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A 36-year-old woman was admitted to the Peking Union Medical College Hospital with a history of fractures for 2 years, limb weakness for 1 year, and ostealgia for 2 months. The patient's examination identified iron deficiency anemia, significantly decreased serum calcium and 25-hydroxyvitamin D3 levels, and increased alkaline phosphatase and parathyroid hormone levels. Imaging showed several typical signs of osteomalacia. Considering the history of Roux-en-Y gastric bypass surgery, the diagnosis was considered to be osteomalacia caused by a postoperative nutritional absorption disorder. The patient was supplemented with calcitriol, calcium, and vitamin D and gradually returned to normal physical activity. The bone metabolism indicators and bone density were significantly improved.
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OBJECTIVE@#To detect the genetic variant of a child with cleidocranial dysplasia (CCD) and to find out the causation of the illness.@*METHODS@#Gene variant was identified by the second generation targeted sequencing and Sanger sequencing.@*RESULTS@#The gene sequencing revealed that the RUNX2 gene had c.196C>T(p.Glu66*) nonsense variant, which was predicted to be a pathogenic variant according to the ACMG guidelines(PVS1+PS2).@*CONCLUSION@#The variant of c.196C > T in the RUNX2 gene may be the cause of the child with CCD, and the novel variant enriches the RUNX2 gene variant spectrum.
Subject(s)
Child , Humans , Asian People/genetics , China , Cleidocranial Dysplasia/genetics , Core Binding Factor Alpha 1 Subunit/genetics , MutationABSTRACT
Objective:To analyze the clinical characteristics and molecular mechanisms of 5 cases of hypoparathyroidism caused by GATA3 gene mutation.Methods:A total of 5 childhood-onset hypoparathyroidism patients with GATA3 mutation were identified from 198 hypoparathyroidism (aged ≤18 years) from 1975 to 2021 in Peking Union Medical College Hospital. Clinical data and biochemical indices of the 5 patients were collected and analyzed retrospectively. Genetic screening was conducted by targeted next-generation sequencing (T-NGS), and bioinformatics analysis was performed to analyze the underline mechanisms.Results:The medium onset age of hypoparathyroidism of the 5 patients was 0.5 (0.1, 1.3) years old, and the time duration from onset to confirmed diagnosis of hypoparathyroidism and hypoparathyroidism- deafness-renal dysplasia syndrome was (7.0±5.2) years and (15.0±5.4) years, respectively. The clinical manifestations included carpopedal spasm accompanied by seizures (5 cases), basal ganglia calcification (5 cases), cataract (1 case), deafness (4 cases), and renal malformations or absence (2 cases). The blood calcium and blood parathormone(PTH) before treatment was (1.65±0.31) mmol/L and (4.64±2.63) ng/L, respectively. The 5 patients carried different heterozygous mutations in GATA3 gene, which caused nonsense mutations, frameshift mutations and splice site mutations, respectively. All the GATA3 gene mutations of the 5 patients are classified as pathogenic or likely pathogenic by the Clin Var database and American College of Medical Genetics and Genomics(ACMG).Conclusions:Attention should be paid to genetic diseases in patients with childhood-onset hypoparathyroidism. The possibility of hypoparathyroidism-deafness-renal dysplasia syndrome should be considered in hypoparathyroidism patients with hearing loss or renal dysplasia. GATA3 gene screening is highly recommended for the confirmation of the diagnosis.
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The majority of primary hyperparathyroidism (PHPT) are sporadic, and less than 10% of cases are hereditary or part of familial syndromes. Glial cell missing 2 (GCM2) was confirmed to be a new pathogenic gene of PHPT in 2016. At present, four GCM2 mutations have been confirmed to have certain correlations with familial or sporadic PHPT. The purpose of this review is to summarize the pathogenesis and clinical features of GCM2 mutation related primary hyperparathyroidism.
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Carney complex(CNC) is a rare disease in endocrinology, with osteochondromyxoma accounting for only 1% of it. This article details the diagnosis and treatment of a young female patient with recurrent fracture, full moon face and perioral spotted pigmentation. Combined with clinical manifestations, auxiliary examination and pathology, Carney complex with osteochondromyxoma was diagnosed. Multiple bone deformities in this case should be differentiated from McCune-Albright syndrome and ectopic ACTH secreting tumor with multiple bone metastases. The report of this case is helpful to improve the understanding of osteochondromyxoma in endocrinology, radiology, orthopedics and other disciplines, so as to avoid missed diagnosis and misdiagnosis.
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We report on two cases of type C insulin resistance syndrome(TCIRS) admitted to the Department of Endocrinology, Peking Union Medical College Hospital from January 2000 to December 2020. Both patients presented with persistent hyperglycemia, low immunoreactive insulin, extreme insulin resistance, high insulin autoantibodies, high total insulin, and large insulin antibody pool. TCIRS is marked by extreme insulin resistance with ketoacidosis and respond to medium to high doses glucocorticoids rather than plasmapheresis.
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Objective To analyze characteristics of muscle activity and changes of corresponding kinematic parameters of the lower limbs for the elderly carrying heavy objects under synchronous stop modes, and explore the effects of hand weight-bearing and stop modes on gait stability and body balance of the elderly. Methods The ankle, knee, hip joint angles and surface electromyography (EMG) signals of bilateral lower limbs were collected under the condition of emergency stop and planned stop by loading 0 kg, 2.5 kg on both hands and 5 kg on right hand. Results Under different weight-bearing modes, the ankle and hip angles of bilateral lower limbs were significantly different (P<0.05), while the knee angles did not change significantly, and different stop modes significantly affected the angle changes in each joint (P <0.001); the average EMG of tibia anterior muscle, lateral femoral muscle, and biceps femoris in braking leg showed higher muscle activity during emergency stop. Conclusions In order to cope with the instability caused by weight-bearing and emergency stop, the elderly will have a corresponding balance mechanism in the lower limbs. During an emergency stop, braking the tibialis anterior muscle of the leg requires a higher muscle activity level to control flexion angle of the ankle joint, thereby reducing amplitude of the ankle joint fluctuation. The single-handed load increases the muscle performance differences between the braking leg and trailing leg, resulting in the lateral instability.
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Objectives@#To compare the effect of eldecalcitol and alfacalcidol on skeletal microstructure by highresolution peripheral QCT (HR-pQCT). @*Methods@#This was a substudy of a randomized, double-blind, active comparator trial. Five female osteoporotic patients with 1-year 0.75 mg/day eldecalcitol and 5 with 1-year 1.0 mg/day alfacalcidol completed HR-pQCT scans before and after treatment were enrolled. @*Results@#Total vBMD [1.67 ± 1.06% (mean ± SD), P ¼ 0.043 versus baseline] and trabecular vBMD (2.91 ± 1.72%, P ¼ 0.043) at the radius increased in eldecalcitol group, while total, trabecular, and cortical vBMD tended to decrease in alfacalcidol group, with a significant reduction in cortical vBMD at the tibia (0.88 ± 0.62%, P ¼ 0.043). Cortical area (1.82 ± 1.92%, P ¼ 0.043) at the radius and thickness (0.87 ± 1.12%, P ¼ 0.043) at the tibia increased in eldecalcitol group, while these parameters decreased with alfacalcidol at the tibia (1.77 ± 1.72%, P ¼ 0.043 for cortical area; 1.40 ± 2.14%, P ¼ 0.042 for cortical thickness). Trabecular thickness at the radius (1.97 ± 1.93%, P ¼ 0.042) and number at the tibia (3.09 ± 3.04%, P ¼ 0.043) increased by eldecalcitol but did not increase by alfacalcidol. Trabecular separation decreased by eldecalcitol (2.22 ± 2.43%, P ¼ 0.043) but tended to increase by alfacalcidol at the tibia. @*Conclusions@#Eldecalcitol has the greater potential to improve cortical and trabecular microstructure at the peripheral bone than alfacalcidol which needs further more studies.
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Pancreatic neuroendocrine neoplasms (pNENs) are highly heterogeneous, and the management of pNENs patients can be intractable. To address this challenge, an expert committee was established on behalf of the Chinese Pancreatic Surgery Association, Chinese Society of Surgery, Chinese Medical Association, which consisted of surgical oncologists, gastroenterologists, medical oncologists, endocrinologists, radiologists, pathologists, and nuclear medicine specialists. By reviewing the important issues regarding the diagnosis and treatment of pNENs, the committee concluded evidence-based statements and recommendations in this article, in order to further improve the management of pNENs patients in China.
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Huang-Qin Decoction (HQD) is a classic prescription for diarrhea in Chinese medicine treatment. Recent studies have demonstrated that HQD and its modified formulation PHY906 could ameliorate irinotecan (CPT-11) induced gastrointestinal (GI) toxicity and enhance its anticancer therapeutic efficacy. Nevertheless, which constituents in HQD are effective is still unclear so far. The study aims to screen out the key bioactive components combination from HQD that could enhance the anticancer effect of CPT-11. First, the potential bioactive constituents were obtained through system pharmacology strategy. Then the bioactivity of each constituent was investigated synthetically from the aspects of NCM460 cell migration, TNF-α release of THP-1-derived macrophage and MTT assay in HCT116 cell. The contribution of each constituent in HQD was evaluated using the bioactive index E
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Objectives@#To compare the effect of eldecalcitol and alfacalcidol on skeletal microstructure by highresolution peripheral QCT (HR-pQCT). @*Methods@#This was a substudy of a randomized, double-blind, active comparator trial. Five female osteoporotic patients with 1-year 0.75 mg/day eldecalcitol and 5 with 1-year 1.0 mg/day alfacalcidol completed HR-pQCT scans before and after treatment were enrolled. @*Results@#Total vBMD [1.67 ± 1.06% (mean ± SD), P ¼ 0.043 versus baseline] and trabecular vBMD (2.91 ± 1.72%, P ¼ 0.043) at the radius increased in eldecalcitol group, while total, trabecular, and cortical vBMD tended to decrease in alfacalcidol group, with a significant reduction in cortical vBMD at the tibia (0.88 ± 0.62%, P ¼ 0.043). Cortical area (1.82 ± 1.92%, P ¼ 0.043) at the radius and thickness (0.87 ± 1.12%, P ¼ 0.043) at the tibia increased in eldecalcitol group, while these parameters decreased with alfacalcidol at the tibia (1.77 ± 1.72%, P ¼ 0.043 for cortical area; 1.40 ± 2.14%, P ¼ 0.042 for cortical thickness). Trabecular thickness at the radius (1.97 ± 1.93%, P ¼ 0.042) and number at the tibia (3.09 ± 3.04%, P ¼ 0.043) increased by eldecalcitol but did not increase by alfacalcidol. Trabecular separation decreased by eldecalcitol (2.22 ± 2.43%, P ¼ 0.043) but tended to increase by alfacalcidol at the tibia. @*Conclusions@#Eldecalcitol has the greater potential to improve cortical and trabecular microstructure at the peripheral bone than alfacalcidol which needs further more studies.
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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.
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Objective:To explore the characteristics of surface electromyography (sEMG) of flat foot in lower extremity muscles when walking flat and stairs. Methods:From March to June, 2019, 20 male subjects (10 with normal feet, 10 with flat feet) were recruited to use sEMG system of Noraxon to collect the average amplitude and integral electromyography of sEMG of tibialis anterio (TA), medialis gastrocnemius (MG), lateralis gastrocnemius (LG), rectus femoris (RF) and biceps femoris (BF) during the flat ground walking and the stair walking. Results:As ascending stairs, the average amplitudes of TA, RF and BF of flat feet were higher than that of normal feet (|t| > 2.461, P < 0.05); as descending stairs, the average amplitude of MG of flat feet was higher (t = -1.976, P < 0.05), and the average amplitude of BF of flat feet was lower than that of normal feet (t = 2.298, P < 0.05). Compared with ground walking, the average amplitudes of TA, RF and BF of flat feet increased when ascending stairs (|t| > 2.257, P < 0.05), and the average amplitudes of RF and BF increased when descending stairs (|t| > 2.630, P < 0.05). As ascending stairs, the integral electromyography of TA, MG, LG, RF and BF of flat feet was higher than that of normal feet (|t| > 2.492, P < 0.01); as descending stairs, the integral electromyography of MG of flat feet was higher (t = -5.271, P < 0.05), and the integral electromyography of BF was lower (t = 2.685, P < 0.05) than that of normal feet. Compared with ground walking, the integral electromyography of TA, MG, LG and BF increased when ascending stairs (|t| > 2.088, P < 0.05), and the integral electromyography of TA, LG and RF decreased when descending stairs (t > 2.059, P < 0.05). Conclusion:The lower extremities muscles of flat foot compensate for the excessive rotation of the joint when walking stairs.
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Objective:To provide more options for preoperative localization diagnosis in patients with primary hyperparathyroidism (PHPT), the diagnostic efficacy of parathyroid 4-dimensional computed tomography (4D-CT) in patients with PHPT was evaluated.Methods:This was a single-center retrospective study including 57 patients with surgical proved PHPT. All of the patients underwent 4D-CT, 99Tc m -sestamibi parathyroid imaging (MIBI), and ultrasonography (US) preoperatively. The reference standard for correct localization was based on operation reports and pathology confirmation. The patients were grouped according to the preoperative serum calcium levels, tumor diameter, or ectopic lesions (yes/no), respectively. The sensitivity, specificity, positive predictive value, negative predictive value and area under the curve (AUC) of 4D-CT, MIBI and US, alone or in combination, were analyzed in total and each subgroup patients. Results:Fifty-seven patients (39 women, 18 men; mean age of 56.5 years) were evaluated, including four cases with multi-gland disease and thirteen cases with ectopic parathyroid lesions. In all the patients, similar diagnostic efficacy was found in 4D-CT (AUC: 0.943) and MIBI (AUC: 0.927), both of which were higher than that of US (AUC: 0.847) ( P = 0.01 for 4D-CT vs. US; P = 0.04 for MIBI vs. US). In a subset analysis for ectopic quadrants, the diagnostic efficacy of 4D-CT was significantly higher than that of MIBI ( P = 0.04) or US ( P = 0.01), with the sensitivity of 100%, 69.2%, and 61.5%, and AUC of 0.989, 0.846, and 0.808 for 4D-CT, MIBI and US, respectively. Conclusions:4D-CT has similar diagnostic efficacy for preoperative localization to MIBI in patients with PHPT, and it is superior to MIBI and US in identifying the ectopic parathyroid gland. 4D-CT can be recommended as an alternative preoperative localization method, especially when parathyroid lesions could not be precisely located by US and MIBI.
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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.
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BACKGROUND@#Osteogenesis imperfecta (OI), a heritable bone fragility disorder, is mainly caused by mutations in COL1A1 gene encoding α1 chain of type I collagen. This study aimed to investigate the COL1A1 mutation spectrum and quantitatively assess the genotype-phenotype relationship in a large cohort of Chinese patients with OI.@*METHODS@#A total of 161 patients who were diagnosed as OI in Department of Endocrinology of Peking Union Medical College Hospital from January 2010 to December 2017 were included in the study. The COL1A1 mutation spectrum was identified by next generation sequencing and confirmed by Sanger sequencing. A new clinical scoring system was developed to quantitatively assess the clinical severity of OI and the genotype-phenotype relationship was analyzed. The independent sample t-test, analysis of variance, Mann-Whitney U-test, Chi-squared test, Pearson correlation, and multiple linear regression were applied for statistical analyses.@*RESULTS@#Among 161 patients with OI, 32.9% missense mutations, 16.8% non-sense mutations, 24.2% splice-site mutations, 24.8% frameshift mutations, and 1.2% whole-gene deletions were identified, of which 38 variations were novel. These mutations led to 53 patients carrying qualitative defects and 67 patients carrying quantitative defects in type I collagen. Compared to patients with quantitative mutations, patients with qualitative mutations had lower alkaline phosphatase level (296 [132, 346] U/L vs. 218 [136, 284] U/L, P = 0.009) and higher clinical score (12.2 ± 5.3 vs. 7.4 ± 2.4, P < 0.001), denoting more severe phenotypes including shorter stature, lower bone mineral density, higher fracture frequency, more bone deformity, vertebral compressive fractures, limited movement, and dentinogenesis imperfecta (DI). Patients would not present with DI if the glycine substitutions happened before the 79th amino acid in triple helix of α1 chains.@*CONCLUSIONS@#This presented distinctive COL1A1 mutation spectrum in a large cohort of Chinese patients with OI. This new quantitative analysis of genotype-phenotype correlation would be helpful to predict the prognosis of OI and genetic counseling.
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Adolescent , Adult , Child , Child, Preschool , Female , Humans , Infant , Infant, Newborn , Male , Middle Aged , Young Adult , Collagen Type I , Genetics , Genetic Association Studies , High-Throughput Nucleotide Sequencing , Mutation , Genetics , Osteogenesis Imperfecta , Genetics , PathologyABSTRACT
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.
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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.
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@#AIM:To study the ocular surface and corneal lesions under different degrees of retinopathy in patients with type 2 diabetes mellitus(T2DM). <p>METHODS: A total of 123 patients(246 eyes)with T2DM were enrolled in this study. All of patients were divided into non-diabetic retinopathy group(46 patients 92 eyes), non-proliferative diabetic retinopathy group(50 patients 100 eyes)and proliferative diabetic retinopathy group(27 patients 54 eyes)according to the type of retinopathy. Dry eye questionnaire, ocular surface disease index(OSDI), Schirmer Ⅰ text(SⅠt), tear break-up time(BUT), fluorescein staining of cornea(FL), corneal endoscopy and central corneal thickness measurement were used to analyze the differences of three groups.<p>RESULTS: There was no statistically significant difference in general data between the three groups. Significant differences existed in eye pain, dry eyes, lacrimation, eye fatigue, burning sensation, vision fluctuations in three groups(<i>P</i><0.05). Foreign body sensation, itchy eyes, red eyes showed no significant difference in groups(<i>P</i>>0.05). There were significant differences in ODSI value, FL positive rate, BUT, SIt, corneal endothelial cell density and central corneal thickness in three groups(<i>P</i><0.05). variable coefficient of corneal endothelial cell showed no Significant difference in groups(<i>P</i>>0.05).<p>CONCLUSION: The findings of this study show that patients with type 2 diabetes mellitus presented obviously discomfort symptoms of ocular surface, decreased tear film stability, increased positive rate of corneal fluorescein staining; decreased density of corneal endothelial cells; increased central corneal thickness in diabetic patients, all of which were associated with degree of retinopathy.
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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.