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1.
Mol Ther ; 2022 Jan 04.
Artigo em Inglês | MEDLINE | ID: mdl-34995801

RESUMO

N6-methyladenosine (m6A) is the most prevalent RNA modification and the effect of its dysregulation on esophageal squamous cell carcinoma (ESCC) development remains unclear. Here, by performing transcriptome-wide m6A sequencing in 16 ESCC tissue samples, we identified the key roles of m6A in TNFRSF1A (also known as TNFR1)-mediated MAPK and NF-κB activation in ESCC. Mechanistically, a functional protein involved in m6A methylation, ATXN2, is identified that augments the translation of TNFRSF1A by binding to m6A-modified TNFRSF1A mRNA. Upregulation of TNFRSF1A protein level, a vital upstream switch for TNFRSF1A-mediated signaling events, activates the NF-κB and MAPK pathways and thus promotes ESCC development. Furthermore, TNFRSF1A m6A modifications and protein levels are upregulated in ESCC, and high levels of TNFRSF1A m6A and protein are correlated with poor ESCC patient survival. These results collectively indicate that the m6A- TNFRSF1A axis is critical for ESCC development and thus might serve as a potential druggable target.

2.
Front Endocrinol (Lausanne) ; 12: 763693, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34867806

RESUMO

Objective: Previously, we found that the presence of maternal serum metals before the 24th week of gestation prospectively increased fasting plasma glucose (FPG) at 24-28 weeks. We further explored the prospective association between levels of metals and neonatal outcomes and assessed the mediating effects of FPG on these relationships. Methods: A total of 7,644 pregnant women were included in a retrospective cohort study, and the relationships between metals [manganese (Mn), copper (Cu), lead (Pb), zinc (Zn), and magnesium (Mg)] and birth outcomes were explored. Quantile and linear regressions were performed to detect the shifts and associations between metals and neonatal size distribution focused on the 10th, 50th, and 90th percentiles. Mediation analysis was performed to assess the mediating effect of FPG on metals and birth outcomes. Results: After adjustment, a 50% increase in Mn and Zn levels was related to a 0.136-cm (95% CI: 0.067-0.205) and 0.120-cm (95% CI: 0.046-0.193) increase in head circumference, respectively. Based on head circumference distribution, the magnitude of the association with Mn was smaller at the upper tail, while the magnitude of correlation with Zn was greater at the upper tail. A 50% increase in Mn and Zn levels was related to a 0.135-cm (95% CI: 0.058-0.212) and 0.095-cm (95% CI: 0.013-0.178) increase in chest circumference, respectively. The magnitude of the association with Mn increased with increasing chest circumference, while the magnitude of correlation with Zn decreased with increasing chest circumference. FPG explained 10.00% and 17.65% of the associations of Mn with head and chest circumference. A positive indirect effect of Zn associated with head circumference (0.004, 95% CI: 0.002-0.006) and chest circumference (0.005, 95% CI: 0.003-0.008) through FPG was also observed, and the estimated proportion of the mediating effect was 13.79% and 26.32%, respectively. Conclusion: Maternal serum Mn and Zn levels before the 24th week of gestation may prospectively increase the circumference of the neonatal head and chest. FPG at 24-28 weeks had positive mediating effects on these relationships. Further research is needed to identify a balance between maternal blood glucose and birth size.

3.
Am J Transl Res ; 13(11): 13017-13023, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34956519

RESUMO

OBJECTIVE: To compare the effectiveness of a new double-uterine-incision, based on Ar's incision, with single-uterine-incision during cesarean section in pregnancy concurrently complicated by placenta previa and placenta accreta spectrum. METHODS: A retrospective cohort study including 260 participants was conducted between January 2014 and June 2019. The participants only underwent Ar's incision in the single-uterine-incision group and participants underwent two uterine incisions in the new double-uterine-incision group. The demographic and clinical characteristics were compared between the two groups. RESULTS: Fifty-six participants (21.5%) underwent a double-incision, and the other 204 underwent a single-incision. The incidence of previous cesarean delivery (91.1% vs. 68.6%) and anterior placenta (76.8% vs. 53.4%) was higher in the double-incision group. The blood loss (3400 ml vs. 1600 ml) and the need for blood transfusion (100.0% vs. 82.8%) were higher in the double-incision group. There was no significant difference between the two groups (one (1.8%) in the double-incision group and 10 (4.9%) in the single-incision group) in need for subtotal hysterectomy. After adjusting for confounding factors, there was no significant difference between the two groups concerning blood loss, blood transfusion, maternal ICU, or length of hospital stay; and the incidence of subtotal hysterectomy was lower in the double-incision group. CONCLUSION: This new double-uterine-incision, based on Ar's incision, is an effective and valuable procedure for pregnant women with placenta previa complicated by placenta accreta spectrum, especially in women with a serious condition. It is an option for pregnant women concurrently complicated by placenta previa and placenta accreta spectrum who desire future fertility.

4.
Genome Med ; 13(1): 183, 2021 Nov 19.
Artigo em Inglês | MEDLINE | ID: mdl-34798904

RESUMO

BACKGROUND: N6-methyladenosine (m6A) is the most abundant modification of RNA in eukaryotic cells and play critical roles in cancer. While most related studies focus on m6A modifications in linear RNA, transcriptome-wide profiling and exploration of m6A modification in circular RNAs in cancer is still lacking. METHODS: For the detection of m6A modification in circRNAs, we developed a new bioinformatics tools called Circm6A and applied it to the m6A-seq data of 77 tissue samples from 58 individuals with pancreatic ductal adenocarcinoma (PDAC). RESULTS: Circm6A performs better than the existing circRNA identification tools, which achieved highest F1 score among these tools in the detection of circRNAs with m6A modifications. By using Circm6A, we identified a total of 8807 m6A-circRNAs from our m6A-seq data. The m6A-circRNAs tend to be hypermethylated in PDAC tumor tissues compared with normal tissues. The hypermethylated m6A-circRNAs were associated with a significant gain of circRNA-mRNA coexpression network, leading to the dysregulation of many important cancer-related pathways. Moreover, we found the cues that hypermethylated m6A-circRNAs may promote the circularization and translation of circRNAs. CONCLUSIONS: These comprehensive findings further bridged the knowledge gaps between m6A modification and circRNAs fields by depicting the m6A-circRNAs genomic landscape of PDAC patients and revealed the emerging roles played by m6A-circRNAs in pancreatic cancer. Circm6A is available at https://github.com/canceromics/circm6a .

5.
J Clin Invest ; 131(22)2021 11 15.
Artigo em Inglês | MEDLINE | ID: mdl-34779408

RESUMO

The tumorigenic mechanism for pancreatic ductal adenocarcinoma (PDAC) is not clear, although chronic inflammation is implicated. Here, we identified an inflammatory cytokine-regulated transfer RNA-derived (tRNA-derived) fragment, tRF-21-VBY9PYKHD (tRF-21), as a tumor suppressor in PDAC progression. We found that the biogenesis of tRF-21 could be inhibited by leukemia inhibitory factor and IL-6 via the splicing factor SRSF5. Reduced tRF-21 promoted AKT2/1-mediated heterogeneous nuclear ribonucleoprotein L (hnRNP L) phosphorylation, enhancing hnRNP L to interact with dead-box helicase 17 (DDX17) to form an alternative splicing complex. The provoked hnRNP L-DDX17 activity preferentially spliced Caspase 9 and mH2A1 pre-mRNAs to form Caspase 9b and mH2A1.2, promoting PDAC cell malignant phenotypes. The tRF-21 levels were significantly lower in PDACs than in normal tissues, and patients with low tRF-21 levels had a poor prognosis. Treatment of mouse PDAC xenografts or patient-derived xenografts (PDXs) with tRF-21 mimics repressed tumor growth and metastasis. These results demonstrate that tRF-21 has a tumor-suppressive effect and is a potential therapeutic agent for PDAC.

6.
Cancer Res ; 81(22): 5638-5651, 2021 Nov 15.
Artigo em Inglês | MEDLINE | ID: mdl-34607841

RESUMO

The majority of human genes have multiple polyadenylation sites, which are differentially used through the process of alternative polyadenylation (APA). Dysregulation of APA contributes to numerous diseases, including cancer. However, specific genes subject to APA that impact oncogenesis have not been well characterized, and many cancer APA landscapes remain underexplored. Here, we used dynamic analyses of APA from RNA-seq (DaPars) to define both the 3'UTR APA profile in esophageal squamous cell carcinoma (ESCC) and to identify 3'UTR shortening events that may drive tumor progression. In four distinct squamous cell carcinoma datasets, BID 3'UTRs were recurrently shortened and BID mRNA levels were significantly upregulated. Moreover, system correlation analysis revealed that CstF64 is a candidate upstream regulator of BID 3'UTR length. Mechanistically, a shortened BID 3'UTR promoted proliferation of ESCC cells by disrupting competing endogenous RNA (ceRNA) cross-talk, resulting in downregulation of the tumor suppressor gene ZFP36L2. These in vitro and in vivo results were supported by human patient data whereby 3'UTR shortening of BID and low expression of ZFP36L2 are prognostic factors of survival in ESCC. Collectively, these findings demonstrate that a key ceRNA network is disrupted through APA and promotes ESCC tumor progression.Significance: High-throughput analysis of alternative polyadenylation in esophageal squamous cell carcinoma identifies recurrent shortening of the BID 3'UTR as a driver of disease progression.

7.
BMC Anesthesiol ; 21(1): 247, 2021 10 19.
Artigo em Inglês | MEDLINE | ID: mdl-34666687

RESUMO

BACKGROUND: The incidence of placenta preiva is rising. Cesarean delivery is identified as the only safe and appropriate mode of delivery for pregnancies with placenta previa. Anesthesia is important during the cesarean delivery. The aim of this study is to assess maternal and neonatal outcomes of patients with placenta previa managed with neuraxial anesthesia as compared to those who underwent general anesthesia during cesarean delivery. METHODS: A retrospective cohort study was performed of all patients with placenta preiva at our large academic institution from January 1, 2014 to June 30, 2019. Patients were managed neuraxial anesthesia and general anesthesia during cesarean delivery. RESULTS: We identified 1234 patients with placenta previa who underwent cesarean delivery at our institution. Neuraxial anesthesia was performed in 737 (59.7%), and general anesthesia was completed in 497 (40.3%) patients. The mean estimated blood loss at neuraxial anesthesia of 558.96 ± 42.77 ml were significantly lower than the estimated blood loss at general anesthesia of 1952.51 ± 180 ml (p < 0.001). One hundred and forty-six of 737 (19.8%) patients required blood transfusion at neuraxial anesthesia, whereas 381 out of 497 (76.7%) patients required blood transfusion at general anesthesia. The rate neonatal asphyxia and admission to NICU at neuraxial anesthesia was significantly lower than general anesthesia (2.7% vs. 19.5 and 18.2% vs. 44.1%, respectively). After adjusting confounding factors, blood loss was less, Apgar score at 1- and 5-min were higher, and the rate of blood transfusion, neonatal asphyxia, and admission to NICU were lower in the neuraxial group. CONCLUSIONS: Our data demonstrated that neuraxial anesthesia is associated with better maternal and neonatal outcomes during cesarean delivery in women with placenta previa.

8.
Nat Commun ; 12(1): 5291, 2021 09 06.
Artigo em Inglês | MEDLINE | ID: mdl-34489433

RESUMO

Esophageal squamous-cell carcinoma (ESCC), one of the most prevalent and lethal malignant disease, has a complex but unknown tumor ecosystem. Here, we investigate the composition of ESCC tumors based on 208,659 single-cell transcriptomes derived from 60 individuals. We identify 8 common expression programs from malignant epithelial cells and discover 42 cell types, including 26 immune cell and 16 nonimmune stromal cell subtypes in the tumor microenvironment (TME), and analyse the interactions between cancer cells and other cells and the interactions among different cell types in the TME. Moreover, we link the cancer cell transcriptomes to the somatic mutations and identify several markers significantly associated with patients' survival, which may be relevant to precision care of ESCC patients. These results reveal the immunosuppressive status in the ESCC TME and further our understanding of ESCC.


Assuntos
Neoplasias Esofágicas/genética , Carcinoma de Células Escamosas do Esôfago/genética , Proteínas de Neoplasias/genética , Células Estromais/imunologia , Transcrição Genética , Adulto , Idoso , Linfócitos B/imunologia , Linfócitos B/patologia , Células Epiteliais/imunologia , Células Epiteliais/patologia , Neoplasias Esofágicas/imunologia , Neoplasias Esofágicas/mortalidade , Neoplasias Esofágicas/patologia , Carcinoma de Células Escamosas do Esôfago/imunologia , Carcinoma de Células Escamosas do Esôfago/mortalidade , Carcinoma de Células Escamosas do Esôfago/patologia , Feminino , Fibroblastos/imunologia , Fibroblastos/patologia , Perfilação da Expressão Gênica , Regulação Neoplásica da Expressão Gênica , Humanos , Masculino , Pessoa de Meia-Idade , Células Mieloides/imunologia , Células Mieloides/patologia , Proteínas de Neoplasias/classificação , Proteínas de Neoplasias/imunologia , Prognóstico , Análise de Célula Única , Células Estromais/patologia , Análise de Sobrevida , Linfócitos T/imunologia , Linfócitos T/patologia , Microambiente Tumoral/genética , Microambiente Tumoral/imunologia , Sequenciamento Completo do Genoma
9.
BMJ Open ; 11(9): e047651, 2021 09 27.
Artigo em Inglês | MEDLINE | ID: mdl-34580092

RESUMO

OBJECTIVE: This meta-analysis aimed to assess the efficacy of antenatal corticosteroids (ACS) on morbidity and mortality among preterm multiple pregnancies. METHODS: The PubMed, Embase, Web of Science and Cochrane Library databases were searched for studies investigating the outcomes among preterm multiple gestations following to ACS, from their inception to 1 November 2020. Two authors independently performed the study selection, risk of bias assessment and data extraction. The primary outcomes were respiratory distress syndrome (RDS) and mortality and secondary outcomes included intraventricular haemorrhage (IVH), periventricular leukomalacia (PVL), necrotising enterocolitis, retinopathy of prematurity and bronchopulmonary dysplasia. Pooled ORs were obtained using random effects models. Subgroup analyses were performed to explain heterogeneity by ACS completeness, administration-to-delivery intervals (≤7 days) and single or multicentre. RESULTS: A total of 16 observational studies with 36 973 newborns were included in the meta-analysis. ACS treatment was associated with a reduction in RDS (OR 0.66; 95% CI 0.54 to 0.82; I2=91.4%; p<0.001), mortality (OR 0.64; 95% CI 0.50 to 0.81; I2=85.9%; p<0.001), IVH (OR 0.67; 95% CI 0.54 to 0.83; I2=77.4%; p<0.001) and PVL (OR 0.65; 95% CI 0.47 to 0.92; I2=75.5%; p<0.001). Subgroup analyses showed ACS completeness, administration-to-delivery interval and multicentre study affected these associations. DISCUSSION: ACS may be beneficial for reducing the risks of RDS, mortality, IVH and PVL among preterm multiple gestations. The efficacy of ACS could be affected by ACS completeness and administration-to-delivery. More robust evidence on the efficacy of ACS treatment among multiple gestations is warranted.


Assuntos
Displasia Broncopulmonar , Síndrome do Desconforto Respiratório do Recém-Nascido , Corticosteroides/uso terapêutico , Displasia Broncopulmonar/epidemiologia , Displasia Broncopulmonar/prevenção & controle , Feminino , Humanos , Recém-Nascido , Morbidade , Estudos Multicêntricos como Assunto , Gravidez , Gravidez Múltipla , Síndrome do Desconforto Respiratório do Recém-Nascido/epidemiologia , Síndrome do Desconforto Respiratório do Recém-Nascido/prevenção & controle
10.
Oncogene ; 40(39): 5814-5828, 2021 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-34345012

RESUMO

5-Methylcytosine (m5C) is a posttranscriptional RNA modification participating in many critical bioprocesses, but its functions in human cancer remain unclear. Here, by detecting the transcriptome-wide m5C profiling in esophageal squamous cell carcinoma (ESCC), we showed increased m5C methylation in ESCC tumors due to the overexpressed m5C methyltransferase NSUN2. Aberrant expression of NSUN2 was positively regulated by E2F Transcription Factor 1 (E2F1). High NSUN2 levels predicted poor survival of ESCC patients. Moreover, silencing NSUN2 suppressed ESCC tumorigenesis and progression in Nsun2 knockout mouse models. Mechanistically, NSUN2 induced m5C modification of growth factor receptor-bound protein 2 (GRB2) and stabilized its mRNA, which was mediated by a novel m5C mediator, protein lin-28 homolog B (LIN28B). Elevated GRB2 levels increased the activation of PI3K/AKT and ERK/MAPK signalling. These results demonstrate that NSUN2 enhances the initiation and progression of ESCC via m5C-LIN28B dependent stabilization of GRB2 transcript, providing a promising epitranscriptomic-targeted therapeutic strategy for ESCC.

11.
Front Bioeng Biotechnol ; 9: 714292, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34381767

RESUMO

Objective: To compare the mechanical parameters and trajectory while operating the oblique pulling manipulation and the cervical rotation-traction manipulation. Methods: An experimental research measuring kinematics parameter and recording motion trajectories of two cervical manipulations were carried out. A total of 48 healthy volunteers participated in this study, who were randomly divided into two groups of 24 representing each of the two manipulations. A clinician performed two manipulations in two groups separately. A motion capture system was used to monitor and analyze kinematics parameters during the operation. Results: The two cervical manipulations have similar thrust time, displacement, mean velocity, max velocity, and max acceleration. There were no significant differences in active and passive amplitudes between the two cervical rotation manipulations. The thrust amplitudes of the oblique pulling manipulation and the cervical rotation-traction manipulation were 5.735 ± 3.041° and 2.142 ± 1.742°, respectively. The thrust amplitudes of the oblique pulling manipulation was significantly greater than that of the cervical rotation-traction manipulation (P < 0.001). Conclusion: Compared with the oblique pulling manipulation, the cervical rotation-traction manipulation has a less thrust amplitudes.

12.
Signal Transduct Target Ther ; 6(1): 322, 2021 Aug 30.
Artigo em Inglês | MEDLINE | ID: mdl-34462423

RESUMO

Radiotherapy remains the mainstay for treatment of various types of human cancer; however, the clinical efficacy is often limited by radioresistance, in which the underlying mechanism is largely unknown. Here, using esophageal squamous cell carcinoma (ESCC) as a model, we demonstrate that guanine nucleotide exchange factor 2 (VAV2), which is overexpressed in most human cancers, plays an important role in primary and secondary radioresistance. We have discovered for the first time that VAV2 is required for the Ku70/Ku80 complex formation and participates in non-homologous end joining repair of DNA damages caused by ionizing radiation. We show that VAV2 overexpression substantially upregulates signal transducer and activator of transcription 1 (STAT1) and the STAT1 inhibitor Fludarabine can significantly promote the sensitivity of radioresistant patient-derived ESCC xenografts in vivo in mice to radiotherapy. These results shed new light on the mechanism of cancer radioresistance, which may be important for improving clinical radiotherapy.

13.
Nature ; 597(7876): 398-403, 2021 09.
Artigo em Inglês | MEDLINE | ID: mdl-34433965

RESUMO

Somatic mutations that accumulate in normal tissues are associated with ageing and disease1,2. Here we performed a comprehensive genomic analysis of 1,737 morphologically normal tissue biopsies of 9 organs from 5 donors. We found that somatic mutation accumulations and clonal expansions were widespread, although to variable extents, in morphologically normal human tissues. Somatic copy number alterations were rarely detected, except for in tissues from the oesophagus and cardia. Endogenous mutational processes with the SBS1 and SBS5 mutational signatures are ubiquitous among normal tissues, although they exhibit different relative activities. Exogenous mutational processes operate in multiple tissues from the same donor. We reconstructed the spatial somatic clonal architecture with sub-millimetre resolution. In the oesophagus and cardia, macroscopic somatic clones that expanded to hundreds of micrometres were frequently seen, whereas in tissues such as the colon, rectum and duodenum, somatic clones were microscopic in size and evolved independently, possibly restricted by local tissue microstructures. Our study depicts a body map of somatic mutations and clonal expansions from the same individual.


Assuntos
Células Clonais/metabolismo , Saúde , Mutagênese , Mutação , Especificidade de Órgãos , Idoso de 80 Anos ou mais , Biópsia , Cadáver , Cárdia/metabolismo , Proliferação de Células , Células Clonais/citologia , Esôfago/metabolismo , Feminino , Genômica , Humanos , Masculino
14.
Artigo em Inglês | MEDLINE | ID: mdl-34449908

RESUMO

OBJECTIVE: To investigate the correlation between lower uterine segment thickness (LUST) and gestational weeks (GW) in women who attempted trial of labor after cesarean section (TOLAC) and to estimate the reference ranges of LUST. METHODS: A prospective cohort study was conducted between January 2019 and December 2020 at a tertiary-care center in Foshan, China. A total of 2588 women who attempted TOLAC were included. LUST was measured in different trimesters using transabdominal ultrasound. Histograms were used to review the mean and standard deviations (SD) of LUST at different GW. RESULTS: The mean LUST of the patients were 6.90 ± 2.86, 4.36 ± 1.87, 2.83 ± 0.65, and 2.57 ± 0.51 mm in the first (12.10 ± 1.28 weeks), second (21.79 ± 3.40 weeks), middle third (34.28 ± 2.64 weeks), and late third (38.20 ± 1.00 weeks) trimesters, respectively. An inverse correlation was noted between LUST and uterine rupture in women who underwent a planned ERCD (P < 0.001), but not in women who attempted TOLAC during the late third trimester (P = 0.629). CONCLUSION: LUST is inversely correlated with GW and decreases faster in the first and second trimesters than in the middle and late third trimesters. TOLAC should be approached with caution for pregnant women with a thin myometrium in late third trimester.

15.
Cancer Res ; 81(20): 5268-5283, 2021 Oct 15.
Artigo em Inglês | MEDLINE | ID: mdl-34362795

RESUMO

Pseudogenes may play important roles in cancer. Here, we explore the mechanism and function of a pseudogene WTAPP1 in the progress of pancreatic ductal adenocarcinoma (PDAC). WTAPP1 RNA was significantly elevated in PDAC and was associated with poor prognosis in patients. Overexpression of WTAPP1 RNA promoted PDAC proliferation and invasiveness in vitro and in vivo. Mechanistically, N 6-methyladenosine (m6A) modification stabilized WTAPP1 RNA via CCHC-type zinc finger nucleic-acid binding protein (CNBP), resulting in increased levels of WTAPP1 RNA in PDAC cells. Excessive WTAPP1 RNA bound its protein-coding counterpart WT1-associated protein (WTAP) mRNA and recruited more EIF3 translation initiation complex to promote WTAP translation. Increased WTAP protein enhanced the activation of Wnt signaling and provoked the malignant phenotypes of PDAC. Decreasing WTAPP1 RNA significantly suppressed the in vivo growth and metastasis of PDAC cell lines and patient-derived xenografts. These results indicate that m6A-mediated increases in WTAPP1 expression promote PDAC progression and thus may serve as a therapeutic target. SIGNIFICANCE: This study reveals how aberrant m6A modification of the WTAPP1 pseudogene results in increased translation of its protein-coding counterpart to promote Wnt signaling, which contributes to pancreatic cancer progression.

16.
Int J Womens Health ; 13: 671-681, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34262357

RESUMO

Background: To compare the maternal and neonatal outcomes of placenta previa (PP) with and without coverage of a uterine scar in Foshan, China. Methods: A retrospective cohort study comparing all singleton pregnancies with PP was conducted at a tertiary, university-affiliated medical center from 1 January 2012 to 31 April 2017 in Foshan, China. Demographic, clinical and laboratory data were extracted from electronic medical records (EMRs). Maternal and neonatal outcomes of PP with and without coverage of a uterine scar were compared by statistical method. Results: There were 58,062 deliveries during the study period, of which 726 (1.25%) were complicated PP in singleton pregnancies and were further classified into two groups: the PP with coverage of a uterine scar group (PPCS, n=154) and the PP without coverage of a uterine scar group (Non-PPCS, n=572). Overall, premature birth (<37 weeks, 67.5% vs 54.8%; P=0.019), cesarean section (100% vs 97.6%; P=0.050), intraoperative blood loss >1000 mL (77.9% vs 16.0%; P<0.001) or >3000mL (29.9% vs 3.0%; P<0.001), bleeding within 2-24 hours after delivery (168.2±370.1 ml vs 49.9±58.4 ml; P<0.001), postpartum hemorrhage (48.7% vs 15.7%; P<0.001), transfusion (34.6% vs 16.1%; P<0.001), hemorrhage shock (7.8% vs 1.9%; P<0.001), hysterectomy (2.6% vs 0.5%; P=0.019), fetal distress (35.7% vs 12.1%; P<0.001) and APGAR score at 1 min (15.2% vs 7.1%; P=0.002) had a significant difference between PPCS group and Non-PPCS group. After grouping by whether complicated with placenta accreta spectrum disorders (PASD), we found that PPCS was significant associated with more intraoperative blood loss >1000mL, intraoperative blood loss >3000mL, bleeding within 2-24 hours after delivery and fetal distress than the Non-PPCS group. Conclusion: The PPCS group had poorer maternal and neonatal outcomes than the Non-PPCS group after grouping by whether pregnancies complicated with PASD or with different placental positions.

17.
BMC Pregnancy Childbirth ; 21(1): 441, 2021 Jun 24.
Artigo em Inglês | MEDLINE | ID: mdl-34167519

RESUMO

BACKGROUND: Placenta previa, a serious obstetric issue, should be managed by experienced teams. The safe and appropriate mode of delivery for placenta previa is by cesarean delivery. However, no studies were found comparing either maternal or neonatal outcomes for different skin incision in women with placenta previa. The aim of this study was to compare maternal and neonatal outcomes by skin incision types (transverse compared with vertical) in a large cohort of women with placenta previa who were undergoing cesarean delivery. METHODS: This was a retrospective cohort study carried out between January 2014 and June 2019. All pregnant women with placenta previa had confirmed by ultrasonologist before delivery and obstetrician at delivery. The primary outcome was the estimated blood loss during the surgery and within the first 24 hours postoperatively. Mean (standard deviation), median (interquartile range) or frequency (percentage) was reported to variables. Appropriate parametric and nonparametric tests were used to analyses. RESULTS: The study included 1098 complete records, 332 (30.24%) cases in the vertical skin incision group and 766 (69.76%) cases in the transverse skin incision group. Those with vertical incision showed a higher percentage of preterm delivery, anterior placenta, abnormally invasive placenta, and history of previous cesarean delivery, and a lower percentage of first pregnancy, in vitro fertilization, and emergency cesarean delivery. After controlling for confounding factors, higher incidence of post-partum hemorrhage (OR 5.47, 95% CI 3.84-7.79), maternal intensive care unit (OR 4.30, 95% CI 2.86-6.45), transfusion (OR 5.97, 95% CI 4.15-8.58), and 5-min APGAR< 7 (OR 9.03, 95% CI 1.83-44.49), a more estimated blood loss (ß 601.85, 95%CI 458.78-744.91), and a longer length of hospital stay after delivery (ß 0.54, 95%CI 0.23-0.86) were found in the vertical skin incision group. CONCLUSIONS: Our data demonstrated that transverse skin incision group showed the better perinatal outcomes in women with placenta previa. Future collaborative studies are needed to be done by centers for placenta previa to have a better understanding of the characteristics and the outcomes of the disease in the choosing skin incision.


Assuntos
Cesárea/métodos , Placenta Prévia/cirurgia , Ferida Cirúrgica/complicações , Adulto , Transfusão de Sangue/estatística & dados numéricos , Cesárea/efeitos adversos , Feminino , Humanos , Incidência , Recém-Nascido , Tempo de Internação/estatística & dados numéricos , Masculino , Hemorragia Pós-Parto/epidemiologia , Hemorragia Pós-Parto/etiologia , Gravidez , Resultado da Gravidez , Nascimento Prematuro/epidemiologia , Nascimento Prematuro/etiologia , Estudos Retrospectivos
18.
BMC Pregnancy Childbirth ; 21(1): 446, 2021 Jun 25.
Artigo em Inglês | MEDLINE | ID: mdl-34172024

RESUMO

BACKGROUND: Twin birth weight percentiles are less popular in clinical management among twin pregnancies compared with singleton ones in China. This study aimed to compare the incidence and neonatal outcomes of small for gestational age (SGA) twins between the use of singleton and twin birth weight percentiles. METHODS: This was a retrospective cohort study of 3,027 pregnancies with liveborn twin pairs at gestational age of > 28 weeks. The newborns were categorized as SGA when a birthweight was less than the 10th percentile based on the singleton and twin references derived from Chinese population. Logistic regression models with generalized estimated equation (GEE) were utilized to evaluate the association between SGA twins and neonatal outcomes including neonatal unit admission, neonatal jaundice, neonatal respiratory distress (NRDS), neonatal asphyxia, ventilator support, hypoxic ischemic encephalopathy (HIE), bronchopulmonary dysplasia (BPD), necrotizing enterocolitis (NEC), intracranial hemorrhage (ICH), culture-proven sepsis, neonatal death within 28 days after birth as well as the composite outcome. RESULTS: The incidence of SGA was 33.1 % based on the singleton reference and 7.3 % based on the twin reference. Both of SGA newborns defined by the singleton and twin references were associated with increases in neonatal unit admission, neonatal jaundice and ventilator support. In addition, SGA newborns defined by the twin reference were associated with increased rates of BPD (aOR, 2.61; 95 % CI: 1.18-5.78) as well as the severe composite outcome (aOR, 1.93; 95 % CI: 1.07-3.47). CONCLUSIONS: The use of singleton birth weight percentiles may result in misdiagnosed SGA newborns in twin gestations and the twin birth weight percentiles would be more useful to identify those who are at risk of adverse outcomes.


Assuntos
Peso ao Nascer , Recém-Nascido Pequeno para a Idade Gestacional , Gêmeos/estatística & dados numéricos , Pesos e Medidas/normas , China/epidemiologia , Doenças em Gêmeos/epidemiologia , Feminino , Idade Gestacional , Humanos , Incidência , Recém-Nascido , Doenças do Recém-Nascido/epidemiologia , Modelos Logísticos , Masculino , Gravidez , Gravidez de Gêmeos , Padrões de Referência , Estudos Retrospectivos
19.
Nat Commun ; 12(1): 3830, 2021 06 22.
Artigo em Inglês | MEDLINE | ID: mdl-34158490

RESUMO

The molecular mechanism underlying pancreatic ductal adenocarcinoma (PDAC) malignancy remains unclear. Here, we characterize a long intergenic non-coding RNA LINC00842 that plays a role in PDAC progression. LINC00842 expression is upregulated in PDAC and induced by high concentration of glucose via transcription factor YY1. LINC00842 binds to and prevents acetylated PGC-1α from deacetylation by deacetylase SIRT1 to form PGC-1α, an important transcription co-factor in regulating cellular metabolism. LINC00842 overexpression causes metabolic switch from mitochondrial oxidative catabolic process to fatty acid synthesis, enhancing the malignant phenotypes of PDAC cells. High LINC00842 levels are correlated with elevated acetylated- PGC-1α levels in PDAC and poor patient survival. Decreasing LINC00842 level and inhibiting fatty acid synthase activity significantly repress PDAC growth and invasiveness in mouse pancreatic xenograft or patient-derived xenograft models. These results demonstrate that LINC00842 plays a role in promoting PDAC malignancy and thus might serve as a druggable target.


Assuntos
Carcinoma Ductal Pancreático/genética , Metabolismo Energético/genética , Regulação Neoplásica da Expressão Gênica , Neoplasias Pancreáticas/genética , Coativador 1-alfa do Receptor gama Ativado por Proliferador de Peroxissomo/genética , RNA Longo não Codificante/genética , Acetilação , Animais , Carcinoma Ductal Pancreático/metabolismo , Carcinoma Ductal Pancreático/terapia , Linhagem Celular Tumoral , Feminino , Células HEK293 , Humanos , Camundongos Endogâmicos BALB C , Camundongos Nus , Neoplasias Pancreáticas/metabolismo , Neoplasias Pancreáticas/terapia , Coativador 1-alfa do Receptor gama Ativado por Proliferador de Peroxissomo/metabolismo , Interferência de RNA , Sirtuína 1/metabolismo , Ensaios Antitumorais Modelo de Xenoenxerto/métodos
20.
J Matern Fetal Neonatal Med ; : 1-15, 2021 May 27.
Artigo em Inglês | MEDLINE | ID: mdl-34044741

RESUMO

BACKGROUND: Gestational weight gain (GWG) has been understudied among twin pregnancies. This systematic review aimed to review the data on the associations between GWG, based on the 2009 Institute of Medicine (IOM) guidelines and pregnancy outcomes among twin gestations. METHODS: A systematic review was performed according to the PRISMA guidelines. A search for eligible studies published from January 2010 to August 2020 was conducted in the EMBASE, PubMed, Web of Science, ScienceDirect, and Cochrane databases. The methodological quality of the included studies was assessed using the Newcastle-Ottawa Scale. Data on study characteristics and main findings were extracted independently by two reviewers using a standard form. Outcomes of interest included (spontaneous) preterm birth (PTB), gestational hypertensive disorder (gestational hypertension and eclampsia), and small for gestational age (SGA). RESULTS: Eighteen observational studies of twin gestations met the inclusion criteria. GWG below the IOM recommendations was reported to be associated with increased PTB and SGA while GWG above the recommendation was associated with increased gestational hypertensive disorder. However, the results were inconsistent. Methodological limitations, such as a retrospective design, the use of weekly GWG, a small sample size and insufficient adjustment, impeded the clarification of the association between GWG and perinatal outcomes. In addition, the optimal GWG for underweight women was not fully studied. CONCLUSIONS: The maintenance of weight gain within the 2009 IOM guidelines would decrease the risks of adverse outcomes among twin pregnancies. However, rigorous studies are warranted to provide robust evidence to refine the optimal GWG among twin gestations.

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