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Objective To analyze the risk factors of recurrent spontaneous abortion(RSA),construct a prediction model based on the risk factors,and evaluate its efficacy in predicting the occurrence of RSA.Methods A total of 324 pregnant women who were registered in the Department of Reproductive Medicine of the Third Affiliated Hospital of Xinxiang Medical University from January 2019 to October 2022 were selected as the research subjects,and they were divided into normal group(n=234)and abortion group(n=90)according to the presence or absence of RSA.Univariate and multivariate logistic regression were used to analyze the risk factors of RSA,a prediction model was constructed based on the selected risk factors,and predictive efficiency of the model was evaluated by drawing the receiver operating characteristic(ROC)curve.Results Univariate analysis showed that there were significant differences in 25-hydroxyvitamin D[25-(OH)D],progesterone(P),homocysteine(Hey),fibrinogen(FIB),D-dimer(D-D),thyroid-stimulating hormone(TSH),thyroglobulin antibody(TGAb),thyroid peroxidase antibody(TPOAb),pulse index(PI),resistance index(RI)and ratio of peak systolic velocity to lowest diastolic velocity(S/D)between the two groups(P＜0.05);there were no significant differences in age,pre-pregnancy body mass index,pre-pregnancy menstrual cycle,gestational sac size,free triiodothyronine(FT3)and free thyroxine(F4)between the two groups(P＞0.05).Multivariate logistic regression analysis showed that low 25-(OH)D and P,as well as high Hey,TPOAb,PI,RI and S/D,were risk factors for RSA in pregnant women(P＜0.05).The ROC curve analysis results showed that the sensitivity,accuracy,positive predictive value and area under the curve of the constructed model in predicting the occurrence of RSA were 92.60％,90.25％,89.26％and 0.914,respectively.Conclusion Decreased 25-(OH)D and P as well as increased Hcy,TPOAb,PI,RI and S/D are risk factors for RSA,and the constructed model based on these risk factors has high efficiency in predicting the occurrence of RSA.
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Objective To investigate the correlation between gene polymorphisms of coagulation factor Ⅻ(FⅫ)rs1801020 and resistin rs1862513 and unexplained recurrent spontaneous abortion(URSA).Methods A total of 189 patients diagnosed with URSA and 191 healthy postpartum women during the same period were selected from the obstetric clinic of Changning Maternity and Infant Health Hospital from January 2020 to December 2022.The probe PCR was used to detect gene polymorphisms of rs1801020 and rs1862513 in peripheral blood,and the differences in genotype distribution between the groups were observed.Results The frequencies of geno-types and alleles for F Ⅻ rs1801020 in the URSA-A group were 4.9％(CC),35.7％(CT),59.5％(TT),22.7％(C),and 77.3％(T),respectively.In the control A group,the frequencies were 8.0％(CC),47.1％(CT),44.9％(TT),31.5％(C)and 68.5％(T).The frequencies of genotypes and alleles for resistin rs1862513 in the URSA-B group were 11.3％(CC),47.3％(CG),41.4％(GG),34.9％(C)and 65.1％(G).In the control B group,the frequencies were 10.2％(CC),34.1％(CG),55.7％(GG),27.3％(C)and 72.7％(G).There was no significant difference in genotype frequency of the two loci(P＞0.05),but there was a sig-nificant difference in allele frequency(P＜0.05).The distribution frequency of F Ⅻ rs1801020 T allele in the URSA group was higher than that in the control group(X2=6.32,OR=1.567,95％CI:1.100-2.238,P=0.012).The distribution frequency of resistin rs1862513 G allele in URSA group was lower than that in con-trol group(X2=4.96,OR=1.433,95％CI:1.050-1.969,P=0.026).The mutation of F Ⅻ rs1801020 C to T was a risk factor for the occurrence of URSA,while the mutation of rs1862513 C to G was a protective factor for the occurrence of URSA(P＜0.05).The combined genotype analysis showed that compared to the popu-lation carrying the rs1801020 CC+rs1862513 CC genotype combination,the population carrying the rs1801020 TT+rs1862513 CG genotype had a significantly higher risk of URSA(OR=5.684,95％CI:1.210-30.920,P=0.035).Conclusion FⅫ rs1801020 T allele may increase the risk of URSA and resistin rs1862513 G al-lele may the risk of URSA.People with rs1801020 TT+rs1862513 CG genotype combination is more likely to develop URSA than those with rs1801020 CC+rs1862513 CC genotype combination.
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Objective To investigate the expression level and clinical significance of hsa_circ_0005075 in serum extracellular vesicles(EVs)of patients with recurrent spontaneous abortion(RSA).Methods Fourteen RSA patients and 14 normal pregnant women from the Department of Obstetrics and Gynecology,Qilu Hospital of Shandong University were enrolled in a training set,and 64 RSA pa-tients and 48 normal pregnant women were enrolled in a validation set.The expression levels of hsa_circ_0005075 in serum EVs were detected by the quantitative real-time PCR(qRT-PCR),and their correlation with clinical pathological parameters of RSA patients were analyzed.Serum anti-thyroid globulin antibody(A-TG)and anti-thyroid peroxidase antibody(A-TPO)were detected by the elec-trochemiluminescence assay.Serum anticardiolipin(ACA)IgA,IgG,and IgM antibodies and anti-β2 glycoprotein 1(β2GP1)IgA,IgG,and IgM antibodies were determined by the chemiluminescence immunoassay.The correlation of these autoantibodies with the lev-els of hsa_circ_0005075 in serum EVs was analyzed by the Pearson correlation.The clinical application value of hsa_circ_0005075 in the diagnosis of RSA was evaluated by the receiver operating characteristic(ROC)curve.Results The detection results of the training set showed that the expression levels of hsa_circ_0005075 in serum EVs of RSA patients(7.69[4.74,42.15])were significantly high-er than that in normal pregnant women(1.02[0.51,4.23],U=28,P＜0.01].Similarly,in the validation set,the expression levels of hsa_circ_0005075 in RSA patients(4.96[1.73,8.89])were also significantly higher than that in normal pregnant women(1.00[0.24,2.96],U=693,P＜0.01).The ROC curve showed that hsa_circ_0005075 in serum EVs had good diagnostic value for RSA(AUCROC=0.774),with 70.3%of sensitivity and75.0%of specificity.In addition,the expression level of hsa_circ_0005075 in serum EVs was significantly correlated with A-TPO(r=0.298,P＜0.05).Conclusion The hsa_circ_0005075 in serum EVs is highly ex-pressed in RSA patients,which may have a potential differential diagnostic value for the diagnosis of RSA.
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An increasing number of studies in recent years have focused on the association between female endometrial microbiota and fertility.Once the endometrial microflora microecology is unbalanced,it will cause a series of endometrial lesions,thereby destroying endometrial receptivity,affecting embryo implantation,resulting in embryo implantation or implantation failure.Among them,the most concerned is the positive significance of lactobacillus-led microbiota on reproductive outcome.Although the relationship between endometrial microbiota and reproductive outcome has not reached a consensus,most studies recognize the positive impact of lactobacillus-led microbiota on reproductive outcome.In this review,the relationship between lactobacillus-dominated microbiota and reproductive outcome is reviewed.
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Objective To observe the effect of Shoutai Pills on endometrial decidualization of mice with recurrent spontaneous abortion(RSA);To explore its possible mechanism in the treatment of RSA based on histone modification.Methods Totally 40 female CBA/J mice were divided into normal group,model group,Shoutai Pills low-dosage group(7.5 g/kg),Shoutai Pills high-dosage group(15 g/kg)and dydrogesterone group(3 mg/kg).The normal group were co housed with BALB/C male mice,while the other groups were co housed with DBA/2 male mice to establish an RSA mouse model.After modeling,the administration groups were given corresponding medication solution by gavage,while the normal group and model group were given equal volume of pure water by gavage for 10 consecutive days.The embryo condition was observed and the embryo loss rate was calculated,ELISA was used to detect serum prolactin(PRL)content,HE staining was used to observe the morphological changes of decidual tissue,RT-PCR was used to detect PRL mRNA expression in decidual tissue,Western blot was used to detect the protein expressions of H4ac,H3K27ac,H3K27me3.Results Compared with the normal group,the model group mice showed a significant increase in embryo loss rate,a significant decrease in serum PRL content,disordered arrangement of decidual cells,and extensive bleeding and necrosis;the expression of PRL mRNA and protein in decidual tissue significantly decreased,the protein expressions of H4ac and H3K27ac significantly decreased,while the expression of H3K27me3 protein significantly increased,with statistical significance(P<0.05).Compared with the model group,the embryo loss rate of Shoutai Pills low-and high-dosage groups and the dexamethasone group significantly decreased,the serum PRL content significantly increased,tightly arranged decidual cells,reduced necrosis,and intact glands;the expression of PRL mRNA and protein in decidual tissue of mice in Shoutai Pills high-dosage group and the dexamethasone group significantly increased,the protein expressions of H4ac and H3K27ac significantly increased,the expression of H3K27me3 protein significantly decreased,with statistical significance(P<0.05).Conclusion Shoutai Pills can promote endometrial decidualization in RSA mice,which is related to the changes of histone modification in endometrial stromal cells.
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Immune factors play an important role in recurrent spontaneous abortion(RSA),and immune imbalance affects embryo implantation,growth,and development.There is currently no consensus on the etiology and pathogenesis of RSA caused by immune factors.Based on the theory of latent toxic in TCM and combined with the pathological mechanism of the dynamic changes of immune abnormal substances in the body,this article proposed that latent toxic is the key cause of RSA caused by immune factors.Furthermore,it expounded the pathogenic characteristics of latent toxic:combination of heat and blood stasis hidden in the womb,and latent toxic plays a role in embryo formation under qi deficiency conditions.It is established that latent toxin stagnation in the membrane is the pathogenic mechanism.Moreover,this article revealed the variable pathological changes such as the blockage of the inner membrane system and the outer membrane system.Treatment should be based on the basic methods of tonifying qi and nourishing blood,tonifying kidney to secure the Thoroughfare Vessel,clearing heat and cooling blood,promoting blood circulation and removing blood stasis.This article could provide a theoretical basis for TCM syndrome differentiation and treatment of RSA caused by immune factors.
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Abstract Background: This study aimed to identify prognostic factors for pregnancy outcomes and construct a prognostic model for pregnancy outcomes in women with Recurrent Spontaneous Abortions (RSA) treated with cyclosporin A. Methods: A total of 154 RSA patients treated with cyclosporin A between October 2016 and October 2018 were retrospectively recruited. Multivariate logistic regression was applied to identify the prognostic factors for pregnancy success in RSA women treated with cyclosporin A. The Receiver Operating Characteristic (ROC) curve was applied to construct prognostic value, and the prognostic performance was assessed using area under the ROC. Results: After adjusting potential confounding factors, the authors noted increased age (OR = 0.771; 95 % CI 0.693‒0.858; p < 0.001) and positive antinuclear antibodies (OR = 0.204; 95 % CI 0.079‒0.526; p = 0.001) were associated with a reduced incidence of pregnancy success, while positive anti-β2 glycoprotein-I-antibody (OR = 21.941; 95 % CI 1.176‒409.281; p = 0.039) was associated with an increased incidence of pregnancy success after treated with cyclosporin A. The AUC of combining these variables for predicting pregnancy failure was 0.809 (95 % CI 0.735‒0.880). Conclusion: This study systematically identified the prognostic factors for pregnancy success in women treated with cyclosporin A, and the constructed prognostic model based on these factors with relatively higher prognostic value. Further large-scale prospective studies should be performed to validate the prognostic value of the constructed model.
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OBJECTIVE@#To investigate the efficacy of Bushen Huoxue Fang (BSHXF, a traditional Chinese medicine formula) for improving recurrent spontaneous abortion (RSA) in mice and the role of tyrosine kinase (JAK2) and transcriptional activator (STAT3) signaling pathway in its therapeutic mechanism.@*METHODS@#Female CBA/J mice were caged with male DBA/2 mice to establish RSA mouse models, which were randomly divided into model group, dydrogesterone group and BSHXF group, with the female mice caged with male BALB/c mice as the control group (n=6). From the first day of pregnancy, the mice were subjected to daily intragastric administration of BSHXF, dydrogesterone, or distilled water (in control and model groups) for 12 days. After the treatments, serum levels of antithrombin III (AT-III), activated protein C (APC), tissue plasminogen activator (t-PA), progesterone, human chorionic gonadotropin (HCG), and estradiol (E2) were detected in each group using ELISA. HE staining was used to observe the morphological changes of the endometrium of the mice. Western blotting was performed to determine the expressions of p-JAK2, p-Stat3 and Bcl-2 in the placenta of the mice.@*RESULTS@#Compared with the control mice, the mouse models of RSA showed a significantly increased embryo loss rate with decreased serum levels of AT-III, T-PA, progesterone, APC and HCG, increased placental expressions of p-JAK2, p-STAT3 and Bax, and decreased expression of Bcl-2 (P < 0.05). Treatments with BSHXF and dydrogesterone both increased serum levels of AT-III, t-PA and HCG in the mouse models; Serum APC level was significantly reduced in BSHXF group and serum progesterone level was significantly increased in dydrogesterone group (P < 0.05).@*CONCLUSION@#BSHXF can improve the prethrombotic state and inhibit cell apoptosis by downregulating the JAK2/STAT3 pathway to increase the pregnancy rate in mouse models of RSA.
الموضوعات
Animals , Mice , Abortion, Habitual/prevention & control , Signal Transduction , Down-Regulation , Disease Models, Animalالملخص
The root of Scutellaria baicalensis Georgi, also called Huangqin, is frequently used in traditional Chinese medicine. In ancient China, S. baicalensis root was used to clear heat, protect the fetus, and avoid a miscarriage for thousands of years. In modern times, pregnancy-related diseases can seriously affect maternal and fetal health, but few systematic studies have explored the mechanisms and potential targets of S. baicalensis root in the treatment of pregnancy-related diseases. Flavonoids (baicalein, wogonin and oroxylin A) and flavonoid glycosides (baicalin and wogonoside) are the main chemical components in the root of S. baicalensis. This study presents the current understanding of the major chemical components in the root of S. baicalensis, focusing on their traditional uses, potential therapeutic effects and ethnopharmacological relevance to pregnancy-related disorders. The mechanisms, potential targets and experimental models of S. baicalensis root for ameliorating pregnancy-related diseases, such as recurrent spontaneous abortion, preeclampsia, preterm birth, fetal growth restriction and gestational diabetes mellitus, are highlighted.
الموضوعات
Infant, Newborn , Humans , Pregnancy , Female , Scutellaria baicalensis , Premature Birth/drug therapy , Flavonoids , Plant Extracts/pharmacology , Medicine, Chinese Traditional , Ethnopharmacology , Chinaالملخص
Objective To investigate the values of nucleoprotein transformation in sperm for predicting recurrent abortion.Methods A total of 521 infertile couples with complete test indicators on fertility were selected from the reproductive medical clinic of our hospital from 2019 to 2022,among which the ages of the male were from 23 to 56 years old.The following factors causing recurrent abortion were excluded,including the age of woman,body mass index,metabolic disease,antiphospholipid syndrome,uterine and accessory abnormalities,history of caesarean section and intrauterine myoma/cervical conectomy,peripheral blood chromosome abnormalities of both the couple,and adverse life history,such as smoking/alcohol abuse.According to the abortion situation,they were divided into the recurrent abortion group(≥two spontaneous abortions),one spontaneous abortion group and no abortion group.Tukey's multiple comparison was performed to compare the differences of nucleoprotein transformation of sperm in each group by using GraphPad6.0 sta-tistical software.The Pearson method was used to analyze the correlation between nucleoprotein transformation and recurrent abortion.The predictive values of nucleoprotein transformation in recurrent abortion were analyzed by the parameters of sensitivity,specificity,positive predictive value,negative predictive value,Youden index and odd ratio.Results The percentages of abnormal nucleoprotein transformation in recurrent abortion group[(33.31±13.83)％]were significantly higher than those in non-abortion group[(26.85± 15.38)％]and the one abortion group[(28.20±12.50)％,P＜0.05].Pearson correlation analysis showed that there was a significant positive correlation between abnormal nucleoprotein transformation and recurrent abortion.The sensitivity and specificity of nucleoprote-in transformation for predicting recurrent abortion were 45.24％and 73.64％,respectively.All of the data of positive predictive value(15.70％),negative predictive value(92.53％),Youden index(18.88％)and odd ratio(2.31)of nucleoprotein transformation in predicting recurrent abortion were higher than those of high DNA stainability(10.64％,90.31％,1.05％and 1.11).Conclusion In the spouses of patients with recurrent abortion,the immaturity of sperm nuclear protein is significantly increased and significantly posi-tively correlated with recurrent abortion.The abnormal nucleoprotein transformation of sperm may be the important factor of recurrent a-bortion in males,and it has high predictive value for recurrent spontaneous abortion in clinical practice.
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Objective Comparing the differences of gut microbiota between healthy women and URSA patients with the syndrome of liver depression and kidney deficiency,and the relationship between gut microbiota and age,abortion times,TCM syndrome score,and DASS-42 in URSA patients.Exploring the relationship between gut microbiota and clinical symptoms.Methods The observation group was 28 unpregnant URSA patients with the syndrome of liver depression and kidney deficiency,and the control group was 43 healthy unpregnant women.General data and stool samples were collected from two groups.Characterizing the composition of the fecal microbiota using bacterial 16S rRNA gene sequencing.The sequencing results were analyzed for diversity and species.TCM syndrome score and DASS-42 were collected from the URSA group,and the relationship between these scores and gut microbiota was analyzed.Results ①Beta diversity analysis shown that the gut microbiota of URSA patients with the syndrome of liver depression and kidney deficiency is different from that of healthy unpregnant women.②At the phylum level,Firmicutes were the most abundant in both groups.Compared with the normal group,the levels of Bacteroidetes and Proteobacteria in the URSA group were higher,and the levels of Actinobacteria were lower.At genus level,the dominant bacteria in URSA group are Faecalibacterium,Bacteroides,Megamonas,Bifidobacterium,Prevotella_9.③In the dominant bacteria of URSA group:Glucerabacter was positively correlated with age,Faecalibacterium was positively correlated with the number of abortions,Catenibacterium was negatively correlated with depression,anxiety,stress,DASS total score,Megasphaera was negatively correlated with depression,TCM syndrome score;In the dominant bacteria of normal group:Erysipelotrichaceae_UCG-003 was positively correlated with stress,the number of abortions,Bifidobacterium was negatively correlated with TCM syndrome score.Conclusion The gut microbiota composition was different between URSA patients with the syndrome of liver depression and kidney deficiency and healthy nonpregnant women,at the phylum and genus levels,the differences in gut microbiota between the two groups were observed,and the differential gut microbiota was associated with URSA patients′TCM syndrome score,suggesting that gut microbiota may be used as an indicator for the diagnosis and treatment of URSA with the syndrome of liver depression and kidney deficiency in the future,which is of clinical significance.
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Objective:To investigate the clinical value of micro-vascular flow(MV-flow)imaging in evaluating the difference of endometrial micro-flow vascularization index(ⅥMV)between recurrent spontaneous abortion and normal reproductive age women.Methods:From June 2022 to June 2023,87 patients with unexplained recurrent spontaneous abortion in West China Second University Hospital,Sichuan University were selected as the abortion group,including 51 patients with 2 miscarriages,26 patients with 3 miscarriages,and 10 patients with≥4 miscar-riages.In addition,90 normal women of childbearing age who did not have a history of miscarriage and visited our hospital during the same period were selected as the healthy group.Endometrial ⅥMV was measured by transvag-inal ultrasound using MV-flow imaging technology in mid-luteal phase of the two groups.The mean values of en-dometrial ⅥMV in 177 women was measured repeatedly within and between observers.The endometrial ⅥMVand clinical data were compared between the two groups.The differences of endometrial ⅥMV and clinical data in pa-tients with different miscarriage times in the abortion group were compared simultaneously.Results:There was no statistically significant difference in age,body mass index,follicle stimulating hormone and luteinizing hormone be-tween the healthy group and the abortion group(P＞0.05).The ⅥMV of endometrium in healthy group was higher than that in abortion group,and the difference was statistically significant(6.10％vs.3.70％,P＜0.05).In the abortion group,endometrial ⅥMV in patients with 2 miscarriages(5.30％)was higher than that in patients with 3(3.25％)miscarriages and≥ 4(3.30％)miscarriages,and the difference was statistically significant(P＜0.05).There was no statistically significant difference in endometrial ⅥMV between patients with 3 miscarriages and ≥4 miscarriages(P＞0.05).The intraobserver and interobserver correlation coefficients of endometrial ⅥMV were 0.978 and 0.945,respectively.Conclusions:MV-flow imaging technology can effectively evaluate the difference of endometrial ⅥMV between recurrent spontaneous abortion and normal childbearing age women,and endometri-al ⅥMV may decrease with the increase of miscarriage frequency.
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Objective:To summarize the nursing care experience of intrauterine infection complicated with septic shock in middle pregnancy for a patient with recurrent spontaneous abortion and postpartum hemorrhage during anti shock treatment.Methods:On June 2020, one patient with recurrent spontaneous abortion was admitted to our hospital with intrauterine infection in the second trimester of pregnancy. Close observation of disease changes, formulate personalized emergency plan, respond quickly when the condition changes, cooperate closely and actively rescue, observation and nursing of postoperative hemorrhage, anti-infective therapy timely, psychological nursing and health education. After active rescue and careful nursing, the patient recovered and discharged 8 days after abortion.Results:After active treatment and careful nursing, the patient recovered well and recovered 8 days after operation.Conclusion:For patients with intrauterine infection, especially patients with recurrent spontaneous abortion, close observation , timely initiation of emergency plans, termination of pregnancy effective anti-infection treatment, and psychological nursing and health guidance are essential to ensure the life safety of patients and promote reproductive health.
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Background Previous studies have confirmed that nicotine exposure is an independent risk factor for miscarriage, but it is not clear whether nicotine causes unexplained recurrent spontaneous abortion (URSA) through oxidative stress. Objective To explore potential mediating effect of oxidative stress on the relationship between nicotine exposure and URSA. Methods Using a 1∶1 matched case-control study, 88 patients with URSA visiting Beijing Obstetrics and Gynecology Hospital affiliated to Capital Medical University from April to October in 2018 were selected as the case group, and 88 pregnant women without adverse pregnancy outcomes and seeking induced abortion in the outpatient clinic of the same hospital were selected as the control group. The levels of 8-hydroxy-2'-deoxyguanosine (8-OHdG) and 8-iso-prostaglandin F2α (8-iso-PGF2α) in urine were determined by enzyme-linked immunosorbent assay, and the level of urinary nicotine was determined by gas chromatography-mass spectrometry. Conditional logistic regression was used to analyze the associations of nicotine, 8-OHdG, and 8-iso-PGF2α with the risk of URSA. Multiple linear regression was used to analyze the association of nicotine with 8-OHdG and 8-iso-PGF2α. The potential mediating effect of oxidative stress on URSA after nicotine exposure was explored by dichotomous mediating model. Results The median concentrations (creatinine corrected) of nicotine, 8-OHdG, and 8-iso-PGF2α in urine of the case group were 7.78, 4.84, and 44.10 μg·g−1, respectively, while those of the control group were 6.48, 3.34, and 29.39 μg·g−1, respectively. The concentrations of nicotine, 8-OHdG, and 8-iso-PGF2α in urine of the case group were all higher than those of the control group (P < 0.05). The results of conditional logistic regression model showed that after adjusting selected confounding factors, compared with the Q1 groups of nicotine and 8-iso-PGF2α, the OR (95%CI) values of URSA in the Q4 groups were 4.20 (1.33-13.29) and 6.25 (1.66-23.59), respectively. Compared with the Q1 group of 8-OHdG, the OR (95%CI) values of URSA in the Q1, Q2, and Q3 groups were 5.47 (1.43-20.93), 4.24 (1.28-14.07), and 6.36 (1.82-22.28), respectively. The results of multiple linear regression showed that after adjusting confounding factors, there was a positive correlation between urinary nicotine and 8-OHdG in both the case group and the control group, and the b (95%CI) values were 0.76 (0.67-0.86) and 0.81 (0.67-0.95) respectively; there was a positive correlation between urinary nicotine and 8-iso-PGF2α in both the case group and the control group, and the b (95%CI) values were 0.65 (0.55-0.75) and 0.76 (0.64-0.87), respectively. The results of dichotomous mediating analysis showed that the mediating effect of 8-iso-PGF2α and its 95%CI on the relationship between nicotine exposure and URSA was 1.518 (0.749-2.311). Conclusion Internal nicotine exposure is a risk factor for URSA and is positively correlated with oxidative stress, and it may lead to URSA through lipid peroxidation damage.
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Objective:To investigate the association between recurrent spontaneous abortion (RSA) and methylenetetrahydrofolate reductase (MTHFR) and plasminogen activator inhibitor-1 (PAI-1) gene polymorphism in pregnant women of appropriate age, and to observe the difference of the serum concentration of patients with different MTHFR genotypes after taking different does of folic acid.Methods:A prospective case-control study was conducted, one handred and eleven pregnant women with a history of unexplained RSA and gestation less than 12 weeks who visited the Department of Obstetrics and Gynecology of Xuancheng People's Hospital of Anhui Province from January 2019 to June 2021 were enrolled into the RSA group, and 100 normal women of childbearing age in the same area with no history of abortion were included in the control group. After venous blood was extracted, the polymorphisms of MTHFR gene C677T, A1298C PAI-1 and the serum folic acid concentration were detected.The comparison between the measurement data groups with normal distribution adopts t-test, and the counting data adopts t-test χ 2 test, Logistic regression analysis was used for multivariate analysis. Results:The genotype and allele of MTHFR C677T (CC:21.62%(24/111) and 51.00%(51/100), TT: 28.83%(32/111) and 12%(12/100)) and allele (C: 46.40%(103/222) and 69.50% (139/200), T: 53.60%(119/222) and 30.50%(61/200)) and PAI-1 (5G5G: 22.52%(25/111) and 48.00%(48/100), 4G4G: 44.14%(49/111)and 16.00%(16/100); 5G: 39.19%(87/222) and 66.00%(132/200), 4G: 60.81%(135/222) and 34.00%(68/200)) were significantly different (χ 2 values were 21.82, 22.96 and 23.51, 30.30; all P <0.001) between the RSA group and control group. Logistic analysis showed that MTHFR C677T ( OR=0.477, 95% CI 0.303-0.750) and PAI-1 genotype ( OR=0.451, 95% CI 0.306-0.665) were closely related to recurrent abortion ( P=0.001 and P<0.001). There were no significant differences in genotype and allele of MTHFR A1298C between the two groups ( P values were 0.270 and 0.149).There was no significant difference in serum concentration of folic acid between the two groups ( P=0.355 for 0.4 mg folic acid and P=0.786 for 0.8 mg or more folic acid) at the same dose of folic acid. Conclusion:The occurrence of recurrent spontaneous abortion in women of childbearing age may be related to MTHFR C677T and PAI-1 site mutation, and may not be related to MTHFR A1298C site mutation.
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ObjectiveTo investigate the regulatory effect of Shoutaiwan on oxidative stress and pyroptosis in lipopolysaccharide （LPS）-induced human extravillous trophoblast （HTR-8/SVneo） cells and provide a new direction for deciphering the mechanism of action of Shoutaiwan. MethodLPS （100 μg∙L-1） was used to induce the injury of HTR-8/SVneo cells （modeling）. Five groups were designed in this study， including a blank group， a model group， a Shoutaiwan （10% Shoutaiwan-containing serum） group， an antioxidant （1 mmol·L-1 NAC） group， and NOD like receptor thermoprotein domain 3 （NLRP3） inhibitor （50 μmol·L-1 MCC950） group. Cell viability was detected by cell counting kit-8 （CCK-8） kit. Hochest 33342/PI double fluorescence staining and flow cytometry were employed to observe cell death. The levels of interleukin-18 （IL-18）， interleukin-1β （IL-1β）， malondialdehyde （MDA）， and superoxide dismutase （SOD） in cell supernatant was determined by enzyme-linked immunosorbent assay （ELISA）. DCFH-DA probe was used to measure the level of intracellular reactive oxygen species （ROS）. Western blot was employed to determine the protein levels of NLRP3， Caspase-1， gastermin D （GSDMD）， and IL-1β in cells， and Real-time fluorescence quantitative polymerase chain reaction（Real-time PCR） to measure the mRNA levels of NLRP3 and Caspase-1 in cells. ResultCompared with the blank group， the modeling decreased the cell viability （P<0.01）， elevated the levels of IL-1β， IL-18， ROS， and MDA， and weakened the activity of SOD （P<0.01）. Furthermore， it up-regulated the protein levels of NLRP3， Caspase-1， GSDMD， and IL-1β and the mRNA levels of NLRP3 and Caspase-1 （P<0.01）. Compared with the model group， Shoutaiwan， NAC， and MCC950 increased the cell viability （P<0.01）. Further， Shoutaiwan and NAC lowered the levels of MDA and ROS and increased the activity of SOD （P<0.01）. Shoutaiwan and MCC950 reduced the IL-1β and IL-18 in cell supernatant （P<0.01）， and down-regulated the protein levels of NLRP3， Caspase-1， GSDMD， and IL-1β and the mRNA levels of NLRP3， Caspase-1， and IL-1β （P<0.05，P<0.01）. ConclusionShoutaiwan can regulate oxidative stress and pyroptosis to attenuate the LPS-induced damage of HTR-8/SVneo cells， which may be the mechanism of Shoutaiwan in preventing recurrent spontaneous abortion.
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Objective To explore the express of formyl peptide receptor 2(FPR2) in villi of recurrent spontaneous abortion ( RSA) , the effect on proliferation, migration and invasion of trophoblast, and the mechanism to clarify the effect of FPR2 on trophoblast function and explore its role and mechanism in recurrent spontaneous abortion. Methods Clinical villus specimens of 30 nonnal and 30 RSA patients were collected. Immunohistochemical staining, Real-time PCR and Western blotting were used to detect the location and expression of FPR2 in villi of patients with RSA and nonnal pregnant women. CRISPR/Cas-9 technique was used to knock down FPR2 in HTR-8/SVneo cells, CCK-8 assay, wound healing and Transwell assays were used to detennine the ability of cell viability, migration and invasion. Immunofluorescent staining and Western blotting were used to analyze the changes of phosphorylated p38 MAPK ( p-p38 MAPK)/p38 MAPK protein expression after applying with p38 MAPK inhibitor SB203580 alone or in combination. Results The expression of FPR2 in villi of patients with RSA increased. FPR2 knock-down improved the biological functions of HTR-8/Svneo cells such as proliferation, migration and invasion significantly. The expression of p-p38 MAPK was up-regulated significantly by FPR2 knock-down, and the ability enhancement of migration and invasion of trophoblasts was reversed partially by SB203580 which inhibits p38 MAPK pathway. FPR2 knock-down caused the change of p38 MAPK signaling pathway related to proteins. Conclusion FPR2 is highly expressed in trophoblasts of RSA patients, and inhibits the migration and invasion of trophoblasts through p38 MAPK signaling pathway, which ma)' play an important role in RSA.
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Objective:To explore the risk factors of borderline subclinical hypothyroidism during first trimester of pregnancy in euthyroid patients with recurrent spontaneous abortion history.Methods:Among the 3 794 outpatients in the Sixth Obstetric Clinic of Shengjing Hospital of China Medical University from July 2017 to July 2019, 302 patients with recurrent spontaneous abortion and euthyroid function before pregnancy were selected after excluding those with abnormality in anatomy, coagulation, genetics, endocrine, infection, and immunology aspects through a systematic etiological screen. Exclusion of 62 patients with pre-pregnancy thyroid stimulating hormone (TSH) above 2.5 mIU/L, 240 recurrent spontaneous abortion patients were finally included. Borderline subclinical hypothyroidism is defined as the level of TSH higher than 2.5 mIU/L but less than the upper limit of pregnancy specific reference range during the first trimester. Among these 240 recurrent spontaneous abortion patients, 84 had borderline subclinical hypothyroidism and 156 were not. After analyzing the history, clinical and laboratory examination results of the two groups of patients, univariate analysis and multivariate logistic regression analysis were applied, to analyze and screen the high-risk factors of borderline subclinical hypothyroidism. Collinear diagnosis of regression analysis and correlation analysis were used to find out the if further relationships among the high-risk factors existed.Results:Univariate analysis suggested that conception method, pre-pregnancy TSH level, anti-nuclear antibody (ANA), lupus anticoagulant (LAC), and anti-β2 glycoprotein 1 (β2GP1) antibody were the potential high-risk factors ( P<0.1). Multivariate logistic regression analysis showed that pre-pregnancy TSH level>1.5 mIU/L ( OR=5.241, 95% CI 2.659-10.330), ANA positive ( OR=3.614, 95% CI 1.866-7.000), anti-β2GP1 antibody positive ( OR=3.415, 95% CI 1.176-9.917), and LAC positive ( OR=2.785, 95% CI 1.024-7.573) were independent risk factors of borderline subclinical hypothyroidism ( P<0.05 or P<0.01). No significant collinearity was found among the factors in the collinearity diagnosis. Except for the thyroid peroxidase antibody and thyroglobulin antibody ( P<0.01), no significant correlation was found among the non-organ-specific antibodies (NOSAs) and antithyroid antibodies. Conclusion:The level of pre-pregnancy TSH and NOSAs before pregnancy are the most important risk factors of borderline subclinical hypothyroidism during first trimester of pregnancy of euthyroid patients with recurrent spontaneous abortion history.
الملخص
Objective:To explore the active components， targets， and signaling pathways responsible for Bushen Zhuyun prescription in treating the recurrent spontaneous abortion （RSA） based on network pharmacology and uncover its potential mechanism by molecular docking and in vitro cell experiments. Method:The active components of Bushen Zhuyun prescription were retrieved from the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform （TCMSP）， Traditional Chinese Medicine Integrated Database （TCMID） and the published articles， followed by the prediction of drug action targets based on such platforms as DrugBank and SwissTargetPrediction. GeneCards and Online Mendelian Inheritance in Man （OMIM） were searched to obtain the RSA targets， which were then intersected with the targets of Bushen Zhuyun Decoction. Following the plotting of Bushen Zhuyun prescription-compound-target-RSA network by Cytoscape 3.7.1， the protein-protein interaction （PPI） network was then constructed with STRING for screening the core network. The resulting common targets were then subjected to Gene Ontology （GO） and Kyoto Encyclopedia of Genes and Genomes （KEGG） enrichment analysis using R software. Autodock Vina 1.1.2 was used for molecular docking. The activation of phosphatidylinositol 3-kinase/protein kinase B （PI3K/AKT） signaling pathway by Bushen Zhuyun prescription was verified in human umbilical vein endothelial cells （HUVEC） <italic>in vitro</italic>. Result:It was found that 49 potential active components of Bushen Zhuyun prescription might act on 133 RSA targets. GO enrichment analysis yielded 470 biological processes， with angiogenesis， vascular development， cellular proliferation， and oxidative activity mainly involved. KEGG enrichment analysis revealed 103 signaling pathways （<italic>P</italic><0.05）， and the PI3K/AKT signaling pathway， advanced glycation end product （AGE）/receptor for advanced glycation end product （RAGE） signaling pathway， and tumor necrosis factor （TNF） signaling pathway were the main ones. As indicated by molecular docking， the Vina scores of the main active component kaempferol with AKT1 and vascular endothelial growth factor A （VEGFA） were the lowest and similar. It was confirmed <italic>in vitro</italic> cell experiments that Bushen Zhuyun prescription activated the PI3K/AKT signaling pathway and up-regulated the expression of VEGFA and downstream AKT protein to promote angiogenesis. Conclusion:Bushen Zhuyun prescription promotes angiogenesis at the maternal-fetal interface by regulating angiogenesis and cellular proliferation， activating the PI3K/AKT pathway， and up-regulated the VEGFA expression， which is beneficial to the formation of placenta in early pregnancy and the maintenance of early pregnancy. This study has provided ideas for new drug development.
الملخص
Background: The objective of this present study was to investigate the possible association of natural killer group (NKG) receptors gene polymorphisms and MHC class I chain-related protein A (MICA) gene polymorphism with recurrent spontaneous abortion (RSA).Methods: Three single-nucleotide polymorphism (SNPs) in NKG2D gene (rs2255336, rs2617160 and rs2617170) and one SNP in MICA gene (MICA129) rs1051792 were assessed in 100 controls and 100 patients employing polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) and agarose gel electrophoresis.Results: NKG2D (rs2617160) and MICA 129 (rs1051792) variants are associated with RSA risk in North Indian women.Conclusions: The NKG2D and MICA129 gene polymorphisms may influence the success of pregnancy in North Indian women population.