1.Impacts of pre-pregnancy exposure to per- and polyfluoroalkyl substances on menstrual characteristics among women undergoing assisted reproductive technology
Huyi TAO ; Yujie CAO ; Yitao PAN ; Jiuru ZHAO ; Zhiwei LIU ; Yu GAO ; Ying TIAN
Journal of Environmental and Occupational Medicine 2025;42(6):652-660
Background Per- and polyfluoroalkyl substances (PFAS) are a class of persistent organic pollutants widely used in various products, leading to population exposure and long-term accumulation. At present, there is a lack of research on the relationships between pre-pregnancy PFAS and menstrual characteristics among women undergoing assisted reproductive technology (ART) in China. Objective To explore the relationships between pre-pregnancy PFAS exposure among women undergoing ART and menstrual characteristics prior to assisted reproductive treatment. Methods This study employed a cross-sectional research design, recruiting women undergoing ART treatment at the Reproductive Clinic of the International Peace Maternity & Child Health Hospital, School of Medicine, Shanghai Jiao Tong University, from 2017 to 2020 as study participants. Ultra-high-performance liquid chromatography-tandem mass spectrometry was used to detect 42 types of PFAS in pre-pregnancy serum samples. Questionnaires were administered to collect information on demographic characteristics, lifestyle habits, and menstrual characteristics (average menstrual cycle length, average menstrual period length, menstrual irregularities, and menstrual bleeding volume) of women undergoing ART. Multiple linear regression, binary logistic regression, and multinomial logistic regression analyses were performed to investigate the relationships between individual PFAS exposure before pregnancy and menstrual characteristics among ART women. Additionally, weighted quantile sum (WQS) model was applied to analyze the association between PFAS mixtures and menstrual characteristics. Results In the pre-pregnancy serum samples of the study population, 15 PFAS were detected in more than 60% of the samples, including perfluoroheptanoic acid (PFHpA), perfluorooctanoic acid (PFOA), perfluorononanoic acid (PFNA), perfluorodecanoic acid (PFDA), perfluoroundecanoic acid (PFUnDA), perfluorododecanoic acid (PFDoDA), perfluorobutanesulfonic acid (PFBS), perfluorohexanesulfonic acid (PFHxS), perfluoroheptanesulfonic acid (PFHpS), perfluorooctanesulfonic acid (PFOS), 6:2 chlorinated polyfluorinated ether sulfonate (6:2 Cl-PFESA), 8:2 chlorinated polyfluorinated ether sulfonate (8:2 Cl-PFESA), perfluoro-2-propoxypropanoic acid (HFPO-DA), perfluoro-2-methoxyacetic acid (PFMOAA), and perfluoro-(3,5,7,9,11-pentaoxadodecanoic) acid (PFO5DoDA). Among them, PFOA had the highest median concentration of 9.160 ng·mL−1. The single PFAS exposure analysis revealed a positive correlation between PFAS and irregular menstrual cycles. Specifically, for every natural-log unit (e) increase in PFOA, PFBS, or PFHxS level, the incidence of irregular menstrual cycles increased by 57%, 42%, or 39%, respectively. Most PFAS were positively correlated with the average number of menstrual cycle days, such as PFHpA (b=1.08, 95%CI: 0.11, 2.05), PFOA (b=1.69, 95%CI: 0.39, 3.00), PFBS (b=1.23, 95%CI: 0.25, 2.22), PFHxS (b=1.47, 95%CI: 0.61, 2.32), PFHpS (b=1.48, 95%CI: 0.35, 2.61), and 6:2 Cl-PFESA (b=0.90, 95%CI: 0.08, 1.72). Furthermore, levels of PFHpA (OR=1.39, 95%CI: 1.06, 1.82), PFOA (OR=1.58, 95%CI: 1.09, 2.30), PFBS (OR=1.37, 95%CI: 1.04, 1.80), PFHxS (OR=1.34, 95%CI: 1.05, 1.71), PFHpS (OR=1.53, 95%CI: 1.10, 2.14), and 6:2 Cl-PFESA (OR=1.34, 95%CI: 1.06, 1.70) were positively correlated with low menstrual blood volume, while PFOA (OR=0.40, 95%CI: 0.23, 0.71), PFHpS (OR=0.45, 95%CI: 0.29, 0.71), and HFPO-DA (OR=0.68, 95%CI: 0.48, 0.97) were negatively correlated with high menstrual blood volume. The mixed exposure model showed that PFAS mixtures were positively correlated with the average number of menstrual cycle days (b=1.60, 95%CI: 0.49, 2.71), irregular menstrual cycles (OR=1.77, 95%CI: 1.19, 2.63), and low menstrual blood volume (OR=1.59, 95%CI: 1.08, 2.35), but negatively correlated with high menstrual blood volume (OR=0.40, 95%CI: 0.22, 0.73). Conclusion Women undergoing ART in Shanghai are widely exposed to PFAS prior to conception. Exposure to PFAS before pregnancy may be related to menstrual characteristics among women seeking ART before undergoing fertility treatments, but additional data from larger populations are required to validate the findings of this study.
2.Data Mining and Experimental Validation of Total Ginsenosides Ameliorating Alcoholic Hepatitis
Shuling CHEN ; Yitao LIU ; Xiao WU ; Duo ZHANG ; Jinhui AI ; Taohua YUAN ; Jianfei SUN
Chinese Journal of Experimental Traditional Medical Formulae 2024;30(21):95-103
ObjectiveTo explore new targets and herbal medicines of total ginsenosides in ameliorating alcoholic hepatitis (AH) by data mining and experimental validation and to provide new directions for the clinical treatment of AH. MethodGSE28619 was selected as the test set from the GEO database and GSE83148 and GSE103580 were selected as the validation sets. The limma package and weighted gene co-expression network analysis (WGCNA) were employed to identify the AH-related differentially expressed genes and modular genes, and Venny was used to extract the common genes. The protein-protein interaction (PPI) network was constructed and the enrichment analysis was carried out. The hub genes were further screened and evaluated for their diagnostic value. After validation with the datasets, new potential targets of AH and traditional Chinese medicine were predicted. Molecular docking between the targets and active ingredients of traditional Chinese medicine was performed, and the results were validated by experiments. Eight out of 48 SD rats were randomly selected into a blank group and received an equal amount of normal saline. The rest rats were subjected to modeling with ethanol by gavage and then randomized into low- (10 mg·kg-1), medium- (20 mg·kg-1), and high-dose (40 mg·kg-1) total ginsenosides, model, and positive control (metadoxine, 117 mg·kg-1) groups. After 3 weeks of gavage, serum samples were collected for the measurement of aspartate aminotransferase (AST) and alanine aminotransferase (ALT) levels, and liver samples were collected for hematoxylin-eosin (HE) staining. Western blot and Real-time PCR were employed to determine the protein and mRNA levels, respectively, of potential targets in the liver tissue. ResultData mining predicted the potential genes: Proto-oncogene FOS and collagen type Ⅰ alpha 2 (COL1A2). Experimental validation showed that the liver injury was alleviated after drug administration compared with that after modeling. The serum AST and ALT levels were reduced after drug administration. The protein and mRNA levels of FOS were significantly up-regulated, while those of COL1A2 were down-regulated after drug administration. ConclusionTotal ginsenosides ameliorate HA via FOS and COL1A2.
3.Effect of Jiuxin Pill (救心丸)on Exercise Tolerance and Quality of Life in Patients of Stable Angina Pectoris:A Randomized,Double-Blind,Placebo-Controlled,Multi-Center Clinical Trial
Xianliang WANG ; Mingjun ZHU ; Daimei NI ; Jianguang WU ; Yitao XUE ; Chenglong WANG ; Xiaohua DAI ; Qian LIN ; Jun LI ; Zhiqiang ZHAO ; Shuai WANG ; Yingfei BI ; Tongzuo LIU ; Zhou ZHOU ; Jingyuan MAO
Journal of Traditional Chinese Medicine 2024;65(24):2549-2557
ObjectiveTo evaluate the effect and safety of Jiuxin Pill (救心丸) on exercise tolerance and quality of life in patients with stable angina pectoris (SAP). MethodsA randomised, double-blind, placebo-controlled, multicentre study design was used to enroll 170 patients of SAP from nine centres, which were divided into 85 patients each in the trial group and control group with 1∶1 ratio. Both groups maintained the original western medicine treatment plan, and added Jiuxin Pill or placebo respectively, 2 pills (0.05 g) each time twicely for 28 days. The main outcomes were total exercise time (TED) in the exercise treadmill test and Seattle Angina Questionnaire (SAQ) scores including physical limitation (PL), angina stability (AS), angina frequency (AF), treatment satisfaction (TS), and disease perception (DP). The secondary outcomes were exercise treadmill test indicators including heart rate recovery in 1 min (HRR1), metabolic equivalents (METs), maximum magnitude of ST-segment depression, and the Borg rating of perceived exertion scale, the average number of angina attacks per week, withdrawal and reduction rate of nitroglycerin, traditional Chinese medicine syndrome scores, incidence of major adverse cardiovascular events. Safety indicators were evaluated and the occurrence of adverse events during the trial was recorded. Data was collected before treatment, day 28±2 in treatment period, and follow-up at day 56 which is 28±2 days after treatment period finished. ResultsEighty-four and eighty-five patients respectively from trial group and control group were included to the full analysis set (FAS) and safety analysis set (SS). Compared with the group before treatment and with the control group after treatment, the trial group had higher TED, HRR1, and METs, and lower maximum magnitude of ST-segment depression and Borg rating of perceived exertion scores after treatment (P<0.01). Compared with the group before treatment and with the control group after treatment and at follow-up, the total SAQ score and scores of AS, AF, TS and DP of the trial group after treatment and at follow-up elevated, while the average number of angina attacks per week and traditional Chinese medicine syndrome scores reduced (P<0.01). There was no statistically significant difference in the withdrawal and reduction rate of nitroglycerin between groups (P>0.05). Major adverse cardiovascular events occurred in 1 case (1/84, 1.19%) in the trial group and 1 case (1/85, 1.18%) in the control group, and the difference between groups was not statistically significant (P>0.05). A total of 3 cases of adverse events occurred in the trial group (3/84, 3.57%), and a total of 6 cases of adverse events occurred in the control group (6/85, 7.06%), and there was no statistically significant difference in the incidence of adverse events between groups (P>0.05). ConclusionIn the treatment of SAP, Jiuxin Pill combined with conventional western medicine can further enhance exercise tolerance, improve quality of life, and demonstrate great safety.
4.Results and discussion on various laboratories proficiency-testing for assays of bismuth potassium citrate capsules by complexometric titration
YANG Yixue ; HUANG Dan ; WANG Yeru ; WU Fengru ; LIU Yitao ; BEI Qihua ; YAN Quanhong ; XIANG Xinhua
Drug Standards of China 2024;25(1):030-034
Objective: To design the proficiency testing (PT) project (No. NIFDC-PT-183) for assays of bismuth potassium citrate capsules and organize to assess the proficiency of complexometric titration in laboratories, and provide some technical analyses and advices.
Methods: Two groups of samples with different concentration were prepared. The uniformity was evaluated with one-way analysis of variance and the stability was confirmed with t-test, whose results all conformed the requirements. The samples with three combinations were randomly distributed to 279 laboratories. The determination was performed according to the assays of bismuth potassium citrate capsules in Volume Ⅱ of the Chinese Pharmacopoeia 2015. The median value and normalized interquartile range (NIQR) of robust statistical analysis was adopted and Z-scores were used to evaluate the results from each of laboratories.
Results: Among 279 laboratories, 240 laboratories results were satisfactory, 23 were questionable, and the other 16 were unsatisfied. The satisfaction rate was 86.0%.
Conclusion: The overall capacity of national laboratories for assays of bismuth potassium citrate capsules is good while a portion of participants require further improvement.
6.Role of androgen receptors in the development of hepatocellular carcinoma
Yitao YANG ; Yu GU ; Ziyan CHEN ; Wenbin LIU ; Guangwen CAO
Shanghai Journal of Preventive Medicine 2023;35(11):1157-1161
Hepatocellular carcinoma (HCC) has emerged as a significant public health concern, posing a serious threat to the lives and health of residents in China. Furthermore, the incidence and mortality rates of HCC are notably higher in males than in females. Androgen receptors (AR) can contribute to the occurrence of male-specific cancers such as prostate cancer, suggesting a potential link to the increased susceptibility of males to HCC. Elucidating the cancer-promoting mechanism of AR and developing specific targeted interventions are effective ways to advance tertiary prevention of HCC and improve patient prognosis. This paper reviews the relevant evidence of AR’s role in promoting the occurrence and development of HCC, summarizes relevant mechanisms discovered to date, including promoting the stemness of HCC cells, altering the immune microenvironment, regulating key signaling pathways, inducing glycolysis in hepatocellular carcinoma, and synergizing with hepatitis B virus to promote HCC. Additionally, research directions for targeted interventions in HCC through AR-related signaling pathways are discussed.
7.Research progress in quality studies and antiviral effect of Qingyan Dropping Pills
Yuli WANG ; Mingrui ZHANG ; Hong ZHOU ; Xuehai ZHOU ; Yubo LI ; Huling LI ; Dandan SHANG ; Jinlei WANG ; He HUANG ; Yitao WANG ; Changxiao LIU
International Journal of Biomedical Engineering 2023;46(3):258-263
Qingyan Dropping Pills have the effects of relieving wind and heat, detoxifying, and promoting the pharynx. It is commonly used in traditional Chinese medicines to treat acute and chronic pharyngitis, as well as sore throats and dry throats caused by surgery. Recently, many studies have shown that Qingyan Dropping Pills have certain effects on bacteriostasis, anti-inflammatory, antioxidant, and antiviral activities. As the coronavirus disease 2019 (COVID-19) pandemic enters the post-epidemic era, the regular use of drugs for COVID-19 pandemic symptoms has become a new trend. Therefore, there is a good market prospect to explore and develop Chinese patent medicines with antiviral effects. A preliminary study on the herbal formula and material basis of Qingyan Dropping Pills revealed that they have potential for antiviral applications. In this paper, the research on the quality study and antiviral effect of Qingyan Dropping Pills was reviewed, and the research direction of its secondary development was discussed to provide ideas and references for the new use of old traditional Chinese medicines.
8.The underlying mechanism of autophagy regulating liver injury with obstructive jaundice in Sprague-Dawley rats
Jianwen YE ; Wenhui CHEN ; Youmei PENG ; Lei QI ; Hongwei TANG ; Wentao LIU ; Yitao WANG
Chinese Journal of Hepatobiliary Surgery 2022;28(2):127-132
Objective:To investigate the effect of autophagy on liver injury with obstructive jaundice in Sprague-Dawley (SD) rats and its underlying mechanism.Methods:Thirty-five healthy male SD rats, SPF grade, aged 6-8 weeks, weighting 200-300 g, were divided into 5 groups with 7 rats in each group, including sham group (simple free common bile duct, without ligation, intraperitoneal injection of normal saline), obstructive jaundice (OJ) group (established by common bile duct ligation, intraperitoneal injection of normal saline), OJ group with 3-MA, OJ group with Rapamycin, and OJ group with 3-MA and VX-765. Morphological changes in liver tissues were analyzed with HE staining. Expression of autophagy-related protein Atg5 was detected by immunohistochemistry staining. Liver function was analyzed by automatic biochemical instrument and the level of serum interleukin (IL)-18 was detected using ELISA assay. Protein levels of autophagy related-proteins and endoplasmic reticulum stressed (ERs)-related apoptosis proteins were detected by Western Blot.Results:The relative expression of autophagy related protein Atg5 in OJ group was significantly higher than that in sham group [(5.0±1.0) vs. (2.8±1.3), t=-3.00, P<0.05]. Compared with sham group, the activity of autophagy was enhanced and the protein levels of Caspase-1/p-65 and IL-18 were significantly increased in OJ group. At the same time, apoptosis was induced by activating ERs. In OJ group, the autophagy inducer 3-MA improved the expression levels of Caspase-1/p-65 and IL-18, and aggravate liver injury. While after applying the autophagy agonist Rapamycin in OJ rat models, the expression of Caspase-1/p-65 and IL-18 was repressed and liver damage was also reduced. In addition, in rat OJ groups with 3-MA, inhibition of Caspase-1 by VX-765 could down regulate the expression of Caspase-1/p-65 and IL-18, and protect against liver injury. Conclusions:Both ERs related apoptosis and autophagy were activated after ligation of common bile duct. Besides, activation of autophagy could reduce OJ-induced liver injury in SD rats by inhibiting the Caspase-1/p-65 inflammatory pathway.
9.Factor analysis of effective platelet-producing ability of fetal liver-derived cells
Mengru YU ; Guanheng YANG ; Guanghui LIU ; Yitao ZENG ; Yan XUE ; Qingwen MA ; Fanyi ZENG
Chinese Journal of Internal Medicine 2022;61(6):664-672
Objective:To study the different factors affecting platelet production post transplantation of hematopoietic stem cells (HSCs) isolated from different sources in order to explore novel options for treating platelet depletion following HSCs transplantation.Methods:HSCs and their downstream derivatives including myeloid and lymphoid cells (i.e., collective of mononuclear cells (MNCs)), were isolated from E14.5 fetal liver (FL) and bone marrow (BM) of 8-week-old mice by Ficoll separation technique. These cells were subsequently transplanted into the tibia bone marrow cavity of recipient mice post lethal myeloablative treatment in order to construct the FL-MNCs and BM-MNCs transplantation mouse model. Routine blood indices were examined in these recipient mice. The chimeric rate of donor cells in recipient peripheral blood cells were determined by flow cytometry. Different groups of cells involved in platelet reconstruction were analyzed. CD41 +megakaryocytes were sorted from fetal liver or bone marrow using magnetic beads, which were then induced to differentiate into platelets in an in vitro assay . Quantitative RT-PCR was used to detect the expression of platelet-related genes in CD41 +megakaryocytes from the two sources. Results:Both the FL-MNCs and the BM-MNCs transplantation groups resumed normal hematopoiesis at the 4th week after transplantation, and the blood cells of the recipient mice were largely replaced by the donor cells. Compared with the mice transplanted with BM-MNCs, the platelet level of mice transplanted with FL-MNCs recovered faster and were maintained at a higher level. At week 4, the PLT level of the FL-MNCs group was (1.45±0.37)×10 12/L, and of the BM-MNCs group was (1.22±0.24)×10 12/L, P<0.05. The FL-MNCs contain a higher proportion of hematopoietic stem cells (Lin -Sca-1 +c-Kit +)(7.60%±1.40%) compared to the BM-MNCs (1.10%±0.46%), P<0.01; the proportion of the megakaryocyte progenitor cells (Lin -Sca-1 -c-Kit +CD41 +CD150 +) and mature megakaryocyte cells (CD41 +CD42b +), also differ significantly between the FL-MNCs (3.05%±0.22%, 1.60%±0.06%, respectively) and the BM-MNCs (0.15%±0.02%, 0.87%±0.11%, respectively) groups, both P<0.01. In vitro functional studies showed that FL-MNCs-CD41 +megakaryocytes could produce proplatelet-like cells more quickly after induction, with proplatelet-like cells formation on day 3 and significant platelet-like particle formation on day 5, in contrast to bone marrow-derived BM-MNCs-CD41 +megakaryocytes that failed to form proplatelet-like cell on day 5. In addition, FL-MNCs-CD41 +cells expressed higher levels of platelet-related genes, Mpl (3.25-fold), Fog1 (3-fold), and Gata1 (1.5-fold) ( P<0.05). Conclusion:Compared with the BM-MNCs group, the FL-MNCs transplantation group appears to have a more efficient platelet implantation effect in the HSCs transplantation recipient in vivo , as well as a higher platelet differentiation rate in vitro. This might be related to a higher proportion of megakaryocytes and higher expression levels of genes such as Mpl, Fog1, and Gata1 that could be important for platelet formation in FL-MNCs-CD41 +cells. Further exploration of the specific functions of these genes and the characteristics of the different proportions of the donor cells will provide valuable clues for the future treatment of platelets reconstitution after HSCs transplantation clinically.
10.Health hazards and hearing loss risk assessment of workers exposed to noise in an automobile manufacturing enterprise
Tao LIU ; Jing LIU ; Cheng HAN ; Yitao LIU ; Qiang ZENG ; Qing GU
Chinese Journal of Industrial Hygiene and Occupational Diseases 2022;40(6):434-438
Objective:To investigate the current situation of occupational exposure to noise among noise workers in an automobile manufacturing enterprise in Tianjin, understand the impact of noise on workers' nervous system and hearing, and assess the risk of hearing loss among noise workers.Methods:In May 2021, 3516 workers in an automobile manufacturing enterprise were investigated by using a self-made questionnaire"Noise Workers Questionnaire" and cluster sampling method. The occupational noise hygiene survey and occupational hazards detection were carried out in their workplaces. They were divided into noise exposure group and non-noise exposure group according to whether they were exposed to noise or not. The general characteristics, hearing and nervous system symptoms of the two groups of workers were compared, and the risk of hearing loss was assessed.Results:There were 758 workers in the noise exposure group, aged (26±5) years old, with a working age of 3.0 (2.0, 6.0) years exposed to noise. 2758 workers in the non-noise exposure group, aged (25±6) years old, with a working age of 2.0 (1.0, 4.0) years. There were statistically significant differences in the distribution of workers'education level, working age and memory loss between the two groups (χ 2=37.98, 38.70, 5.20, P<0.05). The workers in the noise exposure group showed a decreasing trend of insomnia, dreaminess, sweating and fatigue with the increase of working age (χ 2trend=6.16, 7.99, P<0.05). The risk classification of binaural high-frequency hearing loss for workers in all noise positions until the age of 50 and 60 was negligible, the risk of occupational noise deafness was low for workers in stamping and welding noise positions until the age of 60. Conclusion:The occupational noise exposed to automobile manufacturing workers may cause certain harm to their nervous and auditory systems. Noise protection measures should be taken to reduce the risk of hearing loss and occupational noise deafness.

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