Disease burden of osteoarthritis of the knee and hip due to a high body mass index in China and the USA: 1990-2019 findings from the global burden of disease study 2019.

BACKGROUND: Osteoarthritis (OA) is a leading cause of disability and a source of societal costs among older adults, especially with an increasingly obese population. However, very few published studies have investigated the burden of knee and hip OA due to a high body mass index (BMI). Therefore, this study aimed to systematically summarize the trends of knee and hip OA due to a high BMI in China and the USA between 1990 and 2019. METHODS: Data from the Global Burden of Disease Study 2019 were used to estimate the age-standardized prevalence, disability-adjusted life years (DALYs) rates of knee and hip OA, and the burden of knee and hip OA due to a high BMI by sex. Joinpoint regression analysis was used to determine the temporal trend changes in the related DALYs rates of knee and hip OA. RESULTS: The trends in the DALYs rates of knee OA due to a high BMI have shown a steady and large increase in China, while the trends first showed an increase followed by a large decrease near 2001-2005 and finally a steady increase in the USA. The trends in the DALYs rates of hip OA due to a high BMI have shown a steady and large increase in both men and women in China and the USA from 1990 to 2019. For the comparison by age categories from 30 to 34 years to 90-94 years in 2019, the age-standardized DALYs rates due to a high BMI first increased and then decreased after 60-64 years and 70-74 years in both men and women from China and the USA for knee OA, respectively. For hip OA, the age-standardized DALYs rates first increased and then decreased after 70-74 years in both men and women from China and the USA. CONCLUSIONS: The burden of knee and hip OA due to a high BMI is substantially increasing in China and the USA in recent years. Researchers and health policy makers should assess the changing patterns of high BMI on the burden of OA and devise corresponding weight-control strategies.

[Treatment of severe acromioclavicular joint dislocation with double strand titanium cable and clavicular hook plate guided by self-made guide device].

OBJECTIVE: To compare the clinical efficacy of titanium cable biomimetic reconstruction of coracoclavicular ligament and clavicular hook plate in the treatment of acromioclavicular joint dislocation. METHODS: The clinical data of 39 patients with severe acute acromioclavicular joint dislocation from January 2017 to December 2018 were retrospectively analyzed, 19 patients in double strand titanium cable group, including 13 males and 6 females, aged from 26 to 67 years old; Rockwood classification:10 cases of type Ⅲ, 4 cases of type Ⅳ and 5 cases of type Ⅴ;8 cases of traffic injury and 11 cases of fall injury;the time from injury to operation was 3 to 6 days. There were 20 patients in steel plate group, including 15 males and 5 females, aged from 25 to 71 years old. Rockwood classification:11 cases of type Ⅲ, 4 cases of typeⅣ, 5 cases of type Ⅴ;7 cases of traffic injury, 13 cases of fall injury;the time from injury to operation was 2 to 7 days. The length of incision, operation time, intraoperative blood loss, cost, VAS score before and after operation, and Constant-Murley score before and after operation were compared between two groups. Postoperative X-ray films were taken to observe the reduction and maintenance of acromioclavicular joint dislocation. Complications were recorded. RESULTS: Thirty-six patients were followed up for 12 to 14 months. The amount of intraoperative blood loss in the two groups was basically the same. The operation incision in double strand titanium cable group was shorter, the operation time in steel plate group was shorter, and the operation cost in double strand titanium cable group was less. One week and one year after operation, the pain of double strand titanium cable group was less than that of steel plate group. One year after operation, the Constant-Murley score of double strand titanium cable group was higher than that of steel plate group. The postoperative X-ray showed that the acromioclavicular joint in double strand titanium cable group was well reduced, and there was 1 case with slight reduction loss. In the plate group, there was no reduction loss after removal of the clavicular hook plate, and 8 patients had distal clavicular bone atrophy or acromion bone resorption. In steel plate group, 4 cases had long-term postoperative pain, postoperative dysfunction and other complications. CONCLUSION: The clinical effect of coracoclavicular ligament reconstruction with double strand titanium cable is better than that of clavicular hook plate in the treatment of severe acute acromioclavicular joint dislocation, with less trauma (no secondary operation) and lower cost.

Treatment of distal clavicle fracture of Neer type II with locking plate in combination with titanium cable under the guide.

To observe and compare the curative effect of a locking plate plus titanium cable under the Guide device and clavicular hook plate in the treatment of Neer type II distal clavicle fractures. A prospective cohort study was conducted to analyse the clinical data of 36 patients with distal clavicle fractures from January 2016 to January 2019. The results were analysed. According to the random number method, the patients were divided into two groups: the titanium cable group (fixed with a titanium cable in combination with a locking plate) and hook plate group (fixed with a clavicular hook plate only). Under the guidance of a special device (for which a patent was obtained), in the titanium cable group, the coracoclavicular ligament was fixed with tension reduction, and then the distal clavicular fracture was fixed with a locking plate. In the hook plate group, the distal clavicle fracture was fixed with a hook plate. The incision length, operation time, bleeding volume and VAS score before, 1 week after and 1 year after the operation were compared between the two groups. The effect of the operation was evaluated by the Constant-Murley score before and 1 year after the operation. X-ray films were taken 2 days, 3 months, half a year and 1 year after the operation to observe the reduction and healing of fractures. At the same time, complications were recorded. The amount of bleeding was the same in the two groups. The operation time in the hook plate group was relatively short, and the difference was statistically significant (P < 0.05). The VAS score in the titanium cable group was significantly lower than that in the hook plate group one year after the operation. The Constant-Murley score in the titanium cable group and hook plate group was significantly higher 1 year after the operation. The number of postoperative complications in the titanium cable group was significantly lower than that in the hook plate group. The treatment of Neer type II distal clavicle fractures with a titanium cable plus a locking plate has a good curative effect, few complications and good postoperative recovery and thus is worth popularizing.

Comprehensive Analysis of Differentially Expressed Circular RNAs in Patients with Senile Osteoporotic Vertebral Compression Fracture.

AIM: Circular RNAs (circRNAs) have been found to contribute to the regulation of many diseases and are abundantly expressed in various organisms. The present study is aimed at systematically characterizing the circRNA expression profiles in patients with senile osteoporotic vertebral compression fracture (OVCF) and predicting the potential functions of the regulatory networks correlated with these differentially expressed circRNAs. METHODS: The circRNA expression profile in patients with senile OVCF was explored by using RNA sequencing. The prediction of the enriched signaling pathways and circRNA-miRNA networks was conducted by bioinformatics analysis. Real-time quantitative PCR was used to validate the selected differentially expressed circRNAs from 20 patients with senile OVCF relative to 20 matched healthy controls. RESULTS: A total of 884 differentially expressed circRNAs were identified, of which 554 were upregulated and 330 were downregulated. The top 15 signaling pathways associated with these differentially expressed circRNAs were predicted. The result of qRT-PCR of the selected circRNAs was consistent with RNA sequencing. CONCLUSIONS: CircRNAs are differentially expressed in patients with senile OVCF, which might contribute to the pathophysiological mechanism of senile osteoporosis.

Association of Serum Uric Acid Status With Bone Mineral Density in Adolescents Aged 12-19 Years.

Aims: Evidence linking serum uric acid (sUA) and bone mineral density (BMD) in adolescents is very limited. To the best of our knowledge, only one report has focused on the relationship between sUA and BMD in adolescents. Thus, this study aimed to determine the association between sUA and total BMD in adolescents aged 12-19 years. Methods: A cross-sectional study was conducted on a sample composed of non-institutionalized US population from the National Health and Nutrition Examination Survey. Weighted multivariate linear regression models were used to evaluate the association between sUA and total BMD. Subgroup analyses were further performed. Results: sUA positively correlated with total BMD in the multiple regression model after adjusting for potential confounders. However, in the subgroup analyses stratified by sex, age, or race/ethnicity, the association between sUA and total BMD followed an inverted U-shaped curve in female adolescents, adolescents aged 16-19 years, and other race/ethnicity. Conclusions: Our results suggested that the correlation between sUA level and total BMD differed by sex. The increased sUA level would be beneficial to bone health in adolescents with low sUA levels, but for female adolescents, a higher sUA level (turning point, 3.9 mg/dL) may have an adverse effect on bone health.

Associations between serum calcium, 25(OH)D level and bone mineral density in older adults.

BACKGROUND: Calcium and vitamin D play important roles in bone health as essential nutrients. We explored whether serum calcium, 25(OH)D were associated with bone mineral density (BMD) in older adults. METHODS: This cross-sectional study was conducted on a sample of 4595 participants (2281 men and 2314 women) aged ≥ 50 years (from 50 to 85 years, 60.1 ± 8.7 years for men and 62.0 ± 9.7 years for women) from the National Health and Nutrition Examination Survey (NHANES) 2001-2006. The independent variables were serum calcium and 25(OH)D. The dependent variable was lumbar BMD. The other variables were considered potential effect modifiers. We performed weighted multivariate linear regression models and smooth curve fittings to evaluate the associations between them. Subgroup analyses were also performed. RESULTS: We observed a negative association between serum calcium and lumbar BMD in the fully adjusted model. In the subgroup analyses, this association was no longer significant among males and other race/ethnicity. On the other hand, there was a positive association between serum 25(OH)D and lumbar BMD in the fully adjusted model. In the subgroup analyses, this association did not differ in different age groups, between men and women. However, the association between serum 25(OH)D and lumbar BMD followed a U-shaped curve in Mexican Americans. CONCLUSIONS: This cross-sectional study indicated that serum calcium negatively correlated with lumbar BMD, and serum 25(OH)D positively correlated with lumbar BMD in older adults. However, the association between serum calcium and lumbar BMD in males followed a U-shaped curve.

Proton Radiation Effects on Dark Signal Distribution of PPD CMOS Image Sensors: Both TID and DDD Effects.

Four-transistor (T) pinned photodiode (PPD) CMOS image sensors (CISs) with four-megapixel resolution using 11µm pitch high dynamic range pixel were radiated with 3 MeV and 10MeV protons. The dark signal was measured pre- and post-radiation, with the dark signal post irradiation showing a remarkable increase. A theoretical method of dark signal distribution pre- and post-radiation is used to analyze the degradation mechanisms of the dark signal distribution. The theoretical results are in good agreement with experimental results. This research would provide a good understanding of the proton radiation effects on the CIS and make it possible to predict the dark signal distribution of the CIS under the complex proton radiation environments.

The impact of CO2-driven ocean acidification on early development and calcification in the sea urchin Strongylocentrotus intermedius.

The impact of CO2-driven ocean acidification(OA) on early development and calcification in the sea urchin Strongylocentrotus intermedius cultured in northern Yellow Sea was investigated by comparing fertilization success, early cleavage rate, hatching rate of blastulae, larvae survival rate at 70h post-fertilization, larval morphology and calcification under present natural seawater condition (pH=8.00±0.03) and three laboratory-controlled acidified conditions (OA1, △pH=-0.3units; OA2, △pH=-0.4units; OA3, △pH=-0.5units) projected by IPCC for 2100. Results showed that pH decline had no effect on the overall fertilization, however, with decreased pH, delayed early embryonic cleavage, reduced hatching rate of blastulae and four-armed larvae survival rate at 70h post-fertilization, impaired larval symmetry, shortened larval spicules, and corrosion spicule structure were observed in all OA-treated groups as compared to control, which indicated that CO2-driven OA affected early development and calcification in S. intermedius negatively.

Positive enrichment of C-terminal peptides using oxazolone chemistry and biotinylation.

Selective capture of protein C-termini is still challenging in view of the lower reactivity of the carboxyl group relative to amino groups and difficulties in site-specifically labeling the carboxyl group on the C-terminus rather than that on the side chains of acidic amino acids. For highly efficient purification of C-terminus peptides, a novel positive enrichment approach based on the oxazolone chemistry has been developed in this study. A bifunctional group reagent containing biotin and arginine was incorporated into the C-terminus of protein. Together with a streptavidin affinity strategy, the C-terminal peptides could be readily purified and analyzed by mass spectrometry (MS). Unlike the negative enrichment approach, C-terminal peptides, other than non-C-terminal peptides, were captured directly from the peptide mixture in this new method. The labeling efficiency (higher than 90%), enrichment selectivity (purifying C-terminal peptides from mixtures of non-C-terminal peptides at a 1:50 molar ratio), and ionization efficiencies in MS were dramatically improved. Moreover, the highly efficient identification of C-terminal peptides was further achieved by defining biotin as the 21st amino acid and optimizing the database search strategy. We have successfully identified 183 C-terminal peptides from Thermoanaerobacter tengcongensis using this creative method, which affords a highly selective and efficient purification approach for C-terminomics study.

[C-terminal proteomics: strategies for characterization of protein C-terminus using MS-based techniques].

C-termini of proteins often play an important role in various biological processes, such as the transcription and translation from DNA to protein and also participating in various biological regulations. The determination of protein C-terminus is so crucial because it provides not only distinct functional annotation, but also a way to monitor the proteolysis-modified proteins. Based on the biological mass spectrometry, a series of novel methods and technologies were developed both for qualitative and quantitative analyses of protein C-terminus. These methods or technologies can be applied to accurate and effective protein C-terminus profiling, including the sequences and quantitative information of C-termini, which reveals the biological function of C-termini in life's activities and provides a better understanding of the degradation of mature proteins. Combined with our research, this review highlights the improvements in C-terminal proteomics study in the past decades, including the methodologies for recognition and identification of C-terminus, as well as the enrichment strategies for protein C-terminus.

Highly efficient enrichment method for glycopeptide analyses: using specific and nonspecific nanoparticles synergistically.

We invented a new method for highly efficient and specific enrichment of glycopeptides using two different nanomaterials synergistically. One is boronic-acid-functionalized Fe3O4 nanoparticles, enriching glycopeptides through formation of cyclic boronate esters between the boronic acid groups and the cis-diol groups on glycopeptides. The other nanomaterial is conventional poly(methyl methacrylate) nanobeads, which have strong adsorption toward nonglycopeptides. By optimizing the proportion of these two materials, extremely high sensitivity and selectivity are achieved in analyzing the standard glycopeptides/nonglycopeptides mixture solutions. Since the washing step is not necessary for these conditions, the enrichment process is simplified and the recovery efficiency of target glycopeptides reaches 90%. Finally, this approach is successfully applied to analyze human serum with the sample volume as little as 1 µL, in which 147 different N-glycosylation peptides within 66 unique glycoproteins are identified. All these performances by the synergistic enrichment are much better than employing one specific enrichment agent alone.

Approach for identification and quantification of C-terminal peptides: incorporation of isotopic arginine labeling based on oxazolone chemistry.

C-termini of proteins often play an important role in various biological processes. The determination of the protein C-terminus is crucial because it provides not only distinct functional annotation but also a way to monitor the proteolysis-modified proteins. In this study, an isotopic labeling approach based on oxazolone chemistry was developed to achieve the identification and quantification of C-termini. Aminolysis reagents such as arginine selectively react with the α-carboxyl group at the peptide C-terminus via an oxazolone-like intermediate. Side chain carboxyl groups do not participate in this reaction. When an isotopic mixture consisting of 50% arginine ((0)Arg) and 50% C6-arginine ((6)Arg) was introduced to react with C-terminus of protein and followed by proteolysis, the C-terminal peptide could be directly recognized in the mass spectrum due to its unique isotopic paired peaks, and the sequence could be interpreted in MS2. Besides, the incorporation of an additional basic amino acid in the C-terminal peptide greatly enhanced the signal intensity for C-termini detection. Moreover, the isotopic arginine labeling strategy could be applied for relative C-termini quantitation. Our method showed an excellent correlation of the measured ratios to theoretical ratios and high reproducibility within 2 orders of magnitude of the dynamic range. The correlation coefficients (R(2)) were higher than 0.99, with the coefficients of variation (CVs) ranging from 1.16 to 10.91%. Finally, the approach was used to analyze the C-termini from Thermoanaerobacter tengcongensis , which was cultured under different temperatures. As a result, 68 C-termini have been identified, and 53 of them were quantified in total using our strategy. In addition, 24 neo-C-terminal peptides have also been discovered.

Mass spectrometry signal amplification for ultrasensitive glycoprotein detection using gold nanoparticle as mass tag combined with boronic acid based isolation strategy.

We describe a novel method for rapid and ultrasensitive detection of intact glycoproteins without enzymatic pretreatment which was commonly used in proteomic research. This method is based on using gold nanoparticle (AuNP) as signal tag in laser desorption/ionization mass spectrometry (LDI-MS) analysis combined with boronic acid assisted isolation strategy. Briefly speaking, target glycoproteins were firstly isolated from sample solution with boronic acid functionalized magnetic microparticles, and then the surface modified gold nanoparticles were added to covalently bind to the glycoproteins. After that, these AuNP tagged glycoproteins were eluted from magnetic microparticles and applied to LDI-MS analysis. The mass signal of AuNP rather than that of glycoprotein was detected and recorded in this strategy. Through data processing of different standard glycoproteins, we have demonstrated that the signal of AuNP could be used to quantitatively represent glycoprotein. This method allows femtomolar detection of intact glycoproteins. We believe that the successful validation of this method on three different kinds of glycoproteins suggests the potential use for tracking trace amount of target glycoproteins in real biological samples in the near future.

Mechanism exploration of adsorption-immobilized enzymatic reactor using polymer-coated silica microbeads.

A verified mechanism of adsorption-immobilized enzymatic reactor for enhanced proteolysis is presented. Silica microbeads coated with poly (diallyldimethylammonium chloride) (PDDA) or poly (styrene sulfonate) (PSS) were used to trap trypsin and proteins on the surface through electrostatic interactions in order to improve digestion efficiency. Charge states measured by zeta-potentials showed their positively and negatively charged respectively. We found that high proteolytic efficiency could be achieved only if both proteases and proteins were adsorbed by materials. Once the proteins and proteases were confined together in a nanoscopic area, the enrichment of the substrate could lead to a high performance proteolytic effect. Electrostatic interactions were considered as the predominant adsorption factor rather than hydrophilic/hydrophobic interactions. In less than 5 min, in the presence of PSS-coated silica beads, 10 peptides digested from positively-charged cytochrome C were detected by matrix-assisted laser desorption/ionization mass spectrometry (MALDI-TOF), with the high sequence coverage up to 63%, while using PDDA-coated silica beads or conventional in-solution digestion yielded only 5 detectable peptides and 39% sequence coverage was obtained. Ovalbumin seemed incompatible with any kind of charged-material-aided tryptic digestion. The mechanism of adsorption-immobilized enzymatic processes has also been studied in detail. The adsorption equilibrium was proven to be attained in less than one minute, and the proteolytic procedure was regarded as the rate-determining step. This study provides a reasonable mechanism for an adsorption-material catalyzed proteolytic procedure and a promising guideline for designing the next generation of high-performance enzymatic reactors.

Improved proteomic analysis pipeline for LC-ETD-MS/MS using charge enhancing methods.

Electron transfer dissociation (ETD) is a useful and complementary activation method for peptide fragmentation in mass spectrometry. However, ETD spectra typically receive a relatively low score in the identifications of 2+ ions. To overcome this challenge, we, for the first time, systematically interrogated the benefits of combining ion charge enhancing methods (dimethylation, guanidination, m-nitrobenzyl alcohol (m-NBA) or Lys-C digestion) and differential search algorithms (Mascot, Sequest, OMSSA, pFind and X!Tandem). A simple sample (BSA) and a complex sample (AMJ2 cell lysate) were selected in benchmark tests. Clearly distinct outcomes were observed through different experimental protocol. In the analysis of AMJ2 cell lines, X!Tandem and pFind revealed 92.65% of identified spectra; m-NBA adduction led to a 5-10% increase in average charge state and the most significant increase in the number of successful identifications, and Lys-C treatment generated peptides carrying mostly triple charges. Based on the complementary identification results, we suggest that a combination of m-NBA and Lys-C strategies accompanied by X!Tandem and pFind can greatly improve ETD identification.

Immobilization of trypsin on water-soluble dendrimer-modified carbon nanotubes for on-plate proteolysis combined with MALDI-MS analysis.

A novel on-plate digestion method combined with MALDI-MS analysis is reported, using trypsin-linked dendrimer-modified carbon nanotubes (dCNTs) as the enzyme immobilization probe. Excellent digestion performance was achieved in a short time without any complicated reduction and alkylation procedures.