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.

With wide applications of radiation therapy in the treatment of cancer and other diseases and amid the in-creasing concerns about global nuclear safety,the research and development of drugs against radiation damage has become a hot spot.Thanks to its high energy properties,ionizing radiation can not only directly damage cell DNA through targeted effects,but also indirectly affect the cell environment through non-targeted effects,leading to cell dysfunction and even death.In this paper,the mechanism of ionizing radiation damage was analyzed,and the mechanisms of action and clinical applications of four types of anti-radiation drugs,namely,antioxidant,apoptosis inhibitor,cytokine and natural radiation protection agent were discussed.These drugs have huge implications for alleviating the targeted and non-targeted effects caused by ionizing radiation.

Objective:To analyze clinical significance of peripheral blood neutrophil CD64(nCD64)index in patients with anti-neutrophil cytoplasmic antibody(ANCA)-associated vasculitis(AAV).Methods:The clinical data of 98 AAV patients admitted to the First Medical Center of Chinese People's Liberation Army General Hospital from February 1,2023 to February 29,2024 were retrospectively selected,and they were divided into the high-value group(nCD64 index＞1.82,28 patients)and the normal-value group(nCD64 index≤1.82,70 patients)based on the nCD64 index.Ethylenediaminetetraacetic acid(EDTA)-anticoagulated venous blood specimens were collected from patients in both groups,and the mean fluorescence intensity of CD64 expression on the surfaces of polymorphonuclear leukocytes(PMN),lymphocytes(Lym)and monocytes(Mo)was detected by flow cytometry.Clinical manifestations,relevant examination data of hospital,and survival situation of patients with regular follow-up were compared between the two groups.Results:Spearman correlation analysis showed that peripheral blood nCD64 index was positively correlated with Birmingham vasculitis activity score(BVAS)in AAV patients(r=0.216,P＜0.05).There were no statistically significant differences in white blood cells(109/L),blood creatinine(μmol/L),CD8+lymphocytes(amount/μl),CD3-CD16+CD56+lymphocytes(amount/μl),blood sedimentation and interleukin 6 between the two groups.The mean values of BVAS,neutrophils(109/L),CD8+CD28-lymphocytes(％)were respectively(14.96±8.62),(7.51±4.56),(22.16±13.28)in high-value group,which were significantly higher than those[(11.88±7.39),(6.32±3.60)and(17.32±11.27)]in normal-value group,and the mean values of lymphocytes(109/L),platelets(109/L),hemoglobin(g/L),CD3+lymphocytes(amount/Al),CD4+lymphocytes(amount/μl),CD8+CD28+lymphocytes(％)were respectively(1.52±1.01),(216.84±92.32),(106.26±21.99),(1401.15±658.22),(618.43±420.50)and(12.43±5.98)in high-value group,which were significantly lower than those[(1.98±0.95),(248.20±97.21),(114.30±24.71),(1815.43±657.29),(969.15±385.72)and(15.77±7.66)]in normal-value group,and the differences of them between two groups were statistically significant(t=-2.68,-2.04,-2.54,3.25,2.26,2.34,2.02,2.84,3.02,P＜0.05),respectively.Neutrophil/lymphocyte ratio and C-reactive protein of high-value group were higher than those of normal-value group,and eosinophils of high-value group were lower than that of normal-value group,and the differences of them between two groups were statistically significant(Z=-3.370,-2.396,-4.462,P＜0.05),respectively.Conclusions:Peripheral blood nCD64 index is positively correlated with BVAS in AAV patients,which involve in multiple immune cells and inflammatory factors.It has clinically application value in monitoring the disease progression and assessing the prognosis.

Rapid turnover of the intestinal epithelium is a critical strategy to balance the uptake of nutrients and defend against environmental insults, whereas inappropriate death promotes the spread of inflammation. PPARα is highly expressed in the small intestine and regulates the absorption of dietary lipids. However, as a key mediator of inflammation, the impact of intestinal PPARα signaling on cell death pathways is unknown. Here, we show that Pparα deficiency of intestinal epithelium up-regulates necroptosis signals, disrupts the gut vascular barrier, and promotes LPS translocation into the liver. Intestinal Pparα deficiency drives age-related hepatic steatosis and aggravates hepatic fibrosis induced by a high-fat plus high-sucrose diet (HFHS). PPARα levels correlate with TRIM38 and MLKL in the human ileum. Inhibition of PPARα up-regulates necroptosis signals in the intestinal organoids triggered by TNF-α and LPS stimuli via TRIM38/TRIF and CREB3L3/MLKL pathways. Butyric acid ameliorates hepatic steatosis induced by intestinal Pparα deficiency through the inhibition of necroptosis. Our data suggest that intestinal PPARα is essential for the maintenance of microenvironmental homeostasis and the spread of inflammation via the gut-liver axis.

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.

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.

Objective:To comprehensively understand the operational status and existing problems of the neurosurgery professional training bases for standardized residency training in Guangdong Province.Methods:According to the scoring rules of "Standardized Residency Training Evaluation Indicators—Surgery (Neurosurgery) Professional Base" formulated by the Post-Graduation Medical Education Neurosurgery Professional Committee of the Chinese Medical Doctor Association, 28 training bases were supervised and evaluated. The scoring results of the supervision of 28 neurosurgery training bases were collected, and the training bases were divided into two categories according to the traditional teaching history, 6 affiliated hospitals of traditional medical schools and 22 non-traditional affiliated/teaching hospitals. GraphPad 5.0 software was used for statistical analysis of the 14 core indicators, and t-test, variance analysis and Chi-square test were used for analysis. Results:The results showed that there was a statistically significant difference in the compliance rate of 14 core indicators between traditional teaching hospitals and non-traditional teaching hospitals ( P = 0.003), skill operation and type and number of surgeries ( P = 0.041) and student rotation plan ( P = 0.012). The differences were also statistically significant. Conclusion:This study reveals that the comprehensive management ability of training bases in traditional teaching hospitals is significantly better than that in non-traditional teaching hospitals. Additionally, it's suggested to strengthen the construction of professional bases, enhance the institutionalized management of bases, and thus realize the homogenization training of neurosurgery residents.

Objective To study the effect of magnesium/selenium on the expression of matrix metalloproteinases-20(MMP-20) and kallikrein 4(KLK4) during fluorosis in mice and to explore the formation mechanism of dental fluorosis.Methods Eighty SPF male ICR mice were randomly divided into 8 groups according to body weight:control group,magnesium group,selenium group,magnesium-selenium group,fluoride group,magnesium-fluorine group,selenium-fluorine group and magnesium-selenium-fluorine group.Mice in control,magnesium,selenium and magnesium-selenium groups were fed double steamed water,and mice in the other four groups were feddouble steamed water with 50 mg/L F.Mice in control and fluoride groups were fed conventionally.Mice in magnesium and magnesium-fluorine groups were fed conventionally by adding MgSO4·7H2O 162.5 mg/kg.Mice in selenium and selenium-fluorine groups were fed conventionally by adding Na2SeO3·5H2O 2 mg/kg.Mice in magnesium-selenium and magnesium-selenium-fluorine groups were fed conventionally by adding MgSO4· 7 H2O 162.5 mg/kg + Na2SeO3·5H2O 2 mg/kg.Incisor specimens were obtained after the mice were put into death when they were 42 days.The expressions of MMP-20 and KLK4 were observed by using immunohisto-chemicalstain.Results The meangray value of MMP-20 of fluoride group(133.1±10.3) was significantly higher than that of control group(116.8±10.0),magnesium group (113.6 ± 9.6),magnesium-selenium group(108.2 ± 15.2),magnesium-fluorine group(Ill.1 ± 8.1) and magnesium-selenium-fluorine group(108.2 ± 11.0),respectively(F=3.864,P＜0.05).The mean gray value of MMP-20 of magnesium-selenium-fluorine group(108.2 ± 11.0) was significantly lower than that of selenium group(125.4 ± 7.9),fluoride group (133.1 ± 10.3) and selenium-fluorine group(126.2 ± 2.8),respectively(F=3.864,P＜0.05).The mean gray value of KLK4 of magnesium-selenium group(117.2± 11.7) was significantly lower than others(137.3±7.9 of control group,144.2±7.7 of magnesium group,138.9±13.3 of selenium group,149.7± 12.4 of fluoride group,148.9±7.5 of magnesium-fluorine group,140.6± 17.0 of selenium-fluorine group and 140.7 ± 7.3 of magnesium-selenium-fluorine group,F=3.668,P＜0.05).In factorial analysis of fluorosis mice,magnesium had effect on the expression of MMP-20(F=42.613,P＜0.05),selenium had effect on the expression of KLK4(F=6.649,P＜0.05).Conclusions The excessive fluoride could inhibit the expressions of MMP-20.The excessive fluoride hadno significant influence on the expression of KLK4.Magnesium and selenium had antagonistic effect on the dental fluorosis.

Objective To investigate the efficacy and safety of regional citrate anticoagulation (RCA) for continuous veno-venous hemofiltration (CVVH) in patients with severe trauma.Methods Sixty-four patients with severe trauma who needed to apply continuous renal replacement therapy (CRRT) and were admitted into the department of critical care medicine in Tianjin Hospital from June 2013 to August 2015 were enrolled in the study.According to the patient's actual condition,they were divided into two groups:no anticoagulant group (29 cases) and RCA group (35 cases).The filter lifetime,after treatment the activated partial thromboplastin time (APTT),acid-base balance,free calcium ([Ca2+]i) and serum sodium (Na+) concentrations,bleeding episodes were compared between the two groups.Results The average filter lifetime in RCA group was longer than that in no anticoagulant group (hours:50.7 ± 11.3 vs.4.9 ± 1.2,P ＜ 0.01).After the end of treatment,the levels of APTT (s:30.7 ± 8.8 vs.32.1 ± 7.3),pH value (7.41 ± 0.09 vs.7.40 ± 0.07),[Ca2+]i (mmol/L:2.13 ± 0.20 vs.2.21 ± 0.17),and Na+ (mmol/L:139 ± 8 vs.141 ± 6) were ofno significant differences between the RCA group and the no anticoagulant group (all P ＞ 0.05).The incidence of clinicalbleeding in RCA group was lower than that in no anticoagulant group [2.9％ (1/35) vs.13.8％ (4/29)],but the differencewas not statistically significant (P ＞ 0.05).Conclusions RCA-CVVH is a safe and effective therapeutic method inpatients with severe trauma who need for CRRT,the stability of internal environment is not affected and no incidence ofclinical bleeding event is increased.

OBJECTIVETo examine the expression profile and immunofluorescence localization of the major egg antigen p40 of Schistosoma japonicum (Sjp40) during granuloma formation in the liver of infected New Zealand white rabbits.

METHODSNew Zealand white rabbits were infected with S. japonicum cercariae, and the livers were harvested at 29 and 45 days post-infection (dpi). The total RNA of the liver tissues was extracted for expression profiling of Sjp40 by quantitative reverse transcription-PCR (qRT-PCR) with GAPDH of S. japonicum as the endogenous reference gene. The expression of Sjp40 in the liver were detected by Western blotting using anti-Sjp40 monoclonal antibody (mAb) 9G7 or anti-Toxoplasma gondii tSAG1 mAb Y3A8 (control) as the primary antibody. Paraffin sections of the liver were prepared for observing egg granuloma formation using HE staining and for indirect immunofluorescence assay of Sjp40 location in the trapped eggs and egg granulomas.

RESULTSThe level of Sjp40 mRNA in the eggs trapped in rabbit livers was significantly higher at 45 dpi than that at 29 dpi (P<0.05), and Western blotting confirmed the presence of Sjp40 protein in the rabbit livers at both 29 and 45 dpi. Immunofluorescence assay demonstrated localized expression of Sjp40 in the immature eggs in the rabbit liver at 29 dpi, but at 45 dpi fluorescence was detected in clusters of mature eggs containing miracidium and in the surrounding egg granulomas.

CONCLUSIONSThe transcriptional levels of Sjp40 significantly increased with the maturation of eggs trapped in the rabbit livers. Sjp40 protein spread from the eggs to the surrounding egg granuloma at 45 dpi when acute liver granulomatous lesions occur, suggesting that Sjp40 plays a key role in egg granulomas formation in the livers of infected New Zealand white rabbits.

Animals ; Antibodies, Monoclonal ; Antigens, Helminth ; metabolism ; Fluorescent Antibody Technique ; Gene Expression Profiling ; Granuloma ; parasitology ; Helminth Proteins ; metabolism ; Liver ; parasitology ; RNA, Messenger ; Rabbits ; Schistosoma japonicum ; Schistosomiasis japonica