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.

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.

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.

Effect of mirror therapy on upper extremity motor function and activities of daily living in stroke patients:a me-ta-analysis / 中国康复理论与实践

Objective To systematically review whether mirror therapy(MT)intervention can effectively improve upper extremity motor function and activities of daily living(ADL)in stroke patients;whether its improvement is affected by pa-tients'age and disease course;and whether MT's influencing factors,such as intervention period,time,and fre-quency,have a dosage effect on upper extremity motor function and ADL. Methods Seven databases were searched,including Embase,Web of Science,PubMed,Cochrane Library,Wanfang data,VIP and CNKI from establishment to April,2023,and randomized controlled trials of MT for upper extremity motor function and ADL in stroke patients were screened.Quality assessment was performed using Physiothera-py Evidence Database(PEDro).Meta-analysis was performed using RevMan 5.4.1,and network meta-analysis was performed using R software,reticulated meta-analysis tables and cumulative probability tables were drawn for ranked comparisons,and funnel plots were drawn to test for publication bias of the outcome indicators using Stata 17.0 software.GRADE was used to evaluate the quality of evidence for the outcome indicators. Results A total of 13 papers(532 patients)were included.The PEDro score ranged from 6 to 8.Most of the literature did not report the blinding completely or did not implement allocation concealment,which might have some limita-tions.MT could improve the scores of Fugl-Meyer Assessment-Upper Extremities(n = 466,MD = 6.05,95%CI 3.44～8.66,P<0.001),Barthel index(n = 230,MD = 9.95,95%CI 6.23～13.68,P<0.001)and Functional Inde-pendence Measure(n = 147,MD = 4.17,95%CI 2.61～5.72,P<0.001)in stroke patients.Network meta-analysis showed that MT was more effective in upper limb motor function intervention for stroke patients aged 40 to 59 years with a disease course less than three months;and an intervention period less than four weeks,single inter-vention time less than 30 minutes,intervention duration daily more than 30 minutes and intervention twice daily might optimize the effects on upper limb motor function. Conclusion MT is effective on upper limb motor function and ADL in stroke patients,and the effect on upper limb mo-tor function is affected by the age and disease course of the patients,as well as the period,time and frequency of intervention.

Chinesization of the HEMO-FISS-QoL questionnaire and its reliability and validity / 中华行为医学与脑科学杂志

Objective:To evaluate the reliability and validity of the Chinese version of HEMO-FISS-QoL(HF-QoL) questionnaire (HF-QoL-C) in the Chinese population with hemorrhoids.Methods:From November 2021 to November 2022, a self-constructed general information questionnaire, HF-QoL-C, and the 36-item short form health survey (SF-36), Goligher classification, and Giordano severity of hemorrhoid symptom questionnaire (GSQ) were used to conduct a questionnaire survey on 760 hemorrhoid patients in the anorectal department of six hospitals. The data was analyzed for reliability and validity using SPSS 21.0 and AMOS 26.0 software.Results:The Cronbach's α coefficient of HF-QoL-C and its dimension ranged from 0.831 to 0.960, and the split coefficient was 0.832-0.915. Four common factors were extracted through principal component exploratory factor analysis. Confirmatory factor analysis indicated acceptable structural validity( χ2/ df=8.152, RSMEA=0.097, CFI=0.881, IFI=0.881, NFI=0.867). HF-QoL-C was correlated with SF36 and GSQ( r=-0.694, 0.501, both P<0.01). There were differences in the total score and dimensional scores of HF-QoL-C between surgical and drug treated patients, different grades of Goligher classification for hemorrhoidal disease, and different ranges of hemorrhoid prolapse (all P<0.001). No ceiling effect was found in the total score and the scores of each dimension(0.3%-2.0%). There was a floor effect in both psychological function and sexual activity dimensions (16.7%, 35.1%). Conclusion:HF-QoL-C has good reliability and validity, which can be used to measure the quality of life of Chinese hemorrhoid patients.

Concentrations and sociodemographic determinants of per- and polyfluoroalkyl substances in women pregnant using assisted reproduction technology in comparison with women pregnant naturally / 环境与职业医学

Background Per- and polyfuoroalkyl substances (PFAS) are categorized as persistent organic pollutants and commonly detected in humans, and their toxicity has attracted widespread attention. However, few studies have reported comparison of PFAS levels and potential factors between women pregnant using assisted reproduction technology (ART) and women pregnant naturally. Objective To analyze and compare serum concentrations and sociodemographic determinants of PFAS in pregnant women conceiving through ART and conceiving naturally from Shanghai. Methods Based on the China National Birth Cohort (CNBC) in Shanghai from 2017 to 2019, 333 pregnant women conceiving through ART and 689 pregnant women conceiving naturally were recruited during the same period as study subjects. The concentrations of 32 PFAS were measured in early-pregnancy serum of all pregnant women, and four PFAS with the highest co-exposure levels in both groups were included in the subsequent analysis. Multiple linear regression models were performed to evaluate the associations of sociodemographic factors with serum PFAS concentrations in the two groups respectively. Beta coefficients and 95% confidence intervals (CI) were exponentiated to calculate the ratio of the geometric mean (GM) of PFAS concentrations after each unit change in the independent variable. Results Perfluorooctanoic acid (PFOA), perfluorooctanesulfonic acid (PFOS), 6∶2 chlorinated polyfluoroethersulfonic acid (6∶2 Cl-PFESA), and perfluorohexanesulfonic acid (PFHxS) were four major PFAS in serum of pregnant women conceiving through ART and conceiving naturally, and the concentrations of PFOA, PFOS, and 6∶2 Cl-PFESA were higher in pregnant women conceiving through ART than in pregnant women conceiving naturally (P <0.05). The results of multiple linear regression analysis showed that age at pregnancy and household income were associated with serum PFAS levels in both groups. The serum concentrations of PFOS were higher in pregnant women aged ≥35 years old who conceiving through ART (GM ratio=1.26, 95%CI: 1.04, 1.54) and conceiving naturally (GM ratio=1.24, 95%CI: 1.08, 1.42) than pregnant women aged <30 years old respectively. Pregnant women conceiving through ART and conceiving naturally whose household annual income >300000 CNY had lower serum concentrations of PFOA [GM ratio (95%CI): 0.82 (0.72, 0.95) and 0.89 (0.81, 0.97), respectively] and PFHxS [GM ratio (95%CI): 0.66 (0.51, 0.86) and 0.77 (0.66, 0.90), respectively] than those women whose household annual income <200000 CNY. Additionally, pregnant women conceiving naturally with a graduate education or above had lower serum 6∶2 Cl-PFESA concentrations than women with an education below college (GM ratio: 0.81), and multiparous pregnant women conceiving naturally had higher serum concentrations of PFOS, 6∶2 Cl-PFESA, and PFHxS than primiparous pregnant women (GM ratio: 1.14, 1.25, and 1.27 respectively). Conclusion Although differences in serum PFAS levels are found between pregnant women conceiving through ART and women conceiving naturally in this study, maternal age and household income are common determinants of PFAS exposure levels in both populations. We find no special sociodemographic factors to affect PFAS concentrations of pregnant women conceiving through ART compared to pregnant women conceiving naturally. Further research is required to explore other potential factors.

Preconceptional exposure levels and determinants of multiple pesticides among women undergoing assisted reproductive technology in Shanghai / 环境与职业医学

Background Pesticide exposure may impact the reproductive health of women undergoing assisted reproductive technology (ART). However, data on pesticide exposure levels in women undergoing ART in China are scarce, and current research on influencing factors is limited. Objective To evaluate the preconceptional pesticide exposure levels and identify potential determinants among women undergoing ART. Methods This study was designed as a cross-sectional survey and recruited 508 women undergoing ART from July 2017 to December 2018 at the fertility clinic of the International Peace Maternity and Child Health Hospital Affiliated to Shanghai Jiao Tong University School of Medicine. Gas chromatography/liquid chromatography-tandem mass spectrometry was used to determine the metabolite concentrations of organophosphate pesticides (OPs), pyrethroid pesticides (PYRs), and neonicotinoid pesticides (NEOs) in urine. The sum of molar concentrations of the three pesticide classes (∑2OPs, ∑2PYRs, and ∑2NEOs) were calculated. A questionnaire was used to collect demographic characteristics, dietary habits, and behavioral information. Multiple linear regression was employed to analyze the associations of demographic characteristics, dietary habits, and behavioral variables with the concentrations of pesticide metabolites in urine among the participants. Results The median creatinine-adjusted concentrations of ∑2OPs, ∑2PYRs, and ∑2NEOs in this study were 419.77, 2.95, and 20.36 nmol·g−1, respectively. The multiple linear regression results showed that the urinary concentration of ∑2OPs was 42.88% higher in the participants with daily vegetable intake than in those who consumed vegetables ≤3 d per week (P<0.05), and the urinary concentration of ∑2PYRs was 37.24% higher in the participants with daily fruit intake than in those who consumed fruits ≤3 d per week (P<0.01). Similarly, the urinary concentrations of ∑2NEOs were 24.51% and 29.30% higher in the participants who consumed fruits daily and 4-6 d per week, respectively, than in those who consumed fruits ≤3 d per week (P<0.05). Besides, we also found that the urinary concentration of ∑2PYRs was negatively correlated with body mass index (BMI) in the participants (P<0.05). Furthermore, the urinary concentration of ∑2NEOs was not only positively correlated with age (P<0.05), but also significantly associated with pet ownership and infertility causes among the participants. Specifically, the participants who continued to own pets after conception had a 30.11% higher urinary concentration of ∑2NEOs than those who never owned pets (P<0.05), and the participants with infertility due to female factors had a 24.10% lower urinary concentration of ∑2NEOs than those who received ART treatment for infertility caused by male factors (P<0.05). Conclusion The women undergoing ART in Shanghai are widely exposed to pesticides. Age, BMI, frequency of vegetable and fruit intake, pet ownership, and infertility causes may be related to the pesticide exposure levels in this population. However, more human data are needed to confirm these findings.

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.

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.

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.

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 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.

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.

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.

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).

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.

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.

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.

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.