Association between interpregnancy interval and adverse perinatal outcomes among subsequent twin pregnancies: a nationwide population-based study.

BACKGROUND: The existing evidence on the association between interpregnancy interval (IPI) and pregnancy outcomes primarily focuses on singleton pregnancies, with limited research on twin pregnancies. OBJECTIVE: This study aimed to investigate the association between IPI and adverse perinatal outcomes in twin pregnancies. STUDY DESIGN: This population-based, retrospective cohort study analyzed data from the National Center for Health Statistics (NCHS) in the United States between 2016 and 2020. We included multiparous women aged 18 to 45 years with live-born twins without congenital anomalies, born between 26 and 42 weeks of gestation. Poisson regression models, adjusted for potential confounders, were used to evaluate the associations between IPI and adverse outcomes, including preterm birth (PTB) < 36 weeks, small for gestational age (SGA), neonatal intensive care unit (NICU) admission, neonatal composite morbidity and infant death. Missing data on covariates were managed using multiple imputation. Dose-response analyses were performed using the restricted cubic spines (RCS) approach. Subgroup analyses were stratified by maternal age, parity and combination of neonatal sex. Sensitivity analyses were conducted using complete data and excluding pregnancies with intervening events during the IPI. RESULTS: A total of 143,014 twin pregnancies were included in the analysis. Compared to the referent group (IPI of 18-23 months), an IPI of less than 6 months was associated with an increased risk of PTB < 36 weeks (RR, 1.21; 95% CI: 1.17-1.25), SGA (RR, 1.11; 95% CI: 1.03-1.18), neonatal composite morbidity (RR, 1.19; 95% CI: 1.12-1.27), NICU admission (RR, 1.18; 95% CI: 1.14-1.22), and infant death (RR, 1.29; 95% CI: 1.05-1.60). An IPI of 5 years or more was associated with an increased risk of PTB < 36 weeks (RR, 1.18; 95% CI: 1.15-1.21), SGA (RR, 1.24; 95% CI: 1.18-1.30), neonatal composite morbidity (RR, 1.10; 95% CI: 1.05-1.15), and NICU admission (RR, 1.14; 95% CI: 1.11-1.17). The dose-response analyses showed that these outcomes had U-shaped or J-shaped associations with IPI. The associations between IPI and the outcomes slightly differed by advanced maternal age, parity and combination of neonatal sex. The sensitivity analyses yielded similar results to the main findings. CONCLUSIONS: Extreme IPI, less than 6 months or more than 5 years, was associated with adverse outcomes in twin pregnancies. IPI could be used as a predictor for risk stratification in high-risk twin pregnancies.

Optimal gestational weight change associated with improved perinatal outcomes in women with gestational diabetes mellitus: a population-based study in the United States.

BACKGROUND: Optimal gestational weight change (GWC) is little known among pregnant women with gestational diabetes mellitus (GDM). OBJECTIVES: This study aimed to explore the optimal GWC ranges for women with GDM and validate these ranges compared with the Institute of Medicine (IOM) guidelines. METHODS: A population-based cohort study using natality data from the National Center for Health Statistics in the United States included 1,338,460 mother-infant pairs with GDM from 2014 to 2020. Poisson regression models were performed to identify GWC ranges (GDM targets) associated with acceptable risks (<10% increase) for a severity-weighted composite outcome including preterm birth (PTB) <37 wk, large for gestational age (LGA, birthweight >90th percentile) and small for gestational age (SGA, birthweight <10th percentile). These targets were validated in individual outcomes including PTB, LGA, SGA, hypertensive disorders of pregnancy, neonatal intensive care unit admission, and neonatal respiratory morbidity, and compared with the IOM guidelines using logistic regression models with population-attributable fractions (PAFs) calculated. RESULTS: The severity-weighted composite outcome had a U-shaped or a J-shaped relationship with GWC across body mass index categories. The GDM targets were 14.1 to 20.3 kg, 9.0 to 17.0 kg, 4.8 to 13.8 kg, -0.8 to 10.8 kg, -2.4 to 8.2 kg, and -8.3 to 6.0 kg for underweight, normal weight, overweight, class 1 obesity, class 2 obesity, and class 3 obesity, respectively. GWC outside the GDM or the IOM targets was associated with increased adverse perinatal outcomes in validation analyses. PAFs indicated that the IOM guidelines reduced a similar or higher proportion of adverse perinatal outcomes compared with the GDM targets for women with GDM, except for those with class 2 and 3 obesity. CONCLUSIONS: The IOM guidelines are generally applicable for women with GDM, except for women with moderate and severe obesity. The optimal GWC ranges for women with GDM and moderate to severe obesity may be lower than the IOM guidelines.

Association of Optimal Gestational Weight Gain Ranges With Perinatal Outcomes Across Body Mass Index Categories in Twin Pregnancies.

Importance: The existing gestational weight gain (GWG) recommendations for twin pregnancies are lacking for underweight individuals and are not stratified by obesity class. Objective: To identify optimal GWG ranges associated with reduced adverse perinatal outcomes stratified by prepregnancy body mass index (BMI) categories in twin pregnancies. Design, Setting and Participants: This population-based cohort study of twin pregnancies using data from the National Center for Health Statistics was conducted between January 1, 2014, and December 31, 2018. Statistical analysis was performed from October 24, 2021, to May 7, 2022. The study population comprised 262 604 individuals between 18 and 45 years of age with live-born twins without congenital malformation between 24 and 42 weeks of gestation. Two approaches were used to determine the optimal GWG ranges: a statistics-based approach calculating IQRs of GWG in a low-risk population, and an outcome-based approach identifying GWG thresholds below or above which an adverse perinatal outcome increased. Exposure: Gestational weight gain. Main Outcomes and Measures: Preterm birth less than 36 weeks, gestational hypertensive disorders, small for gestational age status, large for gestational age status, and a composite outcome defined as any occurrence of the individual outcomes. Results: The main sample comprised 200 810 individuals with twin pregnancies (mean [SD] maternal age, 30.4 [5.5] years; 1624 [0.8%] American Indian or Alaska Native, 13 031 [6.5%] Asian or Pacific Islander, 36 423 [18.1%] Black, and 149 732 [74.6%] White; and 137 409 [68.4%] multiparous). In the low-risk subgroup (n = 61 794), the IQRs of the total GWG after 36 weeks of gestation as assessed using a statistics-based approach and based on BMI group were 15.9 to 22.7 kg for underweight, 15.4 to 22.7 kg for normal weight, 12.7 to 22.2 kg for overweight, 10.0 to 20.0 kg for class 1 obesity, 7.7 to 18.1 kg for class 2 obesity, and 5.9 to 16.3 kg for class 3 obesity. The absolute risk of the composite outcome showed U-shaped associations with GWG across BMI categories. The optimal GWG ranges by 36 weeks identified using an outcome-based approach and BMI group were 17.5 to 24.9 kg for underweight, 15.0 to 24.9 kg for normal weight, 15.0 to 24.9 kg for overweight, 10.0 to 19.9 kg for class 1 obesity, 7.5 to 17.4 kg for class 2 obesity, and 5.0 to 9.9 kg for class 3 obesity. The multivariable logistic models assessed using the validation sample (n = 49 275) showed that GWG defined outside those optimal ranges was associated with preterm birth at less than 36 weeks, gestational hypertensive disorders, and small or large for gestational age. Conclusions and Relevance: This population-based cohort study found that optimal GWG ranges were similar for individuals with underweight and normal weight but decreased with increasing severity of obesity. The current US Institute of Medicine GWG recommendations may be too high for individuals with moderate or severe obesity.

Analysis of multiple databases identifies crucial genes correlated with prognosis of hepatocellular carcinoma.

Despite advancements made in the therapeutic strategies on hepatocellular carcinoma (HCC), the survival rate of HCC patient is not satisfactory enough. Therefore, there is an urgent need for the valuable prognostic biomarkers in HCC therapy. In this study, we aimed to screen hub genes correlated with prognosis of HCC via multiple databases. 117 HCC-related genes were obtained from the intersection of the four databases. We subsequently identify 10 hub genes (JUN, IL10, CD34, MTOR, PTGS2, PTPRC, SELE, CSF1, APOB, MUC1) from PPI network by Cytoscape software analysis. Significant differential expression of hub genes between HCC tissues and adjacent tissues were observed in UALCAN, HCCDB and HPA databases. These hub genes were significantly associated with immune cell infiltrations and immune checkpoints. The hub genes were correlated with clinical parameters and survival probability of HCC patients. 147 potential targeted therapeutic drugs for HCC were identified through the DGIdb database. These hub genes could be used as novel prognostic biomarkers for HCC therapy.

The Roles of Ubiquitination Factor E4B (UBE4B) in the Postoperative Prognosis of Patients with Renal Cell Carcinoma and in Renal Tumor Cells Growth and Metastasis.

OBJECT: This study aimed at investigating the clinical significance and biological function of ubiquitination factor E4B (UBE4B) in human renal cell carcinoma (RCC). METHODS: 19 paired clear cell renal cell carcinoma (ccRCC) tumor samples and the matched neighboring non-tumor samples were used to detect the expression of UBE4B in RCC tumor by Western blotting and RT-qPCR. UBE4B expression was also detected in 151 ccRCC paraffin-embedded tumor samples by using immunohistochemistry. Overall survival (OS) in different UBE4B expression groups were compared with Log rank test. The prognostic value of UBE4B expression in OS was evaluated with the univariate and multivariate Cox regression models. UBE4B was knocked down by small interfering RNA (siRNA) technology, and the effect of UBE4B on cell proliferation, colony formation, metastasis, apoptosis and cell cycle of RCC cells were examined in vitro. RESULTS: Both protein and mRNA levels of UBE4B were up-regulated in ccRCC tumor tissues in contrast to the corresponding adjacent nontumor ones. UBE4B expression was positively associated with tumor-node-metastasis (TNM) stage and distant metastasis in ccRCC patients. Survival analyses indicated that low expression of UBE4B was associated with increased OS in ccRCC patients. Functional analyses demonstrated that siRNA silencing of UBE4B expression in SKRC39 and ACHN cells further reduced the growth, motility and invasiveness of RCC cells. Moreover, siRNA silencing of UBE4B in the RCC cell lines did not induce apoptosis, and an increase in the cell population was observed during the G0/G1 phase of the cell cycle. CONCLUSION: UBE4B might act as an oncogene in regulating RCC development. Therefore it could be served as an effective indicator to predict OS and a potential biomarker for targeted therapy of RCC patients.

Overexpression of SMOC2 Attenuates the Tumorigenicity of Hepatocellular Carcinoma Cells and Is Associated With a Positive Postoperative Prognosis in Human Hepatocellular Carcinoma.

Secreted modular calcium binding protein-2 (SMOC2), a recently identified matricellular protein that belongs to the SPARC protein family, has been reported to be downregulated in various cancers. The purpose of this study was to investigate the clinical significance and biological function of SMOC2 in human hepatocellular carcinoma. Real-time quantitative PCR and western blotting analyses revealed that SMOC2 mRNA and protein levels were significantly downregulated in human HCC tissues compared to the matched adjacent normal tissues. Clinicopathological analysis indicated that SMOC2 expression was significantly associated with tumor size, number of tumors, tumor-node-metastasis (TNM) stage and distant metastasis. Kaplan-Meier survival analysis showed that high tumor SMOC2 expression was associated with improved overall survival and disease-free survival in patients with HCC. Functional analyses (cell proliferation and colony formation assays, cell migration and invasion assays, cell cycle and apoptosis assays) demonstrated that stable overexpression of SMOC2 using a lentiviral vector significantly inhibited cell proliferation, colony formation, migration and invasion, and induced G0/G1 phase arrest in HCC cells in vitro. In addition, experiments with a mouse model revealed the suppressed effect of SMOC2 on HCC tumorigenicity and metastases in vivo. These results suggest that SMOC2 functions as a tumor suppressor during the development of HCC and may represent an effective prognostic factor and novel therapeutic target for HCC.

Tripartite motif-containing 3 (TRIM3) inhibits tumor growth and metastasis of liver cancer.

BACKGROUND: Reduced expression of tripartite motif-containing 3 (TRIM3) has been reported to be involved in the pathogenesis of human glioblastoma. In our previous research, we found that TRIM3 expression was markedly reduced in human primary hepatocellular carcinoma (HCC) tissues and that low TRIM3 expression was associated with short survival of HCC patients. However, the role of TRIM3 in liver cancer remains unknown. This study aimed to investigate the function of TRIM3 in liver cancer cells. METHODS: The protein levels of TRIM3 in five liver cancer cell lines (SK-Hep1, Hep3B, Huh7, HepG2, Bel-7402) and one normal liver cell line (L02) were detected with Western blotting. HepG2 and Bel-7402 cells with low TRIM3 expression were infected with recombinant lentiviruses overexpressing TRIM3 (LV-TRIM3), whereas Huh7 and Hep3B cells with high TRIM3 expression were transfected with TRIM3-targeted small interfering RNA (siTRIM3). The functions of TRIM3 in the proliferation, colony formation, cell cycle, migration, invasion, and apoptosis of the above cell lines were examined. The effect of TRIM3 on tumor growth and metastases in nude mice was also investigated. RESULTS: TRIM3 was overexpressed in HepG2 and Bel-7402 cells with LV-TRIM3 infection, which further reduced proliferation, colony formation, migration, and invasion of both cell lines. Cell cycle analysis showed that TRIM3 overexpression induced G0/G1 phase arrest in HepG2 and Bel-7402 cells. Moreover, apoptosis was not increased in HepG2 or Bel-7402 cells overexpressing TRIM3. Contrarily, silencing TRIM3 expression in Huh7 and Hep3B cells by siTRIM3 led to significantly decreased percentages of both cells in the G0/G1 phase and promoted cell proliferation, colony formation, migration, and invasion. In vivo experiment results confirmed that TRIM3 overexpression suppressed tumor growth and metastasis. CONCLUSIONS: TRIM3 plays a tumor-suppressing role in the regulation of liver cancer development by reducing cell proliferation through cell cycle arrest at the G0/G1 phase.

Decreased TPD52 expression is associated with poor prognosis in primary hepatocellular carcinoma.

Tumor protein D52 (TPD52) has been indicated to be involved in tumorigenesis of various malignancies. But its role in hepatocellular carcinoma (HCC) is unknown. This study aimed to explore the expression of TPD52 in HCC samples and cell lines using real-time quantitative PCR, western blotting, and immunohistochemistry. The prognostic value of TPD52 in HCC was also analysed. Meanwhile, the mechanism of TPD52 in hepatocarcinogenesis was further investigated by western blotting, immunohistochemistry, over-express and knockdown studies. We found that TPD52 expression was significantly decreased in the HCC tissues and HCC cell lines. TPD52 expression was significantly correlated with tumor-nodes-metastasis (TNM) stage. Kaplan-Meier survival curves showed that high TPD52 expression was associated with improved overall survival (OS) and disease-free survival (DFS) in HCC patients. Multivariate analysis indicated that TPD52 expression was an independent prognostic marker for the OS and DFS of patients. In addition, TPD52 expression was positively correlated with p21 and p53 expression, and was negatively correlated with MDM2, BCL2 and P-GSK-3ß expression in HCC. In conclusions, our findings suggested that TPD52 is a potential tumor suppressor in HCC. It may be a novel prognostic biomarker and molecular therapy target for HCC.