Background: To understand what life is like for US children with a diagnosis of Growth Hormone Deficiency or Idiopathic Short Stature, the impact of short stature on Health related Quality of Life (HrQoL) was qualitat...Background: To understand what life is like for US children with a diagnosis of Growth Hormone Deficiency or Idiopathic Short Stature, the impact of short stature on Health related Quality of Life (HrQoL) was qualitatively examined and needs for care from the young patients and their parents perspective were identified. Methods: Focus group discussions with 26 American-English speaking and nine American-Spanish speaking children and their parents were conducted, transcribed verbatim and subsequently qualitatively analyzed by two independent raters, using an existing coding guideline, based on the multidimensional HrQoL concept and a special software (VERBI-Software MAXQDA 10). Results: A total of 1313 statements for the English-speaking and 447 statements for the Spanish-speaking families were categorized. In the US, the strongest frequency of mention was found for the HrQoL dimension “Social” across respondents, followed by “Treatment” and “Emotion”. Conclusion: Conducting and analyzing data generated from focus groups ensure that young patients’ experiences of disease are represented in the measure of outcomes for use in clinical trials and patient care.展开更多
Hepatocellular carcinoma(HCC)is a highly lethal malignancy with limited treatment options,particularly for patients with advanced stages of the disease.Sorafenib,the standard first-line therapy,faces significant chall...Hepatocellular carcinoma(HCC)is a highly lethal malignancy with limited treatment options,particularly for patients with advanced stages of the disease.Sorafenib,the standard first-line therapy,faces significant challenges due to the development of drug resistance.Yu et al explored the mechanisms by which lncRNA KIF9-AS1 regulates the stemness and sorafenib resistance in HCC using a combination of cell culture,transfection,RNA immunoprecipitation,co-immunoprecipitation,and xenograft tumor models.They demonstrate that N6-methyladenosine-modified long non-coding RNA KIF9-AS1 acts as an oncogene in HCC.This modification involves methyltransferase-like 3 and insulin-like growth factor 2 mRNA-binding protein 1,which play critical roles in regulating KIF9-AS1.Furthermore,KIF9-AS1 stabilizes and upregulates short stature homeobox 2 by promoting its deubiquitination through ubiquitin-specific peptidase 1,thereby enhancing stemness and contributing to sorafenib resistance in HCC cells.These findings provide a theoretical basis for KIF9-AS1 as a diagnostic marker and therapeutic target for HCC,highlighting the need for further investigation into its clinical application potential.展开更多
BACKGROUND A diagnosis of a chronic disease has been shown to predispose patients to the development of feeding and eating disorders(FEDs).AIM To screen children and adolescents with type 1 diabetes mellitus(T1DM)for ...BACKGROUND A diagnosis of a chronic disease has been shown to predispose patients to the development of feeding and eating disorders(FEDs).AIM To screen children and adolescents with type 1 diabetes mellitus(T1DM)for FEDs and compare them to their counterparts with short stature.METHODS A total of 110 children and adolescents(55 with T1DM and 55 with short stature)were enrolled in the study.The SCOFF questionnaire was used to screen for possible FEDs,while anthropometric and dietary data were also collected.RESULTS Approximately 60%of the children with T1DM screened positive for FEDs compared to 30.9%of the children with short stature.Having a T1DM tripled the chances of screening positive for FEDs and halved the annual growth rate of children with T1DM.No differences were noted in the dietary intake between groups.CONCLUSION The results necessitate the education of pediatric endocrinologists and diabetologists on proper screening and identification of children at risk for developing FEDs.A prompt diagnosis might help children catch up growth and attain their genetically predisposed height.展开更多
BACKGROUND Silver-Russell syndrome(SRS)is a clinically heterogeneous entity characterized by intrauterine and postnatal growth restriction,relative macrocephaly at birth,distinct facial features,and body asymmetry com...BACKGROUND Silver-Russell syndrome(SRS)is a clinically heterogeneous entity characterized by intrauterine and postnatal growth restriction,relative macrocephaly at birth,distinct facial features,and body asymmetry combined with other malformations.CASE SUMMARY Herein,we describe four individuals with SRS,focusing on their prenatal phenotype,postnatal presentation,diagnosis,and management.All cases had a typical phenotype,including postnatal growth failure,short stature(chronic malnutrition),and protruding forehead.Individually,they presented with feeding difficulties,leg length discrepancy,triangular face,or relative macrocephaly at birth,and each one exhibited distinct SRS features,including motor and/or speech delay,experiencing frequent hypoglycemic episodes.The fact that each patient exhibited a different combination of clinical findings underlines the heterogeneity of the syndrome.CONCLUSION SRS is diagnosed clinically.However,only 60%of cases are genetically confirmed,while most are sporadic.Although SRS is a well-described syndrome,a delayed diagnosis can have grave consequences on a child’s growth.Recombinant human growth hormone treatment is often initiated shortly after the diagnosis.The follow-up requires a multidisciplinary approach.展开更多
This letter comments on the recently published manuscript by Yu et al,in which the authors revealed a novel mechanism by which the m6A-modified long noncoding RNA kinesin family member 9-antisense RNA 1 promotes stemn...This letter comments on the recently published manuscript by Yu et al,in which the authors revealed a novel mechanism by which the m6A-modified long noncoding RNA kinesin family member 9-antisense RNA 1 promotes stemness and sorafenib resistance of hepatocellular carcinoma(HCC)through ubiquitinspecific peptidase 1-mediated deubiquitination of oncogene short stature homeobox 2.Given the high mortality rate and poor prognosis of HCC,the findings by Yu et al open a new avenue for overcoming HCC burden by focusing on kinesin family member 9-antisense RNA 1 and short stature homeobox 2 as prognostic markers and therapeutic targets.展开更多
Objective:To investigate the clinical efficacy and safety evaluation of Polyethylene Glycol Recombinant Human Growth Hormone Injection(PEG-rhGH)in the treatment of idiopathic short stature.Methods:A total of 1402 pati...Objective:To investigate the clinical efficacy and safety evaluation of Polyethylene Glycol Recombinant Human Growth Hormone Injection(PEG-rhGH)in the treatment of idiopathic short stature.Methods:A total of 1402 patients were enrolled from March 21,2024 to January 13,2025,including 778 males and 624 females,with ages mainly ranging from 5 to 13 years old.Follow-up visits were completed by 488 patients for the first time,174 patients for the second time,and 81 patients for the third time.All patients were treated with PEG-rhGH(Jin Sai Zeng)as the main therapy after admission.The changes in height information,IGF-1,and thyroid examination results of each patient at the initial diagnosis,6,9,and 12 months after treatment were observed and analyzed.Results:There was no statistical difference between the baseline and the initial diagnosis,as well as the second follow-up visit(P<0.05),while there was a statistical difference between the baseline and the first and third follow-up visits(P>0.05).There was a statistically significant difference in IGF-1 between the initial diagnosis and the first follow-up visit(P<0.05),but no statistical difference between the first,second,and third follow-up visits(P>0.05).Additionally,IGF-1 levels increased with time.There was no statistical difference in TSH between the initial diagnosis and the first,second,and third follow-up visits(P>0.05).There was a statistical difference in free T3 between the initial diagnosis and the first and second follow-up visits(P<0.05),but no statistical difference between the second and third follow-up visits(P>0.05).There was no statistical difference in free T4 between the initial diagnosis and the first and second follow-up visits(P>0.05),but there was a statistical difference between the second and third follow-up visits(P<0.05).Conclusion:PEG-rhGH(Jin Sai Zeng)is significantly effective in improving height and IGF-1 levels in patients with idiopathic short stature.展开更多
Objective Research evidence shows a secular trend in Chinese physical growth in recent years.The aim of this study was to analyze and assess changes in stature of children and adolescents during the 25 years from 1985...Objective Research evidence shows a secular trend in Chinese physical growth in recent years.The aim of this study was to analyze and assess changes in stature of children and adolescents during the 25 years from 1985‐2010,using national data.Methods Data came from successive cycles of the Chinese National Survey on Students＇ Constitution and Health（CNSSCH）.Subjects were 7‐ to 18‐year‐old children and adolescents.Results An overall positive secular trend occurred in urban China during 1985‐2010.The overall average rates of increment were 2.4 and 1.7 cm/decade for boys and girls,respectively.Total increases in adult stature for boys and girls were 2.6 and 1.7 cm,yielding rates of 1.0 and 0.7 cm/decade,respectively.Cities with different socioeconomic levels had different characteristic trends.Mean stature increases in big cities were larger than those in moderate and small cities,and boys and girls in moderate and small cities showed greater potential for growth in stature.Conclusion An overall positive secular growth trend was associated with socioeconomic progress and differed with area socioeconomic levels.School policies and strategies should be developed based on increased stature,and should continue narrowing the inequity between different socioeconomic populations.展开更多
Objective To analyze and assess secular change in stature in rural children and adolescents in China from 1985 to 2010. Methods Data were obtained from the 6 rounds of the Chinese National Survey on Student＇s Constit...Objective To analyze and assess secular change in stature in rural children and adolescents in China from 1985 to 2010. Methods Data were obtained from the 6 rounds of the Chinese National Survey on Student＇s Constitution and Health. The subjects enrolled in the study were children and adolescents aged 7-18 years in rural areas of provincial capitals. Results An overall positive secular trend in stature occurred in rural areas of provincial capitals in China from 1985 to 2010. The overall average increase rates were 3.1 and 2.4 cm/decade for boys and girls, respectively. The total body height increases for grown up boys and girls were 3.6 and 2.3 cm and the increase rates were 1.4 and 0.9 cm/decade, respectively. There were differences in body height increase among eastern, central and western regions. The average body height of the children or adolescents in eastern region was highest, followed by central region and western region. The overall increase rates in central region were highest among the three regions. The difference between eastern/central region and western region was obvious. 〈br〉 Conclusion Positive secular trend in stature of children or adolescents has occurred in rural area of China, and rural boys and girls showed a great potential for continuous growth. More attention should be paid to the differences in children＇s body height between western region and eastern/central region.展开更多
To evaluate vital signs and body indices in Helicobacter pylori (H. pylori) positive and negative persons. A total of 22 centres entered the study. They were spread over the whole country, corresponding well to the ge...To evaluate vital signs and body indices in Helicobacter pylori (H. pylori) positive and negative persons. A total of 22 centres entered the study. They were spread over the whole country, corresponding well to the geographical distribution of the Czech population. A total of 1818 subjects (aged 5-98 years) took part in the study, randomly selected out of 38147 subjects. H. pylori infection was investigated by means of a 13C-urea breath test. Data on height, weight, systolic and diastolic blood pressure and heart rate were collected at the clinics of general practitioners. The overall prevalence of H. pylori infection was 30.4% (402/1321) in adults (≥ 18 year-old) and 5.2% (26/497) in children and adolescents (≤ 17 year-old). Once adjusted for age and gender, only a difference in body mass index remained statistically significant with H. pylori positive adults showing an increase of 0.6 kg/m<sup>2</sup> in body mass index. Once adjusted for age and gender, we found a difference in height between H. pylori positive and H. pylori negative children and adolescents. On further adjustment for place of residence, this difference became statistically significant, with H. pylori positive children and adolescents being on average 3.5 cm shorter. H. pylori positive adults were significantly older compared to H. pylori negative subjects. Once adjusted for age and gender, H. pylori infection had no impact on body weight, body mass index and vital signs either in adults or children and adolescents. Chronic H. pylori infection appeared to be associated with short stature in children. H. pylori infection did not influence blood pressure, body weight and body mass index either in adults or children and adolescents.展开更多
Short stature is among the most common endocrinological disease phenotypes of childhood and may occur as an isolated finding or in conjunction with other clinical manifestations.Although the diagnostic utility of clin...Short stature is among the most common endocrinological disease phenotypes of childhood and may occur as an isolated finding or in conjunction with other clinical manifestations.Although the diagnostic utility of clinical genetic testing in short stature has been implicated,the genetic architecture and the utility of genomic studies such as exome sequencing(ES)in a sizable cohort of patients with short stature have not been investigated systematically.In this study,we recruited 561 individuals with short stature from two centers in China during a 4-year period.We performed ES for all patients and available parents.All patients were retrospectively divided into two groups:an isolated short stature group(group I,n=257)and an apparently syndromic short stature group(group II,n=304).Causal variants were identified in 135 of 561(24.1%)patients.In group I,29 of 257(11.3%)of the patients were solved by variants in 24 genes.In group II,106 of 304(34.9%)patients were solved by variants in 57 genes.Genes involved in fundamental cellularprocess played an important role in the genetic architecture of syndromic short stature.Distinct genetic architectures and pathophysiological processes underlie isolated and syndromic short stature.展开更多
BACKGROUND Geleophysic dysplasia(GD)presents the characterized clinical manifestations of acromelic dysplasia,including extremely short stature,short limbs,small hands and feet,stubby fingers and toes,joint stiffness ...BACKGROUND Geleophysic dysplasia(GD)presents the characterized clinical manifestations of acromelic dysplasia,including extremely short stature,short limbs,small hands and feet,stubby fingers and toes,joint stiffness and others.It is clinically distinct from the other acromelic dysplasia in terms of symptoms such as cardiac valvular abnormalities,progressive hepatomegaly and tracheal stenosis.CASE SUMMARY We report on a Chinese 9-year-old girl with GD with the c.5243G>T(p.C1748F)mutation in FBN1(fibrillin 1,OMIM 134797).She was born in Guangxi Zhuang Autonomous Region of China.The patient presented with typical clinical features of GD and recurrent respiratory tract infections over 6 years.Laboratory studies and chest computed tomography(CT)scan indicated bronchopneumonia.Her echocardiography revealed mild mitral valve thickening with regurgitation.Laryngopharyngeal CT and electronic bronchoscopy revealed severe glottic stenosis.Echocardiography examination displayed mild mitral valve thickening and regurgitation.Ophthalmic examination did not reveal myopia or lens dislocation.Treated with ceftriaxone sodium and methylprednisolone sodium succinate for injection as well as methylprednisolone orally,patient’s symptoms had improved.CONCLUSION GD is a rare genetic condition that can cause life-threatening cardiovascular and respiratory problems.This study also found that the identified genotype of GD could be related to different clinical phenotypes.展开更多
BACKGROUND Acromicric dysplasia(AD)is a rare skeletal dysplasia.Its incidence is<1/1000000,and only approximately 60 cases are reported worldwide.It is a disease characterized by severe short stature,short hands an...BACKGROUND Acromicric dysplasia(AD)is a rare skeletal dysplasia.Its incidence is<1/1000000,and only approximately 60 cases are reported worldwide.It is a disease characterized by severe short stature,short hands and feet,facial abnormalities,normal intelligence,and bone abnormalities.Unlike other skeletal dysplasia,AD has a mild clinical phenotype,mainly characterized by short stature.Extensive endocrine examination has not revealed a potential cause.The clinical effect of growth hormone therapy is still uncertain.CASE SUMMARY We report a clinical phenotype of AD associated with mutations in the fibrillin 1(FBN1)(OMIM 102370)gene c.5183C>T(p.Ala1728Val)in three people from a Chinese family.A 4-year-old member of the family first visited the hospital because of slow growth and short stature for 2 years,but no abnormalities were found after a series of laboratory tests,echocardiography,pituitary magnetic resonance imaging,and ophthalmological examination.Recombinant human growth hormone(rhGH)was used to treat the patient for>5 years.The efficacy of rhGH was apparent in the first year of treatment;the height increased from-3.64 standard deviation score(SDS)to-2.88 SDS,while the efficacy weakened from the second year.However,long-term follow-up is required to clarify the efficacy of rhGH.CONCLUSION FBN1-related AD has genetic heterogeneity and/or clinical variability,which brings challenges to the evaluation of clinical treatment.rhGH is effective for treatment of AD,but long-term follow-up is needed to clarify the effect.展开更多
AIM: To estimate the burden of undiagnosed celiac disease (CD) in the Mediterranean area in terms of morbidity, mortality and health cost. METHODS: For statistics regarding the population of each country in the Medite...AIM: To estimate the burden of undiagnosed celiac disease (CD) in the Mediterranean area in terms of morbidity, mortality and health cost. METHODS: For statistics regarding the population of each country in the Mediterranean area, we accessed authoritative international sources (World Bank, World Health Organization and United Nations). The prevalence of CD was obtained for most countries from published reports. An overall prevalence rate of 1% cases/total population was finally estimated to represent the frequency of the disease in the area, since none of the available conf idence intervals of the reported rates significantly excluded this rate. The distribution of symptoms and complications was obtained from reliable reports in the same cohort. A standardized mortality rate of 1.8 was obtained from recent reports. Crude health cost was estimated for the years between symptoms and diagnosis for adults and children, and was standardized for purchasing power parity to account for the different economic prof iles amongst Mediterranean countries. RESULTS: In the next 10 years, the Mediterranean area will have about half a billion inhabitants, of which 120 million will be children. The projected number of CD diagnoses in 2020 is 5 million cases (1 million celiac children), with a relative increase of 11% compared to 2010. Based on the 2010 rate, there will be about 550 000 symptomatic adults and about 240 000 sick children: 85% of the symptomatic patients will suffer from gastrointestinal complaints, 40% are likely to have anemia, 30% will likely have osteopenia, 20% of children will have short stature, and 10% will have abnormal liver enzymes. The estimated standardized medical costs for symptomatic celiac patients during the delay between symptom onset and diagnosis (mean 6 years for adults, 2 years for children) will be about €4 billion (€387 million for children) over the next 10 years. A delay in diagnosis is expected to increase mortality: about 600 000 celiac patients will die in the next 10 years, with an excess of 44.4% vs age-and sexmatched controls. CONCLUSION: In the near future, the burden of CD will increase tremendously. Few Mediterranean countries are able to face this expanding epidemic alone.展开更多
BACKGROUND The SEMA3A gene,which is located at 7q21.11,is involved in hypothalamic neuron migration,heart development,kidney development,and skeleton metabolism.Mutation of the SEMA3A gene is associated with Kallmann ...BACKGROUND The SEMA3A gene,which is located at 7q21.11,is involved in hypothalamic neuron migration,heart development,kidney development,and skeleton metabolism.Mutation of the SEMA3A gene is associated with Kallmann syndrome 16 with or without a normal sense of smell.In addition,two case reports showed that mutation of the SEMA3A gene could cause short stature,low gonadotropin,hypogonadism,thoracic deformity,a high scapula,rib and lower limb deformity,facial deformity(long face,epicanthic folds,backwards ears),and arterial malformation.CASE SUMMARY We reported the case of a 26-year-old Chinese man who was admitted because of short stature.Physical examination showed that he had many abnormal symptoms,including a short neck,facial moles,knee valgus,transverse palm,continuous grade 5/6 murmurs in the pulmonary auscultation area,no whiskers,or pubic hair,no Adam’s apple,short penis and cryptorchidism.Radiological examination showed pituitary,gonad,heart,kidney and skeletal dysplasia.The laboratory tests revealed low growth hormone,luteinizing hormone,folliclestimulating hormone,testosterone and estrogen.Clinical whole-exome detection showed that our patient,unlike previously reported patients,has a new SEMA3A gene mutation(c.950A>G).Now,his height has increased by 3 cm.In addition,he has a good appetite and reduced subcutaneous fat over 3 mo of recombinant human growth hormone injections therapy.Unfortunately,he refuses further treatment about gonad.CONCLUSION Patients who come to a hospital because of their short stature must undergo gene detection if they have other simultaneous abnormal phenotypes.展开更多
BACKGROUND Mutations in the aggrecan(ACAN)gene are identified in patients with:spondyloepiphyseal dysplasia,Kimberley type;short stature with advanced bone age(BA);in the presence or absence of heterozygous ACAN mutat...BACKGROUND Mutations in the aggrecan(ACAN)gene are identified in patients with:spondyloepiphyseal dysplasia,Kimberley type;short stature with advanced bone age(BA);in the presence or absence of heterozygous ACAN mutation-induced early-onset osteoarthritis and/or osteochondritis dissecans;and spondyloepimetaphyseal dysplasia,ACAN type.Heterozygous mutations contribute to spondyloepiphyseal dysplasia,Kimberley type(MIM#608361),which is a milder skeletal dysplasia.In contrast,homozygous mutations cause a critical skeletal dysplasia,which is called spondyloepimetaphyseal dysplasia,ACAN type(MIM#612813).Lately,investigations on exome and genome sequencing have shown that ACAN mutations can also lead to idiopathic short stature with or without an advanced BA,in the presence or absence of early-onset osteoarthritis and/or osteochondritis dissecans(MIM#165800).We herein reported a heterozygous defect of ACAN in a family with autosomal dominant short stature,BA acceleration,and premature growth cessation.CASE SUMMARY A 2-year-old male patient visited us due to growth retardation.The patient presented symmetrical short stature(height 79 cm,<-2 SD)without facial features and other congenital abnormalities.Whole-exome sequencing revealed a heterozygous pathogenic variant c.871C>T(p.Gln291*)of ACAN,which was not yet reported in cases of short stature.This mutation was also detected in his father and paternal grandmother.According to the Human Gene Mutation Database,67 ACAN mutations are registered.Most of these mutations are genetically inheritable,and very few children with short stature are associated with ACAN mutations.To date,heterozygous ACAN mutations have been reported in approximately 40 families worldwide,including a few individuals with a decelerated BA.CONCLUSION Heterozygous c.871C>T(p.Gln291*)variation of the ACAN gene was the disease-causing variant in this family.Collectively,our newly discovered mutation expanded the spectrum of ACAN gene mutations.展开更多
BACKGROUND The incidence of short stature in KBG syndrome is relatively high.Data on the therapeutic effects of growth hormone(GH)on children with KBG syndrome accompanied by short stature in the previous literature h...BACKGROUND The incidence of short stature in KBG syndrome is relatively high.Data on the therapeutic effects of growth hormone(GH)on children with KBG syndrome accompanied by short stature in the previous literature has not been summarized.CASE SUMMARY Here we studied a girl with KBG syndrome and collected the data of children with KBG syndrome accompanied by short stature from previous studies before and after GH therapy.The girl was referred to our department because of short stature.Physical examination revealed mild dysmorphic features.The peak GH responses to arginine and clonidine were 6.22 and 5.40 ng/mL,respectively.The level of insulin-like growth factor 1(IGF-1)was 42.0 ng/mL.Genetic analysis showed a c.2635 dupG(p.Glu879fs)mutation in the ANKRD11 gene.She received GH therapy.During the first year of GH therapy,her height increased by 0.92 standard deviation score(SDS).Her height increased from-1.95 SDS to-0.70 SDS after two years of GH therapy.There were ten children with KBG syndrome accompanied by short stature who received GH therapy in reported cases.Height SDS was improved in nine(9/10)of them.The mean height SDS in five children with KBG syndrome accompanied by short stature increased from-2.72±0.44 to-1.95±0.57 after the first year of GH therapy(P=0.001).There were no adverse reactions reported after GH treatment.CONCLUSION GH treatment is effective in our girl and most children with KBG syndrome accompanied by short stature during the first year of therapy.展开更多
Objective To conduct stature estimation from seven facial measurements of 1901 Tujia adults(858 males,1043 females)in Southern China aged from 18 to 75 years.Methods The present study applied variable statistical meth...Objective To conduct stature estimation from seven facial measurements of 1901 Tujia adults(858 males,1043 females)in Southern China aged from 18 to 75 years.Methods The present study applied variable statistical method,such as multiplication factors,linear regression,multiple regression as well as multiple stepwise regression to explore the relationship between stature and cephalic-facial measurements and the reliability of the estimation method of stature in Tujia.Results All the facial measurements had significant coefficient with stature according to Pearson's analysis.Linear regression was the best method for stature estimation according to cephalic-facial measurements in Tujia among the four method.Overall,the range of the four method based on the reliability was linear regression,multiple regression,multiple stepwise regression and multiplication factors.Conclusion Cephalic-facial measurements can be used to establish stature estimation equation.Horizontal head circumference has the highest correlation in the present study so that the estimating equation based on horizontal head circumference is most accurate.展开更多
Purpose: To assess the growth hormone(GH) response to the Wingate anaerobic test(WAn T) among children with short stature and suspected GH deficiency. We hypothesized that the GH response to the WAn T would be similar...Purpose: To assess the growth hormone(GH) response to the Wingate anaerobic test(WAn T) among children with short stature and suspected GH deficiency. We hypothesized that the GH response to the WAn T would be similar to the GH response to a commonly used pharmacologic provocation test.Methods: Ten children(6 males and 4 females, age range 9.0–14.9 years) participated in the study. Each participant performed 2 tests: a standard all-out WAn T, cycling for 30 s against constant resistance, and a standardized pharmacologic test(clonidine or glucagon). Blood samples for GH were collected before and 10, 30, 45, and 60 min after the beginning of exercise. In addition, we collected pre-and post-exercise blood lactate levels.Results: There was a significant increase in GH levels after the WAn T, yet in 9 of 10 participants, this increase was below the threshold for GH sufficiency. Peak GH after the WAn T was significantly lower compared to the pharmacologic GH provocation tests(with 9 of 10 demonstrating GH-sufficient response).Conclusion: The traditional WAn T cannot be used as a GH provocation test. Further research is needed to develop anaerobic exercise protocols sufficient to promote GH secretion.展开更多
Reduced plant height is one of the most important traits related to lodging resistance and crop yield. The use of reduced height genes has been one of the main features in breeding modern high-yielding wheat varieties...Reduced plant height is one of the most important traits related to lodging resistance and crop yield. The use of reduced height genes has been one of the main features in breeding modern high-yielding wheat varieties with less lodging. A spontaneous dwarf mutant DD399 was identified in a high yielding, gibberellic acid(GA)-insensitive, lodging-resistant variety Nongda 399(ND399). Significant differences in upper internode lengths between mutant DD399 and wild type ND399 were caused by reduced cell elongation. The plant height of ND399 × DD399 F_(1) hybrids was intermediate between the parents, indicating incomplete dominance or a dose–response effect of a reduced height gene. Plant height showed continuous distribution in the F_(2) population, and segregation distortion was observed among the 2292 F_(2:3) progenies. The reduced height mutation was characterized by Illumina 90 K iSelect SNP genotyping and bulked segregant RNA-Seq(BSR-Seq) analysis of the segregating population. A concentrated cluster of polymorphic SNPs associated with the reduced height phenotype was detected in the distal region of chromosome arm 2 BL. Co-segregation of reduced height phenotype with the clustered markers revealed a 36 Mb terminal deletion of chromosome 2 BL in mutant DD399.展开更多
BACKGROUND Hepatocellular carcinoma(HCC)is a prevalent and aggressive tumor.Sorafenib is the first-line treatment for patients with advanced HCC,but resistance to sorafenib has become a significant challenge in this t...BACKGROUND Hepatocellular carcinoma(HCC)is a prevalent and aggressive tumor.Sorafenib is the first-line treatment for patients with advanced HCC,but resistance to sorafenib has become a significant challenge in this therapy.Cancer stem cells play a crucial role in sorafenib resistance in HCC.Our previous study revealed that the long non-coding RNA(lncRNA)KIF9-AS1 is an oncogenic gene in HCC.However,the role of KIF9-AS1 in drug resistance and cancer stemness in HCC remains unclear.Herein,we aimed to investigate the function and mechanism of the lncRNA KIF9-AS1 in cancer stemness and drug resistance in HCC.AIM To describe the role of the lncRNA KIF9-AS1 in cancer stemness and drug resistance in HCC and elucidate the underlying mechanism.METHODS Tumor tissue and adjacent non-cancerous tissue samples were collected from HCC patients.Sphere formation was quantified via a tumor sphere assay.Cell viability,proliferation,and apoptosis were evaluated via Cell Counting Kit-8,flow cytometry,and colony formation assays,respectively.The interactions between the lncRNA KIF9-AS1 and its downstream targets were confirmed via RNA immunoprecipitation and coimmunoprecipitation.The tumorigenic role of KIF9-AS1 was validated in a mouse model.RESULTS Compared with that in normal controls,the expression of the lncRNA KIF9-AS1 was upregulated in HCC tissues.Knockdown of KIF9-AS1 inhibited stemness and attenuated sorafenib resistance in HCC cells.Mechanistically,N6-methyladenosine modification mediated by methyltransferase-like 3/insulin-like growth factor 2 mRNA-binding protein 1 stabilized and increased the expression of KIF9-AS1.Additionally,KIF9-AS1 increased the stability and expression of short stature homeobox 2 by promoting ubiquitin-specific peptidase 1-induced deubiquitination.Furthermore,depletion of KIF9-AS1 alleviated sorafenib resistance in a xenograft mouse model of HCC.CONCLUSION The N6-methyladenosine-modified lncRNA KIF9-AS1 promoted stemness and sorafenib resistance in HCC by upregulating short stature homeobox 2 expression.展开更多
文摘Background: To understand what life is like for US children with a diagnosis of Growth Hormone Deficiency or Idiopathic Short Stature, the impact of short stature on Health related Quality of Life (HrQoL) was qualitatively examined and needs for care from the young patients and their parents perspective were identified. Methods: Focus group discussions with 26 American-English speaking and nine American-Spanish speaking children and their parents were conducted, transcribed verbatim and subsequently qualitatively analyzed by two independent raters, using an existing coding guideline, based on the multidimensional HrQoL concept and a special software (VERBI-Software MAXQDA 10). Results: A total of 1313 statements for the English-speaking and 447 statements for the Spanish-speaking families were categorized. In the US, the strongest frequency of mention was found for the HrQoL dimension “Social” across respondents, followed by “Treatment” and “Emotion”. Conclusion: Conducting and analyzing data generated from focus groups ensure that young patients’ experiences of disease are represented in the measure of outcomes for use in clinical trials and patient care.
基金Supported by National Natural Science Foundation of China,No.82405223Yunling Scholars Program,No.XDYC-YLXZ-2022-0027.
文摘Hepatocellular carcinoma(HCC)is a highly lethal malignancy with limited treatment options,particularly for patients with advanced stages of the disease.Sorafenib,the standard first-line therapy,faces significant challenges due to the development of drug resistance.Yu et al explored the mechanisms by which lncRNA KIF9-AS1 regulates the stemness and sorafenib resistance in HCC using a combination of cell culture,transfection,RNA immunoprecipitation,co-immunoprecipitation,and xenograft tumor models.They demonstrate that N6-methyladenosine-modified long non-coding RNA KIF9-AS1 acts as an oncogene in HCC.This modification involves methyltransferase-like 3 and insulin-like growth factor 2 mRNA-binding protein 1,which play critical roles in regulating KIF9-AS1.Furthermore,KIF9-AS1 stabilizes and upregulates short stature homeobox 2 by promoting its deubiquitination through ubiquitin-specific peptidase 1,thereby enhancing stemness and contributing to sorafenib resistance in HCC cells.These findings provide a theoretical basis for KIF9-AS1 as a diagnostic marker and therapeutic target for HCC,highlighting the need for further investigation into its clinical application potential.
文摘BACKGROUND A diagnosis of a chronic disease has been shown to predispose patients to the development of feeding and eating disorders(FEDs).AIM To screen children and adolescents with type 1 diabetes mellitus(T1DM)for FEDs and compare them to their counterparts with short stature.METHODS A total of 110 children and adolescents(55 with T1DM and 55 with short stature)were enrolled in the study.The SCOFF questionnaire was used to screen for possible FEDs,while anthropometric and dietary data were also collected.RESULTS Approximately 60%of the children with T1DM screened positive for FEDs compared to 30.9%of the children with short stature.Having a T1DM tripled the chances of screening positive for FEDs and halved the annual growth rate of children with T1DM.No differences were noted in the dietary intake between groups.CONCLUSION The results necessitate the education of pediatric endocrinologists and diabetologists on proper screening and identification of children at risk for developing FEDs.A prompt diagnosis might help children catch up growth and attain their genetically predisposed height.
文摘BACKGROUND Silver-Russell syndrome(SRS)is a clinically heterogeneous entity characterized by intrauterine and postnatal growth restriction,relative macrocephaly at birth,distinct facial features,and body asymmetry combined with other malformations.CASE SUMMARY Herein,we describe four individuals with SRS,focusing on their prenatal phenotype,postnatal presentation,diagnosis,and management.All cases had a typical phenotype,including postnatal growth failure,short stature(chronic malnutrition),and protruding forehead.Individually,they presented with feeding difficulties,leg length discrepancy,triangular face,or relative macrocephaly at birth,and each one exhibited distinct SRS features,including motor and/or speech delay,experiencing frequent hypoglycemic episodes.The fact that each patient exhibited a different combination of clinical findings underlines the heterogeneity of the syndrome.CONCLUSION SRS is diagnosed clinically.However,only 60%of cases are genetically confirmed,while most are sporadic.Although SRS is a well-described syndrome,a delayed diagnosis can have grave consequences on a child’s growth.Recombinant human growth hormone treatment is often initiated shortly after the diagnosis.The follow-up requires a multidisciplinary approach.
基金Supported by the National Natural Science Foundation of China,No.82103173 and No.82460461Medical Subject Leader of Yunnan Province(General Surgery),No.D-2024029+1 种基金Yunnan Fundamental Research Project for Excellent Young Scholars,No.202401AW070003the Young and Mid-aged Academic and Technical Leader Reserve Talent Program of Yunnan Province,No.202205AC160063。
文摘This letter comments on the recently published manuscript by Yu et al,in which the authors revealed a novel mechanism by which the m6A-modified long noncoding RNA kinesin family member 9-antisense RNA 1 promotes stemness and sorafenib resistance of hepatocellular carcinoma(HCC)through ubiquitinspecific peptidase 1-mediated deubiquitination of oncogene short stature homeobox 2.Given the high mortality rate and poor prognosis of HCC,the findings by Yu et al open a new avenue for overcoming HCC burden by focusing on kinesin family member 9-antisense RNA 1 and short stature homeobox 2 as prognostic markers and therapeutic targets.
文摘Objective:To investigate the clinical efficacy and safety evaluation of Polyethylene Glycol Recombinant Human Growth Hormone Injection(PEG-rhGH)in the treatment of idiopathic short stature.Methods:A total of 1402 patients were enrolled from March 21,2024 to January 13,2025,including 778 males and 624 females,with ages mainly ranging from 5 to 13 years old.Follow-up visits were completed by 488 patients for the first time,174 patients for the second time,and 81 patients for the third time.All patients were treated with PEG-rhGH(Jin Sai Zeng)as the main therapy after admission.The changes in height information,IGF-1,and thyroid examination results of each patient at the initial diagnosis,6,9,and 12 months after treatment were observed and analyzed.Results:There was no statistical difference between the baseline and the initial diagnosis,as well as the second follow-up visit(P<0.05),while there was a statistical difference between the baseline and the first and third follow-up visits(P>0.05).There was a statistically significant difference in IGF-1 between the initial diagnosis and the first follow-up visit(P<0.05),but no statistical difference between the first,second,and third follow-up visits(P>0.05).Additionally,IGF-1 levels increased with time.There was no statistical difference in TSH between the initial diagnosis and the first,second,and third follow-up visits(P>0.05).There was a statistical difference in free T3 between the initial diagnosis and the first and second follow-up visits(P<0.05),but no statistical difference between the second and third follow-up visits(P>0.05).There was no statistical difference in free T4 between the initial diagnosis and the first and second follow-up visits(P>0.05),but there was a statistical difference between the second and third follow-up visits(P<0.05).Conclusion:PEG-rhGH(Jin Sai Zeng)is significantly effective in improving height and IGF-1 levels in patients with idiopathic short stature.
基金supported by the National Natural Science Foundation of China(30972495,81001249)
文摘Objective Research evidence shows a secular trend in Chinese physical growth in recent years.The aim of this study was to analyze and assess changes in stature of children and adolescents during the 25 years from 1985‐2010,using national data.Methods Data came from successive cycles of the Chinese National Survey on Students＇ Constitution and Health（CNSSCH）.Subjects were 7‐ to 18‐year‐old children and adolescents.Results An overall positive secular trend occurred in urban China during 1985‐2010.The overall average rates of increment were 2.4 and 1.7 cm/decade for boys and girls,respectively.Total increases in adult stature for boys and girls were 2.6 and 1.7 cm,yielding rates of 1.0 and 0.7 cm/decade,respectively.Cities with different socioeconomic levels had different characteristic trends.Mean stature increases in big cities were larger than those in moderate and small cities,and boys and girls in moderate and small cities showed greater potential for growth in stature.Conclusion An overall positive secular growth trend was associated with socioeconomic progress and differed with area socioeconomic levels.School policies and strategies should be developed based on increased stature,and should continue narrowing the inequity between different socioeconomic populations.
基金supported by the National Natural Science Foundation of China(81001249,30972495)
文摘Objective To analyze and assess secular change in stature in rural children and adolescents in China from 1985 to 2010. Methods Data were obtained from the 6 rounds of the Chinese National Survey on Student＇s Constitution and Health. The subjects enrolled in the study were children and adolescents aged 7-18 years in rural areas of provincial capitals. Results An overall positive secular trend in stature occurred in rural areas of provincial capitals in China from 1985 to 2010. The overall average increase rates were 3.1 and 2.4 cm/decade for boys and girls, respectively. The total body height increases for grown up boys and girls were 3.6 and 2.3 cm and the increase rates were 1.4 and 0.9 cm/decade, respectively. There were differences in body height increase among eastern, central and western regions. The average body height of the children or adolescents in eastern region was highest, followed by central region and western region. The overall increase rates in central region were highest among the three regions. The difference between eastern/central region and western region was obvious. 〈br〉 Conclusion Positive secular trend in stature of children or adolescents has occurred in rural area of China, and rural boys and girls showed a great potential for continuous growth. More attention should be paid to the differences in children＇s body height between western region and eastern/central region.
基金Supported by Research project PRVOUK P37-08(from Charles University in Praha,Faculty of Medicine at Hradec Kralove,Czech Republic)
文摘To evaluate vital signs and body indices in Helicobacter pylori (H. pylori) positive and negative persons. A total of 22 centres entered the study. They were spread over the whole country, corresponding well to the geographical distribution of the Czech population. A total of 1818 subjects (aged 5-98 years) took part in the study, randomly selected out of 38147 subjects. H. pylori infection was investigated by means of a 13C-urea breath test. Data on height, weight, systolic and diastolic blood pressure and heart rate were collected at the clinics of general practitioners. The overall prevalence of H. pylori infection was 30.4% (402/1321) in adults (≥ 18 year-old) and 5.2% (26/497) in children and adolescents (≤ 17 year-old). Once adjusted for age and gender, only a difference in body mass index remained statistically significant with H. pylori positive adults showing an increase of 0.6 kg/m<sup>2</sup> in body mass index. Once adjusted for age and gender, we found a difference in height between H. pylori positive and H. pylori negative children and adolescents. On further adjustment for place of residence, this difference became statistically significant, with H. pylori positive children and adolescents being on average 3.5 cm shorter. H. pylori positive adults were significantly older compared to H. pylori negative subjects. Once adjusted for age and gender, H. pylori infection had no impact on body weight, body mass index and vital signs either in adults or children and adolescents. Chronic H. pylori infection appeared to be associated with short stature in children. H. pylori infection did not influence blood pressure, body weight and body mass index either in adults or children and adolescents.
基金funded in part by the Beijing Natural Science Foundation(JQ20032 to N.W.and to 7191007 to Z.W.)National Natural Science Foundation of China(81822030 and 82072391 to N.W.,81772299and 81930068 to Z.W.,81772301 and 81972132 to G.Q.,81672123and 81972037 to J.Z.)+7 种基金Capital's Funds for Health Improvement and Research(2020-4-40114 to N.W.)Tsinghua University-Peking Union Medical College Hospital Initiative Scientific Research ProgramNational Key Research and Development Program of China(2018YFC0910500 to N.W.and Z.W.,2016YFC0901501 to S.Z.)the PUMC Youth Fund and the Fundamental Research Funds for the Central Universities(3332019052 to Y.M.)the CAMS Initiative Fund for Medical Sciences(2016-I2M-3-003 to G.Q.and N.W.,2016-I2M-2-006 and 2017-I2M-2-001 to Z.W.)the Non-profit Central Research Institute Fund of Chinese Academy of Medical Sciences(2019PT320025 to N.W.)sponsored by GeneScience Pharmaceuticals Co.,Ltd.(Changchun,China)funded by the United States National Institutes of Health(UM1HG006542 and K08 HG008986)。
文摘Short stature is among the most common endocrinological disease phenotypes of childhood and may occur as an isolated finding or in conjunction with other clinical manifestations.Although the diagnostic utility of clinical genetic testing in short stature has been implicated,the genetic architecture and the utility of genomic studies such as exome sequencing(ES)in a sizable cohort of patients with short stature have not been investigated systematically.In this study,we recruited 561 individuals with short stature from two centers in China during a 4-year period.We performed ES for all patients and available parents.All patients were retrospectively divided into two groups:an isolated short stature group(group I,n=257)and an apparently syndromic short stature group(group II,n=304).Causal variants were identified in 135 of 561(24.1%)patients.In group I,29 of 257(11.3%)of the patients were solved by variants in 24 genes.In group II,106 of 304(34.9%)patients were solved by variants in 57 genes.Genes involved in fundamental cellularprocess played an important role in the genetic architecture of syndromic short stature.Distinct genetic architectures and pathophysiological processes underlie isolated and syndromic short stature.
文摘BACKGROUND Geleophysic dysplasia(GD)presents the characterized clinical manifestations of acromelic dysplasia,including extremely short stature,short limbs,small hands and feet,stubby fingers and toes,joint stiffness and others.It is clinically distinct from the other acromelic dysplasia in terms of symptoms such as cardiac valvular abnormalities,progressive hepatomegaly and tracheal stenosis.CASE SUMMARY We report on a Chinese 9-year-old girl with GD with the c.5243G>T(p.C1748F)mutation in FBN1(fibrillin 1,OMIM 134797).She was born in Guangxi Zhuang Autonomous Region of China.The patient presented with typical clinical features of GD and recurrent respiratory tract infections over 6 years.Laboratory studies and chest computed tomography(CT)scan indicated bronchopneumonia.Her echocardiography revealed mild mitral valve thickening with regurgitation.Laryngopharyngeal CT and electronic bronchoscopy revealed severe glottic stenosis.Echocardiography examination displayed mild mitral valve thickening and regurgitation.Ophthalmic examination did not reveal myopia or lens dislocation.Treated with ceftriaxone sodium and methylprednisolone sodium succinate for injection as well as methylprednisolone orally,patient’s symptoms had improved.CONCLUSION GD is a rare genetic condition that can cause life-threatening cardiovascular and respiratory problems.This study also found that the identified genotype of GD could be related to different clinical phenotypes.
文摘BACKGROUND Acromicric dysplasia(AD)is a rare skeletal dysplasia.Its incidence is<1/1000000,and only approximately 60 cases are reported worldwide.It is a disease characterized by severe short stature,short hands and feet,facial abnormalities,normal intelligence,and bone abnormalities.Unlike other skeletal dysplasia,AD has a mild clinical phenotype,mainly characterized by short stature.Extensive endocrine examination has not revealed a potential cause.The clinical effect of growth hormone therapy is still uncertain.CASE SUMMARY We report a clinical phenotype of AD associated with mutations in the fibrillin 1(FBN1)(OMIM 102370)gene c.5183C>T(p.Ala1728Val)in three people from a Chinese family.A 4-year-old member of the family first visited the hospital because of slow growth and short stature for 2 years,but no abnormalities were found after a series of laboratory tests,echocardiography,pituitary magnetic resonance imaging,and ophthalmological examination.Recombinant human growth hormone(rhGH)was used to treat the patient for>5 years.The efficacy of rhGH was apparent in the first year of treatment;the height increased from-3.64 standard deviation score(SDS)to-2.88 SDS,while the efficacy weakened from the second year.However,long-term follow-up is required to clarify the efficacy of rhGH.CONCLUSION FBN1-related AD has genetic heterogeneity and/or clinical variability,which brings challenges to the evaluation of clinical treatment.rhGH is effective for treatment of AD,but long-term follow-up is needed to clarify the effect.
基金Supported by European Laboratory for Food Induced Diseases, Federico Ⅱ University of Naples
文摘AIM: To estimate the burden of undiagnosed celiac disease (CD) in the Mediterranean area in terms of morbidity, mortality and health cost. METHODS: For statistics regarding the population of each country in the Mediterranean area, we accessed authoritative international sources (World Bank, World Health Organization and United Nations). The prevalence of CD was obtained for most countries from published reports. An overall prevalence rate of 1% cases/total population was finally estimated to represent the frequency of the disease in the area, since none of the available conf idence intervals of the reported rates significantly excluded this rate. The distribution of symptoms and complications was obtained from reliable reports in the same cohort. A standardized mortality rate of 1.8 was obtained from recent reports. Crude health cost was estimated for the years between symptoms and diagnosis for adults and children, and was standardized for purchasing power parity to account for the different economic prof iles amongst Mediterranean countries. RESULTS: In the next 10 years, the Mediterranean area will have about half a billion inhabitants, of which 120 million will be children. The projected number of CD diagnoses in 2020 is 5 million cases (1 million celiac children), with a relative increase of 11% compared to 2010. Based on the 2010 rate, there will be about 550 000 symptomatic adults and about 240 000 sick children: 85% of the symptomatic patients will suffer from gastrointestinal complaints, 40% are likely to have anemia, 30% will likely have osteopenia, 20% of children will have short stature, and 10% will have abnormal liver enzymes. The estimated standardized medical costs for symptomatic celiac patients during the delay between symptom onset and diagnosis (mean 6 years for adults, 2 years for children) will be about €4 billion (€387 million for children) over the next 10 years. A delay in diagnosis is expected to increase mortality: about 600 000 celiac patients will die in the next 10 years, with an excess of 44.4% vs age-and sexmatched controls. CONCLUSION: In the near future, the burden of CD will increase tremendously. Few Mediterranean countries are able to face this expanding epidemic alone.
文摘BACKGROUND The SEMA3A gene,which is located at 7q21.11,is involved in hypothalamic neuron migration,heart development,kidney development,and skeleton metabolism.Mutation of the SEMA3A gene is associated with Kallmann syndrome 16 with or without a normal sense of smell.In addition,two case reports showed that mutation of the SEMA3A gene could cause short stature,low gonadotropin,hypogonadism,thoracic deformity,a high scapula,rib and lower limb deformity,facial deformity(long face,epicanthic folds,backwards ears),and arterial malformation.CASE SUMMARY We reported the case of a 26-year-old Chinese man who was admitted because of short stature.Physical examination showed that he had many abnormal symptoms,including a short neck,facial moles,knee valgus,transverse palm,continuous grade 5/6 murmurs in the pulmonary auscultation area,no whiskers,or pubic hair,no Adam’s apple,short penis and cryptorchidism.Radiological examination showed pituitary,gonad,heart,kidney and skeletal dysplasia.The laboratory tests revealed low growth hormone,luteinizing hormone,folliclestimulating hormone,testosterone and estrogen.Clinical whole-exome detection showed that our patient,unlike previously reported patients,has a new SEMA3A gene mutation(c.950A>G).Now,his height has increased by 3 cm.In addition,he has a good appetite and reduced subcutaneous fat over 3 mo of recombinant human growth hormone injections therapy.Unfortunately,he refuses further treatment about gonad.CONCLUSION Patients who come to a hospital because of their short stature must undergo gene detection if they have other simultaneous abnormal phenotypes.
文摘BACKGROUND Mutations in the aggrecan(ACAN)gene are identified in patients with:spondyloepiphyseal dysplasia,Kimberley type;short stature with advanced bone age(BA);in the presence or absence of heterozygous ACAN mutation-induced early-onset osteoarthritis and/or osteochondritis dissecans;and spondyloepimetaphyseal dysplasia,ACAN type.Heterozygous mutations contribute to spondyloepiphyseal dysplasia,Kimberley type(MIM#608361),which is a milder skeletal dysplasia.In contrast,homozygous mutations cause a critical skeletal dysplasia,which is called spondyloepimetaphyseal dysplasia,ACAN type(MIM#612813).Lately,investigations on exome and genome sequencing have shown that ACAN mutations can also lead to idiopathic short stature with or without an advanced BA,in the presence or absence of early-onset osteoarthritis and/or osteochondritis dissecans(MIM#165800).We herein reported a heterozygous defect of ACAN in a family with autosomal dominant short stature,BA acceleration,and premature growth cessation.CASE SUMMARY A 2-year-old male patient visited us due to growth retardation.The patient presented symmetrical short stature(height 79 cm,<-2 SD)without facial features and other congenital abnormalities.Whole-exome sequencing revealed a heterozygous pathogenic variant c.871C>T(p.Gln291*)of ACAN,which was not yet reported in cases of short stature.This mutation was also detected in his father and paternal grandmother.According to the Human Gene Mutation Database,67 ACAN mutations are registered.Most of these mutations are genetically inheritable,and very few children with short stature are associated with ACAN mutations.To date,heterozygous ACAN mutations have been reported in approximately 40 families worldwide,including a few individuals with a decelerated BA.CONCLUSION Heterozygous c.871C>T(p.Gln291*)variation of the ACAN gene was the disease-causing variant in this family.Collectively,our newly discovered mutation expanded the spectrum of ACAN gene mutations.
文摘BACKGROUND The incidence of short stature in KBG syndrome is relatively high.Data on the therapeutic effects of growth hormone(GH)on children with KBG syndrome accompanied by short stature in the previous literature has not been summarized.CASE SUMMARY Here we studied a girl with KBG syndrome and collected the data of children with KBG syndrome accompanied by short stature from previous studies before and after GH therapy.The girl was referred to our department because of short stature.Physical examination revealed mild dysmorphic features.The peak GH responses to arginine and clonidine were 6.22 and 5.40 ng/mL,respectively.The level of insulin-like growth factor 1(IGF-1)was 42.0 ng/mL.Genetic analysis showed a c.2635 dupG(p.Glu879fs)mutation in the ANKRD11 gene.She received GH therapy.During the first year of GH therapy,her height increased by 0.92 standard deviation score(SDS).Her height increased from-1.95 SDS to-0.70 SDS after two years of GH therapy.There were ten children with KBG syndrome accompanied by short stature who received GH therapy in reported cases.Height SDS was improved in nine(9/10)of them.The mean height SDS in five children with KBG syndrome accompanied by short stature increased from-2.72±0.44 to-1.95±0.57 after the first year of GH therapy(P=0.001).There were no adverse reactions reported after GH treatment.CONCLUSION GH treatment is effective in our girl and most children with KBG syndrome accompanied by short stature during the first year of therapy.
基金Supported by Natural Science Foundation of China Grant(31671245)
文摘Objective To conduct stature estimation from seven facial measurements of 1901 Tujia adults(858 males,1043 females)in Southern China aged from 18 to 75 years.Methods The present study applied variable statistical method,such as multiplication factors,linear regression,multiple regression as well as multiple stepwise regression to explore the relationship between stature and cephalic-facial measurements and the reliability of the estimation method of stature in Tujia.Results All the facial measurements had significant coefficient with stature according to Pearson's analysis.Linear regression was the best method for stature estimation according to cephalic-facial measurements in Tujia among the four method.Overall,the range of the four method based on the reliability was linear regression,multiple regression,multiple stepwise regression and multiplication factors.Conclusion Cephalic-facial measurements can be used to establish stature estimation equation.Horizontal head circumference has the highest correlation in the present study so that the estimating equation based on horizontal head circumference is most accurate.
基金supported in part by grants from The Meir Medical Center Research Authority and Ferring Israel
文摘Purpose: To assess the growth hormone(GH) response to the Wingate anaerobic test(WAn T) among children with short stature and suspected GH deficiency. We hypothesized that the GH response to the WAn T would be similar to the GH response to a commonly used pharmacologic provocation test.Methods: Ten children(6 males and 4 females, age range 9.0–14.9 years) participated in the study. Each participant performed 2 tests: a standard all-out WAn T, cycling for 30 s against constant resistance, and a standardized pharmacologic test(clonidine or glucagon). Blood samples for GH were collected before and 10, 30, 45, and 60 min after the beginning of exercise. In addition, we collected pre-and post-exercise blood lactate levels.Results: There was a significant increase in GH levels after the WAn T, yet in 9 of 10 participants, this increase was below the threshold for GH sufficiency. Peak GH after the WAn T was significantly lower compared to the pharmacologic GH provocation tests(with 9 of 10 demonstrating GH-sufficient response).Conclusion: The traditional WAn T cannot be used as a GH provocation test. Further research is needed to develop anaerobic exercise protocols sufficient to promote GH secretion.
基金supported by the National Key Research and Development Program of China(2016YFD0100302)the Science and Technology Service Network Initiative of Chinese Academy of Sciences(KFJ-STS-ZDTP-024)。
文摘Reduced plant height is one of the most important traits related to lodging resistance and crop yield. The use of reduced height genes has been one of the main features in breeding modern high-yielding wheat varieties with less lodging. A spontaneous dwarf mutant DD399 was identified in a high yielding, gibberellic acid(GA)-insensitive, lodging-resistant variety Nongda 399(ND399). Significant differences in upper internode lengths between mutant DD399 and wild type ND399 were caused by reduced cell elongation. The plant height of ND399 × DD399 F_(1) hybrids was intermediate between the parents, indicating incomplete dominance or a dose–response effect of a reduced height gene. Plant height showed continuous distribution in the F_(2) population, and segregation distortion was observed among the 2292 F_(2:3) progenies. The reduced height mutation was characterized by Illumina 90 K iSelect SNP genotyping and bulked segregant RNA-Seq(BSR-Seq) analysis of the segregating population. A concentrated cluster of polymorphic SNPs associated with the reduced height phenotype was detected in the distal region of chromosome arm 2 BL. Co-segregation of reduced height phenotype with the clustered markers revealed a 36 Mb terminal deletion of chromosome 2 BL in mutant DD399.
基金Supported by the National Natural Science Foundation of China,No.82271628.
文摘BACKGROUND Hepatocellular carcinoma(HCC)is a prevalent and aggressive tumor.Sorafenib is the first-line treatment for patients with advanced HCC,but resistance to sorafenib has become a significant challenge in this therapy.Cancer stem cells play a crucial role in sorafenib resistance in HCC.Our previous study revealed that the long non-coding RNA(lncRNA)KIF9-AS1 is an oncogenic gene in HCC.However,the role of KIF9-AS1 in drug resistance and cancer stemness in HCC remains unclear.Herein,we aimed to investigate the function and mechanism of the lncRNA KIF9-AS1 in cancer stemness and drug resistance in HCC.AIM To describe the role of the lncRNA KIF9-AS1 in cancer stemness and drug resistance in HCC and elucidate the underlying mechanism.METHODS Tumor tissue and adjacent non-cancerous tissue samples were collected from HCC patients.Sphere formation was quantified via a tumor sphere assay.Cell viability,proliferation,and apoptosis were evaluated via Cell Counting Kit-8,flow cytometry,and colony formation assays,respectively.The interactions between the lncRNA KIF9-AS1 and its downstream targets were confirmed via RNA immunoprecipitation and coimmunoprecipitation.The tumorigenic role of KIF9-AS1 was validated in a mouse model.RESULTS Compared with that in normal controls,the expression of the lncRNA KIF9-AS1 was upregulated in HCC tissues.Knockdown of KIF9-AS1 inhibited stemness and attenuated sorafenib resistance in HCC cells.Mechanistically,N6-methyladenosine modification mediated by methyltransferase-like 3/insulin-like growth factor 2 mRNA-binding protein 1 stabilized and increased the expression of KIF9-AS1.Additionally,KIF9-AS1 increased the stability and expression of short stature homeobox 2 by promoting ubiquitin-specific peptidase 1-induced deubiquitination.Furthermore,depletion of KIF9-AS1 alleviated sorafenib resistance in a xenograft mouse model of HCC.CONCLUSION The N6-methyladenosine-modified lncRNA KIF9-AS1 promoted stemness and sorafenib resistance in HCC by upregulating short stature homeobox 2 expression.
