Hyperthyroidism and severe bradycardia: Report of three cases and review of the literature.

BACKGROUND: Hyperthyroidism often leads to tachycardia, but there are also sporadic reports of hyperthyroidism with severe bradycardia, such as sick sinus syndrome (SSS) and atrioventricular block. These disorders are a challenge for clinicians. CASE SUMMARY: We describe three cases of hyperthyroidism with SSS and found 31 similar cases in a PubMed literature search. Through the analysis of these 34 cases, we found 21 cases of atrioventricular block and 13 cases of SSS, with 67.6% of the patients experiencing bradycardia symptoms. After drug treatment, temporary pacemaker implantation, or anti-hyperthyroidism treatment, the bradycardia of 27 patients (79.4%) was relieved, and the median recovery time was 5.5 (2-8) d. Only 7 cases (20.6%) needed permanent pacemaker implantation. CONCLUSION: Patients with hyperthyroidism should be aware of the risk of severe bradycardia. In most cases, drug treatment or temporary pacemaker placement is recommended for initial treatment. If the bradycardia does not improve after 1 wk, a permanent pacemaker should be implanted.

Research hotspots and development trends of microRNA in ischemia-reperfusion: network analysis of academic journals oriented by bibliometric and visualization.

Background: Ischemia-reperfusion (IR) injury can occur in the heart, brain, liver, lung, kidney, and other important organs, and may greatly increase disease mortality. MicroRNAs (miRNAs) have a variety of functions, including regulating cell differentiation, proliferation, and apoptosis. In the past 10 years, many studies on miRNAs in IR have been conducted. This study involved a visual analysis of these studies, and a discussion of research hotspots, trends, and frontiers of this topic. Methods: A total of 1,518 articles published between 2012 and 2022 on the topic of miRNA and IR and listed in the Web of Science database were analyzed visually using CiteSpace. Cooperative networks, literature citations, and keyword co-occurrence were analyzed. Results: Of the 1,518 articles, most were published after 2018, and a rapid growth in numbers of publications was seen after 2019. Articles from China numbered the highest, followed by the United States and Canada. It has been found that many miRNAs are involved in the occurrence of IR, with various regulatory mechanisms and signaling pathways. The literature clustering generated by literature co-citation analysis and the keyword co-occurrence network showed that the previous miRNA research on IR had mainly focused on the following topics: myocardial infarction, ischemic stroke, acute kidney injury, oxidative stress, and inflammatory response. More attention has been paid to long noncoding RNA (lncRNA) and exosomes, with much exploration having been conducted in these areas. Conclusions: Although miRNA is involved in the occurrence and development of IR, as a clinical intervention target for IR, further research is still needed.

[Relationship between polymorphism of parathyroid hormone and bone mineral density and relevant biochemical indicators in women].

OBJECTIVE: To investigate the distribution of parathyroid hormone (PTH) gene polymorphisms and the relationships of PTH gene polymorphisms with bone mass and serum bone relative biochemical markers. METHODS: Blood samples of 314 normal female volunteers, aged 20 - 80, were collected. Serum PTH, bone alkaline phosphatase (sBAP), cross-linked N-telopeptide of collagen type I (sNTX), cross-linked C-telopeptide of collagen type I (sCTX), osteoprotegerin (OPG) and leptin were determined by ELISA. Polymorphisms of PTH gene were detected by polymerase chain reaction fragment length polymorphisms (PCR-RFLP) of restriction enzyme BstBI. BMD (QDR4500A) of the anteroposterior spine (AP), supine lateral spine (Lat), and femoral neck (FN) were measured. RESULTS: (1) The genotype frequency of BB, Bb, and bb were 75.8%, 23.3% and 0.9% respectively in normal females volunteers. The frequencies of RFLP alleles B and b were 87.5% and 12.5% respectively. There was no difference in the polymorphism frequency of PTH gene between the post- and pre menopausal women. (2) There were no significant differences in the BMD of the AP, Lat, and FN and the serum biochemical markers between the BB and Bb genotypes. (3) Multiple stepwise regression analysis showed that PTH did not influence the BMD values. CONCLUSION: PTH gene polymorphism has no relationship with bone mass and serum bone biochemical markers in normal females.

Age-related changes of serum bone alkaline phosphatase and cross-linked C-telopeptides of type I collagen and the relationship with bone mineral density in Chinese women.

BACKGROUND: Previous studies have shown that bone turnover rate changes with age. At the same time, there is no definitive research regarding age-related changes of bone turnover level and its association with bone mineral density (BMD) in Chinese mainland women. METHODS: In a cohort of 663 Chinese mainland women aged 20-70 years, serum bone alkaline phosphatase (BAP) and serum cross-linked C-telopeptides of type I collagen (sCTX) were measured to evaluate the state of bone formation and resorption, respectively. BMD was measured in the posteroanterior spine, supine lateral spine, hip and forearm using a dual-energy X-ray absorptiometry. RESULTS: The cubic polynomial regression model best fit age-related changes in serum BAP (R2=0.398, p<0.001) and sCTX concentrations (R2=0.148, p<0.001) with largest R2 from comparison 8 different regression models. Their values reached a minimal level in the 30-39 years age group, and increased dramatically in the 40-59 years groups. There was a decreasing trend of BAP in women >60 years. The levels of BAP and sCTX were inversely correlated to BMD in various skeletal regions over the entire population (r=-0.096 to -0.357, p<0.05). sCTX was a significant predictor of a T-score< or =-2.5 of BMD in postmenopausal women with sCTX levels above mean+2 SD of women aged 30-39 years compared with other postmenopausal women, which indicated by odds ratios 1.9-3.7 (p<0.05) for various skeletal regions, especially for the lateral lumbar spine (2.2, p<0.01), Ward's triangle (3.7, p<0.01), and ultradistal end of radius + ulna (2.8, p<0.001). CONCLUSIONS: Age-dependent serum BAP and sCTX were inversely correlated to BMD, and sCTX was a useful parameter for the prediction of a low T-score of BMD at skeletal sites with abundant cancellous bone in postmenopausal women.

Comparison of spine and femur reference data in native Chinese women from different regions of China.

The aim of this study is to explore the differences of BMD reference curves at various skeletal sites among Chinese women from different regions of China and to investigate the feasibility of establishing a unified national BMD reference database for Chinese women. We measured BMD at the posteroanterior (PA) lumbar spine, femoral neck, trochanter and Ward's triangle by dual-energy X-ray absorptiometry bone densitometer in 3,422 Changsha women of South Central China, aged 20-84 years. The documented BMDs of reference populations of women in all other areas included Shanghai ( n =2,111) and Nanjing ( n =3,174) in the East, Shenyang ( n =1,213) in the Northeast, Kunming ( n =523) in the Southwest, Chongqing ( n =811) in the Midwest and Xian ( n =1,320) in the Northwest. We adopted the cubic regression as the fitting model for reference curves of BMD that varied with age, conducted conversions of BMD measured by various bone densitometers from different manufacturers and compared the differences between standardized BMD (sBMD) reference curves and combined ones for women from different areas. Our results revealed that by comparing variances in women from different areas, the average variances of non-standard BMD were 0.8-30.8% at the PA spine, 0.7-24.5% at the femoral neck, 0.6-29.9% at the trochanter and 1.1-54.7% at Ward's triangle, while average variances of sBMD either significantly decreased or disappeared (0.8-3.9% at the PA spine, 0.7-8.6% at the femoral neck, 0.6-8.3% at the trochanter and 1.1-29.9% at Ward's triangle). The sBMD reference curves were highly positive-dependent with combined ones ( r =0.913-0.999, P =0.000). At the PA spine and trochanter, the effect of combined sBMD curves presented well in women from different areas, except for those from Shanghai at the PA spine and Shenyang at the trochanter, indicating that sBMD curves were significantly different from pooled ones; at the femoral neck and Ward's triangle, the effect of combined sBMD reference curves was poor, indicating that sBMD curves demonstrated significant differences from pooled ones in women from a majority of these areas. We conclude that, in high density population areas, sBMD reference curves showed no significant geographic differences in women from various regions. In women from different areas, sBMD reference curves present good pooled results at the PA spine and trochanter. The less ideal combining effect of the sBMD curves at both femoral neck and Ward's triangle might be caused by the intrinsic differences from the different measuring instruments.

[Serum osteoprotegrin and serum bone gamma-carboxyglutamine acid-containing protein are correlated with bone mineral density in normal women].

OBJECTIVE: To study the relationships of serum osteoprotegrin (sOPG), serum bone gamma-carboxyglutamine acid-containing protein (sBGP), and urine deoxypyridinoline (uDPD)/creatinine (Cr) with age and bone mineral density (BMD) in women. METHODS: ELISA was used to examine the sOPG, sBGP, and uDPD/Cr of 672 female volunteers aged 20-80. The BMD (QDR4500A) value of the anteroposterior lumbar spine and femoral neck were measured by DXA. RESULTS: (1) The levels of sOPG, sBGP, and uDPD/Cr in the age group of 30-39 were 2.8 pmol/L +/- 1.4 pmol/L, 5 microg/L +/- 3 microg/L, and 4.9 nmol/mmol +/- 2.5 nmol/mmol respectively, all significantly lower than those in the age groups 40-49, 50-59, and 60-69 (all P < 0.05). (2) In the age group 40-49, the values of sOPG, sBGP, and uDPD in menopausal subjects were significantly higher than those of the non-menopausal subjects (5.7 pmol/L +/- 3.1 pmol/L vs 3.4 pmol/L +/- 2.0 pmol/L, 11 microg/L +/- 5 microg/L vs 6 microg/L +/- 3 microg/L, and 6.9 nmol/mmol +/- 3.3 nmol/mmol vs 5.2 nmol/mmol +/- 3.9 nmol/mmol, all P < 0.001). (3) Age was positively correlated with sOPG, sBGP, uDPD/Cr, and BMD of anteroposterior lumbar spine and femoral neck (r = 0.130, 0.355, 0.106, -0.600, -0.545; P < 0.01). sOPG and sBGP were negatively correlated to anteroposterior lumbar spine BMD (r = -0.183, -0.108, P < 0.01; and r = -0.541, -0.441, P < 0.001). sOPG was positively correlated with sBGP and uDPD/Cr (r = 0.216 and 0.083; both P < 0.05). CONCLUSION: sOPG, sBGP, and uDPD/Cr can be used as sensitive markers to determine the bone turnover status, which is changeable with age, and menopausal status in women, and predict the bone lose prior to BMD determination by DXA.

[Pathology and molecular pathogenesis of spondyloepiphyseal dysplasia tarda with progressive arthropathy caused by compound CCN6 heterogeneous gene mutations].

OBJECTIVE: To characterize the clinical manifestations, features of roentgenography and MR imaging, and the pathology of articular cartilage and matrix of spondyloepiphyseal dysplasia tarda with progressive arthropathy (SEDT-PA), to screen the mutations of the disease-causing CCN6 gene, and try to elucidate the molecular pathogenesis of SEDT-PA. METHODS: A questionnaire survey on the clinical manifestations and history was conducted among a pedigree of SEDT-PA with 57 persons (53 living members) in tolal, including 2 probands, a 19-year old female and a 9-year old male. Physical examination and roentgenography and MR imaging were used on the 2 probands to characterize the features of their joints and articular cartilage. The femoral head extracted during replacement of hip of the proband 1 underwent hematoxylin-eosin staining and toludine blue (TB) staining to observe the pathological changes and ultra-microstructure of the articular chondrocytes and cartilage matrix using electron microscopy. Peripheral blood samples were collected from these 53 living members and 100 healthy controls. PCR was used to examine and sequence the exons of CCN6. 3D-conformational illustration of mutant CCN6 proteins were predicted using the Prospect Software. RESULTS: The clinical manifestations, radiology, and MR imaging established the diagnosis of SEDT-PA. Pathologic examination demonstrated that the articular cartilage chondrocytes became hyper-proliferative and immature, while the density and diameter of matrix collagens were dramatically decreased. Mutation studies showed the two probands carried a deletion (840delT) mutation in maternal allele, that caused the truncated CCN6 protein to miss 43 residues in C-terminus; and a substitution mutation (1000T-->C, Ser334Pro) in paternal allele, which was also inherited down to other 4 members in the SEDT-PA kindred. The predicted 3D-conformational changes of the truncated mutant and the Ser334Pro mutant CCN6 proteins demonstrated that in comparison with the wild CCN6 protein, the single long peptide loop in the region from signal peptide to the beginning 24 amino acid residues in the first domain (IGFBP) was subjected to folding into two smaller cross-loops accompanied with a much shorter C-terminus in 840 delT truncated mutant CCN6 protein, and no substantial 3D-conformational change of Ser334Pro mutant CCN6 protein was detected except for the C-terminal peptide towards the opposite direction. CONCLUSION: Novel 840delT mutation of CCN6 gene is the leading cause of SEDT-PA though coexistence of T1000C substitution is necessary for the clinical onset of SEDT-PA, in which marked abnormalities of cartilage chondrocytes and matrix are morphologically and functionally presented.