Induced abortion in China and the advances of post abortion family planning service

This is a review of current situation of induced abortion and post abortion family planning service in China. Induced abortion is an important issue in reproductive health. This article reviewed the distribution of induced abortion in various time, areas, and population in China, and explored the character, reason, and harm to reproductive health of induced abortion.Furthermore, this article introduces the concept of Quality of Care Program in Family Planning,and discusses how important and necessary it is to introduce Quality of Care Program in Family Planning to China.

Research progress in prevention of postoperative delirium

Postoperative delirium is a common acute confusion state that frequently occurs in patients following surgery.It is characterized by fluctuating consciousness,inattention,disorganized thinking,and altered level of consciousness.Postoperative delirium leads to cognitive decline and dementia,increases the risk of post-operative complications and mortality,and reduces patients’quality of life.Since the pathogenesis of postoperative delirium is unclear and there is no effective treatment,early diagnosis and early intervention are key to preventing and treating postoperative delirium.Currently,the prevention of postoperative delirium is mainly based on non-pharmacological prevention and treatment,whereas some drugs are gradually starting to be used.In the future,efforts are needed to clarify the effect of treatment and to guide the development of a series of more effective and rational delirium treatment strategies adapted to specific national context.

Abnormal function of EPHA2/p.R957P mutant in congenital cataract

AIM:To identify genetic defects in a Chinese family with congenital posterior polar cataracts and assess the pathogenicity.METHODS:A four-generation Chinese family affected with autosomal dominant congenital cataract was recruited.Nineteen individuals took part in this study including 5 affected and 14 unaffected individuals.Sanger sequencing targeted hot-spot regions of 27 congenital cataract-causing genes for variant discovery.The pathogenicity of the variant was evaluated by the guidelines of American College of Medical Genetics and InterVar software.Confocal microscopy was applied to detect the subcellular localization of fluorescence-labeled ephrin type-A receptor 2(EPHA2).Co-immunoprecipitation assay was implemented to estimate the interaction between EphA2 and other lens membrane proteins.The mRNA and protein expression were analyzed by reverse transcription-polymerase chain reaction(qRT-PCR)and Western blotting assay,respectively.The cell migration was analyzed by wound healing assay.Zebrafish model was generated by ectopic expression of human EPHA2/p.R957P mutant to demonstrate whether the mutant could cause lens opacity in vivo.RESULTS:A novel missense and pathogenic variant c.2870G>C was identified in the sterile alpha motif(SAM)domain of EPHA2.Functional studies demonstrated the variant’s impact:reduced EPHA2 protein expression,altered subcellular localization,and disrupted interactions with other lens membrane proteins.This mutant notably enhanced human lens epithelial cell migration,and induced a central cloudy region and roughness in zebrafish lenses with ectopic expression of human EPHA2/p.R957P mutant under differential interference contrast(DIC)optics.CONCLUSION:Novel pathogenic c.2870G>C variant of EPHA2 in a Chinese congenital cataract family contributes to disease pathogenesis.

LM23 is a novel member of the Speedy/Ringo family at the ：rossroads of life and death of spermatogenic cell

LM23 is a gene specifically expressed in the testis of Rattus norvegicus, as previously reported by our laboratory. The aim of the study is to further investigate the biological function of LM23. Several bioinformatic tools were utilized, including PROSITE and BLAST. To determine the subcellullar localization of LM23, a polyclonal antibody specific for LM23 was generated via the immunization of rabbits. The LM23gene was cloned from rat testis tissue, and LM23 protein was expressed in Escherichia co/i. The biological function of LM23 was analyzed with microarray analysis and immunohistochemistry, using a rat model of LM23 gene knockdown. The results suggested that LM23 belongs to the Speedy/Ringo family. LM23 regulated the GI/S and G2/M transitions of the cell cycle during spermatogenesis. Downregulation of the LM23gene during spermatogenesis could lead to the activation of both the Fas-FasL pathway and the mitochondrial pathway. These novel findings indicate that LM23 has a diverse array of functions that are important in both the life and death of the spermatogenic cell.

Predictors for partial suppression of spermatogenesis of hormonal male contraception

Aim： To analyze factors influencing the efficacy of hormonal suppression of spermatogenesis for male contraception. Methods： A nested case-control study was conducted, involving 43 subjects, who did not achieve azoospermia or severe oligozoospermia when given monthly injections of 500 mg testosterone undecanoate （TU）, defined as partial suppressors compared with 855 subjects who had suppressed spermatogenesis （complete suppressors）. Sperm density, serum testosterone, luteinizing hormone （LH） and follicle stimulating hormone （FSH） concentrations at the baseline and the suppression phase were compared between partial and complete suppressors. Polymorphisms of androgen receptor （AR） and three single nucleotide variants and their haplotypes of FSH receptor （FSHR） genes determined by polymerase chain reaction （PCR） and DNA sequencing technique were compared between 29 partial and 34 complete suppressors. Results： Baseline serum LH level was higher and serum LH as well as FSH level during the suppression phase was less suppressed in partial suppressors. Additionally, in a logistic regression analysis larger testis volume, higher serum FSH concentrations alone, or interaction of serum LH, FSH, testosterone and sperm concentrations were associated with degree of suppression. The distribution of polymorphisms of AR or FSH receptor genes did not differ between partial and complete suppressors. In cases with incomplete FSH suppression （FSH 〉 0.2 IU/L）, the chances of reaching azoospermia were 1.5 times higher in the subjects with more than 22 CAG triplet repeats. Conclusion： Partial suppression of spermatogenesis induced by 500 mg TU monthly injections is weakly influenced by hormonal and clinical features but not polymorphism in AR and FSHR genes.

Screening,Preparation,Characterization and Solubility of Polymorphic Forms of Ethinyl Estradiol

Ethinyl estradiol（EE） as a contraceptive,（17α）-19-nopregna-1,3,5-（10）-trien-20-yne-3,17-diol（formula： C（20）H（24）O2, molecular weight： 296.4, CAS number： 57-63-6）, is known to have different pseudo-polymorphic forms. Some EE polymorphs have been synthesized by means of physical or chemical methods, characterized by X-ray powder diffraction（XRPD）, thermogravimetric（TG）, differential scanning calorimetry（DSC） and IR spectra. Dissolution profile was tested by high performance liquid chromatography（HPLC）. Meanwhile, the crystal structure of the new EE solvate（formamide） was characterized by single-crystal X-ray structure analysis（SXRD）. The results confirmed that EE existed polymorphism. Five crystal forms of EE were presented and two of them were reported firstly. Furthermore, five polymorphs＇ dissolution curves were drawn and they could be identified by several analysis methods. Our study on polymorphs of EE could provide a variety of crystal material composition, preparation methods and solubility.

A randomized clinical trial of mifepristone plus different routes of administration of misoprostol for terminating a pregnancy up to 37 days

<正>Objective:To explore the efficacy of 400μg of misoprostol administered sublingually on medical abortion for early pregnancy by comparing with routine administration of misoprostol. Methods;Women presenting for termination of early pregnancy,whose gestational ages were not more than 37 days,were randomly allocated into two groups.Women in group A were given 50 mg of mifepristone orally on the first day and 25 mg of mifepristone 8 to 12 hours later.The schedule on the second day was as the same as above followed by 400μg of misoprostol orally on the third day.Women in group B were given a dose of 150 mg of mifepristone orally followed by 400μg of misoprostol sublingually 36 to 48 hours later.Both completed abortion rates and side effects were evaluated. Results:The completed abortion rates were 93.4%in group A and 91.0%in group B,showing no significant difference(χ~2 =2.3846,P>0.05).About 80%of the women experienced nausea,vomit,dizziness,headache and breast tenderness.There were no significant differences in side effects of the two groups(P all>0.05).The duration of vaginal bleeding in the two groups were(9.08 + 3.49) days and(9.04 + 3.43) days,showing no significant difference(t= 0.15,P>0.05).About 97.3%of validated questionnaires on patient satisfaction were recovered.The proportions of patient satisfaction were 88.1%in group A and 92.0%in group B,showing no significant difference (P>0.05). Conclusion:Administration of 150 mg mifepristone orally followed by 400μg of misoprostol sublingually could be more suitable for termination of early pregnancy due to its higher complete abortion rate and less side effects.

Insights into semen analysis： a Chinese perspective on the fifth edition of the WHO laboratory manual for the examination and processing of human semen

We are very glad to see that the Asian Journal of Andrology published a Special Issue on Semen Analysis in 21st Century Medicine, which well revealed some behind-the-scene controversies of the 5th edition of the WHO laboratory manual for the examination and processing of human semen [1]. Three articles from the special issue, two on the reference values of semen parameters [2, 3] and another presenting the investigation results of 118 laboratories performing semen analysis in China's Mainland [4], are very thoughtprovoking and we would like to share some of our views on these topics.

Construction of HMI Network System for Individualized Maternity Intervention Service against Birth Defects in Community

The paper expounds the community maternity service system against birth defects, from the viewpoint of individualized service in family planning. We have utilized modern information technology to develop health management information （HMI） network with individualized maternity, and to establish the community service system for intervention of birth dejects. The service system applied the concept of modern health management information to implementing informational management for screening, treatment, following up, outcome monitoring, so as to provide a base for promotion of health, diagnosis, treatment as well as scientific research, with the prenatal screening of Down＇s syndrome as a model. The introduction to informational network during the processes of service has been carried out with regards to its composition, function and application, while introducing the effects of computerized case record individualized in prevention, management and research of Down＇s syndrome.

Chinese traditional medicine for induction of ovulation

This is a review paper of some effective recipes of Chinese traditional medicine usedin ovulation induction and treatment of gynecological diseases. Some clinical results bygynecologists using Chinese traditional medicine in combination with western medicineand results from research on traditional medicine with modern technology are presented.A list of frequently used traditional medicine for ovulation induction are selected from the famous Compendium of Materica Medica(本草纲目)by Li Shi-zhen(李时珍).

Two approaches for calculating female fetal DNA fraction in noninvasive prenatal testing based on size analysis of maternal DNA fragments

The concentration of cell-free fetal DNA fragments should be detected before noninvasive prenatal testing(NIPT).The fetal DNA molecules have significant clinical potential in determining the overall performance of NIPT and clinical interpretation.It is important to measure fetal DNA fraction before NIPT.However,there is still little research on how to calculate the concentration of female fetuses.Two estimation approaches were proposed to calculate fetal DNA fraction,including the fragments size-based approach,aneuploid-based approach,which are all approaches based on chromosome segments.Based on high-throughput sequencing data,two approaches to calculate the DNA fraction of male fetuses were tested and obtained the experiment values,which were close to the actual values.The correlation coefficient of fragments size-based approach was 0.9243(P<0.0001)and the aneuploid-based approach reached 0.9339(P<0.0001).We calculated the concentration of female fetuses and obtained remarkable experimental results.We came up with two approaches for calculating the fetal DNA fraction of female fetuses.It provides an important theoretical basis for the detection of female fetal concentration in future clinical diagnosis.

Excessive additive iodine intake reduces sperm production and induces sperm deformity in male rats in early development

Objective:To investigate the effect of excessive additive iodine intake on reproductive organs of male weanling rats. Methods:One hundred and three male weanling rats were fed with feedstuff containing 0,0.5.1.2.5,and 5- fold higher dosage of iodine in standard iodine-additive salt,i.e.200,300,400,700,and 1200μg/kg,respectively, for 130-136 days.The number of rats taking different dosages of iodine was 20,21,21,21,20 respectively.The rats fed 200μg/kg of iodine were taken as the control group.For all groups,their structural changes of reproductive organs and sperm quality were evaluated. Results:The three experiment groups fed with 1,2.5,and 5-fold higher dosage iodine showed apparent reduction in testicular weight(P<0.05-0.01) by 10.76%,14.58%and 25.35%,respectively,compared with the control. But significant reduction in testis/body weight ratio was only observed in the 5-fold higher dosage group.The sperm concentration and total sperm count declined in four experiment groups fed with 0.5-5 fold higher dosage of iodine.The sperm concentration was reduced by 6.59%,22.53%,17.35%and 18.06%respectively.The percentage of sperm with normal and abnormal form significantly changed(P<0.05).The addition of different doses of iodine showed no apparent adverse effects on other reproductive organs or sperm viability. Conclution:These results indicated that excessive iodine intake might cause potential hazards on reproductive organs of male rats with respect to spermatogenesis.

An adaptive biodegradable zinc alloy with bidirectional regulation of bone homeostasis for treating fractures and aged bone defects

Healing of fractures or bone defects is significantly hindered by overactivated osteoclasts and inhibited osteogenesis in patients with abnormal bone metabolism.Current clinical approaches using titanium alloys or stainless steel provide mechanical support but have no biological effects on bone regeneration.Therefore,designing and fabricating degradable metal materials with sufficient mechanical strength and bidirectional regulation of both osteoblasts and osteoclasts is a substantial challenge.Here,this study first reported an adaptive biodegradable Zn-0.8 Mg alloy with bidirectional regulation of bone homeostasis,which promotes osteogenic differentiation by activating the Pi3k/Akt pathway and inhibits osteoclast differentiation by inhibiting the GRB2/ERK pathway.The anti-osteolytic ability of the Zn-0.8 Mg alloy was verified in a mouse calvarial osteolysis model and its suitability for internal fracture fixation with high-strength screws was confirmed in the rabbit femoral condyle fracture model.Furthermore,in an aged postmenopausal rat femoral condyle defect model,3D printed Zn-0.8 Mg scaffolds promoted excellent bone regeneration through adaptive structures with good mechanical properties and bidirectionally regulated bone metabolism,enabling personalized bone defect repair.These findings demonstrate the substantial potential of the Zn-0.8 Mg alloy for treating fractures or bone defects in patients with aberrant bone metabolism.

核分裂率与增殖细胞核抗原指数在监测给予雌、孕激素后大鼠子宫内膜变化中的作用

目的探讨核分裂率（ MI）和增殖细胞核抗原（ PCNA）指数在监测不同剂量雌、孕激素作用不同时间后，大鼠子宫内膜的增殖与抑制变化中的作用。方法选择去势后 SD大鼠作为动物模型，模拟临床雌、孕激素的连续与周期给药方案。分别在给药不同时间后，检测大鼠子宫内膜的 MI与 PCNA指数的变化。结果 PCNA指数可敏感反映不同剂量雌激素作用不同时间对大鼠子宫内膜的增殖作用，同时也反映不同剂量孕激素作用不同时间对大鼠子宫内膜增殖的抑制作用。 MI可反映雌激素对子宫内膜的增殖作用，但在反映孕激素的抑制作用时不敏感。结论 PCNA指数在反映雌、孕激素对子宫内膜的作用时优于 MI。

Deficit of mitochondria-derived ATP during oxidative stress impairs mouse MII oocyte spindles

Although the role of oxidative stress in maternal aging and infertility has been suggested, the underlying mechanisms are not fully understood. The present study is designed to determine the relationship between mitochondrial function and spindle stability in metaphase II (MII) oocytes under oxidative stress. MII mouse oocytes were treated with H2O2 in the presence or absence of permeability transition pores (PTPs) blockers cyclosporin A (CsA). In addition, antioxidant N-acetylcysteine (NAC), F0/F1 synthase inhibitor oligomycin A, the mitochondria uncoupler carbonyl cyanide 4-trifluoro- methoxyphenylhydrazone (FCCP) or thapsigargin plus 2.5 mM Ca^2+ (Th+2.5 mM Ca^2+) were used in mechanistic studies. Morphologic analyses of oocyte spindles and chromosomes were performed and mitochondrial membrane potential (AWm), cytoplasmic free calcium concentration ([Ca^2+]c) and cytoplasmic ATP content within oocytes were also assayed. In a time- and H202 dose-dependent manner, disruption of meiotic spindles was found after oocytes were treated with H202, which was prevented by pre-treatment with NAC. Administration of H2O2 led to a dissipation of AWm, an increase in [Ca^2+]c and a decrease in cytoplasmic ATP levels. These detrimental responses of oocytes to H2O2 treatment could be blocked by pre-incubation with CsA. Similar to H2O2, both oligomycin A and FCCP dissipated AWm, decreased cytoplasmic ATP contents and disassembled MII oocyte spindles, while high [Ca^2+]c alone had no effects on spindle morphology. In conclusion, the decrease in mitochondria-derived ATP during oxidative stress may cause a disassembly of mouse MII oocyte spindles, presumably due to the opening of the mitochondrial PTPs.

Andrology in China： current status and 10 years＇ progress

Andrology has a long history in traditional Chinese medicine. There are records of male sexual health, male sexual dysfunction and male infertility from over thousands of years ago. Modern andrology in China had a late start, with the Chinese Androlo~ Association founded in 1995. Within last decade, andrology in China has grown rapidly. In this review article, we summarized the progress of androlo~ in last 10 years and outlined the current status of Chinese andrology with a special focus on progress in male erectile dysfunction, prostate diseases, male infertility and male hormonal contraception.

Dynamic changes in the systemic immune responses of spinal cord injury model mice

Intraspinal inflammatory and immune responses are considered to play central roles in the pathological development of spinal cord injury.This study aimed to decipher the dynamics of systemic immune responses,initiated by spinal cord injury.The spinal cord in mice was completely transected at T8.Changes in the in vivo inflammatory response,between the acute and subacute stages,were observed.A rapid decrease in C-reactive protein levels,circulating leukocytes and lymphocytes,spleen-derived CD4~+interferon-γ+T-helper cells,and inflammatory cytokines,and a marked increase in neutrophils,monocytes,and CD4~+CD25~+FOXP3~+regulatory T-cells were observed during the acute phase.These systemic immune alterations were gradually restored to basal levels during the sub-acute phase.During the acute phase of spinal cord injury,systemic immune cells and factors showed significant inhibition;however,this inhibition was transient,and the indicators of these serious disorders gradually returned to baseline levels during the subacute phase.All experiments were performed in accordance with the institutional animal care guidelines,approved by the Institutional Animal Care and Use Committee of Experimental Animal Center of Drum Tower Hospital,China(approval No.2019 AE01040)on June 25,2019.

A differentially methylated region of the DAZ1 gene in spermatic and somatic cells

Aim： To investigate the methylation status of the deleted in azoospermia 1（DAZ1） gene promoter region in different cell types. Methods： Using CpG island Searcher software, a CpG island was found in the promoter region of the DAZ1 gene. The methylation status of this region was analyzed in sperm and leukocytes by bisulfited sequencing. Results： The methylation status of the CpG island in the DAZ1 gene promoter region differed in leukocytes and sperm： it was methylated in leukocytes, but unmethylated in sperm. Conclusion： A differentially methylated region of the DAZ1 gene exists in spermatic and somatic cells, suggesting that methylation of this region may regulate DAZ1 gene expression in different tissues. （Asian J Androl 2006 Jan; 8：61-67 ）

Crystal Structures and Physicochemical Properties of Solvated Estradiol

Polymorph screening is currently one of the most important tasks for innovators and for generic companies from both pharmaceutical and intellectual property rights aspects. The hemihydrate form（Form Ⅰ） and formamide solvate（Form Ⅱ） of estradiol are isolated and prepared via systemic crystallization screening in this paper, and the formamide solvate form is reported for the first time. Both polymorphic forms were characterized by single-crystal X-ray structure analysis（SXRD）, powder X-ray diffraction（PXRD）, and thermal analysis（TGA and DSC）. The PXRD experiments indicate that the samples in this study are the pure polymorphic forms via comparing the patterns with the simulated ones. The stability and equilibrium solubility data of the solid-state phase were also examined in order to check the impact of the differences observed in their crystalline structures. It has been found that Forms I and II are of conformational polymorph and Form II is the more thermodynamically stable solid form, while Form I possesses higher solubility, indicating its possibility as an alternate solid form for its further solid formulation development if necessary.

Role of LM23 in cell proliferation and apoptosis and its expression during the testis development

LM23, a gene expressed specifically in the testis in a stage-specific manner, has a diverse range of functions that are important in both the life and death of spermatogenic cells. The aim of this study was to further investigate the expression of LM23 in the developing rat testis and the biological function of LM23 in proliferation and antiapoptosis in vitro. Semiquantitative reverse transcription （RT）-PCR and real-time PCR were used to examine the expression of LM23 in testis at different developmental stages. The results suggested that LM23 mRNA levels in the testis increased progressively after birth. The role of LM23 in proliferation was analyzed with cell counting kit-8 （CCK8）, colony-forming efficiency （CFE） and flow cytometry assays. The results indicated that ectopic expression of LM23 in 293T cells significantly promoted cell proliferation by increasing cell numbers in S phase. Several methods were used, including CCK8, annexin V and propidium iodide staining and western blotting, to determine the role of LM23 in apoptosis. The results showed that LM23 played a protective role in H202-induced apoptosis of 293T cells, mediated at least in part through the Akt/PI3K signal pathway. Taken together, these results provide new insights into the role of LM23 in the development of the testes andspermatogenesis.