Clinical phenotype and genotype analysis of the family with the Usher syndrome / 中华医学遗传学杂志

OBJECTIVE@#To detect potential variants in a family affected with Usher syndrome type I, and analyze its genotype-phenotype correlation.@*METHODS@#Clinical data of the family was collected. Potential variants in the proband were detected by high-throughput sequencing. Suspected variants were verified by Sanger sequencing.@*RESULTS@#The proband developed night blindness at 10 year old, in addition with bilateral cataract and retinal degeneration. Hearing loss occurred along with increase of age. High-throughput sequencing and Sanger sequencing revealed that she has carried compound heterozygous variants of the MYO7A gene, namely c.2694+2T>G and c.6028G>A. Her sister carried the same variants with similar clinical phenotypes. Her daughter was heterozygous for the c.6028G>A variant but was phenotypically normal.@*CONCLUSION@#The clinical features and genetic variants were delineated in this family with Usher syndrome type I. The results have enriched the phenotype and genotype data of the disease and provided a basis for genetic counseling.

Phenotype-genotype analysis and detection of gene variant in six families with osteogenesis imperfecta / 中华医学遗传学杂志

OBJECTIVE@#To analyze the clinical phenotype of six pedigrees affected with osteogenesis imperfecta and their genetic basis.@*METHODS@#Peripheral blood or abortic tissues of the six pedigrees were collected for the extraction of genomic DNA. Next generation sequencing (NGS) was carried out to detect pathological variants in the genome. Sanger sequencing was used for validating suspected variant among the six pedigrees and 100 healthy controls.@*RESULTS@#In pedigree 1, the proband and his daughter both carried a heterozygous c.1976G>C variant of COL1A1. The probands in pedigrees 2 to 6 respectively carried heterozygous variants of c.2224G>A of COL1A2, c.2533G>A of COL1A1, c.2845G>A of COL1A2, c.2532_2540del of COL1A1, and c.1847G>A of COL1A2. The same variants were not detected in their parents and the 100 healthy controls.@*CONCLUSION@#Variants of COL1A1/2 gene probably underlie the pathogenesis for osteogenesis imperfecta in these pedigrees. Discovery of the nevol variants has enriched the spectrum of COL1A1/2 gene variants and facilitated genetic counseling and prenatal diagnosis for the affected pedigrees.

Mutation analysis in a large Chinese pedigree affected with preaxial polydactyly II / 中华医学遗传学杂志

OBJECTIVE@#To detect potential mutation in a large pedigree affected with preaxial polydactyly II.@*METHODS@#With informed consent obtained, peripheral blood samples were collected from the proband, her family members as well as 100 healthy controls. Genomic DNA was extracted. The zone of polarizing activity regulatory sequence (ZRS) of the SHH gene was amplified by PCR and subjected to bi-directional Sanger sequencing.@*RESULTS@#The pedigree had typical preaxial polydactyly II. A heterozygous C>G mutation at position 105 of the ZRS region was detected in all patients but none of the unaffected members and 100 healthy controls.@*CONCLUSION@#The heterozygous 105C>G mutation of the ZRS region probably underlies the disease in this pedigree.

Latest research progress of periprosthetic osteolysis mechanism and related signaling pathway / 国际外科学杂志

Artificial joint replacement is an important means for the treatment of severe joint end-stage diseases such as hip and knee joint,which has obtained satisfactory clinical efficacy,but the postoperative periprosthetic osteolysis (PPO),which is mediated by wear particles,restricts the long-term effect of artificial joints.It is found that wear particles increase the expression of cytokines and inflammatory factors by stimulating the cells around the prosthesis,activate different signaling pathways,promote the imbalance between bone formation mediated by local osteoblasts and bone resorption mediated by osteoclast so as to lose of the local bone mass,and eventually produce osteolysis and aseptic loosening.This article reviews the different signal pathways activated by wear particles in recent years,in order to explore the pathogenesis of PPO and to open up new avenues for its prevention and treatment.

Prenatal diagnosis and intervention to fetal hydrothorax:five cases analysis / 中华妇产科杂志

Objective To research the important of prenatal diagnosis and effect of intervention to fetal hydrothorax. Methods The cases of fetal hydrothorax (n=5) were obtained from the Shengjing Hospital,China Medical University between December 2014 and May 2015. All pregnancies were uncomplicated, excluded congenital organic and chromosomal abnormalities during prenatal diagnosis and with a 37 average gestational weeks. The case 1, 2, 4 were unilateral hydrothorax and the case 3, 5 were bilateral. We performed an antenatal thracocentesis to case 1, 2, 3. In case1, the hydrothorax increased rapidly after 5 days, and the patient underwent a cesarean section and ex utero intrapartum treatment (EXIT);in case 2, the fetal heart rate was decreased to 40-50 bpm suddenly during thracocentesis, and we performed an emergent cesarean section and EXIT for the patient; in case 3, the patient underwent thracocentesis and a meanwhile cesarean section and EXIT procedure. We performed a conservative management to case 4, 5, the hydrothorax resolved spontaneously during the pregnancy and after birth, both patients underwent cesarean section. Results All fetuses were survived, the neonates of case 1, 2 and 3 underwent assited mechanical ventilation, thoracic close drainage, then discharged after hydrothorax resolved and feeding tolerance;in case 4, there was no respiratory distress and hospital treatment;in case 5, the neonate underwent assited mechanical ventilation and conservative management, the hydrothorax has resolved gradually. Conclusions The prenatal diagnosis and antenatal intervention (thracocentesis) may play an important role in fetal hydrothorax treatment. In clinical, we should choose different plan according to the gestation weeks and classification of hydrothorax of the patient.

Analysis of clinical outcome and impact factors of twin-to-twin transfusion syndrome with anterior placenta treated by fetoscopic laser photocoagulation / 中华妇产科杂志

Objective To analyze the clinical outcome and impact factors of twin-to-twin transfusion syndrome (TTTS) with anterior placenta treated by fetoscopic selective laser coagulation of placental vessels(SLCPV). Methods Ten cases of TTTS with anterior placenta and 8 cases with posterior placenta were treated by SLCPV in Shengjing Hospital from July 2011 to April 2014. Clinical data were analyzed retrospectively. Some cases were at Quintero stageⅡor higher stage, others were at Quintero stageⅠbut with cardiovascular score≥5 according to the scoring system of Children′s Hospital of Philadelphia. The anterior placenta cases were treated by curve fetoscopy and the posterior placenta cases were treated by straight fetoscopy. Results (1) Of all the 18 cases, the mean gestational age at SLCPV was 24.1 weeks (17+5 to 27+4 weeks). There were 2 cases at Quintero stageⅠ, 4 at stageⅡand 12 at stageⅢ. The mean gestational age of anterior placenta cases at SLCPV was 25.2 weeks (22 to 27+4 weeks), with 2 cases at Quintero stageⅠ, 2 cases at stage Ⅱ and 6 at stage Ⅲ;5 cases had preterm prelabour rupture of the membranes (PPROM)and 1 case had maternal intestinal obstruction after the operation;the average operation time was 40 minutes. Of the posterior placenta cases, the mean gestational age at SLCPV was 22.7 weeks (17+5 to 27+4 weeks);2 cases were at Quintero stageⅡand 6 cases at stageⅢ. PPROM happened in one case;one case had maternal enterobacter cloacae septicemia;the average operation time was 28 minutes. All the 18 cases could tolerate the operations. There was no intraoperative complication. (2) One anterior placenta case had maternal intestinal obstruction and miscarriage; and one posterior placenta case had enterobacter cloacae septicemia. Karyotype analyses of the all the twins were normal. (3) 17 cases delivered already, including all the 10 anterior placenta cases and 7 posterior placenta cases. One infant had corpus callosum agenesis, but its co-twin was normal. The average gestational age at delivery for anterior placenta cases was 32.6 weeks (24 to 37+1 weeks), an was 28.2 weeks (25+6 to 36+2 weeks) for posterior placenta cases. The fetuses survival rate was 13/17 (one case was still in pregnancy) for at least one twin, and 10/17 for both twins. Both twins survival rates were 5/10, 5/7 for anterior placenta cases and posterior placenta cases, respectively. At least one twin survival rates were 8/10, 5/7 for the two groups respectively. Conclusion SLCPV is suitable for the treatment of TTTS, no matter the placenta is on the anterior wall or posterior wall. The treatment had good outcomes, but more PPROM happened in the anterior placenta cases, which may be associated with operation time and the range of operation.

Clinical management and perinatal outcome of twin reversed arterial perfusion sequence in different stage / 中华妇产科杂志

Objective To discuss the methods and outcomes of twin reversed arterial perfusion sequence in different stage. Methods From August 2012 to December 2013, 11 cases were diagnosed with twin reversed arterial perfusion sequence (TRAP) by 3d color Doppler ultrasound in the Maternal ang Fetal Medicine Center ,Affiliated Shengjing Hospital, China Medical University, including 3 cases in stageⅠa, 7 in stageⅡa and 1 case in stageⅡb. We performed expected therapy to 3 cases in stageⅠa and 4 cases in stageⅡa [1 case (case 9) in stageⅡa developed to stageⅡb and was terminated by emergency cesarean section], radio frequency ablation (RFA) selective reduction to 3 cases in stage Ⅱa, emergency cesarean section to 1 case in stageⅡb. All cases except case 1,4 took cesarean section to terminate pregnancy and would be followed up on the aspect of infant′s growth. Results (1) 3 cases in stageⅠa were monitored by sequential ultrasound examination, all donors grew normally, in which 2 acardias arised spontaneous cessation of flow and were implemented of cesarean section after the normal period of gestation; 1 case suffered premature rupture of membrane and experienced the natural childbirth at 34 gestation weeks plus 5 days. The survived average labor weight was 2 923 g. (2) In the 7 stage Ⅱa cases, 3 cases were implemented of RFA selective reduction, 2 cases survived and the average labor gestation was 35 weeks plus 1 day and average labor weight was 2 050 g;in 3 expected therapy cases, 1 case suffered premature rupture of membrane at 34 gestation weeks plus 5 days and experienced cesarean section; 1 case was observed for 3 weeks and the donor was stillborn; 1 case progressed to stage Ⅱb and experienced cesarean section at 34 gestation weeks plus 5 days;and 1 case was lost of follow up. (3) For 2 cases of stageⅡb cases, one was progressed from stage Ⅱa during expected therapy; the other one had been already in stage Ⅱb since visiting and experimented an emergency cesarean section, but the neonate died of heart failure two days after labor. (4) 7 survived neonates were followed up, all had a normal condition compared to kids of the same age, except one suffering a congenital heart disease, patent ductus arteriosus and atrial septal defect and whose weight (6 kg at 7 months) was lighter. Conclusions We should make the diagnosis of TRAP as early as soon and choose appropriate therapy according to the stage. According to our research, cases in stage Ⅰa can undergo an expected therapy under a sequential ultrasound examination;cases in stageⅡa can undergo a RFA selective reduction to improve the prognosis of the donor, which can make a good perinatal outcome.

Relationship of serum angiotensin converting enzyme level and primary hypertension target organ damage / 中国综合临床

Objective To investigate the relationship of serum angiotensin converting enzyme (ACE) level and primary hypertension target organ damage.Methods According to target organ damage,essential hypertension patients were divided into 3 groups:primary hypertension with coronary artery disease,primary hypertension with cerebral infarction and primary hypertension with kidney injury.There were 60 subjects in each complication group.There were 60 healthy adults in the normal control group.Serum ACE level was detected and compare among the 4 groups.Results Serum ACE level in normal control group was (21.36 ± 6.86) U/L,while that in primary hypertension with coronary artery disease,primary hypertension with cerebral infarction and primary hypertension with kidney injury were (36.09 ±4.87) U/L,(39.15 ±7.03) U/L and (28.34 ±7.23) U/L respectively.Serum ACE level was higher in each complication group than in normal control group (F =343.997,P ＜ 0.01).In the complication groups,serum ACE level was the lowest in the group of primary hypertension with kidney injury.Conclusion High active ACE is associated with target organ damage in primary hypertension,especially kidney injury.

Intrapartum operation on fetuses with birth defects and its outcome / 中华妇产科杂志

Objective To discuss the value of intrapartum operation in management of birth defects and the prognosis. Methods From August 2008 to November 2009, 11 fetuses were identified with birth defects through 3D color Doppler ultrasound and confirmed by MRI and fetal karyotype in the Maternal Fetal Medicine Center, Affiliated Shengjing Hospital, China Medical University including three lymphangiomas,two congenital diaphragmatic hernias (CDH), one sacrococcygeal teratoma, three omphalocele and two gastroschisi. All the above identified birth defects were indications for surgery. All fetuses were born abdominally and received intrapartum operations, including three intrapartum fetal operations with placental infusion (two repairs of CDH, one sacrococcygeal teratoma resection), six ex-utero intrapartum treatment (EXIT; two repairs of omphalocele, two repairs of gastroschisi, two lymphangioma resection) and two surgeries in house (one omphalocele repair and one lymphangioma resection). Both the mothers and fetuses were regularly followed up. Results ( 1 ) Operations: the average operating time for the three intrapartum fetal operations was 89 minites, 5.5 minites for the six EXIT, during which EXIT was performed first,followed by blocking the umbilical circulation and neonatal surgery, and 37 minites for the two surgeries in house. All neonates survived except for one death from severe CDH at 3.5 hours after the operation. The average blood loss for cesarean section and fetal operation was 275 ml. All mothers recovered soon without fever or infection and were discharged three to five days after the operation. (2) Follow-ups: the ten survived neonates were followed up at 1 - 18 mouths at the pediatric clinics and all were growing and developing normally except for one baby with gastroschisi suffered from enteral torsion and feeding intolerance showed lower weight than babies at the same age, but catched up to normal at four months old after posture therapy. One baby with mild CDH developed pulmonary infection at two months after operation with 1/4 pneumothorax on chest X-ray, and were hospitalized for two weeks. At six months old, patent ductus arteriosus was diagnosed in the same baby and chest X-ray was normal. The baby with omphalocele was complicated with ventricular septal defect before operation and the cardiac function was normal during followups for one year. The baby with sacrococcygeal teratoma was reported to have no automatic micturition, but recovered to normal at one month of age. Conclusion Babies with certain birth defects can be managed through intrapartum operation with better outcomes.

The Maternal Prognosis after Intrapartum Fetal Operation Performation / 中国医科大学学报

Objective To investigate the feasibility,security,indication and prophylactic measures of postpartum hemorrhage during the fetalintrapartum operation by analyze the maternal prognosis after intrapartum fetal operation(IFO) performed.Methods We performed a retrospective evaluation of 10 cases that has been performed intrapartum fetal operation(IFO group,n=10) successfully between August 2008 and October 2009 at Department of Obstetrics and Gynecology,Shengjing Hospital,China Medical University.Healthy pregnant women(n=10) were chosen as control group,who received Caesarean section for refusing to vaginal delivery.Between the two groups,we compared the indexes including blood lose during the operation and 24 hours post-operation,the hemoglobin level pre-operation and 24 hours post-operation,the involution of uterus,the puerperal infection,and the follow-up at 42 days post-operation.Results Good involution,no primary and secondary postpartum hemorrhage and no puerperal infection were found in both of the 2 groups.Intra-operation,24 hours post-operation and the total volumes of blood lose,the hemoglobin level before operation,24 hours post-operation and 42 days post-operation had no statistic significant difference between the IFO group and control group(P>0.05).No significant difference was found in the operation time between IFO group and the control group(66.40±53.40 minutes and 34.50±4.97 minutes,respectively.Intra-operation,24 hours post-operation and the total volume of blood lose had no relation to the maternal age and gestational weeks(P>0.05).The blood lose of intra-operation in IFO group had positive linear correlation to the operation time.(Pearson relation coefficient R=0.458,.P=0.021).The linear recurrence equation was:the volumes of blood lose intra-operation(ml)=172.68+1.342x(operation time).Conclusion IFO was safe to the mother.It did not affect the involution of uterus and could not increase the blood lose of postpartum and the puerperal infection morbidity.Through the effective measures of preventing postpartum hemorrhage,the postpartum blood lose of the patients that performed intrapartum fetal operation could be no more than that of the patients that had normal Caesarean section.Improving the technique of the intrapartum fetus operation and shortening the operation time are important to prevent postpartum hemorrhage.

Pharmacokinetics and bioequivalence of piracetam tablets in healthy volunteers / 中国临床药理学与治疗学

AIM: To study the bioequivalence of piracetam tablets in Chinese healthy volunteers. METH-ODS: Twenty volunteers were randomly divided into two groups (test and reference), with double cross-over design and single-dose oral administration. The concentration of piracetam in serum was determined by HPLC. The main pharmacokinetic parameters were calculated and the bioequivalence was evaluated with DAS2.0 practical pharmacokinetics program. RESULTS: The pharmacokinetic parameters of piracetam tablets were as follows: t1/2 were 5.50±1.48 and 4.29±1.00 h, Cmax were 21.47± 6.27 and 20.96±5.10 mg·L-1, Tmax were 0.70±0.46 and 0.66± 0.36 h, AUC0-24h were 93.44± 16.61 and 96.67± 18.50 mg·h·L- 1. The relative bioavailability of the test preparation was 99.8%± 22.7%. CONCLU-SION: The test and reference preparations were bioequivalent and may be prescribed interchangeably.