Per- and polyfluoroalkyl substances (PFAS) are a class of persistent environmental pollutants that are detected globally not only in the natural environment such as air, water, and soil, but also in animal and humans, posing a potential threat to human health. Epidemiological studies showed that PFAS exposure is closely associated with adverse pregnancy outcomes such as miscarriage, preterm birth, low birth weight and length. Studies showed that women of childbearing age have a higher risk of miscarriage and preterm birth after PFAS exposure before and during pregnancy, but the results of many studies at home and abroad are inconsistent, and it is certain that PFAS exposure is negatively correlated with birth weight and length. The mechanism of action of PFAS exposure inducing adverse pregnancy outcomes may include multiple pathways, involving oxidative stress, changes in endocrine hormone levels, abnormal glucose and lipid metabolism, and gene expression. However, the specific mechanism is still unclear. This article reviewed recent epidemiological studies on the relationships between PFAS exposure and adverse pregnancy outcomes, focusing on the effects of PFAS exposure on pregnancy outcomes, and summarized the potential mechanisms of action. This article aimed to clarify the reproductive toxicity of such chemicals, arouse the concern of women of childbearing age and pregnant women, and provide scientific basis for relevant prevention and intervention measures.

OBJECTIVE To study the effects of Zigui yichong formula on premature ovarian insufficiency （POI） in mice through glycolysis metabolic pathway. METHODS Eighty SPF C57BL/6N female mice were divided into normal group， model group， Zigui yichong formula group （14.175 g/kg）， Zigui yichong formula+2-deoxy-D-arabino-hexose （2-DG） group （Zigui yichong formula 14.175 g/kg + glycolysis inhibitor 2-DG 100 mg/kg）， with 20 mice in each group. Except for the normal group， POI model mice were induced by intraperitoneal administration of cyclophosphamide in the other groups. After the model was successfully established， each group was given corresponding drugs. HE staining was employed to observe the pathomorphological changes in ovarian tissue and to count follicles at all developmental stages； radioimmunoassay was conducted to measure the serum levels of estradiol （E2）， anti-Müllerian hormone （AMH）， and follicle-stimulating hormone （FSH）； TUNEL assay was employed to detect apoptosis in ovarian granulosa cells of mice； the activities of hexokinase （HK）， pyruvate kinase （PK） and lactate dehydrogenase （LDH） were detected by colorimetry； Western blot and real-time fluorescence quantitative PCR were employed to analyze the protein and mRNA expressions of B-cell lymphoma-2 （Bcl-2）， Bcl-2 associated X protein （Bax）， caspase-3， HK2， pyruvate kinase M2 （PKM2）， and lactate dehydrogenase A （LDHA）. RESULTS Compared with model group， the number of primordial follicles， growing follicles， antral follicles and granulosa cells were increased significantly（P＜0.05）， and granulosa cells arranged neatly， but the number of atretic follicles and granulosa cells apoptosis were decreased significantly in Zigui yichong formula group （P＜0.05）； the serum levels of E2 and AMH， the activities of HK， PK and LDH， protein and mRNA expressions of Bcl-2， HK2， PKM2 and LDHA were increased significantly （P＜0.05）； the serum levels of FSH， the protein and mRNA expressions of Bax and caspase-3， Bax/Bcl-2 ratio were decreased significantly （P＜0.05）. 2-DG could reverse the improvement effects of Zigui yichong formula on the above indexes of POI model mice. CONCLUSIONS Zigui yichong formula may inhibit the apoptosis of ovarian granulosa cells， reduce follicle atresia and improve ovarian reserve function by promoting glycolysis levels in POI model mice.

Background::Previous studies have reported associations of specific maternal and paternal lifestyle factors with offspring’s cognitive development during early childhood. This study aimed to investigate the prospective associations between overall parental lifestyle and offspring’s cognitive performance during adolescence and young adulthood in China.Methods::We included 2531 adolescents aged 10-15 years at baseline in 2010 from the China Family Panel Studies. A healthy parental lifestyle score (ranged 0-5) was constructed based on the following five modifiable lifestyle factors: Smoking, drinking, exercise, sleep, and diet. Generalized estimating equation models were used to examine the association between baseline parental healthy lifestyle scores and offspring’s fluid and crystallized intelligence in subsequent years (2012, 2014, 2016, and 2018).Results::Offspring in the top tertile of parental healthy lifestyle scores performed better in overall fluid intelligence (multivariable-adjusted β = 0.53, 95% confidence interval [CI]: 0.29-0.77) and overall crystallized intelligence (multivariable-adjusted β = 0.35, 95% CI: 0.16-0.54) than those in the bottom tertile of parental healthy lifestyle scores. The results were similar after further adjustment for the offspring’s healthy lifestyle scores and persisted across the subgroups of parental socioeconomic status. Additionally, maternal and paternal healthy lifestyle scores were independently associated with better offspring’s cognitive performance, with significant contribution observed for paternal never-smoking, weekly exercise, and diversified diet. When both parents and offspring adhered to a healthier lifestyle, we observed the highest level of the offspring’s overall crystallized intelligence. Conclusions::Our study indicates that parental adherence to a healthier lifestyle is associated with significantly better offspring’s cognitive performance during adolescence and early adulthood, regardless of socioeconomic status. These findings highlight the potential cognitive benefits of promoting healthy lifestyles among parents of adolescents.

Interstitial lung disease is a common lung disease of connective tissue disease,which seriously affects the survival rate and quality of life of patients with connective tissue disease.Interstitial lung disease may occur in the whole course of connective tissue disease.Therefore,imaging plays an important role in the whole disease cycle of connective tissue-associated interstitial lung disease.At present,high-resolution computed tomography is the cornerstone of screening,diagnosis and follow-up of connective tissue-associated interstitial lung disease,but ionizing radiation is a potential limiting factor in its clinical application.In recent years,new imaging techniques have developed rapidly,and some promising research results have been achieved in the early screening,diagnosis and efficacy evaluation of connective tissue-associated interstitial lung disease,and they are gradually moving towards non-invasive,low-radiation and accurate imaging analysis techniques.This article reviews the advances in imaging research of connective tissue-associated interstitial lung disease,and analyzes the advantages and disadvantages of various new imaging techniques,as well as the challenges and prospects.

Objective:To explore the protective effect and underlying mechanism of hyperbaric oxygen (HBO) on delayed encephalopathy after carbon monoxide poisoning (DEACMP) in mice.Methods:Totally 225 adult male Kunming mice were selected to establish CO poisoning model via intraperitoneal injection carbon monoxide (CO), and were randomly divided into the air control group, CO poisoning group, and HBO group. Each group was further divided into five time points group, that was 1, 3, 7, 14 and 21 d. The mice in the air control group were injected intraperitoneally with the same amount of air, and the HBO group received HBO treatment at the same time every day. DEACMP mice model was screened by behaviors using the open field test, new object recognition test and nesting test, and the content of myelin basic protein (MBP) were assayed. The mouse brain tissue and mitochondrial were prepared and malonialdehyde (MDA) and adenosine triphosphate (ATP) content were measured with ultraviolet spectrophotometer. MBP content in brain tissue and cytochrome C (CytC) content in the mitochondrial were measured by ELISA. The mitochondria membrane potential (MMP) was measured by flow cytometry.Results:Compared with the air control group, the content of carboxyhemoglobin (COHB) in blood increased significantly and the content of MBP in brain tissue decreased significantly in CO poisoning mice. CO poisoning mice showed motor ability and cognitive dysfunction. Compared with the air control group, the contents of MMP, CytC and ATP were significantly decreased ( P<0.01) in the CO poisoning group; while the MDA content was significantly increased ( P<0.01). Compared with the CO poisoning group, mice behaviors were improved significantly ( P<0.05), the content of MBP, MMP, CytC and ATP were increased ( P<0.05), while the MDA content decreased significantly ( P<0.01) in the HBO group. Conclusions:The abnormal mitochondrial function might be closely related to the occurrence and development of DEACMP, and HBO therapy plays an effective role in preventing and treating the DEACMP mice model via the mitochondrial pathway.

Objective: To investigate the levels of vitamin D and the correlation between DPN and vitamin D in elderly patients with diabetic peripheral neuropathy(DPN). Methods: A total of 849 patients aged 60 years and over admitted into endocrinology department from June 2016 to September 2017 were enrolled in this retrospective case-control study.According to DPN diagnostic criteria, patients were divided into the non-DPN group(n=542)and the DPN group(n=307). The 25(OH)-vitamin D[25(OH)D]level and blood biochemical parameters were determined and compared between the two groups.The risk factors for DPN were analyzed using logistic regression analysis and plotting receiver operating characteristic(ROC)curves. Results: The mean of serum 25(OH)D level in the 849 patients was 43.9±19.4 nmol/L.Serum 25(OH)D level was lower in the DPN patients than in the non-DPN patients[(40.9±20.4)nmol/L vs.(45.7±18.6)nmol/L, P<0.05]. The incidence of 25(OH)D deficiency was higher in the DPN group than in the non-DPN group(72.3% or 222/307 vs. 64.6% or 350/542, P<0.05). Binary logistic regression analysis indicated that 25(OH)D was a protective factor for DPN(OR=0.980, 95% CI: 0.964~0.995, P<0.05)and the disease duration was a risk factor for DPN(OR=1.048, 95% CI: 1.027~1.070, P<0.001). ROC analysis indicated that the diagnostic cut-off value of serum 25(OH)D for predicting DPN was 37.5nmol/L, with a Youden index of 0.17, sensitivity of 0.65 and specificity of 0.52. Conclusions The 25(OH)D level is much lower in diabetic patients, especially in DPN patients.Higher 25(OH)VD level might be a protective factor for DPN, and vitamin D might be one of potential biomarkers for DPN in diabetic patients.

Objective To observe the clinical effect of treating Alzheimer's disease (AD) using transcranial magnetic stimulation.Methods One hundred and ninety-six patients with Alzheimer's disease were randomly divided into an observation group and a control group,each of 98.The observation group was given transcranial magnetic stimulation of the left and right dorsolateral frontal lobes of the brain and simultaneously given "8-shaped" coil stimulation.The stimulation intensity was 80％ of the motor threshold with a sequence of 2 s of stimulation at 5 Hz and 30 s rest for 30 min in each session.There were two sessions a day for 28 days.The control group was treated with identical pseudo-stimulation.Moreover,both groups were treated with intravenous injections of 20 ml of Ginkgo biloba extract dissolved in 250 ml of sodium chloride,or in the control group a glucose injection,one daily for two weeks.Before and after the treatment,the cognition,behavior and neuropsychological symptoms of both groups were evaluated using the mini mental state examination scale (MMSE),the AD rating scale (ADAS-cog),the activity of daily living (ADL) scale,a neuropsychiatric questionnaire (NPI) and an AD behavioral pathology rating scale (BEHAVE-AD) to compare the clinical effects.Results There were no significant differences in the groups' average scores on any of the evaluations before the treatment.After the treatment,the average MMSE and ADAS-cog scores in both groups had improved significantly,but with significantly greater improvement in the observation group.After the treatment,the average ADL,NPI and BEHAVE-AD scores of the observation group and the average ADL score of the control group were significantly lower than before the treatment.No significant differences were observed in the average NPI and BEHAVE-AD scores of the control group.After the intervention,the average ADL,NPI and BEHAVE-AD scores in the observation group were significantly lower than those of the control group.The total effectiveness rate of the observation group (90.8％) was significantly higher than that of the control group (62.2％).Conclusion Transcranial magnetic stimulation can significantly improve the cognitive,behavioral and neuropsychological status of patients with Alzheimer's disease.

With the rapid development of biotechnology, therapeutic peptide has been a hot area in the central nervous system drugs due to its features of easy to design and target specificity. However, therapeutic peptide is difficult to cross the blood brain barrier into the central nervous system and target cells, coupled with its in vivo instability, which seriously restricts its application in central nervous system diseases. This review focuses on the progress of therapeutic peptides across the blood brain barrier targeting the central nervous system, compares and analyses the methods of increasing therapeutic peptides penetration, specificity and stability in combination with other molecules, in order to provide help for the development of central nervous system drugs.

Objective To study the association between serum TB level and target organ damage in elderly metabolic syndrome (MS) patients.Methods Two hundred and forty-five elderly MS patients admitted to our hospital were included in this study.Their general condition was recorded,their serum TB,blood glucose,blood lipids,blood urea nitrogen and creatinine (Cr) levels were measured,and their left ventricular mass (LVM) and left ventricular mass index (LVMI) were detected by parallel echocardiography.Results Correlation analysis showed that the serum TB level was positively related with that of Cr (r=0.168,P=0.009) but not related with LVM,LVMI,serum blood urea nitrogen level,prevalence of chronic renal insufficiency and chronic kidney disease (P＞0.05).Regression analysis showed that serum TB level was an independent risk factor for urea in MS patients (OR=-0.27,95％CI:-0.48-0.06,P=0.01;OR=1.27,95％CI:0.33-2.22,P=0.01).Quantile analysis of serum TB level showed that the serum Cr level was significantly higher in Q76-100 group,Q51-75 group and Q26-50 group than in Q1-25 group (P=0.031).Conclusion Serum TB level is positively related with endogenous Cr clearance in elderly MS patients,suggesting that mildly elevated serum TB level may be a protective factor for impaired renal function in elderly MS patients.

OBJECTIVE:To study induction effect of euphornin on the apoptosis of cervical cancer Hela cells and its mechanism. METHODS:The cervical cancer Hela cells were divided into blank control group,cisplatin group(positive control, 10 mg/L) and euphornin low-dose,medium-dose and high-dose groups (50,100,200 mg/L). They were treated with relevant medicine. The inhibitory effect of Hela cells proliferation was tested by MTT assay after 24,48,72 h of medicine treatment. The apoptotic rate of Hela cells was measured by flow cytometry after 48 h of medicine treatment. Morphology of nucleus was detected by Hoechst 33258 staining. The protein expression of Cyt-C,Bcl-2,Bax,Caspase-3,Caspase-8,Caspase-9 and Caspase-10 were detected by Western blot assay. RESULTS:Compared with blank control group,inhibitory rate of cell proliferation and cell apoptosis rate were increased significantly in cisplatin group and euphornin groups(P＜0.05 or P＜0.01),and obvious staining, deformation,shrinking,fragmentation or apoptotic bodies was found in nucleus. Compared with blank control group,the protein expression levels of Cyt-C,Caspase-8 and Caspase-9 in euphornin low-dose,medium-dose and high-dose groups were increased significantly,while the protein expression level of Bcl-2 and Bcl-2/Bax ratio were decreased significantly(P＜0.05 or P＜0.01);the protein expression levels of Bax,Caspase-3 and Caspase-10 in euphornin medium-dose and high-dose groups were increased significantly(P＜0.05 or P＜0.01). CONCLUSIONS:Euphornin can significantly inhibit the proliferation of Hela cell and promote cell apoptosis,the effect of which will be achieved by activating the Caspase-dependent mitochondrion apoptosis pathway.