Publications by authors named "Dongxin Lin"

249 Publications

CstF64-induced shortening of the BID 3'UTR promotes esophageal squamous cell carcinoma progression by disrupting ceRNA crosstalk with ZFP36L2.

Cancer Res 2021 Oct 4. Epub 2021 Oct 4.

Carcinogenesisi department, CICAMS.

The majority of human genes have multiple polyadenylation sites, which are differentially utilized 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) crosstalk, 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.
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http://dx.doi.org/10.1158/0008-5472.CAN-21-1201DOI Listing
October 2021

Association of antenatal corticosteroids with morbidity and mortality among preterm multiple gestations: meta-analysis of observational studies.

BMJ Open 2021 Sep 27;11(9):e047651. Epub 2021 Sep 27.

Foshan Institute of Fetal Medicine, Southern Medical University Affiliated Maternal & Child Health Hospital of Foshan, Foshan, Guangdong, China.

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; I=91.4%; p<0.001), mortality (OR 0.64; 95% CI 0.50 to 0.81; I=85.9%; p<0.001), IVH (OR 0.67; 95% CI 0.54 to 0.83; I=77.4%; p<0.001) and PVL (OR 0.65; 95% CI 0.47 to 0.92; I=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.
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http://dx.doi.org/10.1136/bmjopen-2020-047651DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8477320PMC
September 2021

Dissecting esophageal squamous-cell carcinoma ecosystem by single-cell transcriptomic analysis.

Nat Commun 2021 09 6;12(1):5291. Epub 2021 Sep 6.

Department of Etiology and Carcinogenesis, National Cancer Center/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China.

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.
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http://dx.doi.org/10.1038/s41467-021-25539-xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8421382PMC
September 2021

VAV2 is required for DNA repair and implicated in cancer radiotherapy resistance.

Signal Transduct Target Ther 2021 Aug 30;6(1):322. Epub 2021 Aug 30.

Department of Etiology and Carcinogenesis, National Cancer Center/National Clinical Research Center/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China.

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.
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http://dx.doi.org/10.1038/s41392-021-00735-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8405816PMC
August 2021

Changes in lower uterine segment thickness during different gestational weeks in pregnant women qualified for trial of labor after cesarean section.

Int J Gynaecol Obstet 2021 Aug 27. Epub 2021 Aug 27.

Foshan Fetal Medicine Institute, Affiliated Foshan Maternity & Child Healthcare Hospital, Southern Medical University (Foshan Maternity & Child Healthcare Hospital), Foshan, China.

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.
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http://dx.doi.org/10.1002/ijgo.13902DOI Listing
August 2021

A body map of somatic mutagenesis in morphologically normal human tissues.

Nature 2021 09 25;597(7876):398-403. Epub 2021 Aug 25.

Department of Etiology and Carcinogenesis, National Cancer Center/Cancer Hospital, Chinese Academy of Medical Sciences (CAMS) and Peking Union Medical College (PUMC), Beijing, China.

Somatic mutations that accumulate in normal tissues are associated with ageing and disease. 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.
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http://dx.doi.org/10.1038/s41586-021-03836-1DOI Listing
September 2021

Mechanical Parameters and Trajectory of Two Chinese Cervical Manipulations Compared by a Motion Capture System.

Front Bioeng Biotechnol 2021 26;9:714292. Epub 2021 Jul 26.

National Key Discipline of Human Anatomy, School of Basic Medical Sciences, Southern Medical University, Guangzhou, China.

To compare the mechanical parameters and trajectory while operating the oblique pulling manipulation and the cervical rotation-traction manipulation. 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. 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 ( < 0.001). Compared with the oblique pulling manipulation, the cervical rotation-traction manipulation has a less thrust amplitudes.
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http://dx.doi.org/10.3389/fbioe.2021.714292DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8351596PMC
July 2021

-methyladenosine-Mediated Upregulation of WTAPP1 Promotes WTAP Translation and Wnt Signaling to Facilitate Pancreatic Cancer Progression.

Cancer Res 2021 Oct 6;81(20):5268-5283. Epub 2021 Aug 6.

State Key Laboratory of Oncology in South China and Collaborative Innovation Center for Cancer Medicine, Guangzhou, Sun Yat-sen University Cancer Center, Guangzhou, China.

Pseudogenes may play important roles in cancer. Here, we explore the mechanism and function of a pseudogene in the progress of pancreatic ductal adenocarcinoma (PDAC). RNA was significantly elevated in PDAC and was associated with poor prognosis in patients. Overexpression of RNA promoted PDAC proliferation and invasiveness and . Mechanistically, -methyladenosine (mA) modification stabilized RNA via CCHC-type zinc finger nucleic-acid binding protein (CNBP), resulting in increased levels of RNA in PDAC cells. Excessive 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 RNA significantly suppressed the growth and metastasis of PDAC cell lines and patient-derived xenografts. These results indicate that mA-mediated increases in expression promote PDAC progression and thus may serve as a therapeutic target. SIGNIFICANCE: This study reveals how aberrant mA modification of the pseudogene results in increased translation of its protein-coding counterpart to promote Wnt signaling, which contributes to pancreatic cancer progression.
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http://dx.doi.org/10.1158/0008-5472.CAN-21-0494DOI Listing
October 2021

NSUN2-mediated RNA 5-methylcytosine promotes esophageal squamous cell carcinoma progression via LIN28B-dependent GRB2 mRNA stabilization.

Oncogene 2021 Sep 3;40(39):5814-5828. Epub 2021 Aug 3.

State Key Laboratory of Oncology in South China and Collaborative Innovation Center for Cancer Medicine, Sun Yat-sen University Cancer Center, Guangzhou, China.

5-Methylcytosine (mC) is a posttranscriptional RNA modification participating in many critical bioprocesses, but its functions in human cancer remain unclear. Here, by detecting the transcriptome-wide mC profiling in esophageal squamous cell carcinoma (ESCC), we showed increased mC methylation in ESCC tumors due to the overexpressed mC 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 mC modification of growth factor receptor-bound protein 2 (GRB2) and stabilized its mRNA, which was mediated by a novel mC 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 mC-LIN28B dependent stabilization of GRB2 transcript, providing a promising epitranscriptomic-targeted therapeutic strategy for ESCC.
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http://dx.doi.org/10.1038/s41388-021-01978-0DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8484015PMC
September 2021

Maternal and Neonatal Outcomes of Placenta Previa with and without Coverage of a Uterine Scar: A Retrospective Cohort Study in a Tertiary Hospital.

Int J Womens Health 2021 6;13:671-681. Epub 2021 Jul 6.

Foshan Fetal Medicine Institute, Affiliated Foshan Maternity & Child Healthcare Hospital, Southern Medical University (Foshan Maternity & Child Healthcare Hospital), Foshan, Guangdong, 528000, People's Republic of China.

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%; =0.019), cesarean section (100% vs 97.6%; =0.050), intraoperative blood loss >1000 mL (77.9% vs 16.0%; <0.001) or >3000mL (29.9% vs 3.0%; <0.001), bleeding within 2-24 hours after delivery (168.2±370.1 ml vs 49.9±58.4 ml; <0.001), postpartum hemorrhage (48.7% vs 15.7%; <0.001), transfusion (34.6% vs 16.1%; <0.001), hemorrhage shock (7.8% vs 1.9%; <0.001), hysterectomy (2.6% vs 0.5%; =0.019), fetal distress (35.7% vs 12.1%; <0.001) and APGAR score at 1 min (15.2% vs 7.1%; =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.
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http://dx.doi.org/10.2147/IJWH.S310097DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8273910PMC
July 2021

Should singleton birth weight standards be applied to identify small-for-gestational age twins?: analysis of a retrospective cohort study.

BMC Pregnancy Childbirth 2021 Jun 25;21(1):446. Epub 2021 Jun 25.

Foshan Institute of Fetal Medicine, Southern Medical University Affiliated Maternal & Child Health Hospital of Foshan, 11 Renminxi Road, Guangdong, 528000, Foshan, China.

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.
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http://dx.doi.org/10.1186/s12884-021-03907-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8234673PMC
June 2021

Maternal and neonatal outcomes in transverse and vertical skin incision for placenta previa : Skin incision for placenta previa.

BMC Pregnancy Childbirth 2021 Jun 24;21(1):441. Epub 2021 Jun 24.

Foshan Institute of Fetal Medicine, Affiliated Foshan Maternity & Child Healthcare Hospital, Southern Medical University, Foshan, 528000, Guangdong, China.

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 (β 601.85, 95%CI 458.78-744.91), and a longer length of hospital stay after delivery (β 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.
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http://dx.doi.org/10.1186/s12884-021-03923-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8229347PMC
June 2021

LINC00842 inactivates transcription co-regulator PGC-1α to promote pancreatic cancer malignancy through metabolic remodelling.

Nat Commun 2021 06 22;12(1):3830. Epub 2021 Jun 22.

Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology in South China and Collaborative Innovation Center for Cancer Medicine, Guangzhou, China.

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.
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http://dx.doi.org/10.1038/s41467-021-23904-4DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8219694PMC
June 2021

Association between gestational weight gain and perinatal outcomes among twin gestations based on the 2009 Institute of Medicine (IOM) guidelines: a systematic review.

J Matern Fetal Neonatal Med 2021 May 27:1-15. Epub 2021 May 27.

Foshan Institute of Fetal Medicine, Southern Medical University Affiliated Maternal & Child Health Hospital of Foshan, Foshan, China.

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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http://dx.doi.org/10.1080/14767058.2021.1918083DOI Listing
May 2021

The association of hypertensive disorders of pregnancy with small for gestational age and intertwin birthweight discordance.

J Clin Hypertens (Greenwich) 2021 07 20;23(7):1354-1362. Epub 2021 May 20.

Foshan Institute of Fetal Medicine, Affiliated Foshan Maternity & Child Healthcare Hospital, Southern Medical University, Foshan, China.

Available evidence shows conflicting results regarding the association between hypertensive disorders of pregnancy (HDPs)/preeclampsia (PE) and small for gestational age (SGA) and birthweight discordance (BWD). This retrospective study of 2131 twin pregnancies aimed to evaluate the association of HDPs/PE with the presence of SGA and BWD. The eligible pregnancies were categorized into four study groups: concordant pairs without SGA fetuses, discordant pairs without SGA fetuses, concordant pairs with SGA fetuses, and discordant pairs with SGA fetuses. We applied binary logistic regression models to compare the incidence of HDPs/PE and multinomial logit regression models to evaluate the severity of PE between the study groups. The models were adjusted for potential confounders. Increases in HDPs were observed in concordant (aOR, 2.33; 95% CI: 1.46-3.73) and discordant (aOR, 3.50; 95% CI: 2.26-5.43) pregnancies with SGA fetuses but not in discordant pregnancies without SGA fetuses (aOR, 1.42; 95% CI: 0.81-2.49); increases in PE were also found in concordant (aOR, 1.87; 95% CI: 1.08-3.23) and discordant (aOR, 3.75; 95% CI: 2.36-5.96) pregnancies with SGA fetuses but not in discordant pregnancies without SGA fetuses (aOR, 1.34; 95% CI: 0.71-2.52). Discordant pregnancies with SGA fetuses were associated with severe PE (aRRR, 3.48; 95% CI: 1.79-6.77), whereas concordant pregnancies with SGA fetuses were associated with only mild PE (aRRR, 2.54; 95% CI: 1.33-4.88). Our results suggest that SGA is associated with the development of HDP/PE, while discordant growth is associated with the severity of PE. These associations need to be further investigated using estimated fetal weight (EFW).
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http://dx.doi.org/10.1111/jch.14257DOI Listing
July 2021

N(6)-methyladenosine-binding protein YTHDF1 suppresses EBV replication and promotes EBV RNA decay.

EMBO Rep 2021 04 19;22(4):e50128. Epub 2021 Feb 19.

State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangdong Key Laboratory of Nasopharyngeal Carcinoma Diagnosis and Therapy, Sun Yat-sen University Cancer Center, Guangzhou, China.

N -methyladenosine (m A) modification of mRNA mediates diverse cellular and viral functions. Infection with Epstein-Barr virus (EBV) is causally associated with nasopharyngeal carcinoma (NPC), 10% of gastric carcinoma, and various B-cell lymphomas, in which the viral latent and lytic phases both play vital roles. Here, we show that EBV transcripts exhibit differential m A modification in human NPC biopsies, patient-derived xenograft tissues, and cells at different EBV infection stages. m A-modified EBV transcripts are recognized and destabilized by the YTHDF1 protein, which leads to the m A-dependent suppression of EBV infection and replication. Mechanistically, YTHDF1 hastens viral RNA decapping and mediates RNA decay by recruiting RNA degradation complexes, including ZAP, DDX17, and DCP2, thereby post-transcriptionally downregulating the expression of EBV genes. Taken together, our results reveal the critical roles of m A modifications and their reader YTHDF1 in EBV replication. These findings contribute novel targets for the treatment of EBV-associated cancers.
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http://dx.doi.org/10.15252/embr.202050128DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8025027PMC
April 2021

Association Between Nausea and Vomiting During Pregnancy and Sleep Quality: Mediating Effect of Depressive Symptoms.

Int J Gen Med 2021 8;14:41-49. Epub 2021 Jan 8.

Department of Obstetrics, Affiliated Foshan Maternity & Child Healthcare Hospital, Southern Medical University, Foshan, People's Republic of China.

Purpose: Nausea and vomiting during pregnancy (NVP) of varying degrees of severity are commonly experienced by pregnant women. This paper explores the association between NVP and poor sleep quality.

Patients And Methods: A cross-sectional study was conducted in an obstetrics clinic. A total of 2494 pregnant women (representing a response rate of 92.7%) completed a self-administered questionnaire.

Results: Of the 2494 participants, the mean sleep duration was 7.76 hours, and 54.3% of them report poor sleep quality (ie, a Pittsburgh Sleep Quality Index global score > 5). In this study, 49.1%, 49.3% and 1.6% women reported mild, moderate, and severe NVP, respectively. Compare with women with mild NVP, women with moderate or severe NVP were more likely to report poor sleep quality ( = 30.16, < 0.001). After adjusted for demographics and gestational age, moderate and severe NVP were associated with poor sleep quality (adjusted odds ratio (AOR) = 1.66, 95% confidence interval (CI) = 1.40-1.96, and AOR = 2.95, 95% CI = 1.44-6.02, respectively). Moreover, depressive symptoms mediated the association between NVP and poor sleep quality (β = 0.060, = 0.033, 95% CI = 0.028-0.180).

Conclusion: Our study suggested that moderate and severe NVP increase the risk of poor sleep quality. Further studies are warranted that focus on the mechanisms of the association between NVP and poor sleep quality.
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http://dx.doi.org/10.2147/IJGM.S290216DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7802779PMC
January 2021

Prospective association of metal levels with gestational diabetes mellitus and glucose: A retrospective cohort study from South China.

Ecotoxicol Environ Saf 2021 Mar 8;210:111854. Epub 2021 Jan 8.

Foshan Fetal Medicine Research Institute, Foshan Women and Children Hospital Affiliated to Southern Medical University, Foshan, China; Department of Obstetrics, Foshan Women and Children Hospital Affiliated to Southern Medical University, Foshan, China. Electronic address:

Objective: To explore the prospective correlation between serum metals before 24 weeks' gestation and gestational diabetes mellitus (GDM) or glucose in the late second trimester among southern Chinese pregnant women.

Methods: A total of 8169 pregnant women were included in our retrospective cohort study. Logistic regression was used to investigate the relationships between metals (Manganese [Mn], copper [Cu], lead [Pb], calcium [Ca], zinc [Zn], magnesium [Mg]) and GDM. Quantile regression was performed to detect the shifts and associations with metals and three time-points glucose distribution of oral glucose tolerance test (OGTT) focused on the 10th, 50th, and 90th percentiles. Weighted quantile sum (WQS) regression was used to explore the relationship of metal mixtures and GDM as well as glucose.

Results: Maternal serum concentrations of metals were assessed at mean 16.55 ± 2.92 weeks' gestation. Women with under weight might have 25% decreased risk of GDM for every 50% increase in Cu concentration within the safe limits. A 50% increase in Mn and Zn levels was related to a 0.051 μmol/L (95% CI: 0.033-0.070) and 0.059 μmol/L (95% CI: 0.040-0.079) increase in mean fasting plasma glucose of OGTT (OGTT0), respectively. The magnitude of association with Mn was smaller at the upper tail of OGTT0 distribution, while the magnitude of correlation with Zn was greater at the upper tail. However, there was a 0.012 mmol/L (95% CI: -0.017 to -0.008), 0.028 mmol/L (95% CI: -0.049 to -0.007), and 0.036 mmol/L (95% CI: -0.057 to -0.016) decrease in mean OGTT0 levels for every 50% increase in Pb, Ca, and Mg, respectively. The negative association of Pb, Ca, and Mg was greater at the lower tail of OGTT0 distribution. No significant relationship was observed in Cu and mean OGTT0 level (-0.010 mmol/L, 95% CI: -0.021 to 0.001), however, it showed a protective effect at the upper tail (-0.034 mmol/L, 95% CI: -0.049 to -0.017). No obvious correlation was found between metals and postprandial glucose levels (OGTT1 and OGTT2 from OGTT). The WQS index was significantly related to OGTT0 (P < 0.001). The contribution of Mn (80.19%) to metal mixture index was the highest related to OGTT0, followed by Cu (19.81%).

Conclusions: Higher Mn and Zn but lower Pb, Ca, and Mg concentrations within a certain range before 24 weeks' gestation might prospectively impair fasting plasma glucose during pregnancy; a greater focus is required on Mn. It could provide early markers of metal for predicting later glucose and suggest implement intervention for pregnant women.
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http://dx.doi.org/10.1016/j.ecoenv.2020.111854DOI Listing
March 2021

Sub-multiplicative interaction between polygenic risk score and household coal use in relation to lung adenocarcinoma among never-smoking women in Asia.

Environ Int 2021 02 29;147:105975. Epub 2020 Dec 29.

Department of Internal Medicine, Kaohsiung Medical University Hospital, School of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan.

We previously identified 10 lung adenocarcinoma susceptibility loci in a genome-wide association study (GWAS) conducted in the Female Lung Cancer Consortium in Asia (FLCCA), the largest genomic study of lung cancer among never-smoking women to date. Furthermore, household coal use for cooking and heating has been linked to lung cancer in Asia, especially in Xuanwei, China. We investigated the potential interaction between genetic susceptibility and coal use in FLCCA. We analyzed GWAS-data from Taiwan, Shanghai, and Shenyang (1472 cases; 1497 controls), as well as a separate study conducted in Xuanwei (152 cases; 522 controls) for additional analyses. We summarized genetic susceptibility using a polygenic risk score (PRS), which was the weighted sum of the risk-alleles from the 10 previously identified loci. We estimated associations between a PRS, coal use (ever/never), and lung adenocarcinoma with multivariable logistic regression models, and evaluated potential gene-environment interactions using likelihood ratio tests. There was a strong association between continuous PRS and lung adenocarcinoma among never coal users (Odds Ratio (OR) = 1.69 (95% Confidence Interval (CI) = 1.53, 1.87), p=1 × 10). This effect was attenuated among ever coal users (OR = 1.24 (95% CI: 1.03, 1.50), p = 0.02, p-interaction = 6 × 10). We observed similar attenuation among coal users from Xuanwei. Our study provides evidence that genetic susceptibility to lung adenocarcinoma among never-smoking Asian women is weaker among coal users. These results suggest that lung cancer pathogenesis may differ, at least partially, depending on exposure to coal combustion products. Notably, these novel findings are among the few instances of sub-multiplicative gene-environment interactions in the cancer literature.
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http://dx.doi.org/10.1016/j.envint.2020.105975DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8378844PMC
February 2021

Genomic and transcriptomic alterations associated with drug vulnerabilities and prognosis in adenocarcinoma at the gastroesophageal junction.

Nat Commun 2020 11 30;11(1):6091. Epub 2020 Nov 30.

Department of Etiology and Carcinogenesis, National Cancer Center/National Clinical Research Center/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China.

Adenocarcinoma at the gastroesophageal junction (ACGEJ) has dismal clinical outcomes, and there are currently few specific effective therapies because of limited knowledge on its genomic and transcriptomic alterations. The present study investigates genomic and transcriptomic changes in ACGEJ from Chinese patients and analyzes their drug vulnerabilities and associations with the survival time. Here we show that the major genomic changes of Chinese ACGEJ patients are chromosome instability promoted tumorigenic focal copy-number variations and COSMIC Signature 17-featured single nucleotide variations. We provide a comprehensive profile of genetic changes that are potentially vulnerable to existing therapeutic agents and identify Signature 17-correlated IFN-α response pathway as a prognostic marker that might have practical value for clinical prognosis of ACGEJ. These findings further our understanding on the molecular biology of ACGEJ and may help develop more effective therapeutic strategies.
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http://dx.doi.org/10.1038/s41467-020-19949-6DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7705019PMC
November 2020

PIWI-interacting RNAs in human cancer.

Semin Cancer Biol 2020 Sep 1. Epub 2020 Sep 1.

Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology in South China and Collaborative Innovation Center for Cancer Medicine, Guangzhou, 510060, China; Department of Etiology and Carcinogenesis, National Cancer Center/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, 100021, China.

P-element-induced wimpy testis (PIWI) interacting RNAs (piRNAs) are a class of small regulatory RNAs mechanistically similar to but much less studied than microRNAs and small interfering RNAs. Today the best understood function of piRNAs is transposon control in animal germ cells, which has earned them the name 'guardians of the germline'. Several molecular/cellular characteristics of piRNAs, including high sequence diversity, lack of secondary structures, and target-oriented generation seem to serve this purpose. Recently, aberrant expressions of piRNAs and PIWI proteins have been implicated in a variety of malignant tumors and associated with cancer hallmarks such as cell proliferation, inhibited apoptosis, invasion, metastasis and increased stemness. Researchers have also demonstrated multiple mechanisms of piRNA-mediated target deregulation associated with cancer initiation, progression or dissemination. We review current research findings on the biogenesis, normal functions and cancer associations of piRNAs, highlighting their potentials as cancer diagnostic/prognostic biomarkers and therapeutic tools. Whenever applicable, we draw connections with other research fields to encourage intercommunity conversations. We also offer recommendations and cautions regarding the general process of cancer-related piRNA studies and the methods/tools used at each step. Finally, we call attention to some issues that, if left unsolved, might impede the future development of this field.
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http://dx.doi.org/10.1016/j.semcancer.2020.08.012DOI Listing
September 2020

Association between IVF/ICSI treatment and preterm birth and major perinatal outcomes among dichorionic-diamnionic twin pregnancies: A seven-year retrospective cohort study.

Acta Obstet Gynecol Scand 2021 01 5;100(1):162-169. Epub 2020 Oct 5.

Foshan Institute of Fetal Medicine, Southern Medical University Affiliated Maternal & Child Health Hospital of Foshan, Foshan, China.

Introduction: This study aimed to evaluate the preterm birth and additional perinatal outcomes between spontaneous and in vitro fertilization (IVF) and intracytoplasmic sperm injection (ICSI) dichorionic-diamnionic (DCDA) twin pregnancies.

Material And Methods: This retrospective cohort study was conducted in a tertiary university-affiliated medical center. All women with DCDA twin pregnancies were considered for inclusion. The primary outcome of interest was preterm birth <37 weeks of gestation and secondary outcomes included spontaneous preterm birth, iatrogenic (induced) preterm birth, gestational diabetes mellitus, pregnancy-induced hypertensive disorder, preeclampsia, preterm premature rupture of membranes (PPROM), intrahepatic cholestasis of pregnancy, placenta previa, neonatal intensive care unit (NICU) admission, birthweight discordance, small for gestational age, neonatal respiratory distress syndrome, ventilator support, and perinatal death and/or severe morbidity. These outcomes were compared between IVF/ICSI and spontaneous twin pregnancies. Multivariable logistic regressions were used to adjust for confounders. General estimated equation models were used to address intertwin correlation.

Results: A total of 1297 twin pregnancies, including 213 spontaneous and 1084 IVF/ICSI DCDA pregnancies, met the inclusion criteria. Women with IVF/ICSI pregnancies were older and had higher body mass index, adherence with prenatal care and proportion of nulliparity. After adjustment for confounders, IVF/ICSI pregnancies were associated with a slight increase in preterm birth <37 weeks of gestation (adjusted odds ratio [aOR] 1.72; 95% CI 1.24-2.39), iatrogenic preterm birth <37 weeks of gestation (aOR 1.41; 95% CI 1.00-1.97) as well as NICU admission (aOR 1.34; 95% CI 1.00-1.80). IVF/ICSI pregnancies were associated with a decrease in PPROM (aOR 0.64; 95% CI 0.42-0.99). There were no differences between IVF/ICSI and spontaneous DCDA pregnancies in terms of spontaneous preterm birth, gestational diabetes mellitus, pregnancy-induced hypertensive disorder, preeclampsia, intrahepatic cholestasis of pregnancy, placenta previa, birthweight discordance, small for gestational age, neonatal respiratory distress syndrome, ventilator support, and perinatal death and/or severe morbidity.

Conclusions: IVF/ICSI DCDA twin pregnancies were associated with a slight increase in preterm birth <37 weeks of gestation, iatrogenic preterm birth <37 weeks of gestation, and NICU admission but with a decrease in PPROM. Other outcomes were comparable between IVF/ICSI and spontaneous DCDA twin pregnancies. Multicenter studies with adequate power remain warranted.
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http://dx.doi.org/10.1111/aogs.13981DOI Listing
January 2021

Serum piRNA-54265 is a New Biomarker for early detection and clinical surveillance of Human Colorectal Cancer.

Theranostics 2020 9;10(19):8468-8478. Epub 2020 Jul 9.

Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology in South China and Collaborative Innovation Center for Cancer Medicine, Guangzhou, China.

Our previous study has demonstrated an oncogenic role of PIWI-interacting RNA-54265 (piR-54265) in colorectal cancer (CRC). Here, we investigate whether it can be a blood biomarker for population screening and clinical applications. Serum piR-54265 levels were determined by a digital PCR method in 209 cancer-free healthy controls, 725 patients with CRC, 1303 patients with other types of digestive cancer and 192 patients with benign colorectal tumors. A prospective case-control analysis was conducted to assess the predictive value of serum piR-54265 for future CRC diagnosis. Receiver operating characteristic (ROC) curve was constructed to quantify the diagnostic performance of serum piR-54265 levels by assessing its sensitivity, specificity and respective areas under curve (AUC). The odds ratios (ORs) were computed using multivariate logistic regression models. Serum piR-54265 levels were significantly elevated only in patients with CRC compared with controls and patients with other cancer types. The AUC for recognizing CRC was 0.896 (95% CI, 0.874-0.914), with a sensitivity and specificity being 85.7% and 65.1% at 1500 copies/µL as a cut-off value. The serum piR-54265 levels in patients declined substantially after surgery but increased significantly again when tumor relapses. The prediagnostic serum piR-54265 levels were significantly associated with future CRC diagnosis, with the ORs of 7.23, 2.80, 2.45, and 1.24 for those whose CRC was diagnosed within 1, 2, 3 and >3 years. Serum piR-54265 test is more sensitive than other blood CRC markers. Serum piR-54265 may serve as a valuable biomarker for CRC screening, early detection and clinical surveillance.
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http://dx.doi.org/10.7150/thno.46241DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7392023PMC
May 2021

Feasibility of Transcatheter Closure of Secundum Atrial Septal Defect in Low Weight Infants Under 2-Year-Old from a 3-year Retrospective Cohort Study.

Am J Cardiol 2020 10 17;132:133-139. Epub 2020 Jun 17.

Department of Cardiac Pediatrics, Guangdong Cardiovascular Institute, Guangdong Academy of Medical Sciences/Guangdong General Hospital, Guangzhou, China. Electronic address:

We aimed to evaluate the feasibility of interventional treatment of atrial septal defect (ASD) in low weight infants under 2-year-old. Seven hundred and ninety-three secundum ASD patients were divided into 2 groups: 665 were above 2-year-old and 128 were under 2-year-old. The basic conditions before the operation, postoperative complications within 24 hours, and adverse outcomes during a three-year follow-up were compared between the 2 groups using multivariate analysis. There were significant differences in age, weight, and the diameter of the ASD between the 2 groups (p <0.001). The immediate success rate of the procedure was 96.7%. There were no significant differences in the success rate of the procedure, the incidence of residual shunt, arrhythmia, procedure-related arrhythmia, and occluder shedding between 2 groups (p >0.05). Similarly, we found no association between age ≤2-year-old and any adverse outcomes postprocedure within 24 hours, including procedure failure (OR = 0.35; 95%CI: 0.04 to 2.93), residual shunt (OR = 1.07; 95%CI: 0.54 to 2.14), arrhythmia (OR = 0.68; 95%CI: 0.32 to 1.43), or procedure-related arrhythmia (OR = 0.34; 95%CI: 0.04 to 2.87). In the follow-up data, we found no association between age ≤2-year-old and arrhythmia (HR = 0.95; 95%CI: 0.50 to 1.80) and procedure-related arrhythmia (HR = 0.96;95%CI:0.25 to 3.64). Kaplan-Meier survival curves indicated no significant difference in the occurrence of arrhythmia between the 2 groups (log-rank test: p = 0.776). In conclusion, percutaneous ASD closure in young and low weight infants has a high success and low complication rate, along with reliable effects.
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http://dx.doi.org/10.1016/j.amjcard.2020.06.011DOI Listing
October 2020

Metformin inhibits pancreatic cancer metastasis caused by SMAD4 deficiency and consequent HNF4G upregulation.

Protein Cell 2021 02 31;12(2):128-144. Epub 2020 Jul 31.

Department of General Surgery, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, 100730, China.

Pancreatic ductal adenocarcinoma (PDAC) has poor prognosis due to limited therapeutic options. This study examines the roles of genome-wide association study identified PDAC-associated genes as therapeutic targets. We have identified HNF4G gene whose silencing most effectively repressed PDAC cell invasiveness. HNF4G overexpression is induced by the deficiency of transcriptional factor and tumor suppressor SMAD4. Increased HNF4G are correlated with SMAD4 deficiency in PDAC tumor samples and associated with metastasis and poor survival time in xenograft animal model and in patients with PDAC (log-rank P = 0.036; HR = 1.60, 95% CI = 1.03-2.47). We have found that Metformin suppresses HNF4G activity via AMPK-mediated phosphorylation-coupled ubiquitination degradation and inhibits in vitro invasion and in vivo metastasis of PDAC cells with SMAD4 deficiency. Furthermore, Metformin treatment significantly improve clinical outcomes and survival in patients with SMAD4-deficient PDAC (log-rank P = 0.022; HR = 0.31, 95% CI = 0.14-0.68) but not in patients with SMAD4-normal PDAC. Pathway analysis shows that HNF4G may act in PDAC through the cell-cell junction pathway. These results indicate that SMAD4 deficiency-induced overexpression of HNF4G plays a critical oncogenic role in PDAC progression and metastasis but may form a druggable target for Metformin treatment.
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http://dx.doi.org/10.1007/s13238-020-00760-4DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7862466PMC
February 2021

Single-cell transcriptomic analysis in a mouse model deciphers cell transition states in the multistep development of esophageal cancer.

Nat Commun 2020 07 24;11(1):3715. Epub 2020 Jul 24.

School of Life Sciences and Tsinghua-Peking Center for Life Sciences, Tsinghua University, Beijing, China.

Esophageal squamous cell carcinoma (ESCC) is prevalent in some geographical regions of the world. ESCC development presents a multistep pathogenic process from inflammation to invasive cancer; however, what is critical in these processes and how they evolve is largely unknown, obstructing early diagnosis and effective treatment. Here, we create a mouse model mimicking human ESCC development and construct a single-cell ESCC developmental atlas. We identify a set of key transitional signatures associated with oncogenic evolution of epithelial cells and depict the landmark dynamic tumorigenic trajectories. An early downregulation of CD8 response against the initial tissue damage accompanied by the transition of immune response from type 1 to type 3 results in accumulation and activation of macrophages and neutrophils, which may create a chronic inflammatory environment that promotes carcinogen-transformed epithelial cell survival and proliferation. These findings shed light on how ESCC is initiated and developed.
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http://dx.doi.org/10.1038/s41467-020-17492-yDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7381637PMC
July 2020

Efficacy and safety of umbilical cord mesenchymal stem cells in treatment of cesarean section skin scars: a randomized clinical trial.

Stem Cell Res Ther 2020 06 25;11(1):244. Epub 2020 Jun 25.

Foshan Institute of Fetal Medicine, Affiliated Foshan Maternity & Child Healthcare Hospital, Southern Medical University, 11 Renminxi Road, Foshan, 528000, Guangdong, China.

Background: Pathological skin scars, caused by cesarean section, affected younger mothers esthetically and psychosocially and to some extent frustrated obstetricians and dermatologists. Umbilical cord mesenchymal stem cells (UC-MSCs), as a population of multipotent cells, are abundant in human tissues, providing several possibilities for their effects on skin scar tissues. Herein, we performed a randomized, double-blind, placebo-controlled, three-arm clinical trial, aiming to assess the efficacy and safety of UC-MSCs in the treatment of cesarean section skin scars among primiparous singleton pregnant women.

Methods: Ninety primiparous singleton pregnant women undergoing elective cesarean section were randomly allocated to receive placebo, low-dose (3 × 10 cells), or high-dose (6 × 10 cells) transdermal hydrogel UC-MSCs on the surface of the skin incision. The primary outcome was cesarean section skin scars followed after the sixth month, assessed by the Vancouver Scar Scale (VSS).

Results: All the participants completed their trial of the primary outcome according to the protocol. The mean score of estimated total VSS was 5.52 in all participants at the sixth-month follow-up, with 6.43 in the placebo group, 5.18 in the low-dose group, and 4.71 in the high-dose group, respectively. No significant difference was found between-group in the mean scores for VSS at the sixth month. Additional prespecified secondary outcomes were not found with significant differences among groups either. No obvious side effects or adverse effects were reported in any of the three arms.

Conclusion: This randomized clinical trial showed that UC-MSCs did not demonstrate the effects of improvement of cesarean section skin scars.

Trial Registration: ClinicalTrials.gov identifier, NCT02772289. Registered on 13 May 2016.
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http://dx.doi.org/10.1186/s13287-020-01695-7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7316165PMC
June 2020

Clinical and genomic characterization of neutral tumor evolution in Head and Neck Squamous Cell Carcinoma.

Genomics 2020 09 20;112(5):3448-3454. Epub 2020 Jun 20.

Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangzhou, China. Electronic address:

Recent studies suggest that a significant proportion of cancers undergo neutral tumor evolution. We applied neutral evolution model in HNSCC patients from The Cancer Genome Atlas (TCGA). To ensure the accuracy of classification results, a sample with the purity of tumor <0.7 was excluded. A tumor sample was considered to evolve neutrally if R ≥ 0.98. We found that about 16% of HNSCC patients undergo neutral tumor evolution. We showed that neutral evolution HNSCC patients have better prognosis and higher activities of immune response pathways, and the numbers of co-occurring mutation events and significantly positive selection mutations are significantly less than non-neutral evolution HNSCC patients. In conclusion, we described a comprehensive clinical and genomic characteristics of neutral tumor evolution in Head and Neck Squamous Cell Carcinoma (HNSCC), and provided evidence that the evolution history of HNSCC has both clinical and biological implications.
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http://dx.doi.org/10.1016/j.ygeno.2020.06.030DOI Listing
September 2020
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