Early-onset gastrointestinal cancer:An epidemiological reality with great significance and implications

During the last few years,epidemiological data from many countries suggest that the incidence and prevalence of many cancers of the digestive system are shifting from the older to the younger ages,the so-called“early-onset cancer”.This is particularly evident in colorectal cancer and secondarily in other malignant digestive neoplasms,mainly stomach and in a lesser degree pancreas,and biliary tract.It should be emphasized that data concerning digestive neoplasms,except for those referring to the colon and stomach,could be characterized as rather insufficient.The exact magnitude of the shift in younger ages is expected to become clearer shortly,as long as relevant epidemiological data from many parts of the world would be available.The most important question concerns the etiology of this phenomenon,since its magnitude cannot be explained solely by the better diagnostic methodology and the preventive programs applied in many countries.The existing data support the assumption that a number of environ-mental factors may play a primary role in influencing carcinogenesis,sometimes from childhood.Changes that have appeared in the last decades related mainly to eating habits,consistency of gut microbiome and an increase of obese people interacting with genetic factors,ultimately favor the process of carcinogenesis.Even these factors however,are not entirely sufficient to explain the age-related changes in the frequency of digestive neoplasms.Studies of the individual effect of each of the already known factors or factors likely to be involved in the etiology of this phenomenon and studies using state-of-the-art technologies to accurately determine the degree of the population exposure to these factors are required.In this article,we attempt to describe the epidemiological data supporting the age-shifting of digestive malignancies and their possible pathogenesis.Finally,we propose some measures regarding the attitude of the scientific community to this alarming phenomenon.

Treatment patterns and survival outcomes in patients with nonmetastatic early-onset pancreatic cancer

BACKGROUND The incidence of patients with early-onset pancreatic cancer(EOPC;age≤50 years at diagnosis)is on the rise,placing a heavy burden on individuals,families,and society.The role of combination therapy including surgery,radiotherapy,and chemotherapy in non-metastatic EOPC is not well-defined.AIM To investigate the treatment patterns and survival outcomes in patients with non-metastatic EOPC.METHODS A total of 277 patients with non-metastatic EOPC who were treated at our institution between 2017 and 2021 were investigated retrospectively.Overall survival(OS),disease-free survival,and progression-free survival were estimated using the Kaplan-Meier method.Univariate and multivariate analyses with the Cox proportional hazards model were used to identify prognostic factors.RESULTS With a median follow-up time of 34.6 months,the 1-year,2-year,and 3-year OS rates for the entire cohort were 84.3%,51.5%,and 27.6%,respectively.The median OS of patients with localized disease who received surgery alone and adjuvant therapy(AT)were 21.2 months and 28.8 months,respectively(P=0.007).The median OS of patients with locally advanced disease who received radiotherapy-based combination therapy(RCT),surgery after neoadjuvant therapy(NAT),and chemotherapy were 28.5 months,25.6 months,and 14.0 months,respectively(P=0.002).The median OS after regional recurrence were 16.0 months,13.4 months,and 8.9 months in the RCT,chemotherapy,and supportive therapy groups,respectively(P=0.035).Multivariate analysis demonstrated that carbohydrate antigen 19-9 level,pathological grade,T-stage,N-stage,and resection were independent prognostic factors for non-metastatic EOPC.CONCLUSION AT improves postoperative survival in localized patients.Surgery after NAT and RCT are the preferred therapeutic options for patients with locally advanced EOPC.

Low-molecular-weight heparin and preeclampsia—does the sword cut both ways?Three case reports and review of literature

BACKGROUND Low-molecular-weight heparins(LMWH)are the most commonly used anticoagulants during pregnancy.It is considered to be the drug of choice due to its safety in not crossing placenta.Considering the beneficial effect in the improvement of microcirculation,prophylactic application of LMWH in patients with preeclampsia became a trend.However,the bleeding risk related with LMWH in preeclampsia patients has seldomly been evaluated.This current study aimed to identify the potential risks regarding LMWH application in patients with preeclampsia.CASE SUMMARY Herein we present a case series of three pregnant women diagnosed with preeclampsia on LMWH therapy during pregnancy.All the cases experienced catastrophic hemorrhagic events.After reviewing the twenty-one meta-analyses,the bleeding risk related with LMWH seems ignorable.Only one study analyzed the bleeding risk of LMWH and found a significantly higher risk of developing PPH in women receiving LMWH.Other studies reported minor bleeding risks,none of these were serious enough to stop LMWH treatment.Possibilities of bleeding either from uterus or from intrabdominal organs in preeclampsia patients on LMWH therapy should not be ignored.Intensive management of blood pressure even after delivery and homeostasis suture in surgery are crucial.CONCLUSION Consideration should be given to the balance between benefits and risks of LMWH in patients with preeclampsia.

Rationale of a Cross-Sectional Descriptive Study on Associated Factors and Prognosis Maternal-Fetal Links to Early Onset Preeclampsia at the University Clinics of Kinshasa, DR Congo

Background: Preeclampsia (PE) is one of the forms of hypertensive diseases that occur during pregnancy. Early-onset preeclampsia (EOP), which occurred before 34 weeks, proved to be the deadliest. Indeed, it is characterized by a poor maternal and fetal prognosis. EOP has a disparate incidence in the world varying between 0.9% and 31%. Several risks factors are associated with the occurrence of EOP, which is responsible of several adverse obstetrical outcomes. Complications can affect up to 85% of pregnant women with EOP, especially when EOP appears very early, before 28 or even 25 weeks’ gestation. Objectives: To determine frequency of EOP at the University Clinics of Kinshasa, to describe sociodemographic and clinical characteristics of pregnant women with EOP and to identify its risks factors and its association adverse obstetrical outcomes. Methods: The study will be a cross-sectional analytical study in University Clinics of Kinshasa from January 2016 to December 2022. The minimal size will be 119. Our study population will consist of pregnant women who consult for antenatal best care and are neonates in our Clinic. Result will be presented as percentage proportion. Comparison and proportion means between groups will be made using Student’s test and Pearson’s chi-square test, respectively. Our test will be statistically significant for a p-value ≤ than less 0.05. Data will be collected and analysed anonymously and confidentiality. Conclusion: We believe that our study should enable us to identify profile of gestational carriers at risk of EOP in our environment, as well as prognosis associated with this entity, with a view to arousing particular interest in EOP.

Early-onset colorectal cancer:A review of current knowledge

Colorectal cancer(CRC)is one of the most prevalent malignancies worldwide.Although most prevalent among older people,its incidence above 50 years old has been decreasing globally in the last decades,probably as a result of better screening.Paradoxically,its incidence in patients below 50 years old[early-onset CRC(EO-CRC)]has been increasing,for reasons not yet fully understood.EOCRC’s increasing incidence is genre independent but shows racial disparities and has been described to occur worldwide.It follows a birth-cohort effect which probably reflects a change in exposure to CRC risk factors.Its incidence is predicted to double until 2030,which makes EO-CRC a serious public health issue.Both modifiable and non-modifiable risk factors have been identified-some are potential targets for preventive measures.EO-CRC is often diagnosed at advanced stages and histological features associated with poor prognosis have been described.EO-CRC presents some distinctive features:Microsatellite instability is common,but another subtype of tumours,both microsatellite and chromosome stable also seems relevant.There are no age-specific treatment protocols and studies on EO-CRC survival rates have shown conflicting data.Due to the higher germline pathological mutations found in EO-CRC patients,an accurate genetic risk evaluation should be performed.In this review,we summarize the current evidence on epidemiological,clinical,histopathological and molecular features of EO-CRC and discuss the contribution of genetics and lifestyle risk factors.We further comment on screening strategies and specific dimensions to consider when dealing with a younger cancer patient.

Molecular genetics of early-onset colorectal cancer

Early-onset colorectal cancer(EOCRC)has been rising in global prevalence and incidence over the past several decades.Environmental influences,including generational lifestyle changes and rising obesity,contribute to these increased rates.While the rise in EOCRC is best documented in western countries,it is seen throughout the world,although EOCRC may have distinct genetic mutations in patients of different ethnic backgrounds.Pathological and molecular characterizations show that EOCRC has a distinct presentation compared with later-onset colorectal cancer(LOCRC).Recent studies have identified DNA,RNA,and protein-level alterations unique to EOCRC,revealing much-needed biomarkers and potential novel therapeutic targets.Many molecular EOCRC studies have been performed with Caucasian and Asian EOCRC cohorts,however,studies of other ethnic backgrounds are limited.In addition,certain molecular characterizations that have been conducted for LOCRC have not yet been repeated in EOCRC,including high-throughput analyses of histone modifications,mRNA splicing,and proteomics on large cohorts.We propose that the complex relationship between cancer and aging should be considered when studying the molecular underpinnings of EOCRC.In this review,we summarize current EOCRC literature,focusing on sporadic molecular alterations in tumors,and their clinical implications.We conclude by discussing current challenges and future directions of EOCRC research efforts.

Maternal TMPRSS6 Gene Polymorphism rs855791SNP in Women with Preeclampsia

Introduction: Preeclampsia can lead to several maternal and perinatal adverse effects. There are few published data on the association between transmembrane serine protease 6 (TMPRSS6) gene polymorphism and preeclampsia. Objective: To assess the association between TMPRSS6 gene polymorphism rs855791SNP in women with preeclampsia compared with healthy pregnant women. Method: A case-control study (60 women in each arm) was conducted at Saad Abuaela Maternity Hospital in Khartoum, Sudan. Sociodemographic and clinical data were gathered through a questionnaire. The participant was genotype for TMPRSS6 gene rs855791SNP using Polymerase Chain Reaction and Restriction Fragment Length Polymorphism (PCR-RFLP). The results were confirmed by DNA sequencing. Result: There was no significant difference in the median of age, parity, and body mass index. The distribution of the genotypes and alleles of TMPRSS6 rs855791 was consistent with the HWE. The overall TMPRSS6 rs855791 polymorphism was not significantly associated with preeclampsia. However, the proportion of heterozygotes (TC) was considerably higher in the women with preeclampsia (46.7%) than in the control group (23.3%) (p = 0.001;OR = 2.71;95% CI = 1.21 - 6.07). The proportion of homozygotes (TT) and T alleles was not significantly different between women with preeclampsia and the control group. Conclusion: The overall TMPRSS6 rs855791 polymorphism was not significantly associated with preeclampsia and healthy control.

Elabela is a reliable biomarker for predicting early onset preeclampsia:A comparative study

BACKGROUND Preeclampsia(PE)is a multisystemic metabolic disease with an undetermined etiology.PE is a worldwide cause of maternal and perinatal morbidity,subdivided into early(EoPE)and late-onset(LoPE)according to 34 wk of gestation as a divider.Many researchers investigated biomarkers for predicting PE to halt its consequences on the feto-maternal outcome.Elabela(Ela)is a newly discovered peptide hormone that was implicated in PE pathogenesis.Earlier rodent studies discussed Ela’s role in controlling blood pressure.Moreover,Ela deficiency was associated with PE development.AIM To test whether plasma Ela could serve as a reliable marker for predicting PE based on the time of onset(EoPE vs LoPE)compared to age and body mass matched healthy controls since no definitive treatment exists for PE but to terminate a pregnancy.METHODS This case-control study recruited(n=90)pregnant who fulfilled inclusion criteria;they were allocated into three groups:EoPE(30/90)(<34 wk of gestation);LoPE(30/90)(≥34 wk of gestation);and healthy pregnant(30/90).Demographic criteria;biochemical,hematological,and maternal plasma Ela levels were recorded for comparison.RESULTS Serum Ela was significantly reduced in EoPE compared to LoPE and healthy controls(P=0.0023).The correlation confirmed a strong inverse relationship with mean atrial blood pressure(r=-0.7,P<0.001),while gestational age and platelets count showed a moderate correlation with(r=0.4 with P<0.0001).No correlation was confirmed between the body mass index(BMI)and urine albumin.The predictive ability of 25 centile serum Ela had an Odds ratio of 5.21,95%confidence interval(1.28,21.24),P=0.02 for predicting EoPE.The receiver operator characteristic curve defined the Ela cutoff value at>9.156 with 96.7%and 93.3%sensitivity and specificity,P<0.0001 in predicting EoPE.CONCLUSION A strong correlation of serum Ela with PE parameters with excellent sensitivity and specificity in distinguishing EoPE independent of the BMI,age,and blood pressure which makes Ela a recommendable marker in screening.Further research is warranted to explore prognostic and therapeutic applications for Ela in PE.

Role of FOXP3 in Immunohistochemical Expression in Preeclampsia

Background: FoxP3 gene variants have been linked to endometriosis, infertility, and autoimmune illnesses, according to numerous researches. Maternal sensitivity to the PE gene and the genetic variations of FoxP3 has not been thoroughly investigated. Objective: Investigation of the immune-histochemical expression of FoxP3 in placental tissue of PE patients. Methods: A total of 26 pre-eclamptic women as a case and 26 ethnically matched healthy pregnant women as a control group aged between 18 and 40 years old of different gravidity and parity referred to the labor ward for delivery either by vaginal delivery or cesarean section was enrolled to investigate the immunohistochemical expression of FOXP3 in placental tissue of PE patients. Results: Lower expression of FOXP3 IHC was statistically significant and noted in the group of preeclampsia compared to the healthy control group. Lower gestational age at delivery and a higher percentage of cesarean section were statistically significant and noted in the group of preeclampsia compared to the healthy control group. Conclusion: In comparison to the healthy control group, preeclampsia patients had statistically significantly lower FOXP3 IHC expression, and FOXP3 polymorphism was associated with the development of PE. Our findings can serve as a guide for statistical analyses and functional investigations that are more in-depth.

UCK2 promotes the proliferation,migration,and invasion of trophoblast cells in preeclampsia by activating the STAT3 pathway

Background:Preeclampsia(PE),characterized by hypertension and proteinuria,leads to serious maternal and infant complications.Uridine-cytidine kinase 2(UCK2)belongs to the UCK family,a class of enzymes that catalyzes the conversion of uridine and cytidine to monophosphate form.However,the role of UCK2 in PE has not been reported.Methods:The expression of UCK2 was detected in the placenta of PE patients and N(ω)-nitro-L-arginine methyl esterinduced PE mouse model.Through forced up-regulation or down-regulation of UCK2 in vitro,we examined the effects of UCK2 on the proliferation,apoptosis,migration,and invasion of trophoblast cells.Stattic,the inhibitor of STAT3 pathway,was used to investigate whether the STAT3 pathway mediates the biological function of UCK2 in trophoblast cells.Results:The present study found that UCK2 showed low expression in the placenta of PE patients and PE mouse model.MTT(3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide)and flow cytometry assays verified that up-regulation of UCK2 promoted the proliferation of trophoblast cells,while the silence of UCK2 suppressed cell proliferation.Besides,flow cytometry and TdT-mediated dUTP Nick-End Labeling assays demonstrated that knockdown of UCK2 resulted in apoptosis of trophoblast cells.The wound healing and transwell assays showed that the migration and invasion activities of the trophoblast cells were facilitated by the overexpression of UCK2 and were blocked by the silence of UCK2.Furthermore,the expression of phosphorylated STAT3 was increased with the upregulation of UCK2 and decreased with the inhibition of UCK2.When the STAT3 pathway was blocked by its inhibitor stattic,the promotion effects of UCK2 on trophoblast cells were suppressed.Conclusion:UCK2 promotes the proliferation,migration,and invasion of trophoblast cells,and these effects may be partly mediated by the activation of the STAT3 pathway.

Rationale of a Cross-Sectional Descriptive Study on Temporal Evolution of Frequency, Risk Factors and Complications of Preeclampsia in the University Clinics of Kinshasa, DR Congo

Background: Knowledge of temporal evolution of preeclampsia (PE) in its various aspects is essential in strategies to reduce maternal and perinatal morbidity and mortality. Preeclampsia is a public health problem due to maternal mortality associated with it worldwide (5.6%). Improving quality of its management is a major challenge in low-income countries where, despite progress made in this field, PE remains a major factor in maternal morbidity and mortality. Objective: To evaluate temporal evolution of frequency, risk factors and complications of PE at the University clinics of Kinshasa (UCK). Methods: Descriptive and cross-sectional study concerning minimum simple size of 119 pregnant women who consulted for antenatal care at the University clinics of Kinshasa from January 2012 to December 2022. Results will be reported as percentage proportion, mean and standard deviation. Comparison of proportion and means between groups will be made using Student’s t-test and Pearson’s chi-square test, respectively. The test will be statistically significant for a p value ≤ less than 0.05. Data will be collected and analysed anonymously and confidentially. Conclusion: This study will allow us to evaluate the effectiveness of different prevention and treatment modalities used over time in management of preeclampsia in our setting.

Effect of yoga practice in reducing blood pressure,platelet blood count,and proteinuria in pregnant women with mild preeclampsia

Objective:In determining the effects of yoga practice on mild preeclampsia,this study examines the blood pressure,blood platelet(PLT)count,and proteinuria status in pregnant women over 20 weeks of pregnancy.Materials and Methods:This research is an experimental study with a pre–post intervention design.We collected forty pregnant women with mild preeclampsia from all populations.All participants agreed to practice 30 min of yoga every week for 1 month.The blood pressure,the blood PLT count,and proteinuria were measured before and after the yoga intervention.The statistical analysis used the t‑test for the blood PLT count variable,the McNemar test for the proteinuria variable,and the Wilcoxon test for the blood pressure variable.Results:The results showed a decrease in systole blood pressure from 134.17±7.17 mmHg before a yoga intervention to 120±4.17 mmHg after yoga intervention(P<0.001)and a decrease in diastole blood pressure from 89.58±5.5 mmHg before the intervention to 79.38±4.25 mmHg after the intervention(P<0.001).However,there was no significant difference in blood PLT count(P=0.104)and proteinuria(P=0.063)before and after a yoga intervention in pregnant women with mild preeclampsia patients.Conclusions:Yoga exercise during pregnancy(upper 20 weeks of gestation)significantly decreased systolic and diastolic blood pressure in mild preeclampsia patients.

Association between Placenta Malaria Parasites and Preeclampsia/Eclampsia among Parturient Mothers in Alex Ekwueme Federal University Teaching Hospital Abakaliki

In tropical countries, malaria and preeclampsia/eclampsia are common diseases of pregnancy;and placenta have been implicated in the pathophysiology of both disease processes. The two diseases have pathophysiologic similarities in the placenta such as placenta ischaemia, endothelial dysfunction and production of pro-inflammatory cytokine. Yet, there is paucity of studies on the association of these two disease processes. Determining the association between the two disease processes may help to unravel the pathogenesis of preeclampsia and also help in its prevention and patient management. Objective: Determined the association between placenta malaria parasitemia and preeclampsia/eclampsia among parturients at Alex Ekwueme Federal University Teaching Hospital Abakaliki. Materials and Methods: This was a case control study that was conducted in the Labour wards of department of Obstetrics and Gynaecology, Alex Ekwueme Federal University Teaching Hospital Abakaliki (AEFUTHA) and Mile 4 Missionary Hospital Abakaliki, a comprehensive health care centre in Abakaliki, Ebonyi state. It was conducted over a period of 6 months between 1st October 2021 and 31st March, 2022. The cases in this study were parturients that developed preeclampsia/eclampsia in the course of pregnancy, while the controls were parturient without preeclampsia/eclampsia. Interviewer-administered questionnaires were used to collect data on socio-demographic characteristics, obstetrics and medical histories. Histological examinations were conducted to isolate plasmodium falciparum parasites from placenta samples obtained from the maternal surface of the placenta. The data was processed using Epi Info software. Categorical variables were analyzed using Mc Nemar X2 test, with a p-value of 0.05 considered statistically significant. Logistic regression models were used to estimate the odds ratios (OR) and 95% CI of the association between placenta malaria parasites and preeclampsia/eclampsia was conducted. Relative risk with 95% CI was used to determine both fetal and maternal outcomes. Results: The prevalence of preeclampsia during the study period was 2.9%. Placenta malaria was positive in twenty one (21) of the 67 cases of preeclampsia/eclampsia analyzed, giving a prevalence of 31.3% and in eleven (11) out of 68 controls (normotensive) patients analyzed, giving a prevalence of 16.2%. The presence of placenta malaria significantly increased the odds of developing preeclampsia/eclampsia among parturients (OR = 2.4, 95% CI = 1.0 - 5.4, P value = 0.04). Presence of placenta malaria in mothers with preeclampsia/eclampsia was associated with adverse pregnancy outcomes such as cerebrovascular accident (RR = 19.2, 95% CI = 1.1 - 341.7, P value = 0.04), DIC (RR = 10.9, 95% CI = 1.4 - 88.0, P value = 0.02), abruptio placenta (RR = 2.4, 95% CI = 1.2 - 4.8, P value = 0.01), pulmonary edema (RR = 2.7, 95% CI = 1.1 - 25.9, P value = 0.03), IUGR (RR = 2.1, 95% CI = 1.1 - 4.5, P value = 0.03) and IUFD (RR = 3.8, 95% CI = 1.3 - 11.7, P value = 0.02). Presence of placenta malaria also increased the risk of NICU admission (RR = 2.6, 95% CI = 1.1 - 6.0, P value = 0.03), Low 1st minute APGAR score (RR = 2.7, 95% CI = 1.2 - 6.1, P value = 0.02) and Low 5th minute APGAR score (RR = 3.0, 95% CI = 1.0 - 8.6, P value = 0.04) among neonates delivered by mothers with preeclampsia/eclampsia. However, presence of placenta malaria did not significantly increase maternal and perinatal mortalities. Conclusion: There is a higher prevalence of placenta malaria among mothers with preeclampsia/eclampsia when compared with normotensive controls and this was associated with increased risk of certain maternal and perinatal morbidities. Placental malaria was not associated with increased risk of either maternal or perinatal mortality.

Effect of Salvia Miltiorrhiza Injection on Blood Pressure and Cardiac Function in Rats with Gestational Hypertension and Preeclampsia

Objective: This study is to observe the effects of Salvia miltiorrhiza injection on blood pressure and cardiac function in rats with pregnancy-induced hypertension and preeclampsia. Methodology: Syncytiotrophoblast microvilli (stbm) and l-arginine nitrosyl methyl ester were screened out via caudal vein injection. Twenty gestational hypertension-preeclampsia model SD (Sprague Dawley) rats successfully induced by L-NAME (L-arginine Nitrosyl methyl ester) were randomly divided into 2 groups (model group and Danshen injection group, n = 10). Then another 10 normal pregnant SD rats without model were selected as blank control group. The Salvia miltiorrhiza injection group was given Salvia miltiorrhiza injection (0.5 g?kg?1?d?1) through tail vein, and the control group and model group were given equal volume of normal saline through tail vein injection. All three groups were treated by tail vein injection once a day (d) for 7 days. After treatment, heart rate (HR), Systolic pressure (SP), diastolic pressure (DP) and mean arterial pressure (MAP) were measured by tail artery. Left ventricular end-diastolic diameter (LVDd) and Left ventricular end systolic diameter (LVDs) were recorded by echocardiography. Left ventricular end diastolic pressure (LVEDP), left ventricular systolic pressure (LVSP), left ventricular ejection fraction (left ventricular ejection) fraction, LVEF) and the maximum rate of increase/decrease of left ventricular pressure during isovolemic systole (+dp/dtmax/?dp/dtmax);Endothelin-1 (ET-1) levels in rat tail vein blood were detected by ELISA. Results: SP, DP, MP, HR, LVSP, LVDs and ?dp/dtmaxx were all decreased, plasma ET-1 expression was low, and LVDd, LVEDP, LVEF, and +dp/dtmax were all increased in the Salvia miltiorroot injection group, with statistical significance compared to the model group (p Conclusion: Salvia miltiorrhiza injection can improve the cardiac function and reduce blood pressure in rats with pregnancy-induced hypertension and preeclampsia, and the mechanism may be related to alleviating systemic arteriolar spasm by regulating ET-1 level.

The expression of TUSC3 in Preeclampsia and the function in trophoblast cell

Objective:In this study,we aimed to explore the expression of TUSC3 in Preeclampsia and to research the potential function of TUSC3 in placental trophoblast cells.Methods:We collected 10 cases of normal placental tissues and preeclampsia placental tissues,respectively.These parturient received treatment at the First Affiliated Hospital of Hainan Medical University between June 1,2020,and December 31,2022.The expression of TUSC3 in placenta was detected by immunohistochemistry.The effect of TUSC3 on the migration and invasion of HTR8/SVneo cells was analyzed by migration assay and Transwell assay.Results:The expression of TUSC3 was slightly increased in placental villis in preeclampsia.Immunohistochemistry and qRT-PCR were used to detect the expression of TUSC3 protein and mRNA in placental tissues.TUSC3 was markedly upregulated in PE placental tissues(P<0.01).The results of migration assay and Transwell assay showed that the migration rate and the number of invasive cells were significantly decreased in HTR8 overexpressing TUSC3(P<0.01).Conclusions:TUSC3 was markedly increased in PE placental tissues and inhibited trophoblast cells migration and invasion.

Construction and validation of a personalized prediction model for postpartum anxiety in pregnant women with preeclampsia

BACKGROUND Preeclampsia is a pregnancy-specific multi-system disease with multi-factor and multi-mechanism characteristics.The cure for preeclampsia is to terminate the pregnancy and deliver the placenta.However,it will reduce the perinatal survival rate,prolong the pregnancy cycle,and increase the incidence of maternal complications.With relaxation of the birth policy,the number of elderly pregnant women has increased significantly,and the prevalence rate of preeclampsia has increased.Inappropriate treatment can seriously affect the normal postpartum life of pregnant women.Studies have shown that postpartum anxiety in women with preeclampsia can affect physical and mental health,as well as infant growth and development.AIM To analyze the factors influencing preeclampsia in pregnant women complicated with postpartum anxiety,and to construct a personalized predictive model.METHODS We retrospectively studied 528 pregnant women with preeclampsia who delivered in Wenzhou Hospital of Integrated Traditional Chinese and Western Medicine between January 2018 and December 2021.Their basic data were collected,and various physiological and biochemical indicators were obtained by laboratory examination.The self-rating anxiety scale was used to determine whether the women had postpartum anxiety 42 d after delivery.The independent factors influ-encing postpartum anxiety in early pregnant women with eclampsia were analyzed with multifactor logistic regression and a predictive model was constructed.The Hosmer-Lemeshow test and receiver operating characteristic(ROC)curve were used to evaluate the calibration and discrimination of the predictive model.Eighty pregnant women with preeclampsia admitted to our hospital from January 2022 to May 2022 were retrospectively selected to verify the prediction model.RESULTS We excluded 46 of the 528 pregnant women with preeclampsia because of loss to follow-up and adverse outcomes.A total of 482 cases completed the assessment of postpartum anxiety 42 d after delivery,and 126(26.14%)had postpartum anxiety.Bad marital relationship,gender discrimination in family members,hematocrit(Hct),estradiol(E2)hormone and interleukin(IL)-6 were independent risk factors for postpartum anxiety in pregnant women with preeclampsia(P<0.05).Prediction model:Logit(P)=0.880×marital relationship+0.870×gender discrimination of family members+0.130×Hct-0.044×E2+0.286×IL-6-21.420.The area under the ROC curve of the model was 0.943(95%confidence interval:0.919-0.966).The threshold of the model was-1.507 according to the maximum Youden index(0.757),the corresponding sensitivity was 84.90%,and the specificity was 90.70%.Hosmer-Lemeshowχ^(2)=5.900,P=0.658.The sensitivity,specificity and accuracy of the model were 81.82%,84.48%and 83.75%,respectively.CONCLUSION Poor marital relationship,family gender discrimination,Hct,IL-6 and E2 are the influencing factors of postpartum anxiety in preeclampsia women.The constructed prediction model has high sensitivity and specificity.

Exosome-derived miR-146a-5p from decidual macrophages in preeclampsia inhibits the viability and invasive ability of trophoblast cells by targeting HIF1α

Objective:To investigate the effect of exosomes secreted by decidual macrophages on trophoblast cells and their molecular mechanism.Methods:The decidual tissues of patients with preeclampsia(PE)and normal-term pregnant women were collected.Macrophages were obtained by the density gradient method and then flow cell sorting,then the exosomes were extracted.The structure of the exosomes was observed by transmission electron microscope.The expression of CD63,a marker protein of the exocrine body,was detected by western blot,and the exosomes were identified.CCK-8 was used to detect the effect of exosomes on trophoblast cell viability.Transwell migration experiment was used to detect the influence on migration ability.The expression of miR-146a-5p in exosomes was detected by qPCR.The effect of exosomes on the expression of HIF1αprotein in trophoblasts was detected by western blot and detection of the binding site between miR-146a-5p and HIF1αby double luciferase reporter gene was conducted.Results:The exosomes of macrophages present a"cake"structure with a middle depression about 30-130 nm in diameter,and CD63 is highly expressed,which conforms to the characteristics of exosomes.Compared with the normal group,the exosomes of decidual macrophages in the PE group inhibited the activity and migration of trophoblast cells(P<0.001).The expression of miR-146a-5p in the exosomes of decidual macrophages in the PE decreased significantly,and after exosomes of PE decidual macrophages treating trophoblast cells,the protein expression of HIF1αin trophoblast cells was significantly increased.There are targeted binding sites between miR-146a-5p and HIF1α.Conclusion:PE decidual macrophage exosomes can inhibit the viability and migration of trophoblast cells,which may be related to the decreased expression of miR-146a-5p in exosomes,thus promoting HIF1αprotein expression of trophoblast cells.

Advantage of log odds of positive lymph nodes in prognostic evaluation of patients with early-onset colon cancer

BACKGROUND Colon cancer(CC)is one of the most common cancers of the digestive tract,the third most common cancer worldwide,and the second most common cause of cancer-related deaths.Previous studies have demonstrated a higher risk of lymph node metastasis(LNM)in young patients with CC.It might be reasonable to treat patients with early-onset locally advanced CC with extended lymph node dissection.However,few studies have focused on early-onset CC(ECC)patients with LNM.At present,the methods of predicting and evaluating the prognosis of ECC patients with LNM are controversial.From the data of patients with CC obtained from the Surveillance,Epidemiology,and End Results(SEER)database,data of young patients with ECC(≤50 years old)was screened.Patients with unknown data were excluded from the study,while the remaining patients were included.The patients were randomly divided into a training group(train)and a testing group(test)in the ratio of 7:3,while building the model.The model was constructed by the training group and verified by the testing group.Using multiple Cox regression models to compare the prediction efficiency of LNM indicators,nomograms were built based on the best model selected for overall survival(OS)and cause-specific survival(CSS).In the two groups,the performance of the nomogram was evaluated by constructing a calibration plot,time-dependent area under the curve(AUC),and decision curve analysis.Finally,the patients were grouped based on the risk score predicted by the prognosis model,and the survival curve was constructed after comparing the survival status of the high and low-risk groups.RESULTS Records of 26922 ECC patients were screened from the SEER database.N classification,positive lymph nodes(PLN),lymph node ratio(LNR)and log odds of PLN(LODDS)were considered to be independent predictors of OS and CSS.In addition,independent risk factors for OS included gender,race,marital status,primary site,histology,grade,T,and M classification,while the independent prognostic factors for CSS included race,marital status,primary site,grade,T,and M classification.The prediction model including LODDS is composed of minimal Akaike information criterion,maximal concordance indexes,and AUCs.Factors including gender,race,marital status,primary site,histology,grade,T,M classification,and LODDS were integrated into the OS nomogram,while race,marital status,primary site,grade,T,M classification,and LODDS were included into the CSS nomogram.The nomogram representing both cohorts had been successfully verified in terms of prediction accuracy and clinical practicability.CONCLUSION LODDS is superior to N-stage,PLN,and LNR of ECC.The nomogram containing LODDS might be helpful in tumor evaluation and clinical decision-making,since it provides an appropriate prediction of ECC.

Clinical implication of platelet to lymphocyte ratio in early onset preeclampsia:A single-center experience

BACKGROUND Preeclampsia(PE)is a pregnancy syndrome of undetermined etiology;inflammation was one of the proposed theories for its development.AIM To examine the platelet to lymphocyte ratio(PLR),an inflammatory biomarker,as a marker to predict poor maternal-neonatal outcomes in early-onset PE(EoPE).METHODS A cross-sectional study enrolled 60 pregnant women with EoPE(at 32-30 wk of gestation)at a university hospital.Demographic criteria and hematological indices were collected,including platelet counts and indices(mean platelet volume and platelet distribution width),PLR,and the Doppler study,which calculated estimated fetal weight(EFW),amniotic fluid index(AFI),resistance index(RI),and pulsatility index(PI).Participants were followed until delivery,where maternal outcomes were recorded,including;delivery mode and reason for cesarean section,and neonatal outcomes,including fetal growth restriction(FGR),meconium-stained liquid,the 5-min Apgar score,and admission to the intensive care unit.RESULTS There was a trend of insignificant increases in cesarean sections.Sixty-one-point two percent(37/60)fetuses were admitted to the neonatal care unit;70.0%of admitted fetuses were meconium-stained liquor,and 56.7%of them had FGR.PLR was positively correlated with AFI and EFW as r=0.98,0.97,P<0.001;PLR showed negative correlations with PI and RI as r=-0.99,-0.98,P<0.001.The Apgar score and the number of days admitted to the intensive care unit had a positive and negative correlation(0.69,-0.98),P<0.0001,respectively.Receiver operating characteristic calculated a PLR cutoff value(7.49)that distinguished FGR at 100%sensitivity and 80%specificity.CONCLUSION Strong,meaningful relationships between PLR and FGR parameters and a poor neonatal outcome with a significant P value make it a recommendable biomarker for screening EoPE-related complications.Further studies are suggested to see the impact on maternal-neonatal health.

子痫前期胎盘组织中神经型Wiskott-Alrdich综合征蛋白的表达及其意义

目的研究子痫前期胎盘组织中神经型Wiskott-Alrdich综合征蛋白(N-WASP)的表达情况及其临床意义。方法选取2020年7月至2021年12月于中国医科大学附属盛京医院分娩的65例孕产妇作为研究对象,并将其分为早发型子痫前期组(15例)、早发对照组(15例)、晚发型子痫前期组(15例)、晚发对照组(20例)。采用实时定量PCR(RT-qPCR)检测各组胎盘组织中N-WASP mRNA的相对表达量,采用Western blotting和免疫组织化学法检测各组胎盘组织中N-WASP蛋白的表达情况及定位情况。结果RT-q PCR、Western blotting结果显示,早发型子痫前期组胎盘组织N-WASP mRNA和蛋白表达水平显著低于早发对照组(0.50±0.19 vs.0.93±0.73,0.35±0.17 vs.0.72±0.21),晚发型子痫前期组胎盘组织中N-WASP mRNA和蛋白表达水平显著低于晚发对照组(0.83±0.34 vs.1.15±0.34,0.39±0.16 vs.0.76±0.20),差异均有统计学意义(均P<0.05)。N-WASP mRNA在胎盘组织中的表达与早发型及晚发型子痫前期的发生均呈负相关(r=-0.37,P=0.042;r=-0.39,P=0.019)。免疫组织化学检测显示N-WASP蛋白定位于合体滋养细胞、细胞滋养细胞、绒毛间质细胞和血管内皮细胞的胞质中。结论N-WASP低表达可能与子痫前期的发生密切相关。