Development of fetal growth charts in twins stratified by chorionicity and mode of conception:a retrospective cohort study in China

Background:Twin pregnancies continue to increase worldwide;however,the current clinical prenatal evaluation for the intrauterine growth of twins still relies on the growth standards of singletons.We attempted to establish a set of fetal biometric references for Chinese twin pregnancies,stratified by chorionicity and conception mode as spontaneously conceived monochorionic diamniotic(SC-MCDA),spontaneously conceived dichorionic diamniotic(SC-DCDA),and assisted reproductive technology dichorionic diamniotic(ART-DCDA)twins.Methods:From 2016 to 2019,the ultrasonographic fetal biometric measurements were longitudinally collected in pregnant women,including fetal weight,biparietal diameter,head circumference,abdominal circumference,femur length,and humerus length.The linear mixed models were used to test the difference of growth patterns between groups,and the growth curve of each biometric parameter was modeled by a generalized additive model for location scale and shape.Results:A total of 929 twin pregnant women and 2019 singleton pregnant women,met the inclusion criteria.Among twin pregnancies,148 were SC-MCDA,215 were SC-DCDA,and 566 were ART-DCDA twins.Overall,SC-DCDA twins grew faster than SC-MCDA twins,while slower than ART-DCDA twins(all P<0.05),and all of the three groups showed significant differences comparing with singletons,especially during the third trimester.Hence,the customized fetal growth charts of each fetal biometric parameter were,respectively,constructed for SC-MCDA,SC-DCDA,and ART-DCDA twins.Conclusions:The fetal biometric trajectories demonstrated characteristic patterns according to chorionicity and conception mode.To fill the gap,we modeled fetal biometric parameters for Chinese SC-MCDA,SC-DCDA,and ART-DCDA twin pregnancies,hoping to provide a reference for the further establishment of fetal growth reference values for Chinese twin fetuses.

Implementation of International Society Guidelines on Chorionicity Determination in Twins:A Multi-Center Cohort Study in China's Mainland

Objective:Ultrasound determination of chorionicity is poor in early pregnancy in China.In an effort to increase the accuracy rate of prompt chorionicity determination,clinical training was provided to primary care physicians.This study assesses the effects of implementing clinical guidelines on chorionicity determination.Methods:A multi-centered cohort study was conducted between January 2014 and June 2017 in 12 hospitals without fetal medicine centers.In 2014,the obstetricians and ultrasound physicians were trained in clinical practice and ultrasound examination relating to chorionicity determination.Linear and binary regression analyses were conducted to identify the effects of introducing the new protocols,including the diagnosis rate of chorionicty and perinatal outcomes,taking the data from 2014 as a baseline.Pregnancy outcomes were additionally adjusted for maternal age.Results:During the period of this study,3,599 twin pregnancies from 12 centers were enrolled,and a total of 2,998 twin pregnancies were extracted.The rate of overall chorionicity determination,including antenatal and postpartum diagnosis,increased successively from 49.5% in 2014 to 93.5% in 2017(P<0.0001).The rate of ultrasonic chorionicity diagnosis before 14 weeks increased from 25.2% in 2014 to 65.0% in 2017(P<0.0001).These changes were associated with decreasing incidence of preterm birth,a lower risk of stillbirth,whether for one(P=0.0456 in 2016)or two fetuses(P=0.0470 in 2016;P=0.0042 in 2017)and a decreased rate of admission to neonatal intensive care unit(43.0% in 2014,37.4% in 2017;P=0.0032).Conclusions:The implementation of a clinical practice guideline improved both overall and early chorionicity determinations.Regular training workshops of antenatal care are recommended to further promote capability in clinical diagnosis and treatment.

Transplantation of human placental chorionic plate-derived mesenchymal stem cells for repair of neurological damage in neonatal hypoxic-ischemic encephalopathy

Neonatal hypoxic-ischemic encephalopathy is often associated with permanent cerebral palsy,neurosensory impairments,and cognitive deficits,and there is no effective treatment for complications related to hypoxic-ischemic encephalopathy.The therapeutic potential of human placental chorionic plate-derived mesenchymal stem cells for various diseases has been explored.However,the potential use of human placental chorionic plate-derived mesenchymal stem cells for the treatment of neonatal hypoxic-ischemic encephalopathy has not yet been investigated.In this study,we injected human placental chorionic plate-derived mesenchymal stem cells into the lateral ventricle of a neonatal hypoxic-ischemic encephalopathy rat model and observed significant improvements in both cognitive and motor function.Protein chip analysis showed that interleukin-3 expression was significantly elevated in neonatal hypoxic-ischemic encephalopathy model rats.Following transplantation of human placental chorionic plate-derived mesenchymal stem cells,interleukin-3 expression was downregulated.To further investigate the role of interleukin-3 in neonatal hypoxic-ischemic encephalopathy,we established an in vitro SH-SY5Y cell model of hypoxic-ischemic injury through oxygen-glucose deprivation and silenced interleukin-3 expression using small interfering RNA.We found that the activity and proliferation of SH-SY5Y cells subjected to oxygen-glucose deprivation were further suppressed by interleukin-3 knockdown.Furthermore,interleukin-3 knockout exacerbated neuronal damage and cognitive and motor function impairment in rat models of hypoxic-ischemic encephalopathy.The findings suggest that transplantation of hpcMSCs ameliorated behavioral impairments in a rat model of hypoxic-ischemic encephalopathy,and this effect was mediated by interleukin-3-dependent neurological function.

Uterine epithelioid trophoblastic tumor with the main manifestation of increased human chorionic gonadotropin:A case report

BACKGROUND Epithelioid trophoblastic tumor(ETT)is an extremely rare malignant gestational trophoblastic neoplasm commonly presenting with abnormal vaginal bleeding,abdominal pain,and increased human chorionic gonadotropin(hCG).This study reported a case of uterine ETT with the main manifestation being increased hCG.CASE SUMMARY A 39-year-old female was referred to the Ningbo Maternal and Child Hospital of China in December 2022,complaining of increased hCG levels for 1 month.Magnetic resonance imaging revealed gestational trophoblastic tumor,and hysteroscopic electrotomy and curettage of intrauterine hyperplasia were performed.The patient was diagnosed with uterine ETT through postoperative pathological examination and immunohistochemical results.Total laparoscopic hysterectomy and bilateral salpingectomy were performed,and hCG levels returned to normal.The patient was without recurrence during the postoperative 3-month follow-up.CONCLUSION This study reported a case of uterine ETT with the main manifestation being increased hCG,highlighting that ETT should be considered in the presence of abnormal hCG.A total laparoscopic hysterectomy is recommended.

Invasive Procedures for Prenatal Diagnosis in Salmaniya Medical Complex in Bahrain: A Retrospective Cross-Sectional Descriptive Study

Background: Prenatal diagnosis is the process of evaluating the presence of disease or potential disease in the fetus, this enables families to be better prepared before the birth of the baby. There are non-invasive prenatal diagnosis procedures and invasive prenatal diagnosis procedures. The invasive prenatal diagnosis procedures are CVS (chorionic villus sampling) and amniocentesis. The American College of Obstetricians and Gynecologists states that invasive diagnostic testing should be available to all women, regardless of age or risk. Objective: To determine the indications, outcome and results of diagnostic invasive prenatal procedures. Study setting: The obstetrics and Gynecology Department in Salmaniya Medical Complex in Kingdom of Bahrain. Study design: Retrospective descriptive study. Study subjects and Methods: This retrospective descriptive study was conducted on 175 pregnant women who underwent invasive prenatal procedures (CVS and amniocentesis) between January 2013 and December 2018 at SMC in Kingdom of Bahrain. All medical records of the participants were reviewed and entered the study. According to the implemented procedures, medical records were categorized into two chorionic villus sampling (CVS) and amniocentesis groups. The study subject will include indications of the procedures which are advanced maternal age, hematological disorders, genetic disorders, metabolic disorders, abnormal structural findings in fetal ultrasound and previous child with aneuploidy. In addition, the study will address the complications, outcome and results of procedures. Results: About half of our indications of the procedures were due to hematological disorders (47.6%) followed by abnormal structural findings in fetal ultrasound (30.1%) then genetic disorders (15.7%), metabolic disorders (4.8%) and advanced maternal age (1.8%). Regarding complications of the procedure;threatened miscarriage or loss of pregnancy within 3 weeks was (2.3%), amniotic fluid leakage (0.7%), abdominal cramps (0.7%) and Insufficient or contaminated sample (6.2%). Regarding outcome of the pregnancy, our results showed that the loss of pregnancy was (4.8%), intrauterine fetal death or still birth was (13.9%), live birth was (63.9%), preterm delivery was (7.8%), preterm premature rupture of membrane (PPROM) was (1.8%), limbs reduction was (0.0%). Termination of pregnancy outside the country was (7.8%) of chorionic villus sampling and amniocentesis. Conclusion: CVS and amniocentesis are useful outpatient procedures to detect diagnosis or to assess whether a patient is at increased risk of having an affected fetus and that will minimize the psychological impact on the patient and to provide a proper antenatal care to the pregnant women by her obstetrician and follow up to the baby by pediatrician. In this study it was observed that most of the patients who underwent the procedure were couples either carrier or affected to sickle cell disease or Beta thalassemia.

Live births from in vitro fertilization-embryo transfer following the administration of gonadotropin-releasing hormone agonist without gonadotropins:Two case reports

BACKGROUND The prevalence of female infertility between the ages of 25 and 44 is 3.5%to 16.7%in developed countries and 6.9%to 9.3%in developing countries.This means that infertility affects one in six couples and is recognized by the World Health Organization as the fifth most serious global disability.The International Committee for Monitoring Assisted Reproductive Technology reported that the global total of babies born as a result of assisted reproductive technology procedures and other advanced fertility treatments is more than 8 million.Advancements in controlled ovarian hyperstimulation procedures led to crucial accomplishments in human fertility treatments.The European Society for Human Reproduction and Embryology guideline on ovarian stimulation gave us valuable evidence-based recommendations to optimize ovarian stimulation in assisted reproductive technology.Conventional ovarian stimulation protocols for in vitro fertilization(IVF)–embryo transfer are based upon the administration of gonadotropins combined with gonadotropin-releasing hormone(GnRH)analogues,either GnRH agonists(GnRHa)or antagonists.The development of ovarian cysts requires the combination of GnRHa and gonadotropins for controlled ovarian hyperstimulation.However,in rare cases patients may develop an ovarian hyper response after administration of GnRHa alone.CASE SUMMARY Here,two case studies were conducted.In the first case,a 33-year-old female diagnosed with polycystic ovary syndrome presented for her first IVF cycle at our reproductive center.Fourteen days after triptorelin acetate was administrated(day 18 of her menstrual cycle),bilateral ovaries presented polycystic manifestations.The patient was given 5000 IU of human chorionic gonadotropin.Twenty-two oocytes were obtained,and eight embryos formed.Two blastospheres were transferred in the frozen-thawed embryo transfer cycle,and the patient was impregnated.In the second case,a 37-year-old woman presented to the reproductive center for her first donor IVF cycle.Fourteen days after GnRHa administration,the transvaginal ultrasound revealed six follicles measuring 17-26 mm in the bilateral ovaries.The patient was given 10000 IU of human chorionic gonadotropin.Three oocytes were obtained,and three embryos formed.Two high-grade embryos were transferred in the frozen-thawed embryo transfer cycle,and the patient was impregnated.CONCLUSION These two special cases provide valuable knowledge through our experience.We hypothesize that oocyte retrieval can be an alternative to cycle cancellation in these conditions.Considering the high progesterone level in most cases of this situation,we advocate freezing embryos after oocyte retrieval rather than fresh embryo transfer.

人绒毛膜提取物的临床试用探讨

88年10月我院从人胚绒毛制备人绒毛膜提取物（human chorionic-abstractHCA）并用于临床。在目前市场绒毛膜促性腺激素HCG货源紧缺时,应用HCA能取得同样的临床疗效,此有着一定的社会效益,值得进一步研究及推广使用,现报告如下。

Perinatal morbidity and early neonatal mortality in twin pregnancies

Purpose: The purpose of this study was to investigate the impact of maternal, fetal and obstetric parameters in twin pregnancies due to chorionicity, perinatal morbidity and early neonatal mortality. Methods: Early neonatal outcome parameters were retrospectively analysed in 240 twin pregnancies (51 monochorionic [MC], 189 dichorionic [DC] twins) over a 7.5 years period. Beside chorionicity, we focused on risk factors affecting perinatal morbidity and early neonatal outcome in the overall study cohort and subgroups 1) late preterm and 2) pregnancies conceived by artificial fertilization (IVF/ICSI). Mixed effects logistic regression models were used for multivariate risk analyses. Results: MC vs DC pregnancies showed significantly lower birth weights (p 25% and amniotic inflammation (amniotic infection syndrome [AIS]). A gestational age >36 completed weeks was accompanied by a decrease of early neonatal complications

Mesenchymal stromal cells from human perinatal tissues: From biology to cell therapy

Cell-based regenerative medicine is of growing interest in biomedical research. The role of stem cells in this context is under intense scrutiny and may help to define principles of organ regeneration and develop innovative therapeutics for organ failure. Utilizing stem and progenitor cells for organ replacement has been conducted for many years when performing hematopoietic stem cell transplantation. Since the first successful transplantation of umbilical cord blood to treat hematological malignancies, non-hematopoietic stem and progenitor cell populations have recently been identified within umbilical cord blood and other perinatal and fetal tissues. A cell population entitled mesenchymal stromal cells (MSCs) emerged as one of the most intensely studied as it subsumes a variety of capacities: MSCs can differentiate into various subtypes of the mesodermal lineage, they secrete a large array of trophic factors suitable of recruiting endogenous repair processes and they are immunomodulatory.Focusing on perinatal tissues to isolate MSCs, we will discuss some of the challenges associated with these cell types concentrating on concepts of isolation and expansion, the comparison with cells derived from other tissue sources, regarding phenotype and differentiation capacity and finally their therapeutic potential.

单克隆抗体的DOT-ELISA方法用于早期妊娠诊断

人绒毛促性腺激素(human chorionic gonadotropin,hCG)是由胎盘产生的糖蛋白,妇女尿或血清中的 hCG 是妊娠的最早指标。利用β-hCG 亚单位的特异性进行免疫分析,是测定体液 hCG 水平的最准确的方法。1985年国外首次报道应用单克隆抗体和酶免测定法测定 hCG。同年,陈捷平等在国内首次生产这一试剂盒并推广至全国。1987年国外报道了更简便的 DOT-ELISA 法检测 hCG,但无方法学详细的报道。

Challenges in the diagnosis and treatment of gestational trophoblastic neoplasia worldwide

Gestational trophoblastic neoplasia(GTN) is a rare tumor that originates from pregnancy that includes invasive mole, choriocarcinoma(CCA), placental site trophoblastic tumor and epithelioid trophoblastic tumor(PSTT/ETT). GTN presents different degrees of proliferation, invasion and dissemination, but, if treated in reference centers, has high cure rates, even in multi-metastatic cases.The diagnosis of GTN following a hydatidiform molar pregnancy is made according to the International Federation of Gynecology and Obstetrics(FIGO)2000 criteria: four or more plateaued human chorionic gonadotropin(hCG)concentrations over three weeks; rise in hCG for three consecutive weekly measurements over at least a period of 2 weeks or more; and an elevated but falling hCG concentrations six or more months after molar evacuation. However,the latter reason for treatment is no longer used by many centers. In addition,GTN is diagnosed with a pathological diagnosis of CCA or PSTT/ETT. For staging after a molar pregnancy, FIGO recommends pelvic-transvaginal Doppler ultrasound and chest X-ray. In cases of pulmonary metastases with more than 1cm, the screening should be complemented with chest computed tomography and brain magnetic resonance image. Single agent chemotherapy, usually Methotrexate(MTX) or Actinomycin-D(Act-D), can cure about 70% of patients with FIGO/World Health Organization(WHO) prognosis risk score ≤ 6(low risk), reserving multiple agent chemotherapy, such as EMA/CO(Etoposide,MTX, Act-D, Cyclophosphamide and Oncovin) for cases with FIGO/WHO prognosis risk score ≥ 7(high risk) that is often metastatic. Best overall cure rates for low and high risk disease is close to 100% and > 95%, respectively. The management of PSTT/ETT differs and cure rates tend to be a bit lower. The early diagnosis of this disease and the appropriate treatment avoid maternal death,allow the healing and maintenance of the reproductive potential of these women.

Complete response to multidisciplinary therapy in a patient with primary gastric choriocarcinoma

Primary gastric choriocarcinoma is a rapidly growing neoplasm with an average survival of several months in untreated patients.Gastrectomy with lymph node dissection followed by chemotherapy is the treatment of choice.Regimens used for gastric adenocarcinoma are usually selected.However,median survival remains less than six months.In this case report,we describe a case of primary gastric choriocarcinoma with a clinical complete response to multidisciplinary treatment including surgery,chemotherapy,and radiofrequency ablation(RFA).The patient was originally referred for general malaise.Esophagogastroduodenoscopy demonstrated a large tumor occupying the fornix,and total gastrectomy with lymph node dissection was performed.Seven days later,multiple liver metastatic recurrences with high serum levels of beta-human chorionic gonadotropin(β-hCG) were recognized.Chemotherapy with a gonadal choriocarcinoma regimen consisting of etoposide,methotrexate,actinomycin D,cyclophosphamide,and vincristine(EMA/CO),was initiated.After three cycles,serum β-hCG decreased markedly and the tumors disappeared.Six months later,multiple lung metastatic recurrences were found.After one cycle of EMA/CO,only one nodule remained.Computed tomography-guided RFA was performed for this oligometastatic tumor.The patient has been alive with no evidence of disease for 10 years after the initial diagnosis.To the best of our knowledge,this patient with recurrent primary gastric choriocarcinoma has achieved the longest survival.The present case is the first report of choriocarcinoma metastatic to the lung successfully treated with RFA.From our retrospective analysis of recurrent or unresectable primary gastric choriocarcinoma,we propose that gonadal choriocarcinoma regimens can be considered as first-line for primary gastric choriocarcinoma.

SUBSTITUTION OF ACUPUNCTURE FOR HCG IN OVULATION INDUCTION

By using human menopausal gonadotropin (HMG) and human chorionic gonadotropin (HCG), fairly good clinical therapeutic efficacy has been obtained in the treatment of infertility. However, difficulties are brought about due to the ovarian hyperstimulation syndrome (OHSS) easily induced by these two drugs. Therefore,

Minimum Dose of hCG to Trigger Final Oocyte Maturation and Prevent OHSS in a Long GnRHa Protocol

This paper was aimed to study the minimum dose of human chorionic gonadotropin （hCG） to effectively trigger maturation of oocytes and prevent ovarian hyperstimulation syndrome （OHSS） in a series of hyper-responders treated with a long gonadotropin releasing hormone agonist （GnRHa） proto- col. Six women at high risk of developing severe OHSS in a long GnRHa protocol were enrolled into this study. Serum hormone levels on the day of and after hCO administration, antral follicle count, oo- cyte retrieval number and quality were determined. In total, 6 women aged between 29 and 36 years and at risk of developing severe OHSS, received 2000 U hCG Five of them were treated with coasting for 1 day and the rest one for 4 days. The mean number of oocytes collected was 19 （range 14-27） and the fertilization rate per collected oocyte was 72.81%. Of the 6 women in the study, only one cancelled em- bryos transfer and all embryos were frozen, and then she delivered two health boys on term in the sub- sequent frozen-thawed embryo transfer （FET） cycle. Pregnancies and births were achieved in 3 patients out of 5 in vitro fertilization-embryo transfer （IVF-ET） cycles. No woman developed moderate or severe OHSS. Triggering with 2000 U hCG is feasible to prevent OHSS in unpredicted hyper-responders undergoing IVF in a long GnRHa protocol.

Predictive Value of Initial Serum Human Chorionic Gonadotropin Levels for Pregnancies after Single Fresh and Frozen Blastocyst Transfer

As one of the earliest markers for predicting pregnancy outcomes, human chorionic gonadotropin(h CG) values have been inconclusive on reliability of the prediction after frozen and fresh embryo transfer(ET). In this retrospective study, patients with positive h CG(day 12 after transfer) were included to examine the h CG levels and their predictive value for pregnancy outcomes following 214 fresh and 1513 vitrified-warmed single-blastocyst transfer cycles. For patients who got clinical pregnancy, the mean initial h CG value was significantly higher after frozen cycles than fresh cycles, and the similar result was demonstrated for patients with live births(LB). The difference in h CG value existed even after adjusting for the potential covariates. The area under curves(AUC) and threshold values calculated by receiver operator characteristic curves were 0.944 and 213.05 m IU/m L for clinical pregnancy after fresh ET, 0.894 and 399.50 m IU/m L for clinical pregnancy after frozen ET, 0.812 and 222.86 m IU/m L for LB after fresh ET, and 0.808 and 410.80 m IU/mL for LB after frozen ET with acceptable sensitivity and specificity, respectively. In conclusion, single frozen blastocyst transfer leads to higher initial h CG values than single fresh blastocyst transfer, and the initial h CG level is a reliable predictive factor for predicting IVF outcomes.

Effect of Mifepristone on the Telomerase Activity in Chorion and Decidua during Early Pregnancy

Objective To investigate telomerase activity in chorion and decidua from abortion induced by mifepristone incorporated with misoprostol at early pregnancy. Methods TRAP-SYBR Green assay was used to detect the expression of telomerase. Forty specimen were obtained from medicinal abortion （experiment group） and forty were from normal induced abortion （control group）. Results Positive expression of chorion telomerase was significantly different between the experimental group （28%, 11/40） and the control group （73%, 29/40） （P〈0.05）. While in decidua, the positive rate was 28% （11/40） in the experimental group and 20% （9/40） in the control group, there was no significant difference （P〉0.05）. Conclusion It is suggested that miferistone may significantly decrease the telomerase activity in chorion but not in decidua.

Second-trimester maternal β-human chorionic gonadotropin level associated with subsequent development of pregnancy-induced hypertension

Objective:To determine whether maternal β-human chorionic gonadotropin(β-hCG) level in second-trimester may be associated with subsequent development of pregnancy-induced hypertension(PIH).Methods:Seven hundred and sixty-two women in mid-trimester were to have maternal urine β-hCG standardized concentrations and maternal serum β-hCG measurements.Their case histories were recorded and reviewed from mid-trimester to delivery.The relation was observed between maternal urine,serum markers and subsequent development of PIH.Results:Among 762 women,504 cases were normal pregnancies,42 cases had PIH,94 cases had premature rupture of membrane (PROM),69 cases had preterm delivery (PD),53 other cases were excluded by various reasons.The levels of maternal urine,serum β-hCG in PIH were (61.75±9.78) IU/L and (304.56±54.17) ng/mg respectively,which were higher significantly than normal pregnancy group ([20.65±7.61] IU/L and [146.34±47.81] ng/mg,P<0.05).When maternal serum,urine β-hCG levels ≥2 MOM(multiple of mean),the incidences of developing PIH were increased significantly as compared with those of β-hCG <2 MOM women.The incidence of PIH increased from 5.1% in pregnancies with urine β-hCG ≥2 MOM to 11.7% in cases with urine β-hCG ≥4 MOM.Conclusion:The elevation of maternal mid-trimester urine,serum β-hCG levels is not only an early signal for dysfunction of placenta but also a dangerous signal for development of PIH.Second-trimester maternal urine β-hCG measurement proves to be superior to serum marker in clinical prediction.

Treatment of hypogonadotropic male hypogonadism: Case-based scenarios

The aim of this study is to review four case-based scenarios regarding the treatment of symptomatic hypogonadism in men. The article is designed as a review of published literature. We conducted a PubMed literature search for the time period of 1989-2014, concentrating on 26 studies investigating the effcacy of various therapeutic options on semen analysis, pregnancy outcomes, time to recovery of spermatogenesis, as well as serum and intratesticular testosterone levels. Our results demonstrated thatexogenous testosterone suppresses intratesticular testosterone production, which is an absolute prerequisite for normal spermatogenesis. Cessation of exogenous testosterone should be recommended for men desiring to maintain their fertility. Therapies that protect the testis involve human chorionic gonadotropin （hCG） therapy or selective estrogen receptor modulators （SERMs）, but may also include low dose hCG with exogenous testosterone. Off-label use of SERMs, such as clomiphene citrate, are effective for maintaining testosterone production long-term and offer the convenience of representing a safe, oral therapy. At present, routine use of aromatase inhibitors is not recommended based on a lack of long-term data. We concluded that exogenous testosterone supplementation decreases sperm production. It was determined that clomiphene citrate is a safe and effective therapy for men who desire to maintain fertility. Although less frequently used in the general population, hCG therapy with or without testosterone supplementation represents an alternative treatment.

Primary hepatic choriocarcinoma in a 49-year-old man:Report of a case

We report a case of hepatic choriocarcinoma in a man diagnosed at autopsy after a rapid downhill clinical course.The patient was a 49-year-old man who presented with acute right-sided abdominal pain.There were no masses palpable on physical examination.Radiographic findings showed large multi-nodular tumors mainly in the right lobe of the liver.Fludeoxyglucosepositron emission tomography scan showed uptake only in the liver,and no uptake in the testes.We initially planned to perform a liver resection for the presumed diagnosis of intra-hepatic cholangiocarcinoma.However,the tumors grew rapidly and ruptured.Multiple lung metastases rapidly developed resulting in respiratory failure,preventing liver resection or even biopsy.He died 60 d after initial presentation with no pathological diagnosis.Postmortem studies included histopathological and immunohistological examinations which diagnosed a primary choriocarcinoma of the liver.Primary hepatic choriocarcinoma is very rare but should be considered in the differential diagnosis of a liver tumor in a middle aged man.Establishing this diagnosis may enable treatment of the choriocarcinoma.Liver biopsy and evaluation of serum human chorionic gonadotropin are recommended in these patients.

Clonal isolation of endothelial colony-forming cells from early gestation chorionic villi of human placenta for fetal tissue regeneration

BACKGROUND Endothelial colony-forming cells(ECFCs)have been implicated in the process of vascularization,which includes vasculogenesis and angiogenesis.Vasculogenesis is a de novo formation of blood vessels,and is an essential physiological process that occurs during embryonic development and tissue regeneration.Angiogenesis is the growth of new capillaries from pre-existing blood vessels,which is observed both prenatally and postnatally.The placenta is an organ composed of a variety of fetal-derived cells,including ECFCs,and therefore has significant potential as a source of fetal ECFCs for tissue engineering.AIM To investigate the possibility of isolating clonal ECFCs from human early gestation chorionic villi(CV-ECFCs)of the placenta,and assess their potential for tissue engineering.METHODS The early gestation chorionic villus tissue was dissociated by enzyme digestion.Cells expressing CD31 were selected using magnetic-activated cell sorting,and plated in endothelial-specific growth medium.After 2-3 wks in culture,colonies displaying cobblestone-like morphology were manually picked using cloning cylinders.We characterized CV-ECFCs by flow cytometry,immunophenotyping,tube formation assay,and Dil-Ac-LDL uptake assay.Viral transduction of CVECFCs was performed using a Luciferase/tdTomato-containing lentiviral vector,and transduction efficiency was tested by fluorescent microscopy and flow cytometry.Compatibility of CV-ECFCs with a delivery vehicle was determined using an FDA approved,small intestinal submucosa extracellular matrix scaffold.RESULTS After four passages in 6-8 wks of culture,we obtained a total number of 1.8×107 CV-ECFCs using 100 mg of early gestational chorionic villus tissue.Immunophenotypic analyses by flow cytometry demonstrated that CV-ECFCs highly expressed the endothelial markers CD31,CD144,CD146,CD105,CD309,only partially expressed CD34,and did not express CD45 and CD90.CV-ECFCs were capable of acetylated low-density lipoprotein uptake and tube formation,similar to cord blood-derived ECFCs(CB-ECFCs).CV-ECFCs can be transduced with a Luciferase/tdTomato-containing lentiviral vector at a transduction efficiency of 85.1%.Seeding CV-ECFCs on a small intestinal submucosa extracellular matrix scaffold confirmed that CV-ECFCs were compatible with the biomaterial scaffold.CONCLUSION In summary,we established a magnetic sorting-assisted clonal isolation approach to derive CV-ECFCs.A substantial number of CV-ECFCs can be obtained within a short time frame,representing a promising novel source of ECFCs for fetal treatments.