ABSTRACT
Objective@#To investigate the association of GNA11 gene polymorphisms with the risk of adult-onset non-surgical hypoparathyroidism (Ns-HypoPT).@*Methods@#Genotyping of GNA11 single nucleotide polymorphisms (SNPs) (rs28685098, rs4806907, rs11084997 and rs78003011) was carried out in 203 patients and 209 healthy participants by sequenom MassArray iPLEX System. These SNPs are located in promoter and 3′untranslated region (3′UTR) of GNA11 gene, respectively.@*Results@#Allele and genotype frequencies of rs11084997 in patients were significantly different from those of controls (genotype GG:60.5% vs. 49.8%, GC: 35.5% vs. 41.6%, CC: 4.0% vs. 8.6%, P=0.038; G allele 78.3% vs. 70.6%, C allele 21.7% vs. 29.4%, P=0.012), and the C allele of rs11084997 carriers had a lower risk to develops Ns-HypoPT in additive and dominant genetic models [OR=0.382 (0.160-0.915), 0.647 (0.437-0.957)]. CC-Haplotype formed by the minor alleles of rs4806907 and rs11084997 was associated with a decreased risk of Ns-HypoPT in additive, dominant and recessive genetic model [OR=0.317 (0.126-0.801), 0.640 (0.430-0.952), 0.367 (0.148-0.912)].@*Conclusion@#The minor allele C of rs11084997 in GNA11 gene promoter was associated with decreased risk of Ns-HypoPT in Chinese population.
ABSTRACT
The anterior pituitary gland drives highly conserved physiologic processes in mammalian species. These hormonally controlled processes are central to somatic growth, pubertal transformation, fertility, lactation, and metabolism. Current cellular models of mammalian anteiror pituitary, largely built on candidate gene based immuno-histochemical and mRNA analyses, suggest that each of the seven hormones synthesized by the pituitary is produced by a specific and exclusive cell lineage. However, emerging evidence suggests more complex relationship between hormone specificity and cell plasticity. Here we have applied massively parallel single-cell RNA sequencing (scRNA-seq), in conjunction with complementary imaging-based single-cell analyses of mRNAs and proteins, to systematically map both cell-type diversity and functional state heterogeneity in adult male and female mouse pituitaries at single-cell resolution and in the context of major physiologic demands. These quantitative single-cell analyses reveal sex-specific cell-type composition under normal pituitary homeostasis, identify an array of cells associated with complex complements of hormone-enrichment, and undercover non-hormone producing interstitial and supporting cell-types. Interestingly, we also identified a Pou1f1-expressing cell population that is characterized by a unique multi-hormone gene expression profile. In response to two well-defined physiologic stresses, dynamic shifts in cellular diversity and transcriptome profiles were observed for major hormone producing and the putative multi-hormone cells. These studies reveal unanticipated cellular complexity and plasticity in adult pituitary, and provide a rich resource for further validating and expanding our molecular understanding of pituitary gene expression programs and hormone production.
ABSTRACT
The anterior pituitary gland drives highly conserved physiologic processes in mammalian species. These hormonally controlled processes are central to somatic growth, pubertal transformation, fertility, lactation, and metabolism. Current cellular models of mammalian anteiror pituitary, largely built on candidate gene based immuno-histochemical and mRNA analyses, suggest that each of the seven hormones synthesized by the pituitary is produced by a specific and exclusive cell lineage. However, emerging evidence suggests more complex relationship between hormone specificity and cell plasticity. Here we have applied massively parallel single-cell RNA sequencing (scRNA-seq), in conjunction with complementary imaging-based single-cell analyses of mRNAs and proteins, to systematically map both cell-type diversity and functional state heterogeneity in adult male and female mouse pituitaries at single-cell resolution and in the context of major physiologic demands. These quantitative single-cell analyses reveal sex-specific cell-type composition under normal pituitary homeostasis, identify an array of cells associated with complex complements of hormone-enrichment, and undercover non-hormone producing interstitial and supporting cell-types. Interestingly, we also identified a Pou1f1-expressing cell population that is characterized by a unique multi-hormone gene expression profile. In response to two well-defined physiologic stresses, dynamic shifts in cellular diversity and transcriptome profiles were observed for major hormone producing and the putative multi-hormone cells. These studies reveal unanticipated cellular complexity and plasticity in adult pituitary, and provide a rich resource for further validating and expanding our molecular understanding of pituitary gene expression programs and hormone production.
ABSTRACT
Objective:To investigate the association of GNA11 gene polymorphisms with the risk of adult-onset non-surgical hypoparathyroidism (Ns-HypoPT).Methods:Genotyping of GNA11 single nucleotide polymorphisms (SNPs) (rs28685098, rs4806907, rs11084997 and rs78003011) was carried out in 203 patients and 209 healthy participants by sequenom MassArray iPLEX System. These SNPs are located in promoter and 3′untranslated region (3′UTR) of GNA11 gene, respectively.Results:Allele and genotype frequencies of rs11084997 in patients were significantly different from those of controls (genotype GG:60.5% vs. 49.8%, GC: 35.5% vs. 41.6%, CC: 4.0% vs. 8.6%, P=0.038; G allele 78.3% vs. 70.6%, C allele 21.7% vs. 29.4%, P=0.012), and the C allele of rs11084997 carriers had a lower risk to develops Ns-HypoPT in additive and dominant genetic models [ OR=0.382 (0.160-0.915), 0.647 (0.437-0.957)]. CC-Haplotype formed by the minor alleles of rs4806907 and rs11084997 was associated with a decreased risk of Ns-HypoPT in additive, dominant and recessive genetic model [ OR=0.317 (0.126-0.801), 0.640 (0.430-0.952), 0.367 (0.148-0.912)]. Conclusion:The minor allele C of rs11084997 in GNA11 gene promoter was associated with decreased risk of Ns-HypoPT in Chinese population.
ABSTRACT
Objective@#To investigate the effectiveness and safety of high-dose native vitamin D versus active vitamin D by retrospective analysis of clinical data in patients with non-surgical hypoparathyroidism (ns-HP) in our hospital.@*Methods@#ns-HP patients with stable therapeutic schedule in recent three years were included. According to the vitamin D agents used, patients were divided into three groups: active vitamin D group, native vitamin D group, and mixed vitamin D group. The effectiveness was evaluated by analysis of markers including post-treatment serum calcium, incidence of hypocalcemia, hypocalcemic symptoms and signs. The safety was evaluated in various groups by analyzing incidences of hypercalcemia and hypercalciuria, glomerular filtration rate, percentage of thiazide diuretic use, nephrocalcinosis or renal stone.@*Results@#Patients in active vitamin D group were more likely to experience episodes of hypocalcemia compared with those in native group (32.94%±21.46% vs 24.86%±10.1%, P<0.05). No significant differences in other indexes for assessing effectiveness and safety were found among three groups (P>0.05).@*Conclusions@#Under the circumstance of regular follow-up, both high-dose native vitamin D and active vitamin D could treat ns-HP effectively and safely. Native vitamin D may be better in maintaining eucalcemia and reducing incidence of hypocalcemia compared with active vitamin D.
ABSTRACT
Objective To investigate the effectiveness and safety of high-dose native vitamin D versus active vitamin D by retrospective analysis of clinical data in patients with non-surgical hypoparathyroidism ( ns-HP) in our hospital. Methods ns-HP patients with stable therapeutic schedule in recent three years were included. According to the vitamin D agents used, patients were divided into three groups: active vitamin D group, native vitamin D group, and mixed vitamin D group. The effectiveness was evaluated by analysis of markers including post-treatment serum calcium, incidence of hypocalcemia, hypocalcemic symptoms and signs. The safety was evaluated in various groups by analyzing incidences of hypercalcemia and hypercalciuria, glomerular filtration rate, percentage of thiazide diuretic use, nephrocalcinosis or renal stone. Results Patients in active vitamin D group were more likely to experience episodes of hypocalcemia compared with those in native group (32.94% ± 21.46% vs 24.86% ± 10.1%, P＜0.05). No significant differences in other indexes for assessing effectiveness and safety were found among three groups ( P＞0.05). Conclusions Under the circumstance of regular follow-up, both high-dose native vitamin D and active vitamin D could treat ns-HP effectively and safely. Native vitamin D may be better in maintaining eucalcemia and reducing incidence of hypocalcemia compared with active vitamin D.
ABSTRACT
Objective To explore the quality of life ( QoL ) and muscle strength in patients with pseudohypoparathyroidism ( PHP ) under regular treatment. Methods Twenty-three patients with PHP regularly followed at Peking Union Medical College Hospital from June 2017 to June 2018 were included. Age- and gender-matched 23 patients with nonsurgical hypoparathyroidism ( nHPT) and 23 healthy controls were also included. Short Form 36 Health Survey questionnaire version 2 ( SF36v2) were used to evaluate the QoL. Grip strength and repeated chair stand ( RCS) were used to assess muscle strength for upper and lower limbs respectively. Results Except for physical functioning, patients of PHP group had reduced scores in all other subdomains of SF36v2 compared to healthy controls ( P<0.05) . Comparing to nHPT patients, PHP patients had a higher score in social functioning, while no difference was found in other subdomains of SF36v2. Grip strength and RCS tests were similar in PHP patients and healthy controls. Conclusions Comparing to healthy controls, patients with PHP still had impaired QoL despite regular management, no significant difference of upper and lower limb muscle strength was found between PHP group and healthy controls.
ABSTRACT
Objective: To explore the relationship between thyroid hormone levels and prolonged recovery after cardiac surgery with cardiopulmonary bypass (CPB) in congenital heart disease (CHD) children younger than 1 year of age. Methods: A total of 186 CHD children younger than 1 year treated in our hospital from 2014-01 to 2015-01 were retrospectively summarized. According to the pediatric intensive care unit (PICU) stay time, the patients were divided into 2 groups: Prolonged recovery group, the patients stated in PICU≥5 days,n=39 and Non-prolonged recovery group, the patients stayed in PICU0.05. Multivariable logistical regression analysis presented that low level of FT3 within 24 hours of operation was the independent risk factor for prolonged recovery (OR= 0.32, 95% CI 0.12-0.84,P=0.02); linear regression analysis indicated that post-operative reduction of thyroid hormone was related to low body weight of the patients (r=0.11,P<0.001). Conclusion: Lower body weight was usually having lower level of FT3 within 24 hours of operation, which was the independent predictor for prolonged recovery in CHD children younger than 1 year after cardiac surgery.