1.Effect modification of amino acid levels in association between polycyclic aromatic hydrocarbon exposure and metabolic syndrome: A nested case-control study among coking workers
Jinyu WU ; Jiajun WEI ; Shugang GUO ; Huixia XIONG ; Yong WANG ; Hongyue KONG ; Liuquan JIANG ; Baolong PAN ; Gaisheng LIU ; Fan YANG ; Jisheng NIE ; Jin YANG
Journal of Environmental and Occupational Medicine 2025;42(3):325-333
Background Exposure to polycyclic aromatic hydrocarbons (PAHs) is associated with the development of metabolic syndrome (MS). However, the role of amino acids in PAH-induced MS remains unclear. Objective To explore the impact of PAHs exposure on the incidence of MS among coking workers, and to determine potential modifying effect of amino acid on this relationship. Methods Unmatched nested case-control design was adopted and the baseline surveys of coking workers were conducted in two plants in Taiyuan in 2017 and 2019, followed by a 4-year follow-up. The cohort comprised 667 coking workers. A total of 362 participants were included in the study, with 84 newly diagnosed cases of MS identified as the case group and 278 as the control group. Urinary levels of 11 PAH metabolites and plasma levels of 17 amino acids were measured by ultrasensitive performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS). Logistic regression was used to estimate the association between individual PAH metabolites and MS. Stratified by the median concentration of amino acids, Bayesian kernel machine regression (BKMR) model was employed to assess the mixed effects of PAHs on MS. Due to the skewed data distribution, all PAH metabolites and amino acids in the analysis were converted by natural logarithm ln (expressed as lnv). Results The median age of the 362 participants was 37 years, and 83.2% were male. Compared to the control group, the case group exhibited higher concentrations of urinary 2-hydroxyphenanthrene (2-OHPhe), 9-hydroxyphenanthrene (9-OHPhe), and hydroxyphenanthrene (OHPhe) (P=0.005, P=0.049, and P=0.004, respectively), as well as elevated levels of plasma branched chain amino acid (BCAA) and aromatic amino acid (AAA) (P<0.05). After being adjusted for confounding factors, for every unit increase in lnv2-OHPhe in urine, the OR (95%CI) of MS was 1.57 (1.11, 2.26), and for every unit increase in lnvOHPhe, the OR (95%CI) of MS was 1.82 (1.16, 2.90). Tyrosine, leucine, and AAA all presented a significant nonlinear correlation with MS. At low levels, tyrosine, leucine, and AAA did not significantly increase the risk of MS, but at high levels, they increased the risk of MS. In the low amino acid concentration group, as well as in the low BCAA and low AAA concentration groups, it was found that compared to the PAH metabolite levels at the 50th percentile (P50), the log-odds of MS when the PAH metabolite levels was at the 75th percentile (P75) were 0.158 (95%CI: 0.150, 0.166), 0.218 (95%CI: 0.209, 0.227), and 0.262 (95% CI: 0.241, 0.282), respectively, However, no correlation between PAHs and MS was found in the high amino acid concentration group. Conclusion Amino acids modify the effect of PAHs exposure on the incidence of MS. In individuals with low plasma amino acid levels, the risk of developing MS increases with higher concentrations of mixed PAH exposure. This effect is partly due to the low concentrations of BCAA and AAA.
2.METTL3 regulates glucose transporter expression in placenta exposed to hyperglycemia through the mTOR signaling pathway
Jie NING ; Jing HUAI ; Shuxian WANG ; Jie YAN ; Rina SU ; Muqiu ZHANG ; Mengtong LIU ; Huixia YANG
Chinese Medical Journal 2024;137(13):1563-1575
Background::Alterations in the placental expression of glucose transporters (GLUTs), the crucial maternal-fetal nutrient transporters, have been found in women with hyperglycemia in pregnancy (HIP). However, there is still uncertainty about the underlying effect of the high-glucose environment on placental GLUTs expression in HIP.Methods::We quantitatively evaluated the activity of mammalian target of rapamycin (mTOR) and expression of GLUTs (GLUT1, GLUT3, and GLUT4) in the placenta of women with normal pregnancies (CTRL, n = 12) and pregnant women complicated with poorly controlled type 2 diabetes mellitus (T2DM, n = 12) by immunohistochemistry. In addition, BeWo cells were treated with different glucose concentrations to verify the regulation of hyperglycemia. Then, changes in the expression of GLUTs following the activation or suppression of the mTOR pathway were also assessed using MHY1485/rapamycin (RAPA) treatment or small interfering RNA (siRNA)-mediated silencing approaches. Moreover, we further explored the alteration and potential upstream regulatory role of methyltransferase-like 3 (METTL3) when exposed to hyperglycemia. Results::mTOR, phosphorylated mTOR (p-mTOR), and GLUT1 protein levels were upregulated in the placenta of women with T2DM compared with those CTRL. In BeWo cells, mTOR activity increased with increasing glucose concentration, and the expression of GLUT1, GLUT3, and GLUT4 as well as GLUT1 cell membrane translocation were upregulated by hyperglycemia to varying degrees. Both the drug-mediated and genetic depletion of mTOR signaling in BeWo cells suppressed GLUTs expression, whereas MHY1485-induced mTOR activation upregulated GLUTs expression. Additionally, high glucose levels upregulated METTL3 expression and nuclear translocation, and decreasing METTL3 levels suppressed GLUTs expression and mTOR activity and vice versa. Furthermore, in METTL3 knockdown BeWo cells, the inhibitory effect on GLUTs expression was eliminated by activating the mTOR signaling pathway using MHY1485. Conclusion::High-glucose environment-induced upregulation of METTL3 in trophoblasts regulates the expression of GLUTs through mTOR signaling, contributing to disordered nutrient transport in women with HIP.
3.Research progress on the relationship between vaginal microbiota and premature cervical remodeling
Xinyi WANG ; Chunyan SHI ; Huixia YANG
Chinese Journal of Perinatal Medicine 2024;27(7):588-594
Preterm birth is the primary cause of neonatal morbidity and mortality in infants under five years of age. Research into its underlying causes and mechanisms is crucial. Preterm birth is a consequence originating from various factors. The etiology can be asynchronous activation of the uterine wall, the choriodecidua, and the cervix, but the phenotype that initiates in the choriodecidua and myometrium also ultimately presents as shortening and softening of the cervix. The initiation of the Human Microbiome Project shed light on more in-depth studies regarding the composition of microbiota in various parts of the human body and its relationship to health. Among these investigations, some progress was achieved on the pregnancy-related vaginal microbiota and dysbiosis, and pathological pregnancies. Based on previous achievements, this article reviews the latest literature discussing the relationship between vaginal microbiota and premature cervical remodeling and the involved mechanisms, seeking to identify unresolved topics in this area, as well as novel preventive and therapeutic strategies.
4.Research on reducing gestational diabetes mellitus incidence in overweight/obese women through interventions
Yihe WANG ; Juan JUAN ; Huixia YANG ; Li MA
Chinese Journal of Perinatal Medicine 2024;27(9):780-784
Overweight/obesity is an important risk factor for gestational diabetes mellitus (GDM). Overweight/obesity and GDM can affect maternal and infants to varying degrees. Reducing the incidence of GDM in overweight/obese people by early intervention is imminent. Current researches on interventions mainly focus on exercise and diet, remote interventions with electronic devices, nutritional supplements, medications, and weight loss surgery. Exercise and diet interventions are the most significant means to reduce the incidence of GDM, and their effectiveness can be affected by the timing, duration, and intervention methods. Maternal compliance is also an essential influencing factor. The efficacy of remote interventions by electronic devices, various nutritional supplements, and drug interventions remains controversial. Weight loss surgery may offer potential benefits but may have some implications on maternal nutritional status and fetal growth and development. Pre-pregnancy weight loss and prevention of excessive weight gain during pregnancy are key initiatives to reduce the incidence of GDM.
5.Pregnancy outcomes of expectant management in women with preterm premature rupture of membranes before 28 weeks
Mengying ZHANG ; Malipati MAERDAN ; Xiao SUN ; Xin ZHANG ; Chunyan SHI ; Huixia YANG
Chinese Journal of Perinatal Medicine 2024;27(10):809-815
Objective:To explore the feasibility of expectant management in pregnant women with preterm premature rupture of membranes (PPROM) before 28 weeks of gestation.Methods:A retrospective analysis was conducted on the clinical data of 92 pregnant women diagnosed with PPROM before 28 weeks and delivered in Peking University First Hospital from January 2015 to March 2023. These women were divided into the termination group or expectant management group, and the latter was further divided based on whether the rupture of membranes occurred before 24 weeks or after. Clinical data of the women and neonates between the two groups and the two subgroups were analyzed. Additionally, all the subjects were divided based on the presence or absence of severe neonatal complications and clinical data of the mothers and their neonates were also analyzed. Statistical analyses were performed using t-tests, Mann-Whitney U tests, Chi-square tests, or Fisher's exact tests. Results:(1) Among the 92 women with PPROM, 53 (57.6%) chose to terminate the pregnancy, while 39 (42.4%) chose expectant management including ten twins and 29 singletons. (2) Compared to the termination group, the expectant management group had a smaller percentage of multiparous women [7.7% (3/39) vs. 32.1% (17/53), Fisher's exact test, P=0.019], greater gestational age at membrane rupture [24 +6 weeks (18-27 +6) weeks vs.21 +3weeks (14 +2-27 weeks), Z=53.14, P=0.042], and a lower incidence of oligohydramnios after membrane rupture [46.2% (18/39) vs. 84.9% (45/53), χ2=6.56, P=0.031]. (3) All of the 39 women in the expectant group gave birth before 37 weeks with the mean gestational age at delivery of 28 +1weeks (25 +1-36 +1 weeks) and 49 live born babies, among which four neonates died giving the survival rate of 91.8%(45/49). There were no statistically significant differences in gestational age at delivery or neonatal outcomes between women with membrane rupture before 24 weeks and those ruptured between 24 and 27 weeks and 6 days of gestation (all P>0.05), but the expectant duration was significantly longer in the former group [55.0 d (20.0-96.0 d) vs. 9.0 d (0.5-52.0 d ), Z=-4.95, P<0.001]. (4) The 49 neonates were further divided into with ( n=9, including the death) or without ( n=40) severe complication subgroups. Those neonates in the non-severe complication subgroup had a significantly greater gestational age at birth compared to those in the other subgroup [30 +6 weeks (27 +5-36 +4 weeks) vs. 27 +5 weeks (25 +1-31 +5 weeks), Z=-3.42, P=0.001], a longer expectant duration [42.0 d (3.0-80.0 d) vs. 19.0 d (0.5-59.0 d), Z=-2.31, P=0.021], a higher birth weight [(1 630±544) g vs. (1 069±272) g, t=4.56, P=0.009], a lower incidence of neonatal asphyxia [2/9 vs. 70.0% (28/40), Fisher's exact test, P=0.012], a shorter hospital stay [37.5 d (3.0-54.0 d) vs. 67.0 d (60.0-105.0 d), Z=-3.01, P=0.003] and a higher proportion of pregnancies completing two courses of fetal lung maturation [5/9 vs. 17.5% (7/40), Fisher's exact test, P=0.029]. (5) Among the ten twin pregnancies, all the 20 babies developed severe complication resulting a higher proportion of twins in the severe complication group than in the non-severe complication group [50% (20/40) vs. 0/9, Fisher's exact test, P=0.005]. Conclusions:For pregnant women with PPROM before 28 weeks, under the premise of informed consent and thorough evaluation, expectant management can be considered if there are no indications for immediate termination of pregnancy, to achieve a higher neonatal survival rate. However, the incidence of severe complications related to preterm infants remains high in the short term, with most having a good prognosis after treatment in the neonatal intensive care unit. Twin pregnancies and lower gestational age at birth are risk factors for severe complications in preterm infants.
6.Factors influencing neonatal hypoglycemia in dichorionic twins
Chinese Journal of Perinatal Medicine 2024;27(10):816-821
Objective:To investigate the factors influencing neonatal hypoglycemia in dichorionic twins.Methods:Clinical data of 304 dichorionic twin pregnancies and their neonates delivered at Peking University First Hospital from January 1, 2022, to December 31, 2023, were retrospectively collected. The cases were divided into a neonatal hypoglycemia group ( n=53) and a control group ( n=251) based on the occurrence of neonatal hypoglycemia. General conditions of the two groups were compared. Additionally, analysis was conducted based on the birth weight difference between the twins, with 18% as the threshold, dividing them into groups with birth weight differences≥18% (56 pregnant women and 112 newborns delivered) and<18% (248 pregnant women and 496 newborns delivered). Data comparisons between groups were performed using t-test, Mann-Whitney U test, Chi-square test, or Fisher's exact test. Paired t-test was used to compare the clinical features between the larger and smaller twins in different birth weight difference groups. Poisson regression analysis was applied to examine the association between maternal clinical characteristics and neonatal hypoglycemia. Results:In the groups with birth weight differences <18% and ≥18%, the incidence of neonatal hypoglycemia in smaller and larger twins were 13.7% (34/248) and 13.3% (33/248), 8.9% (5/56) and 7.1% (4/56), respectively. The umbilical cord blood glucose levels were 3.1 mmol/L (2.7-3.6 mmol/L) and 3.1 mmol/L (2.7-3.6 mmol/L), 3.3 mmol/L (2.8-4.3 mmol/L) and 3.4 mmol/L (3.0-4.3 mmol/L), respectively, with no statistically significant differences (all P>0.05). Poisson regression analysis showed that young gestational age at delivery, hyperglycemia in pregnancy, and fetal lung maturation promotion were risk factors for neonatal hypoglycemia [ RR values (95% CI) were 1.024 (1.002-1.049), 1.707 (1.051- 2.782), and 1.744 (1.011-3.027), respectively, all P<0.05]. Conclusions:Regardless of weight difference, there is no significant difference in umbilical cord blood glucose and the risk of postnatal hypoglycemia between larger and smaller twins. Preterm birth, hyperglycemia in pregnancy and corticosteroid-induced fetal lung maturation are associated with neonatal hypoglycemia in dichorionic twins.
7.A live born boy after in-utero thoracentesis because of a large pulmonary congenital cystic adenomatoid malformation
Jingxue WANG ; Yu SUN ; Huixia YANG ; Lishuang MA ; Ying WANG
Chinese Journal of Perinatal Medicine 2024;27(10):856-859
The course, progression, and prognosis of fetal congenital cystic adenomatoid malformation (CCAM) depend on the size of the mass, whether the mediastinum is displaced, changes in fetal hemodynamics, and the occurrence of fetal hydrops, with large CCAM being relatively rare. In this case, a fetus was suspected of having a large CCAM with fetal hydrops and cardiac insufficiency at 27 weeks of gestation. After multiple imaging evaluations and multidisciplinary consultations, a delivery plan and neonatal resuscitation plan were formulated. At 31 +4 weeks of gestation, in-utero thoracentesis and drainage were performed. Postoperatively, the fetal CCAM was reduced compared to before, and the maternal symptoms of chest tightness and shortness of breath were also improved. Three days after the procedure, the mother experienced premature rupture of membranes and delivered a male infant vaginally at 32 weeks of gestation. On the fifth day after birth, the newborn underwent resection of the pulmonary cystic adenomatoid malformation, confirming the diagnosis. Follow-up for two years post-birth showed good prognosis for both the mother and the child. Therefore, when CCAM is detected during pregnancy, thorough in-utero evaluation should be conducted, and a monitoring plan should be developed based on potential perinatal conditions to avoid unnecessary termination of pregnancy. If the pregnancy continues, multidisciplinary evaluation and preparation for perinatal surgery are necessary.
8.A systematic review of 48 cases of vaginal delivery with rectal buttonhole tears
Sisi XI ; Weijie SUN ; Huixia YANG
Chinese Journal of Perinatal Medicine 2024;27(11):893-898
Objective:To review the literature and summarize the clinical characteristics and treatment methods of rectal buttonhole tears associated with vaginal delivery.Methods:Using the keywords "rectal tear and delivery" "rectal laceration and delivery" "rectal lesion and delivery", and "rectal buttonhole tear", we conducted a search for Chinese-language papers published on the Yiigle, CNKI (China National Knowledge Infrastructure), Wanfang Data Knowledge Service Platform, and VIP Chinese Journal Service Platform. Additionally, using the same keywords in English, we searched for papers published on PubMed and Embase. The search period covers from the establishment of the databases up to November 15, 2023. Cases with a clear diagnosis of rectal buttonhole tears associated with vaginal delivery were included. Data on maternal age, parity, gestational weeks, neonatal birth weight, time of rectal tear discovery, whether episiotomy was performed, whether instrumental delivery was used, details of the rectal tear, management after discovering the tear, and prognosis were analyzed. Descriptive statistical analysis was used.Results:A total of 30 papers were included, published from 1952 to 2023, encompassing 48 cases of vaginal delivery with rectal buttonhole tears. (1) Age and parity: The median age of patients was 28.0 years (range 21-44 years), with primiparas and multiparas accounting for 72.5% (29/40) and 27.5% (11/40), respectively. (2) Gestational weeks: The median gestational age at delivery was 39.0 weeks (range 36.0-41.0 weeks). (3) Neonatal birth weight: The median birth weight of the neonates was 3 595 g (range 2 320-4 250 g), with four cases of macrosomia (birth weight≥4 000 g), accounting for 9.5% (4/42) of singleton births. (4) Time at identification of rectal buttonhole tear: Rectal tears were discovered before fetal delivery in 26.7% (12/45) of cases and after delivery in 73.3% (33/45) of cases. (5) Location: Rectal buttonhole tears most commonly occurred at the midline of the posterior vaginal wall (65.6%, 21/32), followed by the right side of the episiotomy wound (12.5%, 4/32). (6) Relationship between rectal buttonhole tears and delivery mode: Rectal buttonhole tears can occur in spontaneous vaginal delivery, episiotomy, and instrumental vaginal delivery. They may occur during the first or second stage of labor. (7) Timing of rectal tear suturing and prognosis: 93.4% (45/48) of patients underwent primary rectal suturing, among whom, 93.3% (42/45) had good healing, while 6.7% (3/45) developed rectovaginal fistula postoperatively.Conclusions:Rectal buttonhole tear is a rare complication of vaginal delivery and should be recognized. If identified promptly and repaired with primary suturing, the prognosis is generally favorable.
9.Clinical study of 15 cases of primary non-immunodeficient central nervous system lymphoma in children
Huixia GAO ; Ningning ZHANG ; Chunju ZHOU ; Ling JIN ; Jing YANG ; Shuang HUANG ; Meng ZHANG ; Nan LI ; Yonghong ZHANG ; Yanlong DUAN
Chinese Journal of Hematology 2024;45(2):190-194
Clinical data of 15 primary central nervous system lymphoma (PCNSL) children aged ≤18 years admitted to our hospital between May 2013 to May 2023 were retrospectively analyzed. Our goal was to summarize the clinical features of children and investigate the therapeutic effect of a high-dose methotrexate (HD-MTX) based chemotherapy regimen on this disease. The male-to-female ratio was 2.7∶1, and the median age was 7.2 (2.3-16.4) years at diagnosis. The initial clinical symptoms were primarily cranial hypertension, with imaging findings revealing multiple lesions. Pediatric PCNSL with normal immune function has a favorable prognosis with HD-MTX-based chemotherapy. Patients with a stable disease can be treated with minimal or no maintenance. HD-MTX-based chemotherapy remains effective when the disease progresses or recurs after an initial course of non-HD-MTX-based chemotherapy.
10.Research progress of glutathione peroxidase 4/glutathione ferroptosis defense system in the treatment of triple-negative breast cancer
Yuan ZHOU ; Yang LYU ; Xuerui LI ; Xiaoyue YANG ; Jiaqi SONG ; Huixia LU
Journal of Xinxiang Medical College 2024;41(10):991-995
Ferroptosis is a way of cell death with lipid peroxides as the core.Cells can reduce ferroptosis sensitivity by relying on glutathione peroxidase 4(GPX4)/glutathione(GSH)antioxidant systems.Triple-negative breast cancer(TNBC)cells are more dependent on the intracellular antioxidant mechanism than normal cells,thus induction of ferroptosis based on the GPX4/GSH system has shown bright anti-TNBC prospects.This paper reviews the recent research on TNBC treatment with ferroptosis in the background of GPX4/GSH,in order to provide references for the clinical treatment of TNBC.

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