Objective: To summarize the clinical data and prognosis of children with Philadelphia chromosome-like acute lymphoblastic leukemia (Ph-like ALL) common genes. Methods: This was a retrospective cohort study.Clinical data of 56 children with Ph-like ALL common gene cases (Ph-like ALL positive group) treated from January 2017 to January 2022 in the First Affiliated Hospital of Zhengzhou University, Henan Children's Hospital, Henan Cancer's Hospital and Henan Provincial People's Hospital were collected, 69 children with other high-risk B cell acute lymphoblastic leukemia (B-ALL) at the same time and the same age were selected as the negative group. The clinical characteristics and prognosis of two groups were analyzed retrospectively. Comparisons between groups were performed using Mann-Whitney U test and χ2 test. Kaplan-Meier method was used for survival curve, Log-Rank test was used for univariate analysis, and the Cox regression model was used for multivariate prognosis analysis. Results: Among 56 Ph-like ALL positive patients, there were 30 males and 26 females, and 15 cases were over 10 years old. There were 69 patients in Ph-like ALL negative group. Compared with the negative group, the children in positive group were older (6.4 (4.2, 11.2) vs. 4.7 (2.8, 8.4) years), and hyperleukocytosis (≥50×109/L) was more common (25% (14/56) vs. 9% (6/69)), the differences were statistically significant (both P<0.05). In the Ph-like ALL positive group, 32 cases were positive for IK6 (1 case was co-expressed with IK6 and EBF1-PDGFRB), 24 cases were IK6-negative, of which 9 cases were CRLF2 positive (including 2 cases with P2RY8-CRLF2, 7 cases with CRLF2 high expression), 5 cases were PDGFRB rearrangement, 4 cases were ABL1 rearrangement, 4 cases were JAK2 rearrangement, 1 case was ABL2 rearrangement and 1 case was EPOR rearrangement. The follow-up time of Ph-like ALL positive group was 22 (12, 40) months, and 32 (20, 45) months for negative group. The 3-year overall survival (OS) rate of positive group was significantly lower than the negative group ((72±7) % vs. (86±5) %, χ2=4.59, P<0.05). Compared with the 24 IK6-negative patients, the 3-year event free survival (EFS) rate of 32 IK6 positive patients was higher, the difference was statistically significant ((88±9) % vs. (65±14) %, χ2=5.37, P<0.05). Multivariate Cox regression analysis showed that the bone marrow minimal residual disease (MRD) not turning negative at the end of first induction (HR=4.12, 95%CI 1.13-15.03) independent prognostic risk factor for patient with Ph-like ALL common genes. Conclusions: Children with Ph-like ALL common genes were older than other high-risk B-ALL patients at diagnosis, with high white blood cells and lower survival rate. The bone marrow MRD not turning negative at the end of first induction were independent prognostic risk factor for children with Ph-like ALL common gene.

本文主要探究了出生缺陷的原因以及营养摄入的重要性,阐述了爱孕坊各主要成分对孕妇自身和胎婴儿生长发育的功效;通过引用诸多文献的研究成果发现,爱孕坊作为孕早期专用营养品,除了有效缓解孕早期反应之外,能促进胚胎发育以及胎儿神经系统雏形的分化建立,促进胎儿大脑发育,有效预防出生缺陷的发生.

OBJECTIVE:To evaluate the efficacy and safety of domestic human recombinant FSH(rhFSH)in women with anovulation of WHO group Ⅱ. METHODS:A randomized, blind, parallel-controlled, non-inferiority and multicenter study was performed. A total of 534 admitted to 13 hospitals from May 2008 to August 2009. There were 531 women with ovulatory disorder was included in the statistical analysis, were randomly divided into test group(domestic rhFSH, n=352)and control group(imported rhFSH, n=179). Percentage of cycle with mature follicle, ovulation rate, clinical pregnancy rate, multiple pregnancy rate, ovarian hyperstimulation syndrome(OHSS)and adverse events were observed. RESULTS:No statistical significant differences(P>0.05)were observed between the two groups in terms of the efficiency on mature follicle[91.8%(323/352)versus 88.8%(159/179)], ovulation rate[91.3%(295/323)verus 90.6%(144/159)], clinical pregnancy rate[19.2%(62/323)verus 18.2%(29/159)], the number of the follicles<14 mm, the level of serum LH and progesterone, the thickness of endometrium on the day of hCG administration. The number of follicle≥18 mm and 14 mm≤follicle<18 mm and the level of serum estradiol on the day of hCG in the test group were significantly higher than those in the control group(P<0.05). The number of days of rhFSH administration in the test group was significantly less than that in the control group[(9.8±2.2)versus(11.4± 0.6)days, P<0.05], the dosage of rhFSH was significantly lower than that in the control group[(879 ± 419)versus(1 043±663)U, P<0.05]. The multiple pregnancy rate in the test group was significantly higher than that in the control group[21%(13/62)versu 10%(3/29), P<0.05]. The incidence of OHSS and adverse events were similar between the two groups(P>0.05), and no other adverse events were observed in test group during treatment. CONCLUSION:Ovarian stimulation with domestic rhFSH is effective, safe and economical in women with anovulation of WHO group Ⅱ.

目的:探讨影响卵裂期冷冻胚胎移植妊娠结局的相关因素.方法:回顾性分析2011年1月至2014年12月在北京大学第一医院进行卵裂期冻胚移植的1008个周期,探讨患者年龄、不孕年限、不孕类型、内膜准备方式、内膜厚度及类型、受精方式、胚胎冷冻方法、辅助孵化、胚龄、移植胚胎数量及质量等对冷冻胚胎移植妊娠结局的影响.结果:1008个胚胎解冻周期,复苏胚胎2883个,存活2503个(86.8％),完成冻胚移植周期981个(97.3％),临床妊娠周期413个(42.9％),胚胎种植率23.6％,早期流产率14.0％.年轻患者、全胚冷冻后第一次冻胚移植、选择玻璃化冷冻方法、移植≥2枚胚胎尤其是≥2枚优质胚胎的冷冻胚胎移植妊娠率较高.结论:在诸多因素中,年龄、冷冻方法、是否全胚胎冷冻、移植胚胎数目及质量对冻胚移植妊娠结局影响显著.

Objectives:To discuss the effects of dydrogesterone using for luteal phase support,instead of intramuscular progesterone,on IVF obstetric outcomes.Methods:The data of patients treated with IVF/ICSI in our department from July 1 ,201 0 to December 31 ,201 1 were reviewed.The clinical pregnancy rate and live birth rate between 1 28 patients who were treated with intramuscular injection of 40mg progesterone combined with 20mg oral dydrogesterone for luteal support and patients who were treated with intramuscular injection of 60mg progesterone were compared.Results:In dydrogesterone group,the clinical pregnancy rate was 47. 3% and the live birth rate was 40. 7%.Both the two rates had no difference with the patients treated with progesterone in the same period. When only selecting patients treated with short-acting GnRHa long protocol for down-regulation and patients trea-ted with ICSI,the clinical pregnancy and live birth rate of dydrogesterone group did not differ from these of the other two groups.Conclusions:Dydrogesterone,used for luteal phase support,did not affect the obstetric outcomes of the patients who received IVF treatment.

Objectives:To investigate the clinical manifestations,diagnosis,therapy and outcomes of heter-otopic pregnancy after in vitro fertilization and embryo transfer (IVF -ET).Methods:3 cases of heterotopic preg-nancy after IVF -ET were analyzed retrospectively between January 2001 and December 2013 in Peking University First Hospital.Results:The 1st patient received emergency laparotomy bilateral tubal resection for the broken of sac caused by ruptured ectopic pregnancy.And the pregnancy continues until found abortion without any obvious incen-tive after 16 weeks.The 2nd one found intrauterine fetal demise when admitted into the hospital.And the ultrasound found ectopic gestational sac,then the patient received curettage and laparoscopic tubal resection.The last patient was found heterotopic pregnancy by transvaginal ultrasound and was received salpingectomy (right tube removed) with laparoscopic.Now the intrauterine gestational sac continued to develop.Conclusion:It is difficult to diagnose at the early stage of heterotopic pregnancy for the shortage of typical clinical manifestations.Clinicians should pay more attention to it and take timely treatment based on surgery,so as to protect patients,their fertility and embryo.

Objective To investigate the clinical significance of the cytogenetic abnormality in the infertile males. Methods Cytogenetics of patients was examined by culturing peripheral-blood lymphocyte and G-banding technology, and karyotyping analysis technique were used to study the abnormality and the polymorphism of chromosomes. Results Of 813 infertile men, 55 (6.76%) were detected to have chromosomal abnormalities in chromosomal analysis, including 36 cases with the numeric abnormality (4.43%), 17 cases with chrom osomal rearrangement (2.09%). In 55 cases with chromosomal abnormalities, the constituted ratios of numeric aberration and the rearrangement were 65.4%and 30.91%respectively. Two cases of male pseudohermaphroditism were detected. Klinefelter syndrome and balanced reciprocal translocations were the most common aberration of the chromosomal abnormalities. In addition, 44 cases were detected to have polymorphic variations (5.41%,44/813), including 11 cases with the somatic chromosomal polymorphic variations (1.35%,11/813), 21 cases with the big Y(2.58%,21/813) and 12 cases with bit Y chromosomal(1.48%,12/813). The somatic chromosomal polymorphism included secondary constriction increases, satellite increases in the D/G group. Y chromosomal polymorphism was the most common chromosomal polymorphism. The main clinical features of the male infertility attributing to the chromosomal abnormality and polymorphism were azoospermia, abnormal spermatozoa (oligozoospermia, asthenospermia and teratozoospermia). Conclusion Chromosome and abnormality polymorphisms showed negative effects on the male fertile function. The infertile males with chromosomal abnormality or polymorphisms definitely had an increasing risk in heredity. Karyotype testing screening is necessary for the infertile males, and PGD is helpful to decrease the genetic risk.

To investigate the effects of bit Y chromosome configuration on male fertility and to evaluate the relevant clinical significance.Methods:The relevant cases were divided into two groups,where A group included male infertile cases while B group included cases whose wife had adverse pregnancy history or the ab-normal amniotic fluid punctures.Cytogenetics of patients was examined by culturing peripheral-blood lymphocyte and G-banding technology,and karyotyping analysis technique was used to study the bit Y chromosome in two dif-ferent groups.Results:Among the 2139 cases,30 cases were found with abnormal karyotype of bit Y chromo-some.,including 12 ones in group A and 18 ones in group B,with no significant difference (P=0.971).The main clinical effects of bit Y were azoospermia,oligozoospermia,miscarriage,embryonic diapause and fetal anomalies,et al.Conclusion:The bit Y chromosomal abnormality may have some potential clinical effects which may affect the spermatogenesis and adverse pregnancy.Therefore,a detailed mechanism study needs to be further investigated.

Objectives:To analyze the clinical significance of the inversion abnormality of chromosome on the adverse pregnancy events.Methods:Cytogenetics of patients was examined by culturing peripheral-blood lym-phocyte and G-banding technology,and karyotyping analysis technique was used to study the relationship between the chromosomal inversion abnormality and the fertile dysfunction in 1408 couples with adverse pregnancy outcome. Results:Among 2816 cases with adverse pregnancy events,31cases (16 male and 15 female)were found with chromosomal inversion abnormality,and the abnormal rate was 1.10%.There was no significant difference in the abnormal rate of chromosomal inversion between the different genders (male:1.13%,female:1.06%,P>0.05). 25 cases with inv (9)were detected and the detectable rate was 0.89%(25/2816).The other types of inversion abnormality included:one case with inv (6)(q11q21),one case inv (7)(p15q36),one case with inv (18) (p11q21),one case with inv (1)(q34q22),one case with inv(X)(p22q26)and one case with inv (10) (q12q22).The clinical symptoms of inversion abnormality were miscarriage,embryonic diapause,fetal anomalies and et al.Conclusion:During the inversion abnormality related to the fertile dysfunction couples,inv (9 )is the most common type.Inv (9)maybe have some potential effect on the adverse pregnancy events.There is no signifi-cant difference of the detectable rate of inversion abnormality between the different genders.Therefore,the couples with adverse pregnancy outcome should both receive cytogenetically examination at the same time.Possibly,the PGD and ICSI may be helpful to the patients with the inversion abnormality,but the detailed issues need to be fur-ther investigated.

OBJECTIVETo investigate the effects of big and bit Y chromosome configurations on male fertility and to evaluate the relevant clinical significance.METHODSThe relevant cases were divided into A and B groups. Group A included male infertile cases. Group B included cases whose wives had adverse pregnancy history or the abnormal amniotic fluid punctures. The cytogenetics of the patients were examined by culturing peripheral-blood lymphocytes and G-banding technology, and karyotyping analysis techniques were used to study the big and bit Y chromosomes in the two different groups.RESULTSAmong 2 139 cases, 98 cases were found with abnormal karyotype of big and bit Y chromosomes. There was no significant difference in the abnormal rate of the length variation of the Y chromosomal karyotypes between the male infertility group and the adverse pregnancy outcome group. In the male infertile group (group A), there was no significant difference in the abnormal rate between the big Y chromosome and the bit Y chromosome. In the group with adverse pregnancy outcomes (group B), the abnormal rate of the big Y chromosome karyotyping was significantly higher than that of the bit Y chromosome karyotyping. The main clinical effects of groups A and B were azoospermia, oligozoospermia, poor spermia, abortion, embryonic diapause and fetal anomalies, etc .CONCLUSIONThe big and bit Y chromosomal abnormality results in not only the male infertility directly, but also an important and continuous reason of adverse pregnancy outcomes, of which the detailed mechanism needs to be further investigated.

不良孕产结局包括自然流产、死胎、死产、畸胎、生育先天性疾病患儿及染色体异常患儿史等.广义的男性生殖功能障碍包括夫妻虽然能够妊娠,但不能正常维持整个妊娠过程并分娩健康活婴,导致不良妊娠结局.染色体异常是导致不良妊娠结局的重要原因之一,包括染色体数目异常和染色体结构异常,可由亲代遗传而来,也可在内外因素的作用下染色体畸变而来[1-4].

目的:探讨大Y染色体核型对男性生育力的影响及其临床意义.方法:回顾性分析2139例男性患者的外周血细胞核型分析结果,并将其分为两组,包括不良妊娠结局或羊水穿刺胎儿染色体异常者(A组),严重少、弱精症或无精症等男性不育者(B组).比较不同组别之间的大Y检出率之间的差异并进行临床分析.结果:A组1326例,B组813例,共检出68例大Y染色体核型.其中,A组检出大Y核型47例,检出率为3.54%;B组检出大Y核型21例,检出率为2.58%.对于A组中大Y核型检出者其配偶同时进行染色体核型分析.对检出的68例大Y核型进行分析,临床效应表现为弱精症者13例,占19.11%;无精症者8例,占11.76%;其配偶曾有胚胎停育11例,占16.17%;自然流产者6例,占8.82%;羊水穿刺胎儿染色体异常者16例,占23.52%,两组间大Y核型检出率比较无统计学显著差异.结论:大Y染色体核型,作为一种遗传多态性,可能具备一定的临床效应,与男性生精功能降低及对胚胎发育的影响,值得关注及深入研究.

Objective To determine the pregnancy outcome in women with endometrial atypical hyperplasia after conservative treatment.Methods From March 1,2009 to August 31,2012,four patients with endometrial atypical hyperplasia who had received satisfactory conservative therapy were treated in the Center of Reproduction and Genetics,Peking University First Hospital.All patients achieved clinical intrauterine pregnancies.One patient became pregnant twice.We reviewed the data of five pregnancies in these four patients.The data for each patient were recorded,including endometrium pathology diagnoses before pregnancy,fertilitysparing approaches,assisted reproductive technologies for conceiving,pregnancy complications,termination time of their pregnancies,the delivery mode and the postpartum status.Results All the patients underwent dilatation and curettage.The endometrium pathology diagnoses in each patient were complex mild-moderate atypical hyperplasia,complex moderate atypical hyperplasia,complex atypical hyperplasia and extensive atypical hyperplasia with endometrial intraepithelial neoplasia (EIN),respectively.Cases 1,2 and 3 received medroxyprogesterone acetate 250 mg/d for eleven,eight and four months,respectively.Case 4 received megestrol acetate 160 mg/d for eight months.Endometrial atypical hyperplasia was not found by dilatation and curettage after treatment.Case 1 achieved a singleton pregnancy following follicle stimulating hormone-induced ovulation three months after drug withdrawal.Case 2 and 4 achicvcd a singleton pregnancy by inspection ovulation the month after drug withdrawal.The first pregnancy in Case 2 resulted in embryo diapause at nine weeks of gestation,and the second singleton pregnancy by inspection ovulation occurred six months after curettage.Case 3 failed to conceive following clomiphene citrate-induced ovulation for two months.The patient underwent repeat dilatation and curettage due to abnormal uterine bleeding and was diagnosed with EIN.She was retreated with megestrol acetate 160 mg/d for eight months.The patient then received in vitro fertilization and embryo transfer and achieved a twin pregnancy,but aborted at 22+6 weeks.Case 1,2 (the second pregnancy) and 4 achieved full-term pregnancy.In five pregnancies,one case underwent embryo diapause in early pregnancy,one case underwent late pregnancy abortion,and three cases achieved full term pregnancies and three healthy infants.Conclusions Patients with endometrial atypical hyperplasia who receive conservative treatment can conceive successfully and have an optimistic pregnancy outcome after appropriate assisted reproductive technology.However,complications,such as abortion,are more common in these patients.Close monitoring is required during pregnancy to determine abnormal conditions and administer appropriate and timely treatment.

目的:探讨子宫内膜非典型增生患者经保守治疗满意后进行助孕的策略.方法:回顾性分析北大医院生殖中心接诊的4例经药物保守治疗满意后的子宫内膜非典型增生症患者病例资料.结果:4例患者诊断性刮宫病理诊断为不同程度的内膜非典型增生,其中2例同时诊断子宫内膜上皮内瘤变.患者不孕时间为8~120个月,根据情况分别进行了监测排卵、促排卵及IVF治疗,2例足月分娩,1例晚期流产,1例妊娠中.结论:子宫内膜非典型增生具有较高的复发率及恶变率.这类患者如有生育要求,无论是否达到不孕症的诊断标准,均应在保守治疗满意后积极协助其尽早妊娠.选择适当的助孕方式,帮助患者尽早妊娠,降低复发率.进行IVF治疗时,可考虑首选GnRHa超长方案降调节.

Objective To investigate the molecular mechanism of LOH by analyzing the effect of Cox7a2 on the LH-induced testosterone production through the interconnection of Cox7a2 and Ras-ERK. Methods Cox7a2 and its site-mutant vectors were cloned by RT-PCR and sequence analysis. The relevant fluorescent protein vectors were constructed and transfected into TM3 cells and were observed by fluorescent microscope. The phosphorylation of ERK1/2 (extra cellular signal regulated kinase1/2) was detected in TM3 Leydig cells by Western blott. Results Cox7a2 inhibited ERK1/2 phosphorylation in TM3 mouse Leydig cells stimulated with LH. Ras protein affected the sub-cellular location of Cox7a2. Conclusion Ras-ERK signaling pathway may be involved in the development of LOH. Cox7a2 mediates testosterone productionby inactivation of ERK1/2, which need to be further investigated.

目的:探讨精液中白细胞对精液各主要参数的影响.方法:回顾性分析216例男性不育患者的精液质量,根据WHO推荐的方法进行精液常规及精子形态学分析,利用联苯胺法进行白细胞检测,并将患者分为白细胞精子症(＞1×106/mL)和非白细胞精子症(≤1×106/mL)两组.结果:与非白细胞精子症组(n=152)相比,白细胞精子症组(n=64)的精子密度明显降低[(38.36±23.16)×106/mL vs (47.14±19.70)×106/mL,P＜0.01],活动率明显下降(43.50％±11.49％ vs 48.17％±10.28％,P＜0.01),a+b级精子比率明显下降(31.00％±10.64％ vs 35.87％±10.66,P＜0.01),正常形态精子百分率明显降低(10.75％±4.40％ vs12.31％±3.84％,P＜0.05),而白细胞精子症组的精液液化异常发生率较非白细胞精子症组明显增高(14.06％vs 4.61％,P＜0.05).结论:白细胞精子症可导致精子密度、活动率及正常形态精子百分率的降低,并可引起精液液化异常发生率的增高.

OBJECTIVE:To study pregnancy outcome and recurrence in patients with different type of endometriosis related infertility treated by conservative surgery. METHODS:From January 2005 to December 2010, 79 patients with endometriosis related infertility underwent conservative laparoscopic surgery in Peking University First Hospital, including 16 cases with deep infiltrating endometriosis, 39 cases with ovarian endometriosis and 24 cases with peritoneal endometriosis. At 1 to 5 years follow-up after surgery, natural pregnancy outcome and recurrence were studied. RESULTS:(1) The accumulated pregnancy rate were 6/16 in deep infiltrating endometriosis group, 36% (14/39) in ovarian endometriosis group, and 46% (11/24) in peritoneal endometriosis group, which did not reached statistical difference (P > 0.05). (2) The median interval between pregnancy and surgery were 38.5 months in deep infiltrating endometriosis group, 9.5 in ovarian endometriosis group and 6.0 months in peritoneal endometriosis group. The median interval in deep infiltrating endometriosis was significantly longer than that in peritoneal endometriosis group and ovarian endometriosis group (P < 0.01). Total of 11 patients in peritoneal endometriosis group and 11 patients in ovarian endometriosis group acquired pregnancy at 18 months after surgery. (3) The recurrent rate were 5/16 in deep infiltrating endometriosis group, 13% (5/39) in ovarian endometriosis group and 4% (1/24) peritoneal endometriosis group, respectively (P > 0.05). CONCLUSIONS:There was no difference among these three groups in accumulated pregnancy rate. However, the interval between pregnancy and surgery was significantly longer in patients with deep infiltrating endometriosis when compared with those in the other groups.

Objectives: To study the relationship between the rate of human normal morphology sperm and the clinical outcomes of in vitro fertilization-embryo transfer(IVF-ET) treatment.Methods: This study retrospectively analyzed 238 IVF-ET cycles.Sperm morphology was evaluated by Diff-Quik Staining methods according to the WHO criterion.Based on the results of morphological evaluation,the 238 cycles were divided into three groups,which defined morphologically normal sperm 5% and ≤10% as group A,10% and 15% as group B,and ≥15% as group C.The relationship between sperm morphology and the outcomes of IVF-ET treatment was compared and analyzed among these three groups.Results: There was no significant difference among these three groups in female age,infertile years,male age,base FSH level,days of using Gn,dosage of Gn,E2 and P level of hCG on each day,endometrial thickness,oocyte number and MⅡ oocyte number(P0.05).Meanwhile,no statistically significant differences were observed in the rates of fertilization,2PN fertilization,multi-PN fertilization,cleavage,quality embryos,implantation,pregnancy,abortion and the multi-fetal rate among these three groups(P0.05).Conclusion: There is no significant impact of human sperm morphology on outcomes of IVF-ET treatment when morphologically normal sperm more than 5%.

OBJECTIVE:To investigate the co-sub-cellular-location of Cox7a2 and Ras.METHODS:Ras and its mutant plasmid were cloned by RT-PCR and sequence analysis. Cox7a2-pEYFP-N1, Ras-pEYFP-N1 and N17-Ras-pEYFP-N1 fluorescent protein vectors were constructed and transfected into TM3 cells.RESULTS:Cox7a2 was located in the mitochondria, but its location was changed by the expression of Ras. When the dominant negative ras was expressed in the cells, the Cox7a2 located into the mitochondria again.CONCLUSION:Cox7a2 mediated testosterone production, which might be at least in part related with the Ras signaling pathway. Ras may be the regulating target and further investigation is needed to make it clear.

<正>近30余年来,随着辅助生殖技术的建立和发展,生殖医学领域发生了令世人瞩目的变化,同时,社会经济的发展也促进了不孕症诊治行业的发展。按照世界卫生组织(WHO)的标准,夫妇同居未避孕,有正常性