Objective:To investigate the influencing factors and perinatal outcomes associated with monozygotic twins (MZT) following elective single embryo transfer (eSET) via in vitro fertilization or intracytoplasmic sperm injection and embryo transfer (IVF/ICSI-ET). Methods:A retrospective cohort study was conducted on 12 079 patients who achieved pregnancy after undergoing IVF/ICSI-eSET at Reproductive Health Hospital of the Third Affiliated Hospital of Zhengzhou University between January 2015 and September 2023. Patients were stratified into two groups based on ultrasound findings 30 d post-transfer: singleton pregnancy group and MZT pregnancy group. Finally, 300 MZT and 1 500 single pregnancies, which were randomly matched according to 1∶5 were included by study period. General patients' characteristics, embryo-related factors, and perinatal outcomes were compared between the two groups. A multivariate logistic regression model was employed to identify risk factors for MZT after single embryo transfer, adjusting for potential confounding variables.Results:The incidence of twin pregnancy following single embryo transfer was 2.48% (300/12 079), which was higher than that of naturally conceived monozygotic twin pregnancy. No significant difference was found in baseline characteristics between the two groups (all P>0.05). The blastocyst transfer rate was higher in the MZT pregnancy group [93.3% (280/300)] than in the singleton pregnancy group [88.8% (1 332/1 500), P=0.022]. Multivariate logistic regression analysis also showed that blastocyst transfer was associated with an increased risk of MZT ( OR=0.552, P=0.016, 95% CI: 0.341-0.894). Analysis of blastocyst cycles showed that the risk of MZT was higher when transferring high-quality blastocysts [79.6% (223/280) vs. 67.8% (903/1 332), P<0.001], where as a trophectoderm (TE) grading of C [20.4% (57/280) vs. 32.2% (429/1 332), P<0.001] had a lower risk of MZT. After adjusting for confounding factors, the risk of MZT was found to increase with the transfer of blastocysts with a B-grade inner cell mass (ICM) ( OR=0.601, P=0.001, 95% CI: 0.442-0.819) and A/B grade TE (grade A: OR=2.951, P<0.001, 95% CI: 1.980-4.399; grade B: OR=1.840, P<0.001, 95% CI: 1.315-2.576). The risk of complications during pregnancy [47.7% (143/300) vs. 19.3% (289/1 500), P<0.001], preterm labor [55.1% (140/254) vs. 7.4% (101/1 368), P<0.001], and the risk of stillbirth [3.7% (11/300) vs. 1.5% (22/1 500), P=0.016] were significantly higher in the MZT pregnancy group than in the singleton pregnancy group. Conclusion:Assisted reproductive technology may contribute to the risk of MZT. Transfer of blastocysts, particularly those with loose ICM arrangement and dense TE arrangement, appears to increase the risk of MZT in patients undergoing eSET.

Objective:To explore the effects of Levothyroxine Sodium (L-T4) treatment on coagulation function and adverse pregnancy outcomes in patients with hypothyroidism during pregnancy in early and mid-to-late pregnancy.Methods:A total of 120 patients with hypothyroidism during pregnancy who were treated by L-T4 in Linyi Central Hospital from Mar. 2021 to Mar. 2024 were included, and their clinical data were retrospectively analyzed. According to the gestational age of the patients at the time of treatment, 64 cases with a gestational age of <12 weeks were included in the early pregnancy group, and 56 cases with a gestational age of ≥12 weeks were included in the mid-to-late pregnancy group. The serum thyroid hormone indexes, coagulation function indexes, adverse pregnancy outcomes, and neuropsychological development of the offspring were compared between the two groups. Statistical analyses were conducted using independent/paired t-tests and chi-square tests.Results:After treatment, there were no significant differences in the thyroid hormone indexes and coagulation function indexes between the early pregnancy group and the middle and late pregnancy group ( P>0.05). The incidence of fetal growth restriction and gestational hypertension in the early pregnancy group was 10.94% (7/64) and 17.19% (11/64), and that in the middle and late pregnancy group was 26.79% (15/56) and 33.93% (19/56), respectively. The incidence in the early pregnancy group was significantly lower than that in the middle and late pregnancy group ( χ2=5.010, 4.464, P<0.05). The developmental quotient (DQ) of the offspring in the early pregnancy group at 6 months of age in various areas of neuropsychological development (social behavior, language, adaptability, fine motor skills and gross motor skills) was significantly higher than that in the middle and late pregnancy group. The DQ of the first trimester group was (97.82±7.25) points, (94.59±6.85) points, (95.87±8.02) points, (96.08±7.25) points, and (98.34±8.07) points. The DQ of the second trimester group was (92.54±7.06) points, (90.45±6.14) points, (91.01±7.51) points, (91.24±7.08) points, and (92.74±7.38) points. The DQ of the first trimester group was significantly higher than that of the second trimester group ( t=4.029, 3.466, 3.411, 3.688, 3.946, P<0.05) . Conclusion:L-T4 treatment in early or mid- to late-pregnancy patients with gestational hypothyroidism can effectively improve their thyroid hormone levels and coagulation function, but treatment in early pregnancy is beneficial to reduce the incidence of adverse pregnancy outcomes such as fetal growth restriction and alleviate the impact of the disease on the neuropsychological development of offspring.

Objective:To investigate the influencing factors and perinatal outcomes associated with monozygotic twins (MZT) following elective single embryo transfer (eSET) via in vitro fertilization or intracytoplasmic sperm injection and embryo transfer (IVF/ICSI-ET). Methods:A retrospective cohort study was conducted on 12 079 patients who achieved pregnancy after undergoing IVF/ICSI-eSET at Reproductive Health Hospital of the Third Affiliated Hospital of Zhengzhou University between January 2015 and September 2023. Patients were stratified into two groups based on ultrasound findings 30 d post-transfer: singleton pregnancy group and MZT pregnancy group. Finally, 300 MZT and 1 500 single pregnancies, which were randomly matched according to 1∶5 were included by study period. General patients' characteristics, embryo-related factors, and perinatal outcomes were compared between the two groups. A multivariate logistic regression model was employed to identify risk factors for MZT after single embryo transfer, adjusting for potential confounding variables.Results:The incidence of twin pregnancy following single embryo transfer was 2.48% (300/12 079), which was higher than that of naturally conceived monozygotic twin pregnancy. No significant difference was found in baseline characteristics between the two groups (all P>0.05). The blastocyst transfer rate was higher in the MZT pregnancy group [93.3% (280/300)] than in the singleton pregnancy group [88.8% (1 332/1 500), P=0.022]. Multivariate logistic regression analysis also showed that blastocyst transfer was associated with an increased risk of MZT ( OR=0.552, P=0.016, 95% CI: 0.341-0.894). Analysis of blastocyst cycles showed that the risk of MZT was higher when transferring high-quality blastocysts [79.6% (223/280) vs. 67.8% (903/1 332), P<0.001], where as a trophectoderm (TE) grading of C [20.4% (57/280) vs. 32.2% (429/1 332), P<0.001] had a lower risk of MZT. After adjusting for confounding factors, the risk of MZT was found to increase with the transfer of blastocysts with a B-grade inner cell mass (ICM) ( OR=0.601, P=0.001, 95% CI: 0.442-0.819) and A/B grade TE (grade A: OR=2.951, P<0.001, 95% CI: 1.980-4.399; grade B: OR=1.840, P<0.001, 95% CI: 1.315-2.576). The risk of complications during pregnancy [47.7% (143/300) vs. 19.3% (289/1 500), P<0.001], preterm labor [55.1% (140/254) vs. 7.4% (101/1 368), P<0.001], and the risk of stillbirth [3.7% (11/300) vs. 1.5% (22/1 500), P=0.016] were significantly higher in the MZT pregnancy group than in the singleton pregnancy group. Conclusion:Assisted reproductive technology may contribute to the risk of MZT. Transfer of blastocysts, particularly those with loose ICM arrangement and dense TE arrangement, appears to increase the risk of MZT in patients undergoing eSET.

Objective:To explore the effects of Levothyroxine Sodium (L-T4) treatment on coagulation function and adverse pregnancy outcomes in patients with hypothyroidism during pregnancy in early and mid-to-late pregnancy.Methods:A total of 120 patients with hypothyroidism during pregnancy who were treated by L-T4 in Linyi Central Hospital from Mar. 2021 to Mar. 2024 were included, and their clinical data were retrospectively analyzed. According to the gestational age of the patients at the time of treatment, 64 cases with a gestational age of <12 weeks were included in the early pregnancy group, and 56 cases with a gestational age of ≥12 weeks were included in the mid-to-late pregnancy group. The serum thyroid hormone indexes, coagulation function indexes, adverse pregnancy outcomes, and neuropsychological development of the offspring were compared between the two groups. Statistical analyses were conducted using independent/paired t-tests and chi-square tests.Results:After treatment, there were no significant differences in the thyroid hormone indexes and coagulation function indexes between the early pregnancy group and the middle and late pregnancy group ( P>0.05). The incidence of fetal growth restriction and gestational hypertension in the early pregnancy group was 10.94% (7/64) and 17.19% (11/64), and that in the middle and late pregnancy group was 26.79% (15/56) and 33.93% (19/56), respectively. The incidence in the early pregnancy group was significantly lower than that in the middle and late pregnancy group ( χ2=5.010, 4.464, P<0.05). The developmental quotient (DQ) of the offspring in the early pregnancy group at 6 months of age in various areas of neuropsychological development (social behavior, language, adaptability, fine motor skills and gross motor skills) was significantly higher than that in the middle and late pregnancy group. The DQ of the first trimester group was (97.82±7.25) points, (94.59±6.85) points, (95.87±8.02) points, (96.08±7.25) points, and (98.34±8.07) points. The DQ of the second trimester group was (92.54±7.06) points, (90.45±6.14) points, (91.01±7.51) points, (91.24±7.08) points, and (92.74±7.38) points. The DQ of the first trimester group was significantly higher than that of the second trimester group ( t=4.029, 3.466, 3.411, 3.688, 3.946, P<0.05) . Conclusion:L-T4 treatment in early or mid- to late-pregnancy patients with gestational hypothyroidism can effectively improve their thyroid hormone levels and coagulation function, but treatment in early pregnancy is beneficial to reduce the incidence of adverse pregnancy outcomes such as fetal growth restriction and alleviate the impact of the disease on the neuropsychological development of offspring.

Objective:To discuss the effects of different doses of ganoderic acid A(GAA)on the biological activities,glycolysis,and the expression of rate-limiting enzymes of non-small cell lung cancer(NSCLC)PC9 cells,and to clarify the mechanism.Methods:The NSCLC PC9 cells were cultured in vitro and divided into blank control group,low dose(25 μmol·L-1)of GAA group,medium dose(50 μmol·L-1)of GAA group,and high dose(100 μmol·L-1)of GAA group.The methylthiazolydiphenyltetrazolium(MTT)assay was used to detect the survival rates of the PC9 cells in various groups;Transwell chamber assay was used to detect the number of migration cells of the PC9 cells in various groups;the glucose uptakes of the PC9 cells in various groups were detected by glucose assay kit;the levels of ATP in the PC9 cells in various groups were detected by ATP assay kit;the levels of lactic acid in the PC9 cells in various groups were detected by lactate assay kit;the expression levels of hexokinase 2(HK2)and pyruvate kinase M2(PKM2)mRNA in the PC9 cells in various groups were detected by real-time fluorescence quantitative PCR(RT-qPCR)method;the expression levels of HK2 and PKM2 proteins in the PC9 cells in various groups were detected by Western blotting method.Results:The MTT assay results showed that,at 24,48,and 72 h of culture,compared with blank control group,the survival rates of the cells in medium and high doses of GAA groups were significantly decreased(P<0.05).At 72 h of culture,compared with low dose of GAA group,the survival rate of the cells in high dose of GAA group was significantly decreased(P<0.05).The Transwell chamber assay results showed that compared with blank control group,the numbers of migration cells in medium and high doses of GAA groups were significantly decreased(P<0.05);compared with low doses of GAA group,the number of migration cells in high dose of GAA group was significantly decreased(P<0.05).Compared with blank control group,the glucose uptakes and levels of lactic acid in the cells in medium and high dose of GAA groups were significantly decreased(P<0.05),and the level of ATP in the cells in high dose of GAA group was significantly decreased(P<0.05).The RT-qPCR results showed that compared with blank control group,the expression levels of HK2 and PKM2 mRNA in the cells in medium and high doses of GAA groups were significantly decreased(P<0.05).The Western blotting results showed that compared with blank control group,the expression levels of HK2 and PKM2 proteins in the cells in medium and high doses of GAA groups were significantly decreased(P<0.05).Conclusion:Medium and high doses of GAA can inhibit the biological activities of proliferation and migration of the PC9 cells,reduce the glycolysis,and its mechanism may be related to the inhibition of the expressions of the key rate-limiting enzymes HK2 and PKM2.

OBJECTIVE To investigate the efficacy and safety of clobazam in the additional treatment of refractory epilepsy in children， and provide reference for clinically safe and rational drug use. METHODS The literatures about additional clobazam treatment for refractory epilepsy in children were searched from PubMed， The Cochrane Library， Embase， CNKI， VIP and Wanfang database during the inception to November 2023. After literature screening and data extraction， the quality of included literature was evaluated according to quality evaluation tool for methodological evaluation indicators of non-randomized controlled trial， and then meta-analysis of single-group rate and sensitivity analysis were performed by using RevMan 5.3 software. RESULTS Finally， 18 one-arm studies were included， with a total of 1 424 children. The results showed that compared with before additional treatment， the proportion of patients with seizures-free （proportion of patients with seizure reduction of 100%） was 24%[95%CI （0.18，0.32）， P＜0.000 01] after conversion； the proportion of patients with seizure reduction ≥75% was 32%[95%CI（0.25，0.40）， P＜0.000 1] after conversion； the proportion of patients with seizure reduction ≥50% was 53%[95%CI（0.44，0.61），P＜0.000 01]； the proportion of patients with seizure reduction ＜50% or no change was 35%[95%CI（0.24，0.49），P＝0.04] after conversion； the proportion of patients with seizure increase was 9%[95%CI（0.05，0.18），P＜0.000 01] after conversion. The proportion of patients with adverse reactions was 31%[95%CI（0.23，0.40），P＜0.000 1] after conversion； the proportion of patients with discontinuation due to adverse reactions was 10%[95%CI（0.07， 0.15）， P＜0.000 01] after conversion. The common adverse drug reactions were drowsiness， fatigue and behavior change， etc. The results of the sensitivity analysis showed that the study was robust. CONCLUSIONS Clobazam is an effective additional therapy for refractory epilepsy in children， but its adverse effects should be vigilant.

Objective:To analyze the predictive value of combined insulin autoantibody (IAA), islet cell antibody (ICA), and serum glutamic acid decarboxylase antibody (GADA) testing for pregnancy outcome in patients with gestational diabetes mellitus (GDM) .Methods:One hundred and twenty patients with GDM were retrospectively selected for the study, and were divided into a poor pregnancy outcome group and a normal pregnancy outcome group based on the pregnancy outcome at follow-up to delivery, which were 37 and 83 cases, respectively. The occurrence of adverse pregnancy outcomes in the study population was counted, and univariate and multivariate analyses of adverse pregnancy outcomes in GDM were performed.Results:Adverse pregnancy outcomes were seen in 37 of the 120 study subjects, including 12, 13 and 9 cases of macrosomia, caesarean section and neonatal hypoglycaemia, respectively, and 1 case of premature rupture of the foetal hairs, placenta previa and neonatal asphyxia. The percentage of IAA, ICA, and GADA positivity was higher in the adverse pregnancy outcome group than in the normal pregnancy outcome group ( P<0.05). Multifactorial regression analysis showed that IAA ( OR=3.180, 95% CI 1.394-7.258), ICA ( OR=3.459, 95% CI 1.592-7.517), and GADA ( OR=3.219, 95% CI 1.508-6.872) positivity were independent risk factors for adverse pregnancy outcomes in GDM ( P<0.05). The AUC values for the combined IAA, ICA, and GADA for the detection of adverse pregnancy outcomes in GDM were higher than those for IAA, ICA, and GADA alone ( Z=2.607, 2.600, and 2.527, P<0.05) . Conclusion:Positive IAA, ICA, and GADA are risk factors for adverse pregnancy outcomes in patients with GDM, and combined testing has a higher predictive value.

Objective:To analyze the predictive value of combined insulin autoantibody (IAA), islet cell antibody (ICA), and serum glutamic acid decarboxylase antibody (GADA) testing for pregnancy outcome in patients with gestational diabetes mellitus (GDM) .Methods:One hundred and twenty patients with GDM were retrospectively selected for the study, and were divided into a poor pregnancy outcome group and a normal pregnancy outcome group based on the pregnancy outcome at follow-up to delivery, which were 37 and 83 cases, respectively. The occurrence of adverse pregnancy outcomes in the study population was counted, and univariate and multivariate analyses of adverse pregnancy outcomes in GDM were performed.Results:Adverse pregnancy outcomes were seen in 37 of the 120 study subjects, including 12, 13 and 9 cases of macrosomia, caesarean section and neonatal hypoglycaemia, respectively, and 1 case of premature rupture of the foetal hairs, placenta previa and neonatal asphyxia. The percentage of IAA, ICA, and GADA positivity was higher in the adverse pregnancy outcome group than in the normal pregnancy outcome group ( P<0.05). Multifactorial regression analysis showed that IAA ( OR=3.180, 95% CI 1.394-7.258), ICA ( OR=3.459, 95% CI 1.592-7.517), and GADA ( OR=3.219, 95% CI 1.508-6.872) positivity were independent risk factors for adverse pregnancy outcomes in GDM ( P<0.05). The AUC values for the combined IAA, ICA, and GADA for the detection of adverse pregnancy outcomes in GDM were higher than those for IAA, ICA, and GADA alone ( Z=2.607, 2.600, and 2.527, P<0.05) . Conclusion:Positive IAA, ICA, and GADA are risk factors for adverse pregnancy outcomes in patients with GDM, and combined testing has a higher predictive value.

Objective:To explore the expression of serum inflammatory factors in patients with thyroid tumor and their correlation with thyroid hormones.Methods:A total of 92 patients with thyroid tumors (48 cases of thyroid cancer and 44 cases of thyroid adenoma) admitted to Department of Endocrinology in Linyi Central Hospital in Shandong Province from Jan. 2020 to Oct. 2021 were enrolled. 50 healthy volunteers who received physical examination in the hospital during the same period were enrolled in the control group. The serum inflammatory factors [tumor necrosis factor-α (TNF-α) , interleukin-6 (IL-6) , interleukin-17 (IL-17) ] and thyroid hormone expression levels [thyroid stimulating hormone (TSH) , free thyroxin T4 (FT4) , free triiodothyronine (FT3) ] of the three groups were detected. Analysis of variance was used for multi-group comparison, independent sample t test was performed for comparison between groups, Spearman correlation analysis and Logistic regression analysis were made for the risk factors of thyroid cancer. The expression of serum inflammation and thyroid hormones in patients with different stages of thyroid cancer was observed. Results:Serum TNF-α, IL-17, IL-6 from high to low were in the thyroid cancer group (74.61±7.94 ng/L, 68.65±7.05 ng/L, 20.52±2.84 ng/L) , thyroid adenoma group (26.97±3.42 ng/L, 46.31±5.31 ng/L, 13.61±1.58 ng/L) , control group (18.82±2.63 ng/L, 34.52±4.02 ng/L, 8.97±1.06 ng/L) ( F=1596.271, 468.602, 423.351, all P<0.001) ; Serum TSH levels from high to low were in the thyroid cancer group (8.64±1.34 mU/L) , the thyroid adenoma group (5.21±1.02 mU/L) , the control group (3.94±0.85 mU/L) ( F=242.182, P=0.000) . There was no significant difference in serum FT4 or FT3 levels among the three groups ( P=0.753, 0.634) . Correlation analysis indicated that serum TNF-α, IL-17, and IL-6 were positively correlated with the expression level of serum TSH ( r=0.936, 0.726, 759, all P<0.05) . The expression level of TNF- α, IL-17, IL-6 and TSH was significantly higher in patients of stage III and IV than that in patients of stage I and II ( t=2.541, 4.394, 6.390, 4.962, P=0.015, P<0.001, P<0.001, P<0.001) . Multivariate Logistic regression analysis suggested serum TNF-α, IL-17, IL-6 and TSH were all risk factors for thyroid cancer. Conclusions:Serum inflammatory factors and some thyroid hormones (TSH) are generally highly expressed in patients with thyroid tumors, the expression levels of serum inflammatory factors are correlated with the expression of TSH. There are statistically significant differences in the expression levels of serum inflammatory factors and TSH between patients with thyroid cancer of different stages, serum inflammatory factors and TSH are also involved in the occurrence and development of thyroid cancer, and are risk factors for thyroid cancer.

With the rapid development and adaptation of high-throughput sequencing in clinical settings, application of exome sequencing (ES) has been gradually expanded from pediatric to prenatal diagnosis in recent years. There is an urgent need to establish criteria for clinical grade ES in order to facilitate such a complex testing. The standardization of pre- and post-test consultation, quality control for sample processing process and validation of bioinformatics data analysis, and more importantly data interpretation and reporting, as well as appropriate reporting scope, is of great importance for health care stakeholders. To achieve this, a committee composed of a wide range of healthcare professionals has proposed an ES standard for prenatal diagnosis. This has provided expert opinion on the genetic counseling and reporting standards of prenatal ES for the purpose of applying ES technology in prenatal setting.