The association of urinary heavy metal exposure with frailty susceptibility and mortality in middle-aged and older adults: a population-based study.

Heavy metals' presence as environmental pollutants has a close link to adverse health effects. Frailty, a clinical syndrome hallmarked by elevated vulnerability to stressors, presents a substantial challenge in healthcare. However, the association between exposure to heavy metals and frailty largely remains unexplored. Utilizing data from the National Health and Nutrition Examination Survey (NHANES) spanning 2003-2018 and correlated with the U.S. National Death Index (NDI) from 2019, we investigated mortality outcomes. Logistic regression, Cox regression, Kaplan-Meier survival curves, weighted quantile-sum (WQS) regression, and Bayesian kernel machine regression (BKMR) were employed to assess the association between heavy metal exposure and frailty incidence and mortality in the frail population. Eight metals were measured in urine using inductively coupled plasma mass spectrometry with values adjusted for urinary creatinine, which was used to reflect heavy metal exposure. The cohort incorporated 5370 female participants aged 45 and above, with 1518 diagnosed with frailty. The findings indicated a substantial correlation between exposure to specific heavy metals, namely tungsten (odds ratio [OR]: 1.94, 95% confidence interval [CI]: 1.31-2.89), cobalt (OR: 1.64, 95% CI: 1.40-1.93), cadmium (OR: 1.93, 95% CI: 1.52-2.43), and uranium (OR: 7.36, 95% CI: 1.53-35.28), and an elevated risk of frailty. WQS and BKMR regression models identified cadmium, cobalt, and tungsten as main contributors to frailty. Cox regression analysis, after adjustment for covariates, suggested that the higher the exposure levels to cadmium and lead, the higher the risk of death in frail patients, with associated hazard ratios (HR) of 95% CI: 1.96 (1.53, 2.52) and 1.30 (1.13, 1.49), respectively. Our study revealed a significant positive correlation between exposure to heavy metal mixtures and frailty onset in middle-aged and older adults, along with increased mortality in frail patients. Cobalt, cadmium, and tungsten emerged as prominent contributors to frailty, with cobalt and cadmium directly impacting the long-term life expectancy of frail patients.

Association between niacin intake and knee osteoarthritis pain and function: a longitudinal cohort study.

BACKGROUND: This research investigates the relationship between niacin intake and knee osteoarthritis (OA) severity, focusing on pain and functional ability due to niacin's role as a NAD(P)+ precursor, promoting cellular energy, and offering anti-inflammatory, analgesic, and antioxidant effects. METHODS: The population-based Osteoarthritis Initiative (OAI) cohort with radiographically confirmed knee OA was analyzed through a Food Frequency Questionnaire determining niacin intake and scores from the Knee Injury and Osteoarthritis Outcome Score (KOOS) and Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC), using generalized additive mixed models. RESULTS: A significant correlation was pinpointed in 2375 OA patients (1001 men and 1374 women; 55.96% aged between 45 and 65 and 44.04% aged ≥65) between niacin intake and reduced knee pain and functional degrees after a 48-month follow-up, evident in improved KOOS and WOMAC scores (P < 0.05). The fully adjusted models estimated a decrease of 0.26 points for every additional 1 unit of Ln-niacin intake of daily niacin intake on the WOMAC pain subscale, 0.83 points on the WOMAC function subscale, and an increase of 1.71 and 1.58 on the KOOS pain and quality of life score. Strikingly, subgroups including middle-aged individuals, women, white race, obese individuals, and those with specific dietary habits showed a more substantial improvement with increased niacin. CONCLUSION: The association between increased niacin intake and reduced pain and function scores, as well improved quality of life in knee OA patients, is significant. Certain cohorts, according to a stratified analysis, could see more considerable benefits with increased niacin consumption. HIGHLIGHTS: • Increased niacin intake is linked to reduced knee pain and better function in OA patients. • Specific subgroups, such as middle-aged individuals, women, and those with certain dietary habits, benefit more from increased niacin consumption. • Niacin shows promise for enhancing the quality of life in knee OA patients by reducing pain and improving function.

Genome-wide identification and expression analysis of growth-regulating factors in Dendrobium officinale and Dendrobium chrysotoxum.

Background: Dendrobium, one of the largest genera in Orchidaceae, is popular not only for its aesthetic appeal but for its significant medicinal value. Growth-regulating factors (GRFs) play an essential role in plant growth and development. However, there is still a lack of information about the evolution and biological function analysis of the GRF gene family among Dendrobiumspecies. Methods: Growth-regulating factors from Dendrobium officinale Kimura et Migo and Dendrobium chrysotoxum Lindl. were identified by HMMER and BLAST. Detailed bioinformatics analysis was conducted to explore the evolution and function of GRF gene family in D. officinale and D. chrysotoxum using genomic data, transcriptome data and qRT-PCR technology. Results: Here, we evaluated the evolution of the GRF gene family based on the genome sequences of D. officinale and D. chrysotoxum. Inferred from phylogenetic trees, the GRF genes were classified into two clades, and each clade contains three subclades. Sequence comparison analysis revealed relatively conserved gene structures and motifs among members of the same subfamily, indicating a conserved evolution of GRF genes within Dendrobiumspecies. However, considering the distribution of orthologous DoGRFs and DcGRFs, and the differences in the number of GRFs among species, we suggest that the GRF gene family has undergone different evolutionary processes. A total of 361 cis-elements were detected, with 33, 141, and 187 related to plant growth and development, stress, and hormones, respectively. The tissue-specific expression of GRFs showed that DoGRF8 may have a significant function in the stem elongation of D. officinale. Moreover, four genes were up-regulated under Methyl-jasmonic acid/methyl jasmonate (MeJA) treatment, showing that DoGRFs and DcGRFs play a crucial role in stress response. These findings provide valuable information for further investigations into the evolution and function of GRF genes in D. officinale and D. chrysotoxum.

The influence of zinc and iron intake on osteoarthritis patients' subchondral sclerosis progression: A prospective observational study using data from the osteoarthritis Initiative.

Objective: The purpose of this investigation was to elucidate the relationship between the zinc and iron intake and the advancement of subchondral sclerosis among patients with osteoarthritis (OA). The goal was to establish personalized, nutritionally-informed strategies designed to retard the progression of subchondral sclerosis and conserve joint structure. Methods: For the purposes of this research, we derived data from the Bone Ancillary Study (BAS), a constituent study of the Osteoarthritis Initiative (OAI). The intake of zinc and iron was evaluated via a food frequency questionnaire. Magnetic Resonance Imaging trabecular morphometry was employed to ascertain the microarchitecture of the subchondral bone. For the analysis of collected data, we employed logistic regression along with generalized additive models (GAMs). Results: The participant cohort was comprised of 474 OA patients (216 females, 258 males, mean [SD] age 64.1[9.2]). Notably, an increment in zinc consumption was linked with a significantly reduced likelihood of deterioration in Tb.N (OR = 0.967, 95 % CI, 0.939-0.996, P-value = 0.026), Tb.Th (OR = 0.958, 95 % CI, 0.929-0.989, P-value = 0.008), and Tb.Sp (OR = 0.967, 95 % CI, 0.939-0.996, P-value = 0.013). An elevation in iron intake seemed to enhance the risk of subchondral sclerosis, as indicated by the GAM. Subgroup analysis revealed an interaction between the effectiveness of zinc intake and factors such as gender, age, radiographic severity, and macronutrient consumption. An increased intake of calcium amplified the beneficial impact of zinc on subchondral sclerosis. Conclusions: Our findings indicate a positive association between elevated zinc intake and a slowdown in the progression of subchondral sclerosis in OA patients, notably among females, middle-aged individuals, and those with higher calcium and magnesium intake. Conversely, a higher iron intake might intensify subchondral sclerosis. These results suggest that personalized, diet-based interventions focusing on zinc consumption, in tandem with adequate calcium intake, could potentially decelerate the progression of subchondral sclerosis in individuals afflicted with OA.

Mitochondrial genome comparison and phylogenetic analysis of Dendrobium (Orchidaceae) based on whole mitogenomes.

BACKGROUND: Mitochondrial genomes are essential for deciphering the unique evolutionary history of seed plants. However, the rules of their extreme variation in genomic size, multi-chromosomal structure, and foreign sequences remain unresolved in most plant lineages, which further hindered the application of mitogenomes in phylogenetic analyses. RESULTS: Here, we took Dendrobium (Orchidaceae) which shows the great divergence of morphology and difficulty in species taxonomy as the study focus. We first de novo assembled two complete mitogenomes of Dendrobium wilsonii and Dendrobium henanense that were 763,005 bp and 807,551 bp long with multichromosomal structures. To understand the evolution of Dendrobium mitogenomes, we compared them with those of four other orchid species. The results showed great variations of repetitive and chloroplast-derived sequences in Dendrobium mitogenomes. Moreover, the intergenic content of Dendrobium mitogenomes has undergone expansion during evolution. We also newly sequenced mitogenomes of 26 Dendrobium species and reconstructed phylogenetic relationships of Dendrobium based on genomic mitochondrial and plastid data. The results indicated that the existence of chloroplast-derived sequences made the mitochondrial phylogeny display partial characteristics of the plastid phylogeny. Additionally, the mitochondrial phylogeny provided new insights into the phylogenetic relationships of Dendrobium species. CONCLUSIONS: Our study revealed the evolution of Dendrobium mitogenomes and the potential of mitogenomes in deciphering phylogenetic relationships at low taxonomic levels.

Genome-Wide Identification and Analysis of TCP Gene Family among Three Dendrobium Species.

Dendrobium orchids, which are among the most well-known species of orchids, are appreciated for their aesthetic appeal across the globe. Furthermore, due to their strict living conditions, they have accumulated high levels of active ingredients, resulting not only in their medicinal value but also in their strong ability to respond to harsh environments. The TCP gene family plays an important role in plant growth and development, and signal transduction. However, these genes have not been systematically investigated in Dendrobium species. In this study, we detected a total of 24, 23, and 14 candidate TCP members in the genome sequences of D. officinale, D. nobile, and D. chrysotoxum, respectively. These genes were classified into three clades on the basis of a phylogenetic analysis. The TCP gene numbers among Dendrobium species were still highly variable due to the independent loss of genes in the CIN clade. However, only three gene duplication events were detected, with only one tandem duplication event (DcTCP9/DcTCP10) in D. chrysotoxum and two pairs of paralogous DoTCP gene duplication events (DoTCP1/DoTCP23 and DoTCP16/DoTCP24) in D. officinale. A total of 25 cis-acting elements of TCPs related to hormone/stress and light responses were detected. Among them, the proportions of hormone response, light response, and stress response elements in D. officinale (100/421, 127/421, and 171/421) were similar to those in D. nobile (83/352, 87/352, and 161/352). Using qRT-PCR to determine their expression patterns under MeJA treatment, four DoTCPs (DoTCP2, DoTCP4, DoTCP6, and DoTCP14) were significantly upregulated under MeJA treatment, which indicates that TCP genes may play important roles in responding to stress. Under ABA treatment, seven DoTCPs (DoTCP3, DoTCP7, DoTCP9, DoTCP11, DoTCP14, DoTCP15, and DoTCP21) were significantly upregulated, indicating that TCP genes may also play an important role in hormone response. Therefore, these results can provide useful information for studying the evolution and function of TCP genes in Dendrobium species.

Association between dietary folate intake and bone mineral density in a diverse population: a cross-sectional study.

BACKGROUND: Osteoporosis is a major public health problem, yet the association between dietary folate intake and bone health has been rarely studied. This study aimed to investigate the relationship between dietary folate intake and bone mineral density (BMD) in the general population of the USA. METHODS: Utilizing data from the National Health and Nutrition Examination Survey, dietary folate intake was gauged through 24-h dietary recall and BMD was determined via dual-energy X-ray absorptiometry. Multivariate linear regression models and generalized additive models were employed for correlation analysis. RESULTS: The study incorporated 9839 participants (48.88% males, aged 20-85 years, mean age: 47.62 ± 16.22). The average dietary folate intake stood at 401.1 ± 207.9 µg/day. And the average total femur, femoral neck, trochanter, intertrochanter, and lumbar BMD were 0.98 ± 0.16 g/cm2, 0.84 ± 0.15 g/cm2, 0.73 ± 0.13 g/cm2, 1.16 ± 0.19 g/cm2, and 1.03 ± 0.15 g/cm2, respectively. The higher quartiles of dietary folate intake directly correlated with increased total femoral, femoral neck, intertrochanteric, and lumbar BMD (P for trend = 0.003, 0.016, < 0.001, and 0.033, respectively). A consistent positive association between folate intake and BMD across age groups was observed, with significant findings for individuals over 80 years and non-Hispanic whites. Physical activity level and serum 25-hydroxyvitamin D levels influenced the association, with an optimal daily folate intake of 528-569 µg recommended for postmenopausal women. CONCLUSION: In summary, our study reveals a significant positive association between dietary folate intake and BMD, across different age groups and particularly among individuals over 80 years old. Non-Hispanic whites benefit the most from increased folate intake. Physical activity level and serum 25-hydroxyvitamin D levels interact with this association. Screening and early intervention for osteoporosis may be essential for individuals with low dietary folate intake.

Screening for autophagy/hypoxia/ferroptosis/pyroptosis-related genes of tendon injury and repair in a rat model after celecoxib and lactoferrin treatment.

BACKGROUND: Tendon injuries are among the most common musculoskeletal disorders. Celecoxib possesses an effective anti-inflammatory activity in the tendon injury treatment. Lactoferrin has a great potential for the tendon regeneration. However, the efficacy of celecoxib combined with lactoferrin in the treatment of tendon injury has not been reported. In this study, we aimed to investigate the effect of celecoxib and lactoferrin on tendon injury and repair, and screen for the crucial genes associated with the tendon injury and repair. METHODS: The rat tendon injury models were established and divided into four groups: normal control group (n = 10), tendon injury model group (n = 10), celecoxib treatment group (n = 10), and celecoxib + lactoferrin treatment group (n = 10). Then, RNA sequencing was performed to identify differentially expressed lncRNAs (DElncRNAs), miRNAs (DEmiRNAs) and mRNAs (DEmRNAs) in celecoxib treatment group and celecoxib + lactoferrin treatment group. Next, autophagy/hypoxia/ferroptosis/pyroptosis-related DEmRNAs were further identified. Subsequently, functional enrichment, protein-protein interaction (PPI) network and transcriptional regulatory network construction for these genes were performed. RESULTS: The animal study demonstrated that combinational administration of celecoxib with lactoferrin rescued the harmful effects caused by celecoxib in the treatment of tendon injury. Compared to tendon injury model group, 945 DEmRNAs, 7 DEmiRNAs and 34 DElncRNAs were obtained in celecoxib treatment group, and 493 DEmRNAs, 8 DEmiRNAs and 21 DElncRNAs were obtained in celecoxib + lactoferrin treatment group, respectively. Subsequently, 376 celecoxib + lactoferrin treatment group-specific DEmRNAs were determined. Then, 25 DEmRNAs associated with autophagy/hypoxia/ferroptosis/pyroptosis were identified. CONCLUSIONS: Several genes, such as, Ppp1r15a, Ddit4, Fos, Casp3, Tgfb3, Hspb1 and Hspa8, were identified to be associated with tendon injury and repair.

The climate changes promoted the chloroplast genomic evolution of Dendrobium orchids among multiple photosynthetic pathways.

Dendrobium orchids have multiple photosynthetic pathways, which can be used as a model system for studying the evolution of crassulacean acid metabolism (CAM). In this study, based on the results of the net photosynthetic rates (Pn), we classified Dendrobium species into three photosynthetic pathways, then employed and compared their chloroplast genomes. The Dendrobium chloroplast genomes have typical quartile structures, ranging from 150,841-153,038 bp. The apparent differences in GC content, sequence variability, and IR junctions of SSC/IRB junctions (JSBs) were measured within chloroplast genomes among different photosynthetic pathways. The phylogenetic analysis has revealed multiple independent CAM origins among the selected Dendrobium species. After counting insertions and deletions (InDels), we found that the occurrence rates and distribution densities among different photosynthetic pathways were inconsistent. Moreover, the evolution patterns of chloroplast genes in Dendrobium among three photosynthetic pathways were also diversified. Considering the diversified genome structure variations and the evolution patterns of protein-coding genes among Dendrobium species, we proposed that the evolution of the chloroplast genomes was disproportional among different photosynthetic pathways. Furthermore, climatic correlation revealed that temperature and precipitation have influenced the distribution among different photosynthetic pathways and promoted the foundation of CAM pathway in Dendrobium orchids. Based on our study, we provided not only new insights into the CAM evolution of Dendrobium but also provided beneficial genetic data resources for the further systematical study of Dendrobium.

Denosumab biosimilar (LY06006) in Chinese postmenopausal osteoporotic women: A randomized, double-blind, placebo-controlled, multicenter phase III study.

Objectives: This study assessed the efficacy, safety, pharmacokinetics (PK), and immunogenicity profiles of a denosumab biosimilar (LY06006) in Chinese postmenopausal osteoporotic women with a high risk of fracture. Methods: In this multicenter, randomized, double-blind, placebo-controlled, phase 3 trial, 448 postmenopausal women aged 50-85 years with osteoporosis were enrolled at 49 centers in China and were randomly assigned (3:1) to receive 60 â€‹mg of the denosumab biosimilar (LY06006) or placebo subcutaneously every 6 months for 1 year. Lumbar spine bone mineral density (BMD) change was the primary endpoint. Results: Of the 448 randomized patients, 409 (LY06006, n â€‹= â€‹311; placebo, n â€‹= â€‹98) completed the study. All 448 (100.0%) subjects were included in the intent-to-treat (ITT) trial, 427 (95.3%) were included in the full analysis set (FAS), 408 (91.1%) were included in the per protocol set (PPS), 446 (99.6%) were included in the safety set (SS), and 336 (75.0%) were included in the pharmacokinetics concentration set (PKCs). For the primary endpoint, a 4.71% (95% CI, 3.81%, 5.60%) treatment difference in percent change in lumbar spine BMD from baseline to month 12 was observed in the LY06006 group compared with the placebo group (P â€‹< â€‹0.0001). For the secondary endpoints, LY06006 was associated with increased lumbar spine BMD levels measured at month 6, BMD levels at the femoral neck, total hip, and trochanter measured at months 6 and 12 and reduced serum C-terminal telopeptide of type 1 collagen (CTX) and procollagen type 1 â€‹N-peptide (P1NP) levels at months 1, 6, and 12. Safety analysis was based on the safety analysis set (SS), and 264 (78.6%) subjects in the LY06006 group and 83 (75.5%) in the placebo group experienced adverse events (AEs). Most events were mild or moderate and not related to the study drugs. Conclusion: In postmenopausal women with a high risk of fracture, LY06006 increased the BMD and decreased bone resorption; thus, LY06006 might be an effective treatment for osteoporosis. LY06006 was generally safe and well tolerated without unexpected adverse reactions, similar to the reference drug Prolia®. The characteristics of effectiveness and safety were similar to those reported in previous studies. The translational potential of this article: In this multi-center, randomized, double-blind, placebo-controlled phase 3 study, LY06006 showed substantially efficacy to increase BMD and well tolerance without unexpected adverse reactions, which is comparable to the reference drug Prolia ®. The presented results are encouraging and can offer some valuable evidence for the clinical practice.

Evolution patterns of NBS genes in the genus Dendrobium and NBS-LRR gene expression in D. officinale by salicylic acid treatment.

BACKGROUND: Dendrobium officinale Kimura et Migo, which contains rich polysaccharides, flavonoids and alkaloids, is a Traditional Chinese Medicine (TCM) with important economic benefits, while various pathogens have brought huge losses to its industrialization. NBS gene family is the largest class of plant disease resistance (R) genes, proteins of which are widely distributed in the upstream and downstream of the plant immune systems and are responsible for receiving infection signals and regulating gene expression respectively. It is of great significance for the subsequent disease resistance breeding of D. officinale to identify NBS genes by using the newly published high-quality chromosome-level D. officinale genome. RESULTS: In this study, a total of 655 NBS genes were uncovered from the genomes of D. officinale, D. nobile, D. chrysotoxum, V. planifolia, A. shenzhenica, P. equestris and A. thaliana. The phylogenetic results of CNL-type protein sequences showed that orchid NBS-LRR genes have significantly degenerated on branches a and b. The Dendrobium NBS gene homology analysis showed that the Dendrobium NBS genes have two obvious characteristics: type changing and NB-ARC domain degeneration. Because the NBS-LRR genes have both NB-ARC and LRR domains, 22 D. officinale NBS-LRR genes were used for subsequent analyses, such as gene structures, conserved motifs, cis-elements and functional annotation analyses. All these results suggested that D. officinale NBS-LRR genes take part in the ETI system, plant hormone signal transduction pathway and Ras signaling pathway. Finally, there were 1,677 DEGs identified from the salicylic acid (SA) treatment transcriptome data of D. officinale. Among them, six NBS-LRR genes (Dof013264, Dof020566, Dof019188, Dof019191, Dof020138 and Dof020707) were significantly up-regulated. However, only Dof020138 was closely related to other pathways from the results of WGCNA, such as pathogen identification pathways, MAPK signaling pathways, plant hormone signal transduction pathways, biosynthetic pathways and energy metabolism pathways. CONCLUSION: Our results revealed that the NBS gene degenerations are common in the genus Dendrobium, which is the main reason for the diversity of NBS genes, and the NBS-LRR genes generally take part in D. officinale ETI system and signal transduction pathways. In addition, the D. officinale NBS-LRR gene Dof020138, which may have an important breeding value, is indirectly activated by SA in the ETI system.

Association between vitamin D3 levels and frailty in the elderly: A large sample cross-sectional study.

Background: Frailty is recognized as a cornerstone of geriatric medicine. Accurately screening and identifying frailty can promote better quality and personalized medical services for the elderly. Previous studies have shown that the association between vitamin D and frailty in the elderly population is still controversial. More research is needed to explore the association between them. Materials and methods: We used three waves of data from the National Health and Nutrition Examination Survey (NHANES). Based on the widely accepted AAH FRAIL Scale, we measured and evaluated the participants' frailty from five aspects: fatigue, resistance, ambulation, illness, and loss of weight. All possible relevant variables are included. Machine learning XGboost algorithm, the Least Absolute Shrinkage Selection Operator (LASSO) regression and univariate logistic regression were used to screen variables, and multivariate logistic regression and generalized additive model (GAM) were used to build the model. Finally, subgroup analysis and interaction test were performed to further confirm the association. Results: In our study, XGboost machine learning algorithm explored the relative importance of all included variables, which confirmed the close association between vitamin D and frailty. After adjusting for all significant covariates, the result indicated that for each additional unit of 25-hydroxyvitamin D3, the risk of frailty was reduced by 1.3% with a statisticaldifference. A smooth curve was constructed based on the GAM. It was found that there was a significant negative correlation between 25-hydroxyvitamin D3 and the risk of frailty. Conclusion: There may be a negative correlation between 25-hydroxyvitamin D3 and the risk of frailty. However, more well-designed studies are needed to verify this relationship.

Mapping knowledge structure and themes trends of biodegradable Mg-based alloy for orthopedic application: A comprehensive bibliometric analysis.

Background: Since Lambotte and Payr first studied Mg-based alloys for orthopedics in 1900, the research of this field has finally ushered in vigorous development in the 21st century. From the perspective of quantitative analysis, this paper clearly demonstrated the global research trend from 2005 to 2021 by using bibliometrics and scientometric analysis. Methods: We obtained the publications from the Web of Science Core Collection (WoSCC) database. The bibliometric and scientometric analysis was conducted by using R software, CiteSpace software, VOSviewer software, Pajek software and Microsoft Excel program. Results: In total, 1921 publications were retrieved. It can be found that the number of publications is gradually increasing year by year. We can find that the most prolific countrie, institution and researcher are China, Chinese Academy of Sciences and Zheng Yufeng, respectively. The most influential journals in this field are Acta Biomaterialia and Biomaterials, with 16,511 and 12,314 total citations, respectively. By conducting the co-cited documents-based clustering analysis, 16 research hotspots and their representative studies have been identified. Besides, by conducting analysis of keywords, we divided the keyword citation bursts representing the development of the field into three stages. Conclusion: The number of researches on the biodegradable Mg-based alloys increased sharply all over the world in the 21st century. China has made significant progress in biodegradable Mg-based alloy research. More focus will be placed on osteogenic differentiation, fabrication, graphene oxide, antibacterial property, bioactive glass and nanocomposite, which may be the next popular topics in the field.

Genome-wide identification and expression analysis of the Hsp20, Hsp70 and Hsp90 gene family in Dendrobium officinale.

Dendrobium officinale, an important orchid plant with great horticultural and medicinal values, frequently suffers from abiotic or biotic stresses in the wild, which may influence its well-growth. Heat shock proteins (Hsps) play essential roles in the abiotic stress response of plants. However, they have not been systematically investigated in D. officinale. Here, we identified 37 Hsp20 genes (DenHsp20s), 43 Hsp70 genes (DenHsp70s) and 4 Hsp90 genes (DenHsp90s) in D. officinale genome. These genes were classified into 8, 4 and 2 subfamilies based on phylogenetic analysis and subcellular predication, respectively. Sequence analysis showed that the same subfamily members have relatively conserved gene structures and similar protein motifs. Moreover, we identified 33 pairs of paralogs containing 30 pairs of tandem duplicates and 3 pairs of segmental duplicates among these genes. There were 7 pairs in DenHsp70s under positive selection, which may have important functions in helping cells withstand extreme stress. Numerous gene promoter sequences contained stress and hormone response cis-elements, especially light and MeJA response elements. Under MeJA stress, DenHsp20s, DenHsp70s and DenHsp90s responded to varying degrees, among which DenHsp20-5,6,7,16 extremely up-regulated, which may have a strong stress resistance. Therefore, these findings could provide useful information for evolutional and functional investigations of Hsp20, Hsp70 and Hsp90 genes in D. officinale.

Efficacy of generic teriparatide and alendronate in Chinese postmenopausal women with osteoporosis: a prospective study.

The efficacy of generic teriparatide in improving BMD at lumbar spine in patients with osteoporosis was similar to that of alendronate. It provided a new choice for osteoporosis treatment in Chinese population. INTRODUCTION: To determine whether the efficacy of generic teriparatide is noninferior to alendronate for Chinese postmenopausal women with osteoporosis. METHODS: Eligible patients were randomly assigned (2:1) in a 48-week, open-label design to receive 20 µg sc daily teriparatide or 70 mg oral weekly alendronate. Primary outcome was percentage change in BMD at the lumbar spine from baseline to 48 weeks and was assessed for non-inferiority. The same outcome was further assessed for superiority as a secondary endpoint. RESULTS: Three hundred ninety-one and 196 participants were randomly assigned to the teriparatide or alendronate group, of whom 379 and 194 receiving at least one dose of teriparatide and alendronate treatment were eligible for the efficacy analysis. Teriparatide was non-inferior to alendronate for BMD change at lumbar spine (treatment difference: 0.7%, 95% CI: - 0.3 to 1.7%), which excluded the predefined non-inferiority margin of - 1.5%. However, teriparatide was not statistically superior to alendronate in improving BMD at lumbar spine (P = 0.169). At 48 weeks, changes in BMD at total hip were - 1.0% and 2.2% in teriparatide and alendronate group, respectively (P < 0.001). The incidence of new fracture showed no statistical difference between groups (P = 0.128). Serum P1NP and ß-CTX levels significantly increased in the teriparatide group and markedly decreased in alendronate group (all P < 0.001 vs baseline). The adverse events (AEs) and serious AEs were more common in the teriparatide group than in the alendronate group, which were mainly teriparatide-related hypercalcemia, elevated alkaline phosphatase or parathyroid hormone, dizziness, and arthralgia. CONCLUSIONS: Teriparatide was not inferior to alendronate in increasing BMD at lumbar spine in Chinese postmenopausal women, and they achieved these effects through different mechanisms.

Research Hotspots and Trends Analysis of Patellar Instability: A Bibliometric Analysis from 2001 to 2021.

Background: Patellar instability is a common multifactorial disease in orthopedics, which seriously affects the quality of life. Because of the unified pathogeny, diagnosis and treatment, patellar instability has gradually attracted the interest of more scholars these years, resulting in an explosive growth in the research output. This study aims to summarize the knowledge structure and development trend in the field from the perspective of bibliometrics. Methods: The data of articles and reviews on patellar instability was extracted from the Web of Science database. The Microsoft Excel, R-bibliometrix, CiteSpace, VOSviewer, Pajek software are comprehensively used to scientifically analyze the data quantitatively and qualitatively. Results: Totally, 2,155 papers were identified, mainly from North America, Western Europe and East Asia. Until December 31, 2021, the United States has contributed the most articles (1,828) and the highest total citations (17,931). Hospital for Special Surgery and professor Andrew A Amis are the most prolific institutions and the most influential authors respectively. Through the analysis of citations and keywords based on a large number of literatures, "medial patellofemoral ligament construction", "tibial tubercle-trochlear groove (TT-TG) distance", "epidemiological prevalence", "multifactor analysis of etiology, clinical outcome and radiographic landmarks " were identified to be the most promising research directions. Conclusions: This is the first bibliometric study to comprehensively summarize the research trend and development of patellar instability. The result of our research provides the updated perspective for scholars to understand the key information in this field, and promote future research to a great extent.

Development and Validation of a Web-Based Dynamic Nomogram to Improve the Diagnostic Performance of Subscapularis Tendon Tear.

Background: There are still some challenges in diagnosing subscapularis (SSC) tendon tears as accurately as posterosuperior rotator cuff tears on magnetic resonance imaging (MRI). The omission of SSC tendon tears can lead to muscle atrophy, fatty infiltration and increased tear accompanied by aggravated shoulder pain and loss of function. An effective noninvasive evaluation tool will be beneficial to early identification and intervention. The study aims to identify sensitive predictors associated with SSC tendon tears and develop a dynamic nomogram to improve diagnostic performance. Methods: From July 2016 to October 2021, 528 consecutive cases of patients who underwent shoulder arthroscopic surgery with preoperative shoulder MRI were retrospectively analyzed. The least absolute shrinkage and selection operator (LASSO) method was used to identify the sensitive factors associated with SSC tendon tears, which were then incorporated into the nomogram. The prediction performance of the nomogram was evaluated by concordance index (C index) and calibrated with 1,000 bootstrap samples combined with external validation of another cohort. Results: The LASSO method showed that six items including coracohumeral distance (oblique sagittal plane), effusion (Y-face), effusion (subcoracoid), malposition of the long head tendon of the biceps, multiple posterosuperior rotator cuff tears, and considering SSC tendon tears on MRI (based on direct signs) were determined as sensitive predictors. The nomogram achieved a good C index of 0.878 (95% CI, 0.839-0.918) with a good agreement on the risk estimation of calibration plots. The areas under the receiver operator characteristic (ROC) curves of the two methods showed that dynamic nomograms had better prediction performance than MRI diagnosis based on direct signs (training set 0.878 vs. 0.707, validation set 0.890 vs. 0.704). Conclusion: The study identified sensitive predictors associated with SSC tendon tears and first developed a web-based dynamic nomogram as a good supplementary evaluation tool for imaging diagnosis that could provide an individualized risk estimate with superior prediction performance, even in patients with small or partial tears.

[Development of a risk stratification model for subscapularis tendon tear based on patient-specific data from 528 shoulder arthroscopy].

Objective: To identify and screen sensitive predictors associated with subscapularis (SSC) tendon tear and develop a web-based dynamic nomogram to assist clinicians in early identification and intervention of SSC tendon tear. Methods: Between July 2016 and December 2021, 528 consecutive cases of patients who underwent shoulder arthroscopic surgery with completely MRI and clinical data were retrospectively analyzed. Patients admitted between July 2016 and July 2019 were included in the training cohort, and patients admitted between August 2019 and December 2021 were included in the validation cohort. According to the diagnosis of arthroscopy, the patients were divided into SSC tear group and non-SSC tear group. Univariate analysis, least absolute shrinkage and selection operator (LASSO) method, and 10-fold cross-validation method were used to screen for reliable predictors highly associated with SSC tendon tear in a training set cohort, and R language was used to build a nomogram model for internal and external validation. The prediction performance of the nomogram was evaluated by concordance index (C-index) and calibration curve with 1 000 Bootstrap. Receiver operating curves were drawn to evaluate the diagnostic performance (sensitivity, specificity, predictive value, likelihood ratio) of the predictive model and MRI (based on direct signs), respectively. Decision curve analysis (DCA) was used to evaluate the clinical implications of predictive models and MRI. Results: The nomogram model showed good discrimination in predicting the risk of SSC tendon tear in patients [C-index=0.878; 95% CI(0.839, 0.918)], and the calibration curve showed that the predicted results were basically consistent with the actual results. The research identified 6 predictors highly associated with SSC tendon tears, including coracohumeral distance (oblique sagittal) reduction, effusion sign (Y-plane), subcoracoid effusion sign, biceps long head tendon displacement (dislocation/subluxation), multiple posterosuperior rotator cuff tears (≥2, supra/infraspinatus), and MRI suspected SSC tear (based on direct sign). Compared with MRI diagnosis based on direct signs of SSC tendon tear, the predictive model had superior sensitivity (80.2% vs. 57.0%), positive predictive value (53.9% vs. 53.3%), negative predictive value (92.7% vs. 86.3%), positive likelihood ratio (3.75 vs. 3.66), and negative likelihood ratio (0.25 vs. 0.51). DCA suggested that the predictive model could produce higher clinical benefit when the risk threshold probability was between 3% and 93%. Conclusion: The nomogram model can reliably predict the risk of SSC tendon tear and can be used as an important tool for auxiliary diagnosis.

Effects of geographic isolation on the Bulbophyllum chloroplast genomes.

BACKGROUND: Because chloroplast (cp) genome has more conserved structures than nuclear genome and mitochondrial genome, it is a useful tool in estimating the phylogenetic relationships of plants. With a series of researches for cp genomes, there have been comprehensive understandings about the cp genome features. The genus Bulbophyllum widely distributed in Asia, South America, Australia and other places. Therefore, it is an excellent type genus for studying the effects of geographic isolation. RESULTS: In this study, the cp genomes of nine Bulbophyllum orchids were newly sequenced and assembled using the next-generation sequencing technology. Based on 19 Asian (AN) and eight South American (SA) Bulbophyllum orchids, the cp genome features of AN clade and SA clade were compared. Comparative analysis showed that there were considerable differences in overall cp genome features between two clades in three aspects, including basic cp genome features, SSC/IRB junctions (JSBs) and mutational hotspots. The phylogenetic analysis and divergence time estimation results showed that the AN clade has diverged from the SA clade in the late Oligocene (21.50-30.12 mya). After estimating the occurrence rates of the insertions and deletions (InDels), we found that the change trends of cp genome structures between two clades were different under geographic isolation. Finally, we compared selective pressures on cp genes and found that long-term geographic isolation made AN and SA Bulbophyllum cp genes evolved variably. CONCLUSION: The results revealed that the overall structural characteristics of Bulbophyllum cp genomes diverged during the long-term geographic isolation, and the crassulacean acid metabolism (CAM) pathway may play an important role in the Bulbophyllum species evolution.

Identifying key factors associated with subscapularis tendon tears and developing a risk prediction model to assist diagnosis.

BACKGROUND: There are still some challenges in diagnosing subscapularis (SSC) tendon tears as accurately as posterosuperior rotator cuff tears on MRI. The omission of SSC tendon tear can lead to muscle atrophy, fatty infiltration, and increased tearing accompanied by aggravated shoulder pain and loss of function. An effective non-invasive evaluation tool will be beneficial to early identification and intervention. The study aims to identify sensitive predictors associated with SSC tendon tears and develop a risk prediction model to assist in diagnosis. METHODS: Data on 660 patients who received shoulder arthroscopic surgery with preoperative shoulder MRI were collected retrospectively. Of these, patients with SSC tendon tears were defined as the SSC tear group, and patients with intact SSC tendon were enrolled in the non-SSC tear group. Logistic regression analysis was used to identify the key predictors of SSC tendon tears which were then incorporated into the nomogram. RESULTS: Among 22 candidate factors, five independent factors including coracohumeral distance (CHD, oblique sagittal plane) (OR, 0.75; 95%CI, [0.67-0.84]), fluid accumulation (Y-face) (OR, 2.29; 95%CI, [1.20-4.38]), long head of biceps tendon (LHB) dislocation/subluxation (OR, 3.62; 95%CI, [1.96-6.68]), number of posterosuperior (PS) rotator cuff tears (OR, 5.36; 95%CI, [3.12-9.22]), and MRI diagnosis (based on direct signs) (OR, 1.88; 95%CI, [1.06-3.32]) were identified as key predictors associated with SSC tendon tears. Incorporating these predictors, the nomogram achieved a good C index with a good agreement on the risk estimation of calibration plots. Higher total points of the nomogram were associated with a greater risk of SSC tendon tears. CONCLUSION: When evaluating the severity of SSC tendon injury, the combination of reliable predictors can improve the sensitivity and diagnostic performance of MRI. This model provides an individualized probability of risk prediction, which is convenient for clinicians to identify patients at high risk for SSC tendon tears to avoid missed diagnosis.