The visual system is affected by neurodegenerative diseases caused by the degeneration of specific retinal neurons,the leading cause of irreversible blindness in humans.Throughout vertebrate phylogeny,the retina has t...The visual system is affected by neurodegenerative diseases caused by the degeneration of specific retinal neurons,the leading cause of irreversible blindness in humans.Throughout vertebrate phylogeny,the retina has two kinds of specialized niches of constitutive neurogenesis:the retinal progenitors located in the circumferential marginal zone and Müller glia.The proliferative activity in the retinal progenitors located in the circumferential marginal zone in precocial birds such as the chicken,the commonest bird model used in developmental and regenerative studies,is very low.This region adds only a few retinal cells to the peripheral edge of the retina during several months after hatching,but does not seem to be involved in retinal regeneration.Müller cells in the chicken retina are not proliferative under physiological conditions,but after acute damage some of them undergo a reprogramming event,dedifferentiating into retinal stem cells and generating new retinal neurons.Therefore,regenerative response after injury occurs with low efficiency in the precocial avian retina.In contrast,it has recently been shown that neurogenesis is intense in the retina of altricial birds at hatching.In particular,abundant proliferative activity is detected both in the circumferential marginal zone and in the outer half of the inner nuclear layer.Therefore,stem cell niches are very active in the retina of altricial birds.Although more extensive research is needed to assess the potential of proliferating cells in the adult retina of altricial birds,it emerges as an attractive model for studying different aspects of neurogenesis and neural regeneration in vertebrates.展开更多
The Black-headed Duck (Heteronetta atricapilla) is unique among obligate avian brood parasites because its highly precocial young leave the host nest shortly after hatching and impose no post-hatching costs on their h...The Black-headed Duck (Heteronetta atricapilla) is unique among obligate avian brood parasites because its highly precocial young leave the host nest shortly after hatching and impose no post-hatching costs on their hosts. Accordingly, we might expect host-parasite interactions in this parasite to differ strikingly from those of other brood parasites — they should be able to parasitize a broad diversity of hosts and be highly successful with these hosts. We conducted the second detailed study ever completed on patterns of host use in Black-headed Ducks. Based on four years of systematic searches of multiple marshes in Argentina, we found no evidence that Black-headed Ducks ever had nests of their own, confirming the previous conclusion that Black-headed Ducks are, indeed, true obligate brood parasites. Contrary to expectation, however, we found that Heteronetta is ecologically dependent on a surprisingly small number of host species — two species of coots and a gull — all of which are widespread and locally abundant species. Other species are numerically less important as hosts either because they are relatively uncommon, or because they are avoided by the ducks. In the three main host species, hatching success of the duck eggs was also surprisingly low (≤ 28%), based on expectations for a precocial parasite, mainly due to host rejection or neglect. Mortality due to predation on host nests, in contrast, was low for all three primary host species. These observations corroborate Weller’s observations from a single-year study. The combination of a dependence on few primary hosts and a relatively low hatching success are inconsistent with some previous hypotheses for the evolution of obligate brood parasitism in Heteronetta. Instead, our observations, and those of Weller, suggest that intense nest predation in Austral wetlands, coupled with an abundance of a few common host species that aggressively defend their nests and obtain high nest success rates, may have been an important factor in the evolution of obligate parasitism in this enigmatic duck.展开更多
Background:Makorin ring finger protein 3 gene(MKRN3)gene mutation is the most common genetic cause of central precocious puberty(CPP)in children.Due to the lack of ideal MKRN3-modified animal model(MKRN3-modified mice...Background:Makorin ring finger protein 3 gene(MKRN3)gene mutation is the most common genetic cause of central precocious puberty(CPP)in children.Due to the lack of ideal MKRN3-modified animal model(MKRN3-modified mice enter puberty only 4–5 days earlier than normal mice),the related research is limited.Methods:Therefore,the MKRN3-modified rabbit was developed using CRISPR(clus-tered regularly interspaced short palindromic repeats)gene editing technology.The genotype identification and phenotype evaluation of MKRN3-modified rabbits were carried out.Results:The first estrus of MKRN3-modified female rabbits was observed~27 days earlier than that of wild-type female rabbits,with a typical CPP phenotype.This study found increased gonadotropin releasing hormone(GnRH)and decreased gonadotropin inhibiting hormone(GnIH)in the hypothalamus of the CPP rabbit model with MKRN3 gene mutation.Although this study failed to fully clarify the pathogenesis of CPP caused by MKRN3 mutation,it found some differentially expressed genes and potential pathways through transcriptome sequencing.Conclusions:This study established a novel CPP model:paternal MKRN3 gene-modified rabbit.It is hoped that the establishment of this model will help researchers better understand,treat,and prevent CPP in the future.展开更多
Embryonic development is a critical period for phenotype formation.Environmental variation during embryonic development can induce changes in postnatal phenotypes of animals.The thyroxine secretion and aerobic metabol...Embryonic development is a critical period for phenotype formation.Environmental variation during embryonic development can induce changes in postnatal phenotypes of animals.The thyroxine secretion and aerobic metabolic activity of small birds are important phenotypes closely related to their winter survival.In the context of climate change,it is necessary to determine whether temperature variation during incubation in birds leads to developmental plasticity of these cold responsive phenotypes.We incubated Japanese Quail(Coturnix japonica)eggs at 36.8℃,37.8℃,and 38.8℃,and raised the chicks to 35-day old at 22℃with same raising conditions,then all the quails were exposed to gradually temperature dropping environment(from 15℃to 0℃).After cold treatment,serum T3 level,resting metabolic rate,skeletal muscle and liver metabolomes of the birds were measured.The serum T3 levels were significantly lower in the 38.8℃group and significantly higher in the 36.8℃group compared to the 37.8℃group.The metabolic rate in the 38.8℃group was significantly lower compared to the 37.8℃group.Compared with the 37.8℃group,metabolites involved in the tricarboxylic acid cycle in the liver were significantly lower in the 38.8℃group,and metabolites related to lipid oxidation metabolism and fatty acid biosynthesis were significantly lower in the skeletal muscles in the 38.8℃group but significantly higher in the 36.8℃group.These results indicate that incubation temperature variation can lead to developmental plasticity in cold responsive physiological phenotypes.Higher incubation temperature may impair the capacity of birds coping with cold challenge.展开更多
The endochondral ossification of hindlimb is essential to a bird’s ability to stand,walk and fly.Most hindlimb is ossified in the embryos before hatching in precocial birds.However,the molecular mechanisms of hindlim...The endochondral ossification of hindlimb is essential to a bird’s ability to stand,walk and fly.Most hindlimb is ossified in the embryos before hatching in precocial birds.However,the molecular mechanisms of hindlimb ossification in birds is still unclear.Therefore,we tried to examine the process of hindlimb ossification and its molecular regulation by using an animal model—Japanese Quail(Coturnix japonica).We selected four critical stages(Embryo Day:E6,E8,E12 and E16) of skeletal development of embryonic quails for hindlimb skeleton staining to show the process of endochondral ossification and to examine the molecular regulation of endochondral osteogenesis by RNA-Seq analysis.The results showed that ossification became increased with embryonic development and most hindlimb was ossified before hatching.RNA-Seq analysis revealed that various signaling pathways were involved with endochondral ossification with thyroid hormone signaling and WNT signaling pathway particularly enriched.Moreover,the expression levels of 42 genes were continuously upregulated and 14 genes were continuously downregulated from E6 to E16.The present study might provide new insights into complex molecular mechanisms in regulation of endochondral ossification.展开更多
OBJECTIVE:To elucidate the mechanism of the nourishing Yin and purging fire Chinese herbal mixture(NYPF)in delaying light-induced premature puberty in rats.METHODS:Twenty-one days old female SpragueDawley rats were ra...OBJECTIVE:To elucidate the mechanism of the nourishing Yin and purging fire Chinese herbal mixture(NYPF)in delaying light-induced premature puberty in rats.METHODS:Twenty-one days old female SpragueDawley rats were randomly assigned to normal group(N),long light exposure group(L),NYPF and normal saline group(NS).Rats in the L,NYPF and NS groups were exposed to 16 h:350 lux light/8 h:dark,while rats in the N group were exposed to 12 h:50 lux light/12 h:dark.NYPF and normal saline was administered to the rats in the NYPF group or NS group,respectively,from day 21.Five rats in every group were sacrificed at 9 p.m.on day 28(P28),on the day when rat's vulva opened in the L group(L-VO),on the day when the first estrous interphase occurred in rats of L group(L-E1),and on the day when the second estrous interphase occurred in rats of L group(L-E2),respectively.RESULITS:On day 34,all rats in the L group,80%of rats in the NS group,40%of rats in the N group,and 20%of rats in the NYPF group showed complete opening of the vulva.At P28,m RNA level of hypothalamic kisspeptin(Kiss-1)in the L group was significantly higher than that in the N group(P<0.05).The rats in the L and NS groups had significantly lower hypothalamic argininephenylalanine-amide(RFamide)-related peptide 3(RFRP-3)m RNA levels than those in the N group(P<0.05),whereas RFRP-3 m RNA level was significantly higher in the NYPF group than that in the L group(P<0.05).At L-VO,the ovarian index of the L and NS groups was significantly higher than that of the N group(P<0.05)and estradiol(E2)level of the NYPF group was significantly lower than that of the N and NS groups(P<0.05);hypothalamic Kiss-1 m RNA level in the L and NS groups was significantly higher than that in the N and NYPF groups(P<0.05),whereas hypothalamic RFRP-3 m RNA level in the L,NYPF,and NS groups was significantly lower than that in the N group(P<0.05).At L-E1,E2 level of the L and NS groups was significantly higher than that of the N group(P<0.01),whereas it was significantly lower in the NYPF group than that of the N,L,and NS groups(P<0.01),and serum luteinizing hormone level of the L and NS groups was significantly higher than that of the N group(P<0.05);levels of serum melatonin and ovarian melatonin receptor 1(MT-1)m RNA in the L,NYPF,and NS groups were significantly lower than those in the N group(P<0.05).At L-E2,the uterine organ index of the NYPF group was significantly lower than that of the L group(P<0.05);and ovarian MT-1 m RNA level of the L and NS groups was significantly lower than that in the N group(P<0.05).CONCLUSIONS:NYPF can delay puberty onset in rats exposed to strong light for a prolonged duration,and regulation of the gene expression of Kiss-1 and RFRP-3 in the hypothalamus has been suggested as one of the mechanisms.展开更多
Central precocious puberty secondary to Leydig cell tumors is rare in children. We retrospectively analyzed the mid- to long-term follow-up data of patients with Leydig cell tumors. The clinical data of 12 consecutive...Central precocious puberty secondary to Leydig cell tumors is rare in children. We retrospectively analyzed the mid- to long-term follow-up data of patients with Leydig cell tumors. The clinical data of 12 consecutive patients who were treated at Beijing Children’s Hospital, Capital Medical University (Beijing, China), between January 2016 and October 2023 were retrospectively reviewed. Clinical evaluations, including physical examination, hormone examination, serum tumor marker analysis, abdominal and scrotal ultrasound, chest X-ray, and bone age measurement, were conducted before surgery and at follow-up time points. Surgical approaches were selected according to the individual conditions. Patients with an abnormal hormonal status and suspected of having central precocious puberty were referred to endocrinologists to confirm the diagnosis. Subsequently, gonadotropin-releasing hormone analog therapy was proposed. The mean patient age was 81.3 (range: 40–140) months at the time of the operation. Ten patients had peripheral precocious puberty at admission. All patients had elevated preoperative testosterone levels, whereas tumor marker levels were normal. Testis-sparing surgery was performed in eleven patients, and radical orchiectomy was performed in one patient. The follow-up duration (mean ± standard deviation) was 36.2 ± 25.3 months. Five patients had central precocious puberty, with a mean duration of 3.4 (range: 1–6) months postoperatively. Three patients were receiving gonadotropin-releasing hormone analog therapy, and good suppression of puberty was observed. No risk factors were found for secondary central precocious puberty. There was a high prevalence of central precocious puberty secondary to Leydig cell tumors in our study. Gonadotropin-releasing hormone analog therapy has satisfactory treatment effects. Larger sample sizes and long-term follow-up are needed in future studies.展开更多
BACKGROUND At present,the clinical mechanisms underlying precocious puberty remain unclear,making effective intervention for children experiencing this condition and rapidly progressive puberty essential.AIM To explor...BACKGROUND At present,the clinical mechanisms underlying precocious puberty remain unclear,making effective intervention for children experiencing this condition and rapidly progressive puberty essential.AIM To explore the effects of Zhibai dihuang pills and gonadotropin-releasing hormone analogue(GnRHa)on growth and ovarian function in girls with precocious puberty.METHODS The clinical data of 84 adolescent girls with precocious puberty and rapidly progressive puberty from February 2017 to August 2023 were retrospectively analyzed.Girls were divided into a control group and an observation group,with 42 cases in each group.The control group received diet intervention combined with GnRHa treatment,while the observation group received diet intervention combined with Zhibai dihuang pills+GnRHa treatment.Outcomes such as clinical efficacy,growth indicators,ovarian function,and adverse reactions were compared between the two groups.RESULTS The observation group showed superior clinical efficacy compared to the control group(P<0.05).Prior to the intervention,no significant differences were found in growth or ovarian function between the groups(P>0.05).Post-intervention,the observation group exhibited significantly lower rates in growth,height,and bone age,along with reduced levels of progesterone,testosterone,estradiol,prolactin,luteinizing hormone,and follicle-stimulating hormone compared to the control group(P<0.05).The incidence of adverse reactions was similar across both groups(P>0.05).CONCLUSION Combining Zhibai dihuang pills with GnRHa and dietary intervention effectively improves growth,enhances ovarian function,and minimizes adverse reactions in adolescent girls with precocious and rapidly progressive puberty.展开更多
Objective:This study aimed to evaluate the therapeutic effects of leuprolide acetate extended-release microspheres for injection in children with pediatric precocious puberty.Methods:A total of 110 cases of pediatric ...Objective:This study aimed to evaluate the therapeutic effects of leuprolide acetate extended-release microspheres for injection in children with pediatric precocious puberty.Methods:A total of 110 cases of pediatric precocious puberty admitted between January 2019 and December 2021 were selected and randomized into two groups using a random number table,with 55 cases in the control group and 55 cases in the experimental group.The control group received conventional treatment,while the experimental group was treated with leuprolide acetate extended-release microspheres for injection.The therapeutic effects were observed,and changes in sex hormone levels,ovarian volume,growth indices,and the incidence of adverse reactions were statistically compared between the groups.Results:The experimental group demonstrated superior outcomes in terms of sex hormone levels,ovarian volume,and growth indices compared to the control group.Additionally,the incidence of adverse reactions in the experimental group was significantly lower(P<0.05).Conclusion:The application of leuprolide acetate extended-release microspheres for the treatment of pediatric precocious puberty is associated with improved therapeutic effects and higher safety.展开更多
In boys, central precocious puberty （CPP） is the appearance of secondary sex characteristics driven by pituitary gonadotropin secretion before the age of 9 years. In the last years, relevant improvements in the trea...In boys, central precocious puberty （CPP） is the appearance of secondary sex characteristics driven by pituitary gonadotropin secretion before the age of 9 years. In the last years, relevant improvements in the treatment of CPP have been achieved. Because CPP is rare in boys, the majority of papers on this issue focus on girls and do not address specific features of male patients regarding end results and safety. In the present paper, recent advances of CPP management with GnRH analogs in men are summarized. End results in untreated and treated patients are also reviewed by an analysis of the recently published literature on treatment of CPP in men. The available data indicate that therapy with GnRH analogs can improve final height into the range of target height without significant adverse short-term and long-term effects, but longer follow-up of larger series of patients is still required to draw definitive conclusions.展开更多
OBJECTIVE: To evaluate the effect of ZiYin Xiehuo granules(ZYXH) and Zishen Qinggan granules(ZSQG) on partial precocious puberty(PPP).METHODS: This was a multicenter, randomized, single-blind, positive-controlled tria...OBJECTIVE: To evaluate the effect of ZiYin Xiehuo granules(ZYXH) and Zishen Qinggan granules(ZSQG) on partial precocious puberty(PPP).METHODS: This was a multicenter, randomized, single-blind, positive-controlled trial. A total of 143 pa-tients were assigned to either the ZYXH group or the ZSQG group using a random number table. The ZYXH group received ZYXH three times daily for 6 months and the ZSQG group received ZSQG three times daily for 6 months. Mammary nucleus diameter; the results of uterus, ovarian, and maximum follicle measures; and Chinese medicine symptom pattern scores were compared at baseline and after 3 months and 6 months of treatment.RESULTS: After 3 months' treatment, there were no significant differences between the two groups in mammary nucleus index changes(left 3.4 ± 3.1 vs3.5 ± 3.1, P = 0.790; right 3.0 ± 2.9 vs 3.6 ± 3.0, P =0.719). The uterine volume in the ZYXH group was smaller than that in the ZSQG group(2.1 ± 1.6 vs2.6 ± 2.2, P = 0.006). There were no significant between-group differences in ovarian volume and maximum follicular diameter on either side(ovarian volume: left 1.2 ± 0.7 vs 1.3 ± 0.6, P = 0.8; right1.2 ± 0.7 vs 1.4 ± 1.1, P = 0.984; maximum follicular diameter: left 3.9 ± 1.7 vs 3.5 ± 2.2, P = 0.158; right3.5 ± 1.7 vs 3.9 ± 2.1, P = 0.314).CONCLUSION: ZYXH granules and ZSQG granules both affected the size of the mammary nucleus in girls with PPP, and improved Chinese medicine symptom patterns. ZYXH granules showed slight advantages over ZSQG granules in terms of the decrease in the size of the uterus, ovaries, and ovarian follicles.展开更多
Objective:To study expressions of netrin-1 and its receptor UNC5 C in female precocious puberty rat hypothalamus,and explore its effect on precocious puberty process.Methods:Forty female one-week-old SD rats were rand...Objective:To study expressions of netrin-1 and its receptor UNC5 C in female precocious puberty rat hypothalamus,and explore its effect on precocious puberty process.Methods:Forty female one-week-old SD rats were randomly divided into four groups:experimental group A(precocious puberty early youth),experimental group B(precocious puberty medium youth),group A(normal pre-puberty).group B(normal early youth) with 10 rats in each group.Precocious puberty experimental rats were induced with Danazol and rals in control group were injected with saline.Uterus and ovaries were removed,specimens were weighed,litems index and ovarian index were calculated,and amount of luteinizing hormone(LH) and follicle-stimulating hormone(FSH) were detected from the blood by ELISA.Real-time PCR was used to delect netrin-1 and its receptor UNC5 C.as well as hypothalamic gonadolropinreleasing hormone(GnRH) mRNA expression in hypothalamus tissues:and then,a coimmunoprecipitation study of interactions between netrin-1 and its receptor UNC5 C was carried out.Results:Relative target gene expression levels of control group A,control group B.experimental group A,and experimental group B(with,3-actin as an internal control for normalization) were as follows:Netrin-1:3.5±0.9,5.4±0.7.4.9±1.0.5.3±0.3:UNC5C:0.8±0.04.1.7±0.2.1.82±0.23.1.58±0.4:GnRH:1.2±0.3.2.7±0.3.2.4±0.7.3.2±0.4.Conclusions:LH and FSH concentrations,netrin-1 and its receptor expression are increased in precocious puberty animal models.展开更多
It is found that the drugs for nourishing yin to reduce pathogenic fire can significantly down-regulate,and the drugs for tonifying the kidney to replenish essence can up-regulate mRNA expression of the hypothalamic G...It is found that the drugs for nourishing yin to reduce pathogenic fire can significantly down-regulate,and the drugs for tonifying the kidney to replenish essence can up-regulate mRNA expression of the hypothalamic GnRH,pituitary FSH,LH and osteoblastic BGP,indicating that the Chinese drugs for tonifying the kidney can regulate gene expression of the hypothalamic GnRH,pituitary FSH,LH,and osteoblastic BGP,which is possibly one of the main mechanisms of the Chinese drug for tonifying the kidney,regulating ephebic development process and improving skeletal development in sexual precocity children.展开更多
OBJECTIVE:To establish a quantification model of Traditional Chinese Medicine(TCM)syndromes by sampling patients undergoing idiopathic precocious puberty(IPP)and early puberty.METHODS:A questionnaire for classifying a...OBJECTIVE:To establish a quantification model of Traditional Chinese Medicine(TCM)syndromes by sampling patients undergoing idiopathic precocious puberty(IPP)and early puberty.METHODS:A questionnaire for classifying and quantifying TCM syndromes was designed and administered.All the results were analyzed;the relationship between 3 types of syndrome and 47symptoms were summated.Meanwhile,the frequency distribution of each symptom or sign was aggregated.Fuzzy mathematics was used to develop a quantification model ofTCM syndromes.RESULTS:We found that precocious puberty had 3types of syndrome,including hyperactivity of fire due to Yin deficiency(Syndrome I),depressed liver Qi transforming into fire(Syndrome II),and end retention of damp heat(Syndrome III).In the IPP group,Syndrome I was the most common principal syndrome(100%).Forty-six patients(43.81%)werediagnosed with Syndrome I accompanied by Syndrome II and 11(10.48%)were diagnosed with Syndrome I accompanied by Syndrome III.In the early puberty group,Syndrome I was also the main syndrome(98.39%).The degrees of most symptoms were mild to moderate.Reddened tongue was the most common tongue manifestation(62.86%prevalence)in the IPP group.The most common pulse manifestations were slippery pulse,thread pulse,and taut pulse.The Asymptotic Normalization Coefficient(ANC)method was used to quantify the TCM syndromes in 167 cases.Diagnostic accuracy rate reached 91%,comparable to expert diagnosis.CONCLUSION:We find that there are 3 types of syndrome in the IPP group and in the early puberty group.Syndrome I(hyperactivity of fire due to Yin deficiency)is the main syndrome in the two groups.ANC may be an appropriate for quantification model ofTCM syndromes.展开更多
In order to assess the feasibility of subcutaneous administration of Triptorelin with 6-week intervals for the suppression of pituitary-gonadal axis and changes of clinical signs in girls with idiopathic central preco...In order to assess the feasibility of subcutaneous administration of Triptorelin with 6-week intervals for the suppression of pituitary-gonadal axis and changes of clinical signs in girls with idiopathic central precocious puberty （ICPP）, 46 girls with ICPP were treated with GnRHa. Triptorelin （Decapeptyl, 3.75 mg） was administered subcutaneously （SC） at 6-weeks intervals or intramuscularly （IM） at 4-weeks intervals randomly for more than 12 months consecutively. During GnRHa therapy, clinical parameters and laboratory data, including height, weight, pubertal stage, bone age, uterine volume and ovarian size, serum levels of luteinizing hormone （LH）, follicle stimulating hormone （FSH） and estradiol （E2）, were monitored and analyzed. It was found that both treatment regimes led to regression of precocious puberty and reversal of secondary sexual characteristics. Breast developments regressed. Uterine volume was decreased after treatment, but there was no statistically significant difference. Mean ovarian volume did not change significantly during treatment. The height velocity was decreased significandy from 6.3±1.4 cm/year to 5.8：1：1.2 cm/year in group SC and 6.7±1.3 cm/year to 5.4±1.0 cm/year in group IM, respectively. The rate of bone maturation was reduced significantly during treatment. The ratio of deltaBAgdeltaCA was 1.2±0.2 or 1.3±0.3 at the onset of therapy and decreased significantly after the treatment to 0.7±0.2 or 0.9±0.1, respectively. The predicted adult height was increased significantly and progressively during therapy. The levels of serum LH, FSH and E2 returned to the prepubertal condition. No significant side effects of therapy were noted. The most common side effect during SC treatment was that a non-irritating, 1 cm in di- ameter mass was palpated at the site of subcutaneous injection in the abdominal wall of patients, which disappeared after 6- 12 weeks. Two girls had minimal withdrawal vaginal bleeding episodes after the first injection. It was concluded that both IM and SC triptorelin administrations were clinically effective. They induce profound suppression of hypothalamic-pituitary-gonadal axis while stabilizing height velocity, slowing bone maturation and increasing predicted adult height. These results suggest that subcutaneous injection of triptorelin in 6-weeks intervals at a dosage of 3.75 mg be a safe and acceptable regimen for ICPP.展开更多
BACKGROUND Caused by premature activation of the hypothalamic-pituitary-gonadal axis,there is increasing incidence of central precocious puberty(CPP),especially in girls.Makorin ring finger protein 3(MKRN3),a maternal...BACKGROUND Caused by premature activation of the hypothalamic-pituitary-gonadal axis,there is increasing incidence of central precocious puberty(CPP),especially in girls.Makorin ring finger protein 3(MKRN3),a maternal imprinted gene with a highly conserved sequence,is the most common genetic etiology associated with CPP.Approximately 50 different mutations in MKRN3 have been found in CPP.CASE SUMMARY This case report involves identical twin sisters presenting with premature thelarche at the age of 6 years.The left hand bone age of both patients revealed advanced age(9 years).Pelvic B ultrasound indicated enlargement of the ovaries.Luteinizing hormone(LH)releasing hormone testing confirmed CPP.Wholeexome sequencing detected the c.841C>T mutation in MKRN3,leading to a single base substitution,in the twins.This mutation was inherited from the father and paternal grandmother.After 3 mo of treatment with a gonadotropin-releasing hormone analog,levels of LH,follicle-stimulating hormone,and estradiol in the proband’s sister returned to normal levels.CONCLUSION Here,we report a rare mutation(c.841C>T)in MKRN3 in identical twin sisters with CPP.展开更多
The effect of obesity on idiopathic central precocious puberty（ICPP） girls is still under discussion. The relationship between body mass index（BMI） and sexual hormone levels of gonadotropin-releasing hormone（GnRH...The effect of obesity on idiopathic central precocious puberty（ICPP） girls is still under discussion. The relationship between body mass index（BMI） and sexual hormone levels of gonadotropin-releasing hormone（GnRH） stimulation test in ICPP girls is controversial and the underlying mechanism is unclear. This study aims to further explore the independent effect of excess adiposity on peak luteinizing hormone（LH） level of stimulation test in ICPP girls and the role of other related factors. A retrospective cross-sectional study was performed on 618 girls diagnosed as having ICPP, including 355 cases of normal weight, 99 cases of overweight and 164 cases of obese. The results showed that obese group had more progressed Tanner stage and no significant difference（P=0.28） in LH peak was found as basal LH value was used as a covariate. The obese group had higher total testosterone（TT）, adrenocorticotrophic hormone（ACTH）, 17-α hydroxyprogesterone（17-αOHP） and androstendione（AN）, with significantly increased fasting insulin（FIN） and homeostasis model of assessment for insulin resistance index（HOMA-IR）. Stratified analysis showed inconsistency of the relationship between BMI-standard deviation score（BMI-SDS） and LH peak in different Tanner stages（P for interaction=0.017）. Further smoothing plot showed linear and non-linear relationship between BMI-SDS and LH peak in three Tanner stages. Then linear regression model was used to analyze the relationship between BMI-SDS and LH peak in different Tanner stages, with and without different confounding factors being adjusted. In B2 stage, BMI-SDS was negatively associated with LH peak. In B3 stage, when BMI-SDS 〈1.5, as BMI-SDS increased, the level of LH peak decreased（model Ⅰ： β=–1.8, 95% CI=–4.7 to 1.1, P=0.214）. When BMI-SDS ≥1.5, BMI-SDS was significantly positively associated with LH peak（model Ⅰ： β=4.5, 95% CI=1.7 to 7.4, P=0.002）. In B4 stage, when BMI-SDS 〈1.5, BMI-SDS was negatively associated with LH peak（model Ⅰ： β=–11.6, 95% CI=–22.7 to –0.5, P=0.049）. When BMI-SDS ≥1.5, BMI-SDS was positively associated with LH peak（model Ⅰ： β=–4.2, 95% CI=–3.3 to 11.7, P=0.28）. It is concluded that there is an independent correlation between BMI-SDS and LH peak of stimulation test in ICPP girls, their relationships are different in different Tanner stages, and the effect of BMI-SDS can be affected by adrenal androgens, estradiol and glucose metabolism parameters.展开更多
Children are currently starting pubertal development much earlier than 20 to 30 years ago. Data from the National Health and Nutrition Examination Survey (NHANES III) conducted from 1988-1994 revealed that the median ...Children are currently starting pubertal development much earlier than 20 to 30 years ago. Data from the National Health and Nutrition Examination Survey (NHANES III) conducted from 1988-1994 revealed that the median age for breast development in white girls was approximately 9.7 years and 8 years in African-American girls versus 10.9 years ago. More recent data, however, indicate that some children are starting pubertal development even earlier (age 7 or 8 in girls or age 9 in boys). Very early pubertal development is identified as precocious puberty, a phenomenon that brings great concern to others besides parents: the child, their peers, school nurses, teachers and counselors. This paper discusses precocious pubertal development, possible causes or relationships, related risks, treatment and helping strategies.展开更多
Objective:To observe the clinical efficacy of different dosage forms of lepraline acetate(LA)in the treatment of girls with central precocious puberty(CPP).Methods:72 CPP girls treated in the Department of Pediatrics ...Objective:To observe the clinical efficacy of different dosage forms of lepraline acetate(LA)in the treatment of girls with central precocious puberty(CPP).Methods:72 CPP girls treated in the Department of Pediatrics of Huai'an First People's Hospital from February 2021 to August 2022 were included as subjects and divided into two groups:3-month LA group(n=34)and 1-month LA group(n=38).Both group girls were treated for 6 months.Serum hormone levels,body mass index(BMI),bone age/chronological age(BA/CA)and pelvic color ultrasound were detected at 0 and 6 months after treatment,and the changes of various indexes were compared before and after treatment.Results:1)There were no significant differences in baseline data between the two groups before treatment(P>0.05).2)After 6 months of treatment,BA/CA decreased,growth rate slowed down,and predicted adult height increased in both groups(P<0.05),but there were no significant differences between groups(P>0.05).3)After 6 months of treatment,there waere no significant differences in luteinizing hormone(LH)inhibition ratio between the 3 month and 1 month dosage groups(P>0.05).After treatment,the peak value of serum LH and FSH,estradiol level,uterine volume,bilateral ovarian volume,maximum follicle diameter and the number of follicles 4mm were significantly decreased in the two groups,but there were no significant differences between the two groups(P>0.05).4)There were no significant differences in the levels of thyroid hormone,fasting blood glucose and triglyceride between the two groups before and after treatment(P>0.05).Total cholesterol levels were increased after treatment(P<0.05),but there was no significant difference between groups(P>0.05).5)No serious adverse reactions occurred during the treatment of the two dosage forms of LA,but the 3-month dosage form of LA reduced the treatment cost and improved the treatment compliance.Conclusion:The short-term efficacy of 3-month LA in the treatment of CPP in girls is similar to that of 1-month LA.The 3-month dosage form LA is a safe,effective,and economical method for the treatment of CPP in girls.展开更多
Isosexual precocious puberty in girls has several etiologies. Juvenile granulose cell tumor is one of the rarest causes that only stands for 1.5% of ovarian cancers. This tumor mostly encounters in first 2 decades of ...Isosexual precocious puberty in girls has several etiologies. Juvenile granulose cell tumor is one of the rarest causes that only stands for 1.5% of ovarian cancers. This tumor mostly encounters in first 2 decades of life. This paper is a report of an 8-year-old girl with precocious puberty that within five months developed breast enlargement followed by menarche. Works which are done to find the underlying cause of precocious puberty revealed juvenile granulosa cell tumor in her left ovary. She then under went laparoscopic surgery and 3 courses of chemotherapy. She did not experience any vaginal bleeding after that and the serum level of estradiol lay among its normal ranges, but after that the tumor relapsed and presented as abdominal pain and a huge mass which under went resection of all afflicted tissues. After 2 courses of chemotherapy, her status deteriorated and unfortunately she died after 6 months from the time of diagnosis. Treatment for this disease is consists of resection surgery and chemotherapy. If this tumor is diagnosed in its early stages, it will be curable, but in its advanced stages, up to 80% of patients die from recurrent tumors. The reported patient was diagnosed at stage IIIC that had poor prognosis.展开更多
基金This work was supported by grants from the Spanish Ministerio de Ciencia y Tecnología(BFU2007-67540)Ministerio de Economía y Competitividad(CGL2015-64650P)+1 种基金Dirección General de Investigación del Ministerio de Educación y Ciencia(BFU2017-85547-P)Junta de Extremadura,Fondo Europeo de Desarrollo Regional,“Una manera de hacer Europa”(GR15158,GR18114,IB18113).
文摘The visual system is affected by neurodegenerative diseases caused by the degeneration of specific retinal neurons,the leading cause of irreversible blindness in humans.Throughout vertebrate phylogeny,the retina has two kinds of specialized niches of constitutive neurogenesis:the retinal progenitors located in the circumferential marginal zone and Müller glia.The proliferative activity in the retinal progenitors located in the circumferential marginal zone in precocial birds such as the chicken,the commonest bird model used in developmental and regenerative studies,is very low.This region adds only a few retinal cells to the peripheral edge of the retina during several months after hatching,but does not seem to be involved in retinal regeneration.Müller cells in the chicken retina are not proliferative under physiological conditions,but after acute damage some of them undergo a reprogramming event,dedifferentiating into retinal stem cells and generating new retinal neurons.Therefore,regenerative response after injury occurs with low efficiency in the precocial avian retina.In contrast,it has recently been shown that neurogenesis is intense in the retina of altricial birds at hatching.In particular,abundant proliferative activity is detected both in the circumferential marginal zone and in the outer half of the inner nuclear layer.Therefore,stem cell niches are very active in the retina of altricial birds.Although more extensive research is needed to assess the potential of proliferating cells in the adult retina of altricial birds,it emerges as an attractive model for studying different aspects of neurogenesis and neural regeneration in vertebrates.
基金supported by the Kananaskis Field Stations of the University of Calgary and University of Californiathe Dennis G. Raveling Endowment
文摘The Black-headed Duck (Heteronetta atricapilla) is unique among obligate avian brood parasites because its highly precocial young leave the host nest shortly after hatching and impose no post-hatching costs on their hosts. Accordingly, we might expect host-parasite interactions in this parasite to differ strikingly from those of other brood parasites — they should be able to parasitize a broad diversity of hosts and be highly successful with these hosts. We conducted the second detailed study ever completed on patterns of host use in Black-headed Ducks. Based on four years of systematic searches of multiple marshes in Argentina, we found no evidence that Black-headed Ducks ever had nests of their own, confirming the previous conclusion that Black-headed Ducks are, indeed, true obligate brood parasites. Contrary to expectation, however, we found that Heteronetta is ecologically dependent on a surprisingly small number of host species — two species of coots and a gull — all of which are widespread and locally abundant species. Other species are numerically less important as hosts either because they are relatively uncommon, or because they are avoided by the ducks. In the three main host species, hatching success of the duck eggs was also surprisingly low (≤ 28%), based on expectations for a precocial parasite, mainly due to host rejection or neglect. Mortality due to predation on host nests, in contrast, was low for all three primary host species. These observations corroborate Weller’s observations from a single-year study. The combination of a dependence on few primary hosts and a relatively low hatching success are inconsistent with some previous hypotheses for the evolution of obligate brood parasitism in Heteronetta. Instead, our observations, and those of Weller, suggest that intense nest predation in Austral wetlands, coupled with an abundance of a few common host species that aggressively defend their nests and obtain high nest success rates, may have been an important factor in the evolution of obligate parasitism in this enigmatic duck.
基金National Natural Science Foundation of China,Grant/Award Number:82101937Guangdong Medical Science and Technology Research Fund Project,China,Grant/Award Number:B2024069Guangzhou Science and Technology Plan Project,China,Grant/Award Number:2024A04J4923 and SL2023A04J02229。
文摘Background:Makorin ring finger protein 3 gene(MKRN3)gene mutation is the most common genetic cause of central precocious puberty(CPP)in children.Due to the lack of ideal MKRN3-modified animal model(MKRN3-modified mice enter puberty only 4–5 days earlier than normal mice),the related research is limited.Methods:Therefore,the MKRN3-modified rabbit was developed using CRISPR(clus-tered regularly interspaced short palindromic repeats)gene editing technology.The genotype identification and phenotype evaluation of MKRN3-modified rabbits were carried out.Results:The first estrus of MKRN3-modified female rabbits was observed~27 days earlier than that of wild-type female rabbits,with a typical CPP phenotype.This study found increased gonadotropin releasing hormone(GnRH)and decreased gonadotropin inhibiting hormone(GnIH)in the hypothalamus of the CPP rabbit model with MKRN3 gene mutation.Although this study failed to fully clarify the pathogenesis of CPP caused by MKRN3 mutation,it found some differentially expressed genes and potential pathways through transcriptome sequencing.Conclusions:This study established a novel CPP model:paternal MKRN3 gene-modified rabbit.It is hoped that the establishment of this model will help researchers better understand,treat,and prevent CPP in the future.
基金funded by the National Natural Science Foundation of China(32071515 to S.Z.)Graduate Research and Practice Projects of Minzu University of China(SZKY2024035 to R.Z.)。
文摘Embryonic development is a critical period for phenotype formation.Environmental variation during embryonic development can induce changes in postnatal phenotypes of animals.The thyroxine secretion and aerobic metabolic activity of small birds are important phenotypes closely related to their winter survival.In the context of climate change,it is necessary to determine whether temperature variation during incubation in birds leads to developmental plasticity of these cold responsive phenotypes.We incubated Japanese Quail(Coturnix japonica)eggs at 36.8℃,37.8℃,and 38.8℃,and raised the chicks to 35-day old at 22℃with same raising conditions,then all the quails were exposed to gradually temperature dropping environment(from 15℃to 0℃).After cold treatment,serum T3 level,resting metabolic rate,skeletal muscle and liver metabolomes of the birds were measured.The serum T3 levels were significantly lower in the 38.8℃group and significantly higher in the 36.8℃group compared to the 37.8℃group.The metabolic rate in the 38.8℃group was significantly lower compared to the 37.8℃group.Compared with the 37.8℃group,metabolites involved in the tricarboxylic acid cycle in the liver were significantly lower in the 38.8℃group,and metabolites related to lipid oxidation metabolism and fatty acid biosynthesis were significantly lower in the skeletal muscles in the 38.8℃group but significantly higher in the 36.8℃group.These results indicate that incubation temperature variation can lead to developmental plasticity in cold responsive physiological phenotypes.Higher incubation temperature may impair the capacity of birds coping with cold challenge.
基金supported by the National Natural Science Foundationof China (No. 33372201)。
文摘The endochondral ossification of hindlimb is essential to a bird’s ability to stand,walk and fly.Most hindlimb is ossified in the embryos before hatching in precocial birds.However,the molecular mechanisms of hindlimb ossification in birds is still unclear.Therefore,we tried to examine the process of hindlimb ossification and its molecular regulation by using an animal model—Japanese Quail(Coturnix japonica).We selected four critical stages(Embryo Day:E6,E8,E12 and E16) of skeletal development of embryonic quails for hindlimb skeleton staining to show the process of endochondral ossification and to examine the molecular regulation of endochondral osteogenesis by RNA-Seq analysis.The results showed that ossification became increased with embryonic development and most hindlimb was ossified before hatching.RNA-Seq analysis revealed that various signaling pathways were involved with endochondral ossification with thyroid hormone signaling and WNT signaling pathway particularly enriched.Moreover,the expression levels of 42 genes were continuously upregulated and 14 genes were continuously downregulated from E6 to E16.The present study might provide new insights into complex molecular mechanisms in regulation of endochondral ossification.
基金Supported by National Natural Science Foundation-funded Project:Study on the Experimental Animal Model of Precocious Puberty with Syndrome of Yin Deficiency and Fire Hyperactivity by Changing the Cycle of Light Exposure(No.81373692)The Constructive Project of Flagship Hospital of Integrated TCM with Western Medicine in Children’s Hospital of Fudan University[No.ZY(2021-2023)-0205-03]the Network Coverage of Coordinated Medical Practice Combined TCM with Western Medicine in Fudan Pediatric Medical Partnerships Union[ZY(2021-2023)-0206-06]。
文摘OBJECTIVE:To elucidate the mechanism of the nourishing Yin and purging fire Chinese herbal mixture(NYPF)in delaying light-induced premature puberty in rats.METHODS:Twenty-one days old female SpragueDawley rats were randomly assigned to normal group(N),long light exposure group(L),NYPF and normal saline group(NS).Rats in the L,NYPF and NS groups were exposed to 16 h:350 lux light/8 h:dark,while rats in the N group were exposed to 12 h:50 lux light/12 h:dark.NYPF and normal saline was administered to the rats in the NYPF group or NS group,respectively,from day 21.Five rats in every group were sacrificed at 9 p.m.on day 28(P28),on the day when rat's vulva opened in the L group(L-VO),on the day when the first estrous interphase occurred in rats of L group(L-E1),and on the day when the second estrous interphase occurred in rats of L group(L-E2),respectively.RESULITS:On day 34,all rats in the L group,80%of rats in the NS group,40%of rats in the N group,and 20%of rats in the NYPF group showed complete opening of the vulva.At P28,m RNA level of hypothalamic kisspeptin(Kiss-1)in the L group was significantly higher than that in the N group(P<0.05).The rats in the L and NS groups had significantly lower hypothalamic argininephenylalanine-amide(RFamide)-related peptide 3(RFRP-3)m RNA levels than those in the N group(P<0.05),whereas RFRP-3 m RNA level was significantly higher in the NYPF group than that in the L group(P<0.05).At L-VO,the ovarian index of the L and NS groups was significantly higher than that of the N group(P<0.05)and estradiol(E2)level of the NYPF group was significantly lower than that of the N and NS groups(P<0.05);hypothalamic Kiss-1 m RNA level in the L and NS groups was significantly higher than that in the N and NYPF groups(P<0.05),whereas hypothalamic RFRP-3 m RNA level in the L,NYPF,and NS groups was significantly lower than that in the N group(P<0.05).At L-E1,E2 level of the L and NS groups was significantly higher than that of the N group(P<0.01),whereas it was significantly lower in the NYPF group than that of the N,L,and NS groups(P<0.01),and serum luteinizing hormone level of the L and NS groups was significantly higher than that of the N group(P<0.05);levels of serum melatonin and ovarian melatonin receptor 1(MT-1)m RNA in the L,NYPF,and NS groups were significantly lower than those in the N group(P<0.05).At L-E2,the uterine organ index of the NYPF group was significantly lower than that of the L group(P<0.05);and ovarian MT-1 m RNA level of the L and NS groups was significantly lower than that in the N group(P<0.05).CONCLUSIONS:NYPF can delay puberty onset in rats exposed to strong light for a prolonged duration,and regulation of the gene expression of Kiss-1 and RFRP-3 in the hypothalamus has been suggested as one of the mechanisms.
文摘Central precocious puberty secondary to Leydig cell tumors is rare in children. We retrospectively analyzed the mid- to long-term follow-up data of patients with Leydig cell tumors. The clinical data of 12 consecutive patients who were treated at Beijing Children’s Hospital, Capital Medical University (Beijing, China), between January 2016 and October 2023 were retrospectively reviewed. Clinical evaluations, including physical examination, hormone examination, serum tumor marker analysis, abdominal and scrotal ultrasound, chest X-ray, and bone age measurement, were conducted before surgery and at follow-up time points. Surgical approaches were selected according to the individual conditions. Patients with an abnormal hormonal status and suspected of having central precocious puberty were referred to endocrinologists to confirm the diagnosis. Subsequently, gonadotropin-releasing hormone analog therapy was proposed. The mean patient age was 81.3 (range: 40–140) months at the time of the operation. Ten patients had peripheral precocious puberty at admission. All patients had elevated preoperative testosterone levels, whereas tumor marker levels were normal. Testis-sparing surgery was performed in eleven patients, and radical orchiectomy was performed in one patient. The follow-up duration (mean ± standard deviation) was 36.2 ± 25.3 months. Five patients had central precocious puberty, with a mean duration of 3.4 (range: 1–6) months postoperatively. Three patients were receiving gonadotropin-releasing hormone analog therapy, and good suppression of puberty was observed. No risk factors were found for secondary central precocious puberty. There was a high prevalence of central precocious puberty secondary to Leydig cell tumors in our study. Gonadotropin-releasing hormone analog therapy has satisfactory treatment effects. Larger sample sizes and long-term follow-up are needed in future studies.
文摘BACKGROUND At present,the clinical mechanisms underlying precocious puberty remain unclear,making effective intervention for children experiencing this condition and rapidly progressive puberty essential.AIM To explore the effects of Zhibai dihuang pills and gonadotropin-releasing hormone analogue(GnRHa)on growth and ovarian function in girls with precocious puberty.METHODS The clinical data of 84 adolescent girls with precocious puberty and rapidly progressive puberty from February 2017 to August 2023 were retrospectively analyzed.Girls were divided into a control group and an observation group,with 42 cases in each group.The control group received diet intervention combined with GnRHa treatment,while the observation group received diet intervention combined with Zhibai dihuang pills+GnRHa treatment.Outcomes such as clinical efficacy,growth indicators,ovarian function,and adverse reactions were compared between the two groups.RESULTS The observation group showed superior clinical efficacy compared to the control group(P<0.05).Prior to the intervention,no significant differences were found in growth or ovarian function between the groups(P>0.05).Post-intervention,the observation group exhibited significantly lower rates in growth,height,and bone age,along with reduced levels of progesterone,testosterone,estradiol,prolactin,luteinizing hormone,and follicle-stimulating hormone compared to the control group(P<0.05).The incidence of adverse reactions was similar across both groups(P>0.05).CONCLUSION Combining Zhibai dihuang pills with GnRHa and dietary intervention effectively improves growth,enhances ovarian function,and minimizes adverse reactions in adolescent girls with precocious and rapidly progressive puberty.
文摘Objective:This study aimed to evaluate the therapeutic effects of leuprolide acetate extended-release microspheres for injection in children with pediatric precocious puberty.Methods:A total of 110 cases of pediatric precocious puberty admitted between January 2019 and December 2021 were selected and randomized into two groups using a random number table,with 55 cases in the control group and 55 cases in the experimental group.The control group received conventional treatment,while the experimental group was treated with leuprolide acetate extended-release microspheres for injection.The therapeutic effects were observed,and changes in sex hormone levels,ovarian volume,growth indices,and the incidence of adverse reactions were statistically compared between the groups.Results:The experimental group demonstrated superior outcomes in terms of sex hormone levels,ovarian volume,and growth indices compared to the control group.Additionally,the incidence of adverse reactions in the experimental group was significantly lower(P<0.05).Conclusion:The application of leuprolide acetate extended-release microspheres for the treatment of pediatric precocious puberty is associated with improved therapeutic effects and higher safety.
文摘In boys, central precocious puberty （CPP） is the appearance of secondary sex characteristics driven by pituitary gonadotropin secretion before the age of 9 years. In the last years, relevant improvements in the treatment of CPP have been achieved. Because CPP is rare in boys, the majority of papers on this issue focus on girls and do not address specific features of male patients regarding end results and safety. In the present paper, recent advances of CPP management with GnRH analogs in men are summarized. End results in untreated and treated patients are also reviewed by an analysis of the recently published literature on treatment of CPP in men. The available data indicate that therapy with GnRH analogs can improve final height into the range of target height without significant adverse short-term and long-term effects, but longer follow-up of larger series of patients is still required to draw definitive conclusions.
基金Supported by the Shanghai Integrated Chinese and Western Medicine Key Diseases Construction Projects(No.zxbz2012-14)a Medical Guidance Item of the Shanghai Science and Technology Commission(No.12401906900)+1 种基金by the Chinese Medicine Prescription Project of the Shanghai Shenkang Hospital Development Center(No.SHDC12012414)by the Development Project of the Shanghai Peak
文摘OBJECTIVE: To evaluate the effect of ZiYin Xiehuo granules(ZYXH) and Zishen Qinggan granules(ZSQG) on partial precocious puberty(PPP).METHODS: This was a multicenter, randomized, single-blind, positive-controlled trial. A total of 143 pa-tients were assigned to either the ZYXH group or the ZSQG group using a random number table. The ZYXH group received ZYXH three times daily for 6 months and the ZSQG group received ZSQG three times daily for 6 months. Mammary nucleus diameter; the results of uterus, ovarian, and maximum follicle measures; and Chinese medicine symptom pattern scores were compared at baseline and after 3 months and 6 months of treatment.RESULTS: After 3 months' treatment, there were no significant differences between the two groups in mammary nucleus index changes(left 3.4 ± 3.1 vs3.5 ± 3.1, P = 0.790; right 3.0 ± 2.9 vs 3.6 ± 3.0, P =0.719). The uterine volume in the ZYXH group was smaller than that in the ZSQG group(2.1 ± 1.6 vs2.6 ± 2.2, P = 0.006). There were no significant between-group differences in ovarian volume and maximum follicular diameter on either side(ovarian volume: left 1.2 ± 0.7 vs 1.3 ± 0.6, P = 0.8; right1.2 ± 0.7 vs 1.4 ± 1.1, P = 0.984; maximum follicular diameter: left 3.9 ± 1.7 vs 3.5 ± 2.2, P = 0.158; right3.5 ± 1.7 vs 3.9 ± 2.1, P = 0.314).CONCLUSION: ZYXH granules and ZSQG granules both affected the size of the mammary nucleus in girls with PPP, and improved Chinese medicine symptom patterns. ZYXH granules showed slight advantages over ZSQG granules in terms of the decrease in the size of the uterus, ovaries, and ovarian follicles.
基金Project supported by the natural science foundation of Hebei province(No.H2013209314)
文摘Objective:To study expressions of netrin-1 and its receptor UNC5 C in female precocious puberty rat hypothalamus,and explore its effect on precocious puberty process.Methods:Forty female one-week-old SD rats were randomly divided into four groups:experimental group A(precocious puberty early youth),experimental group B(precocious puberty medium youth),group A(normal pre-puberty).group B(normal early youth) with 10 rats in each group.Precocious puberty experimental rats were induced with Danazol and rals in control group were injected with saline.Uterus and ovaries were removed,specimens were weighed,litems index and ovarian index were calculated,and amount of luteinizing hormone(LH) and follicle-stimulating hormone(FSH) were detected from the blood by ELISA.Real-time PCR was used to delect netrin-1 and its receptor UNC5 C.as well as hypothalamic gonadolropinreleasing hormone(GnRH) mRNA expression in hypothalamus tissues:and then,a coimmunoprecipitation study of interactions between netrin-1 and its receptor UNC5 C was carried out.Results:Relative target gene expression levels of control group A,control group B.experimental group A,and experimental group B(with,3-actin as an internal control for normalization) were as follows:Netrin-1:3.5±0.9,5.4±0.7.4.9±1.0.5.3±0.3:UNC5C:0.8±0.04.1.7±0.2.1.82±0.23.1.58±0.4:GnRH:1.2±0.3.2.7±0.3.2.4±0.7.3.2±0.4.Conclusions:LH and FSH concentrations,netrin-1 and its receptor expression are increased in precocious puberty animal models.
文摘It is found that the drugs for nourishing yin to reduce pathogenic fire can significantly down-regulate,and the drugs for tonifying the kidney to replenish essence can up-regulate mRNA expression of the hypothalamic GnRH,pituitary FSH,LH and osteoblastic BGP,indicating that the Chinese drugs for tonifying the kidney can regulate gene expression of the hypothalamic GnRH,pituitary FSH,LH,and osteoblastic BGP,which is possibly one of the main mechanisms of the Chinese drug for tonifying the kidney,regulating ephebic development process and improving skeletal development in sexual precocity children.
基金Supported by the National Natural Science Foundation of China(No.81072841)the Shanghai Science and Technology Research Grant Program(No.09dZ1971600)State Key Clinical Department of TCM pediatrics
文摘OBJECTIVE:To establish a quantification model of Traditional Chinese Medicine(TCM)syndromes by sampling patients undergoing idiopathic precocious puberty(IPP)and early puberty.METHODS:A questionnaire for classifying and quantifying TCM syndromes was designed and administered.All the results were analyzed;the relationship between 3 types of syndrome and 47symptoms were summated.Meanwhile,the frequency distribution of each symptom or sign was aggregated.Fuzzy mathematics was used to develop a quantification model ofTCM syndromes.RESULTS:We found that precocious puberty had 3types of syndrome,including hyperactivity of fire due to Yin deficiency(Syndrome I),depressed liver Qi transforming into fire(Syndrome II),and end retention of damp heat(Syndrome III).In the IPP group,Syndrome I was the most common principal syndrome(100%).Forty-six patients(43.81%)werediagnosed with Syndrome I accompanied by Syndrome II and 11(10.48%)were diagnosed with Syndrome I accompanied by Syndrome III.In the early puberty group,Syndrome I was also the main syndrome(98.39%).The degrees of most symptoms were mild to moderate.Reddened tongue was the most common tongue manifestation(62.86%prevalence)in the IPP group.The most common pulse manifestations were slippery pulse,thread pulse,and taut pulse.The Asymptotic Normalization Coefficient(ANC)method was used to quantify the TCM syndromes in 167 cases.Diagnostic accuracy rate reached 91%,comparable to expert diagnosis.CONCLUSION:We find that there are 3 types of syndrome in the IPP group and in the early puberty group.Syndrome I(hyperactivity of fire due to Yin deficiency)is the main syndrome in the two groups.ANC may be an appropriate for quantification model ofTCM syndromes.
文摘In order to assess the feasibility of subcutaneous administration of Triptorelin with 6-week intervals for the suppression of pituitary-gonadal axis and changes of clinical signs in girls with idiopathic central precocious puberty （ICPP）, 46 girls with ICPP were treated with GnRHa. Triptorelin （Decapeptyl, 3.75 mg） was administered subcutaneously （SC） at 6-weeks intervals or intramuscularly （IM） at 4-weeks intervals randomly for more than 12 months consecutively. During GnRHa therapy, clinical parameters and laboratory data, including height, weight, pubertal stage, bone age, uterine volume and ovarian size, serum levels of luteinizing hormone （LH）, follicle stimulating hormone （FSH） and estradiol （E2）, were monitored and analyzed. It was found that both treatment regimes led to regression of precocious puberty and reversal of secondary sexual characteristics. Breast developments regressed. Uterine volume was decreased after treatment, but there was no statistically significant difference. Mean ovarian volume did not change significantly during treatment. The height velocity was decreased significandy from 6.3±1.4 cm/year to 5.8：1：1.2 cm/year in group SC and 6.7±1.3 cm/year to 5.4±1.0 cm/year in group IM, respectively. The rate of bone maturation was reduced significantly during treatment. The ratio of deltaBAgdeltaCA was 1.2±0.2 or 1.3±0.3 at the onset of therapy and decreased significantly after the treatment to 0.7±0.2 or 0.9±0.1, respectively. The predicted adult height was increased significantly and progressively during therapy. The levels of serum LH, FSH and E2 returned to the prepubertal condition. No significant side effects of therapy were noted. The most common side effect during SC treatment was that a non-irritating, 1 cm in di- ameter mass was palpated at the site of subcutaneous injection in the abdominal wall of patients, which disappeared after 6- 12 weeks. Two girls had minimal withdrawal vaginal bleeding episodes after the first injection. It was concluded that both IM and SC triptorelin administrations were clinically effective. They induce profound suppression of hypothalamic-pituitary-gonadal axis while stabilizing height velocity, slowing bone maturation and increasing predicted adult height. These results suggest that subcutaneous injection of triptorelin in 6-weeks intervals at a dosage of 3.75 mg be a safe and acceptable regimen for ICPP.
基金by the key Research and Development Program of Zhejiang Province(No.2020C03121).
文摘BACKGROUND Caused by premature activation of the hypothalamic-pituitary-gonadal axis,there is increasing incidence of central precocious puberty(CPP),especially in girls.Makorin ring finger protein 3(MKRN3),a maternal imprinted gene with a highly conserved sequence,is the most common genetic etiology associated with CPP.Approximately 50 different mutations in MKRN3 have been found in CPP.CASE SUMMARY This case report involves identical twin sisters presenting with premature thelarche at the age of 6 years.The left hand bone age of both patients revealed advanced age(9 years).Pelvic B ultrasound indicated enlargement of the ovaries.Luteinizing hormone(LH)releasing hormone testing confirmed CPP.Wholeexome sequencing detected the c.841C>T mutation in MKRN3,leading to a single base substitution,in the twins.This mutation was inherited from the father and paternal grandmother.After 3 mo of treatment with a gonadotropin-releasing hormone analog,levels of LH,follicle-stimulating hormone,and estradiol in the proband’s sister returned to normal levels.CONCLUSION Here,we report a rare mutation(c.841C>T)in MKRN3 in identical twin sisters with CPP.
基金supported by grants from 12th five-year Plan National Key Technology R&D Program(No.2012BAI09B04)Program for Changjiang Scholars and Innovative Research Team in University(No.PCSIRT1131)
文摘The effect of obesity on idiopathic central precocious puberty（ICPP） girls is still under discussion. The relationship between body mass index（BMI） and sexual hormone levels of gonadotropin-releasing hormone（GnRH） stimulation test in ICPP girls is controversial and the underlying mechanism is unclear. This study aims to further explore the independent effect of excess adiposity on peak luteinizing hormone（LH） level of stimulation test in ICPP girls and the role of other related factors. A retrospective cross-sectional study was performed on 618 girls diagnosed as having ICPP, including 355 cases of normal weight, 99 cases of overweight and 164 cases of obese. The results showed that obese group had more progressed Tanner stage and no significant difference（P=0.28） in LH peak was found as basal LH value was used as a covariate. The obese group had higher total testosterone（TT）, adrenocorticotrophic hormone（ACTH）, 17-α hydroxyprogesterone（17-αOHP） and androstendione（AN）, with significantly increased fasting insulin（FIN） and homeostasis model of assessment for insulin resistance index（HOMA-IR）. Stratified analysis showed inconsistency of the relationship between BMI-standard deviation score（BMI-SDS） and LH peak in different Tanner stages（P for interaction=0.017）. Further smoothing plot showed linear and non-linear relationship between BMI-SDS and LH peak in three Tanner stages. Then linear regression model was used to analyze the relationship between BMI-SDS and LH peak in different Tanner stages, with and without different confounding factors being adjusted. In B2 stage, BMI-SDS was negatively associated with LH peak. In B3 stage, when BMI-SDS 〈1.5, as BMI-SDS increased, the level of LH peak decreased（model Ⅰ： β=–1.8, 95% CI=–4.7 to 1.1, P=0.214）. When BMI-SDS ≥1.5, BMI-SDS was significantly positively associated with LH peak（model Ⅰ： β=4.5, 95% CI=1.7 to 7.4, P=0.002）. In B4 stage, when BMI-SDS 〈1.5, BMI-SDS was negatively associated with LH peak（model Ⅰ： β=–11.6, 95% CI=–22.7 to –0.5, P=0.049）. When BMI-SDS ≥1.5, BMI-SDS was positively associated with LH peak（model Ⅰ： β=–4.2, 95% CI=–3.3 to 11.7, P=0.28）. It is concluded that there is an independent correlation between BMI-SDS and LH peak of stimulation test in ICPP girls, their relationships are different in different Tanner stages, and the effect of BMI-SDS can be affected by adrenal androgens, estradiol and glucose metabolism parameters.
文摘Children are currently starting pubertal development much earlier than 20 to 30 years ago. Data from the National Health and Nutrition Examination Survey (NHANES III) conducted from 1988-1994 revealed that the median age for breast development in white girls was approximately 9.7 years and 8 years in African-American girls versus 10.9 years ago. More recent data, however, indicate that some children are starting pubertal development even earlier (age 7 or 8 in girls or age 9 in boys). Very early pubertal development is identified as precocious puberty, a phenomenon that brings great concern to others besides parents: the child, their peers, school nurses, teachers and counselors. This paper discusses precocious pubertal development, possible causes or relationships, related risks, treatment and helping strategies.
基金Jiangsu Province Maternal and Child Health Care Project (No.FYX202213)。
文摘Objective:To observe the clinical efficacy of different dosage forms of lepraline acetate(LA)in the treatment of girls with central precocious puberty(CPP).Methods:72 CPP girls treated in the Department of Pediatrics of Huai'an First People's Hospital from February 2021 to August 2022 were included as subjects and divided into two groups:3-month LA group(n=34)and 1-month LA group(n=38).Both group girls were treated for 6 months.Serum hormone levels,body mass index(BMI),bone age/chronological age(BA/CA)and pelvic color ultrasound were detected at 0 and 6 months after treatment,and the changes of various indexes were compared before and after treatment.Results:1)There were no significant differences in baseline data between the two groups before treatment(P>0.05).2)After 6 months of treatment,BA/CA decreased,growth rate slowed down,and predicted adult height increased in both groups(P<0.05),but there were no significant differences between groups(P>0.05).3)After 6 months of treatment,there waere no significant differences in luteinizing hormone(LH)inhibition ratio between the 3 month and 1 month dosage groups(P>0.05).After treatment,the peak value of serum LH and FSH,estradiol level,uterine volume,bilateral ovarian volume,maximum follicle diameter and the number of follicles 4mm were significantly decreased in the two groups,but there were no significant differences between the two groups(P>0.05).4)There were no significant differences in the levels of thyroid hormone,fasting blood glucose and triglyceride between the two groups before and after treatment(P>0.05).Total cholesterol levels were increased after treatment(P<0.05),but there was no significant difference between groups(P>0.05).5)No serious adverse reactions occurred during the treatment of the two dosage forms of LA,but the 3-month dosage form of LA reduced the treatment cost and improved the treatment compliance.Conclusion:The short-term efficacy of 3-month LA in the treatment of CPP in girls is similar to that of 1-month LA.The 3-month dosage form LA is a safe,effective,and economical method for the treatment of CPP in girls.
文摘Isosexual precocious puberty in girls has several etiologies. Juvenile granulose cell tumor is one of the rarest causes that only stands for 1.5% of ovarian cancers. This tumor mostly encounters in first 2 decades of life. This paper is a report of an 8-year-old girl with precocious puberty that within five months developed breast enlargement followed by menarche. Works which are done to find the underlying cause of precocious puberty revealed juvenile granulosa cell tumor in her left ovary. She then under went laparoscopic surgery and 3 courses of chemotherapy. She did not experience any vaginal bleeding after that and the serum level of estradiol lay among its normal ranges, but after that the tumor relapsed and presented as abdominal pain and a huge mass which under went resection of all afflicted tissues. After 2 courses of chemotherapy, her status deteriorated and unfortunately she died after 6 months from the time of diagnosis. Treatment for this disease is consists of resection surgery and chemotherapy. If this tumor is diagnosed in its early stages, it will be curable, but in its advanced stages, up to 80% of patients die from recurrent tumors. The reported patient was diagnosed at stage IIIC that had poor prognosis.
