morin on the expression levels of proteins related to the Akt/mTOR/STAT3 pathway was verified by Western blot. Compared with the control group, the morin groups showed decreased viability of SK-HEP-1 cells in a time-and concentration-dependent manner, increased number of apoptotic cells, up-regulated expression level of apoptosis marker PARP, up-regulated phosphorylation level of apoptosis-regulating protein H2AX, decreased number of positive cells and the colony formation rate, an upward trend of expression levels of autophagy-related proteins LC3-Ⅱ, Atg5, and Atg7, and decreased phosphorylation levels of Akt, mTOR, and STAT3. These results suggest that morin can promote apoptosis, inhibit proliferation, and induce autophagy in hepatocellular carcinoma cells, and its mechanism of action may be related to the Akt/mTOR/STAT3 pathway.

Inhibitory effect and molecular mechanism of sinomenine on human hepatocellular carcinoma HepG2 and SK-HEP-1 cells / 中国中药杂志

This study aimed to investigate the effect and molecular mechanism of sinomenine on proliferation, apoptosis, metastasis, and combination with inhibitors in human hepatocellular carcinoma HepG2 cells and SK-HEP-1 cells. The effect of sinomenine on the growth ability of HepG2 and SK-HEP-1 cells were investigated by CCK-8 assay, colony formation assay, and BeyoClick~(TM) EdU-488 staining. The effect of sinomenine on DNA damage was detected by immunofluorescence assay, and the effect of sinomenine on apoptosis of human hepatocellular carcinoma cells was clarified by Hoechst 33258 staining and CellEvent~(TM) Cystein-3/7Green ReadyProbes~(TM) reagent assay. Cell invasion assay and 3D tumor cell spheroid invasion assay were performed to investigate the effect of sinomenine on the invasion ability of human hepatocellular carcinoma cells in vitro. The effect of sinomenine on the regulation of protein expression related to the protein kinase B(Akt)/mammalian target of rapamycin(mTOR)/signal transducer and activator of transcription 3(STAT3) signaling pathway in HepG2 and SK-HEP-1 cells was examined by Western blot. Molecular docking was used to evaluate the strength of affinity of sinomenine to the target cysteinyl aspartate specific proteinase-3(caspase-3) and STAT3, and combined with CCK-8 assay to detect the changes in cell viability after combination with STAT3 inhibitor JSI-124 in combination with CCK-8 assay. The results showed that sinomenine could significantly reduce the cell viability of human hepatocellular carcinoma cells in a concentration-and time-dependent manner, significantly inhibit the clonogenic ability of human hepatocellular carcinoma cells, and weaken the invasive ability of human hepatocellular carcinoma cells in vitro. In addition, sinomenine could up-regulate the cleaved level of poly ADP-ribose polymerase(PARP), a marker of apoptosis, and down-regulate the protein levels of p-Akt, p-mTOR, and p-STAT3 in human hepatocellular carcinoma cells. Molecular docking results showed that sinomenine had good affinity with the targets caspase-3 and STAT3, and the sensitivity of sinomenine to hepatocellular carcinoma cells was diminished after STAT3 was inhibited. Therefore, sinomenine can inhibit the proliferation and invasion of human hepatocellular carcinoma cells and induce apoptosis, and the mechanism may be attributed to the activation of caspase-3 signaling and inhibition of the Akt/mTOR/STAT3 pathway. This study can provide a new reference for the in-depth research and clinical application of sinomenine and is of great significance to further promote the scientific development and utilization of sinomenine.

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.

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.

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.

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.

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.