双胎输血综合征研究现状及新进展

双胎输血综合征（twin-twin transfusion syndrome,TTTS）是单绒毛膜双胎最常见的一种并发症。TTTS的发病机制尚不完全明确,胎盘间存在血管交通是其发病的必要条件,但它难以解释胎儿所有的病理生理,而内分泌改变为TTTS的发病机制提供了一种可能的解释。TTTS的临床诊断主要依靠超声。Quintero分期是目前使用最广泛的分期标准,但其不能提供预测信息,存在一定的局限性。治疗方面,选择性胎儿镜下激光消融术有着较好的胎儿存活率及神经系统预后,优于传统治疗方法,有较好的发展前景。     

双胎输血综合征治疗进展

双胎输血综合征治疗方法有羊水减量术、胎儿镜下激光凝结胎盘血管交通支术、羊膜中隔打孔术和选择性减胎术。本文就TTTS的治疗做一综述。     

产前超声对双胎输血综合征的诊断价值探讨

目的探讨产前超声对双胎输血综合征(TTTS)的临床诊断价值。方法收集2015年2月～2018年2月在我院治疗的66例双胎输血综合征孕妇产后胎盘病理检查以及围产儿生长发育情况等相关资料,并进行比较产前超声诊断的准确性。结果产前超声诊断TTTS 54例,准确率为81.82%。其中TTTSⅢ级28例(51.85%),TTTSⅣ级5例(9.26%),TTTSⅤ级6例(11.11%)。对产前超声确诊的TTTS影像学资料进行分析发现,54例TTTS均表现为受血儿羊水过多,供血儿羊水过少;供血儿中29例(53.70%)为贴壁儿,26例(48.15%)脐动脉舒张期血流中断,19例(35.19%)膀胱不显示,16例(29.63%)受血儿脐动脉S/D增高且供血儿脐动脉舒张期血流中断,32例(59.26%)选择引产。结论对双胎输血综合征产妇进行诊断时,采用产前超声检查具有较高的诊断准确率,临床诊断价值较高。     

双胎妊娠一胎宫内死亡18 例临床分析

目的:探讨双胎妊娠中一胎宫内死亡的原因、对母亲和存活胎儿的影响及临床处理方法。方法:对2001年1月至2011年10月分娩的双胎妊娠之一胎宫内死亡的18例产妇临床资料进行回顾性分析。结果:双胎妊娠一胎宫内死胎的发生率占双胎的1.08%,其中单绒毛膜双羊膜囊双胎(monochorionic-diamniotic twin,MCDA)11例(61.11%),双绒毛膜双羊膜囊双胎(dichorionic-diamniotic twin,DCDA)7例(38.89%)。胎儿死因:胎盘脐带因素3例(16.67%),胎儿畸形1例(5.56%),妊娠并发症3例(16.67%),双胎输血综合征(twin-twin transfusion syndrome,TTTs)3例(16.67%),宫内感染3例(16.67%),不明原因5例(27.78%)。另一胎选择剖宫产者13例,阴道分娩3例。双胎一胎死亡后对母体的凝血功能影响不大(P>0.05)。结论:单绒毛膜双胎较双绒毛膜双胎母儿结局存在差别;双胎一胎宫内死亡对母体及存活儿有一定影响。对于孕周小,胎儿尚不成熟的病例,可严密监测存活胎儿宫内情况,行期待治疗延长孕龄至足月再分娩。     

脊髓型颈椎病的发病机制及治疗的研究进展

在中老年人群中脊髓型颈椎病是造成脊髓功能障碍的主要原因,其发病机制复杂,主要有静态和动态因素、缺血、内皮细胞损伤和血脊髓屏障的破坏、炎症及细胞凋亡等学说,每一种学说并不能够完美的解释脊髓型颈椎病的发病机制,仍需进一步实验研究探索其机制。对于进行性发展的脊髓型颈椎病多采用手术治疗,手术方式主要有前路、后路及前后路联合手术,如何选择手术方案仍是临床医生关注的焦点,本文就该病的发病机制及手术治疗的相关进展作一综述。     

mTOR信号通路在糖尿病肾病发病机制中的研究进展

糖尿病肾病（diabetic nephropathy,DN）是糖尿病最常见的并发症之一,因其具有高发病率且与晚期肾病、心血管疾病和过早死亡等风险相关,糖尿病肾病已成为全球性的公共健康问题,但目前其发病机制尚不清楚。雷帕霉素靶蛋白（mammalian target of rapamycin,mTOR）是一种丝氨酸/苏氨酸的蛋白酶,在延迟细胞凋亡以及促进细胞分裂、细胞存活、血管生成中发挥着重要作用。近年来有研究表明,mTOR存在于DN进展的关键步骤中,包括自噬、炎症及氧化应激等。因此,就mTOR介导的自噬、炎症及氧化应激信号通路在DN发病机制中的相关研究进展做一综述,以期为DN治疗及预防提供理论参考。     

多胎妊娠对新生儿的影响

一次妊娠两个或两个以上的胎儿称多胎妊娠，其中以双胎妊娠较常见。双胎妊娠属高危妊娠，其早产发生率与围生儿死亡率都较正常妊娠高，其分娩期的处理是影响多胎妊娠新生儿预后的重要环节。降低新生儿死亡率是产科工作的关键问题，现对我院154例双胎妊娠资料总结，以双胎妊娠为例探讨多胎妊娠对新生儿的影响。     

肝细胞程序性坏死与非酒精性脂肪性肝病

非酒精性脂肪性肝病是目前世界上最常见的慢性肝病,其发病机制尚不清楚。肝细胞死亡与该病的相关性已被广泛报道。程序性坏死是一种细胞死亡形式。研究发现,肝细胞程序性坏死在非酒精性脂肪性肝病的发展过程中发挥重要作用。本文就近年来肝细胞程序性坏死在非酒精性脂肪性肝病中的研究进展作一综述,旨在为非酒精性脂肪性肝病的发病机制与药物治疗提供新思路。     

血小板:动脉粥样硬化的诱导者和推动者

动脉粥样硬化是一个复杂的病理过程,已有很多理论从不同的角度来解释动脉粥样硬化的发病机制,但任何一种学说都不能全面地解释其发病机制。在动脉粥样硬化的形成与发展中,内皮细胞、白细胞、血小板和内膜平滑肌细胞作为主要参与者,通过与细胞因子、生长因子等作用,组成一个复杂的网络结构,诱发动脉粥样硬化的发生、发展。血小板在动脉粥样硬化形成过程中的重要作用也日益被人们所认知并接受。在动脉粥样硬化形成的初级阶段,血小板在一定程度上诱导了斑块的形成,而在晚期的并发症中也起了重要作用。本文侧重总结了血小板与动脉粥样硬化进程的重要关系,以期为推动动脉粥样硬化的早期诊断和抗血小板治疗提供重要的理论依据。     

谷氨酸循环障碍与抑郁症

抑郁症是当今社会较多发的严重影响人类生活质量的疾病,迄今为止,抑郁症病因与发病机制还不完全明确,在过去的很多年,单胺类神经递质假说一直处在相对重要的位置,然而,近年越来越多的临床证据表明,单胺类递质假说并不能完全解释抑郁症的发病机制与其所起到的治疗作用,是否还有另一种机制参与其中呢?近期大量实验研究表明谷氨酸能系统在抑郁症的发病及治疗中扮演了重要的角色,本文就谷氨酸能系统在抑郁症的发病及治疗中发挥的疗效作用综述如下。     

A mathematical model of twin-twin transfusion syndrome with pulsatile arterial circulations

The twin-twin transfusion syndrome (TTTS) is a severe complication of monochorionic twin pregnancies caused by a net transfusion of blood from one twin (the donor) to the other (the recipient) through placental anastomoses. To examine the pathophysiology of TTTS evolving through clinical stages I to IV, we extended our mathematical model to include pulsating circulations propagating along the arterial tree as well as placental and cerebral vascular resistances, and arterial wall thickness and stiffness. The model demonstrates that abnormal umbilical arterial flow (TTTS stage III) in the donor twin results from increased placental resistance as well as reduced resistance in the cerebral arteries. In contrast, recipient twin abnormal umbilical arterial flow requires a significantly greater increase in placental resistance, resulting from the compressive effects of high amniotic fluid pressure. Thus simulated abnormalities of donor umbilical arterial pulsations occur in the donor more commonly and earlier than in the recipient. The "normal" staging sequence (I, II, III, IV) correlates with the presence of compensating placental anastomoses, constituting the majority of monochorionic twin placentas. However, TTTS stage III may occur before manifestations of stage II (lack of donor bladder filling), in our model correlating with severe TTTS from a single arteriovenous anastomosis, an infrequent occurring placental angioarchitecture. In conclusion, this mathematical model describes the onset and development of the four stages of TTTS, reproduces a variety of clinical manifestations, and may contribute to identifying the underlying pathophysiology of the staging sequence in TTTS.     

Anticipating twin-twin transfusion syndrome in monochorionic twin pregnancy. Is there a role for nuchal translucency and ductus venosus blood flow evaluation at 11-14 weeks?

Twin-twin transfusion syndrome is a major complication of monochorionic twin pregnancies. In foetuses from monochorionic twinning the presence of increased nuchal translucency thickness (NT) has been associated with an increased risk of developing this syndrome. One of the presumed mechanisms of increased NT is early cardiac failure, indirectly indicated by abnormal blood flow in the ductus venosus. We present eleven cases of monochorionic twin pregnancies in which nuchal translucency thickness and ductus venosus blood flow evaluation was performed at 11-14 weeks. In the two cases presenting with nuchal translucency discrepancy between the two foetuses along with anomalous ductus venosus blood flow in the foetus with increased nuchal translucency, twin-twin transfusion syndrome (TTTS) eventually developed. In none of the twins displaying no inter-twin difference in NT measurements and in those with discrepant NT but normal flow in both ductus venosus, was the progression to TTTS observed. In the two cases which developed TTTS, foetoscopic laser coagulation of the vascular anastomosis was successfully carried out at 18 weeks and normalisation of the venous return was registered. These findings suggest that the association of increased NT and abnormal flow in the ductus venosus in monochorionic twins may be an early manifestation of haemodynamic imbalance between the donor and the recipient eventually manifested as twin-twin transfusion syndrome. Further studies, however, are necessary to establish the potential role of the combination of NT and ductus venosus blood flow assessment as a screening method for TTTS.     

Modeling a hydropic recipient twin in twin-twin transfusion syndrome

We developed a mathematical model of twin-twin transfusion syndrome (TTTS) that includes a hydropic recipient twin, adding interstitial and intracellular fluid compartments, fetal congestive cardiac failure, and the dynamics of renin-angiotensin system (RAS) mediators to our previous TTTS model. Ten differential equations for each twin, coupled by the net fetofetal transfusion of blood and blood components, i.e., colloids, osmoles, and RAS mediators, describe the development of fetal arterial and venous blood volumes, blood osmolality and colloid osmotic pressure (COP), interstitial fluid volume and COP, intracellular fluid volume, amniotic fluid volume and osmolality, and RAS mediator concentration. We included varying placental anastomoses, placental sharing, and amnionicity. The 20 differential equations were solved numerically from 0 to 40 wk with a 0.6-s time step. Consistent with clinical experience, model predictions are as follows. Unidirectional arteriovenous anastomoses and arteriovenous anastomoses inadequately compensated by oppositely directed anastomoses cause severe TTTS that includes a hydropic recipient. Adequately compensated arteriovenous anastomoses simulated TTTS without hydrops. The probability that oppositely directed anastomoses prevent onset of a hydropic recipient after TTTS onset, i.e., the largest interval between onset of TTTS and onset of hydrops in the recipient, was best for a venovenous anastomosis, closely followed by an arterioarterial and finally an oppositely directed arteriovenous anastomosis. Hydropic recipients have decreased amniotic fluid volume. Unequal placental sharing and amnionicity modify hydrops onset. In conclusion, our model simulates a sequence of events that results in a hydropic recipient twin in severe TTTS. The model may allow an assessment of the efficacy of current therapeutic interventions for TTTS cases that include a hydropic recipient twin.     

Amniotic fluid and hemodynamic model in monochorionic twin pregnancies and twin-twin transfusion syndrome

We developed a mathematical model of monochorionic twin pregnancies and twin-twin transfusion syndrome (TTTS), combining both fetal fluid dynamics and fetoplacental growth and circulation alterations and assuming that transplacental fluid flow from mother to fetus accounts for normal fetal and amniotic fluid volumes. Ten coupled differential equations, describing fetal total body and amniotic fluid volumes, their osmolalities, and fetal blood colloid osmotic pressure, for both donor and recipient twins, were solved numerically. Amniotic flows are controlled by fetal plasma osmolality and hydrostatic and colloid osmotic pressures. We included varying placental anastomoses and placental sharing of the circulations. Consistent with clinical experience, model predictions are: fetofetal transfusion from unidirectional arteriovenous anastomoses cause oligo-polyhydramnios, a normal size recipient but hypovolemic donor; compensating oppositely directed deep and superficial anastomoses moderate discordant development; and anhydramnios results from mild and severe TTTS, where milder forms may even present earlier in gestation than severe TTTS. Unequal placental circulatory sharing may exacerbate discordant development. In conclusion, our model simulates a wide variety of realistic manifestations of amniotic fluid volume and fetal growth in TTTS related to placental angioarchitecture. The model may allow an assessment of the efficacy of current therapeutic interventions for TTTS.     

Natural history of 11 cases of twin-twin transfusion syndrome without intervention.

The natural history of 11 cases of twin-twin transfusion syndrome (TTTS) in monochorionic diamniotic (MCDA) twin pregnancies has been reviewed. Seven cases before 28 weeks and four pregnancies after 28 weeks had been followed up without intervention. Eight cases had premature uterine contractions. All seven pregnancies before 28 weeks aborted, leading to a 100% mortality rate. After 28 weeks all mothers delivered live births. The diagnosis of TTTS before 28 weeks, and with premature uterine contraction, seems to be a poor prognostic sign.     

Maternal metabolic abnormalities in twin-to-twin transfusion syndrome at mid-pregnancy.

We report abnormal maternal laboratory parameters in twin-to-twin transfusion syndrome (TTTS) at mid-pregnancy. A retrospective chart review was undertaken of 109 patients with TTTS evaluated for placental laser surgery. Complete blood count (CBC), blood type and Rh factor, urine analysis and serum chemistry panel were obtained preoperatively, with the CBC and serum albumin repeated on the first postoperative day. The mean gestational age was 21.2+/-1.7 weeks. Initial abnormal values included hematocrit (32.1+/-3.0%), hemoglobin (11.0+/-1.03 g/dl), serum magnesium (1.71+/-0.17 mg/dl), total protein (6.08+/-0.55 g/dl) and albumin (3.06+/-0.34 g/dl). Despite minimal blood loss and conservative fluid replacement mean hematocrit, hemoglobin, and albumin were 27.3+/-2.74%, 9.3+/-0.94 g/dl and 2.56+/-0.23 g/dl, respectively on postoperative day one. Weight gain (8.0+/-5.5 lb.) and low urinary output were characteristic peri-operative events. Maternal hypoproteinemia and anemia occur in TTTS at mid-pregnancy. This may contribute independently to amniotic fluid production rates in the fetuses, and explain in part the maternal sensitivity to intravenous fluids in multiple pregnancy.     

The outcome of twin pregnancies complicated by single fetal death after 20 weeks of gestation.

A retrospective study involving 972 twin births was conducted to evaluate the maternal and fetal outcomes of twin pregnancies complicated by single fetal death. The incidence of single fetal death in twin pregnancies after 20 weeks was 3.3%. Preterm birth rates for 37 and 32 gestational weeks were 81.3% and 41.6% respectively. The median interval between the diagnosis of fetal death and the delivery was 11 days (range 1-27 days). Eighteen (56%) infants were delivered by cesarean and 14 (43%) vaginally. Twin-twin transfusion syndrome (TTTS) was the cause of single fetal death in 8 of 32 twin pregnancies (25%). Ten of the surviving co-twins were lost in the neonatal period (31.3%) and half of those neonatal deaths were due to TTTS. TTTS is the major contributor for perinatal mortality in same-sex twins complicated by single fetal death. The death of one twin in utero should not be the only indication for preterm delivery, and in case of severe prematurity with a stable intrauterine environment; expectant management may be advisable until fetal lung maturation ensues.     

Early changes in vascular dynamics in relation to twin-twin transfusion syndrome.

A clearer understanding of the early determinants of normal and abnormal vascular development is pivotal in order to identify those at increased risk of later vascular disease, and perhaps to prevent it by early intervention. Measurement of pulse wave velocity(PWV) has been used in the postnatal evaluation of the monochorionic(MC) twins. They are genetically identical and those with twin-twin transfusion syndrome(TTTS) provide an ideal natural model in whom to study the influence of differing haemodynamic stresses on the developing vascular tree. We investigated firstly whether surviving twin pairs with TTTS have altered arterial distensibility in childhood by comparing PWV in the radial arteries of surviving MC twin pairs with TTTS and in two control groups, one cohort of MC twins without TTTS and another dichorionic group (DC) Secondly, we tested a cohort of TTTS twin pair survivors treated with laser photocoagulation. The co-twin pairs in the group managed palliatively with amnioreduction showed increased PWV in the donor and reduced PWV in the recipient twins. This was neither seen in the laser-treated, nor in the control groups. Our studies suggest that a period of haemodynamic imbalance gives rise to changes in a muscular conduit artery that persist at least into infancy and it seems that by correcting the abnormal haemodynamics relatively soon after the disease process had begun, the alterations in elasticity are prevented. These studies are the first to demonstrate fetal programming of the vascular bed in humans, and prevention or reversal of this programming by an intervention in mid-gestation.     

Influence of maternal obesity and metabolic and vascular mediators in twin-twin transfusion syndrome

Obesity is a risk factor for complications in singleton and twin pregnancies; however, there are limited data regarding maternal body mass index (BMI) in the setting of twin-twin transfusion syndrome (TTTS). We hypothesized that increased BMI in TTTS is associated with adverse perinatal outcomes and vascular pathology. A retrospective study of twin reversed arterial perfusion (n = 4), selective intrauterine growth restriction (n = 10) and TTTS (n = 33) was conducted. Treatment included fetoscopic laser photocoagulation (FLP) (n = 35) or Solomon technique (n = 12). Ex vivo placental intravascular injections, immunohistochemistry, and perinatal outcomes were compared by maternal BMI. In pregnancy complicated by TTTS, 16/33 women were obese (BMI > 30 kg/m²) and 11/33 were overweight (BMI 25–29.9 kg/m²). Women who were overweight or obese had an increased rate of premature rupture of membranes (PPROM), cesarean delivery, and/or concomitant co-morbidities when compared to the normal weight group. Duration of neonatal intensive care unit (NICU) admission was longer in neonates of overweight/obese women versus normal weight. Placental examination of FLP sites in the obese group showed larger infarcts, increased adipose triglyceride lipase, and a proangiogenic phenotype. Increased BMI is common in our TTTS cohort and it is associated with higher rate of co-morbidity, PPROM, prolonged NICU stay, and an imbalance of placental metabolic and vascular mediators.