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.

Incidence of hip fracture among middle-aged and older Chinese from 2013 to 2015: results from a nationally representative study.

China is experiencing remarkable changes in people aging and migration. Therefore, the incidence and associated factors for hip fracture might differ from previous results. A nationally representative study of hip fracture enables policymakers to formulate preventive strategies and provide information on resource allocation. PURPOSE: To estimate the incidence of hip fracture, between 2013 and 2015, among the middle-aged and older Chinese population. METHODS: Individuals with hip fractures between 2013 and 2015 were identified from the China Health and Retirement Longitudinal Study. The sex-specific incidence and the associated factors of hip fracture were assessed. RESULTS: Among 19,112 individuals (51.4% women; mean age 60.5 years) included in the analysis, 408 (2.13%) had a hip fracture between 2013 and 2015. Moreover, the annual incidence of hip fracture for men and women were 1065 and 1069 per 100,000, respectively. The incidence of hip fracture increased with age (p < 0.001). A history of chronic disease, being unmarried, and individuals without insurance were associated with a higher incidence of hip fracture. Interestingly, the incidence of hip fracture was higher among individuals with fewer years of education (p = 0.002). The North-East regions of China had the lowest incidence of hip fracture (1022 per 100,000) between 2013 and 2015, followed by the North (1602 per 100,000), South-Central (2055 per 100,000), East (2173 per 100,000), and South-West (2537 per 100,000) regions. Finally, the incidence was highest among participants living in the North-West region (3244 per 100,000). CONCLUSION: Between 2013 and 2015, the incidence of hip fracture is high among the middle-aged and older Chinese population. Furthermore, it varied significantly according to sociodemographic and geographic factors. Therefore, the support of targeted health policies and cost-effective preventive strategies are warranted in China.

Corrigendum: Global Trends in Intertrochanteric Hip Fracture Research From 2001 to 2020: A Bibliometric and Visualized Study.

[This corrects the article DOI: 10.3389/fsurg.2021.756614.].

Influencing factors for the decline of limb muscle strength and the association with all-cause mortality: evidence from a nationwide population-based cohort study.

BACKGROUND: The decline of muscle strength, a typical characteristic of sarcopenia, greatly affects aging-related health outcomes; however, prospective data on influencing factors and mortality in the Chinese population are relatively sparse. AIMS: We investigated the influencing factors for the declined limb muscle strength and the association with all-cause mortality among the elderly Chinese individuals aged ≥ 65 years in a large long-term prospective cohort study. METHODS: We used data from the China Health and Retirement Longitudinal Study (CHARLS). Logistic regression analyses were performed to investigate the influencing factors of declined limb muscle strength. Cox proportional hazard models were used to analyze the impact on all-cause mortality, whose performance was evaluated by train-test cross-validation. RESULTS: The prevalences of declined upper and lower limb strength, which were defined by low hand grip strength (HS) and gait speed (GS), respectively, were 34.4% and 59.7%. The declined HS was significantly associated with older age (p < 0.001), female (p < 0.001), lower educational level (p < 0.001), lower BMI (p < 0.001), and combined with chronic diseases (p = 0.001). Moreover, the declined limb muscle strength was correlated with all-cause mortality (HR: 1.13, 95% CI 1.03-1.21 for HS; HR: 1.09, 95% CI 1.04-1.15 for GS), according to a multi-adjusted model with moderate predictive ability (C-index: 0.714, AUC of 7 year follow-up: 0.716). CONCLUSIONS: The decline of limb muscle strength was prevalent among elderly Chinese individuals and had a strong impact on all-cause mortality. Identification of key populations and tailored interventions on their influencing factors should be implemented in further research.

Global Trends in Intertrochanteric Hip Fracture Research From 2001 to 2020: A Bibliometric and Visualized Study.

Background: Intertrochanteric femur fractures, which are common geriatric osteoporotic fractures, have imposed a huge economic and social burden. This study clarified the global status of research on intertrochanteric fractures between 2001 and 2020 and predicted future research trends in this field using bibliometric and visualized studies. Methods: Publications related to intertrochanteric fractures were retrieved from the Web of Science (WoS) database. All studies were published between 2001 and 2020. Bibliometric and co-occurrence analyses were conducted using VoS viewer software. Results: In total, 2,632 studies were retrieved. The number of global publications regarding intertrochanteric fractures increased annually. The United States was the largest contributor, ranking first in total publications, citations, and the H-index. Switzerland had the highest average citation frequency among the 10 countries with the highest number of publications. The journal that published the most articles regarding intertrochanteric fractures was the Injury International Journal of The Care of The Injured, with 290 articles published. This journal also ranked first in the citation frequency. MJ Parker, an author, published the most papers in the field, and the University of California research team at San Francisco contributed the most publications in this field. During the co-occurrence analysis, all keywords were divided into four clusters: internal fixation study, complication study, risk-factor study, and survival and prognosis analysis study. The internal fixation and survival and prognosis analysis studies were predicted as the next hot topics in the field of intertrochanteric fractures. Conclusions: Intertrochanteric fractures are gaining increasing research attention according to the current global trend, and the number of publications regarding intertrochanteric hip fractures will continue to increase. The United States currently publishes the most articles on intertrochanteric fractures. The number of studies related to internal fixation, survival, and prognosis analysis is increasing, suggesting that these topics may become the next research hotspots in the area of intertrochanteric fractures.

Use of pH-Active Catechol-Bearing Polymeric Nanogels with Glutathione-Responsive Dissociation to Codeliver Bortezomib and Doxorubicin for the Synergistic Therapy of Cancer.

Synergistic therapy holds promising potential in cancer treatment. Here, the inclusion of catechol moieties, a disulfide cross-linked structure, and pendent carboxyl into the network of polymeric nanogels with glutathione (GSH)-responsive dissociation and pH-sensitive release is first disclosed for the codelivery of doxorubicin (DOX) and bortezomib (BTZ) in synergistic cancer therapy. The pendent carboxyl groups and catechol moieties are exploited to absorb DOX through electrostatic interaction and conjugate BTZ through boronate ester, respectively. Both electrostatic interactions and boronate ester are stable at neutral or alkaline pH, while they are instable in an acidic environment to further recover the activities of BTZ and DOX. The polymeric nanogels possess a superior stability to prevent the premature leakage of drugs in a physiological environment, while their structure is destroyed in response to a typical endogenous stimulus (GSH) to unload drugs. The dissociation of the drug-loaded nanogels accelerates the intracellular release of DOX and BTZ and further enhances the therapeutic efficacy. In vitro and in vivo investigations revealed that the dual-drug loaded polymeric nanogels exhibited a strong ability to suppress tumor growth. This study thus proposes a new perspective on the production of multifunctional polymeric nanogels through the introduction of different functional monomers.

Prevalence of pediatric Kashin-Beck disease in Tibet.

INTRODUCTION: To estimate the prevalence of Kashin-Beck disease (KBD) among children in 2017 in Changdu of Tibet. METHODS: We adopted a four-step recruitment to include children aged 7-12 years from seven identified historically endemic counties in Changdu. Posterior-anterior radiographs of right hand and wrist were taken and were graded at four sites (metaphysis, epiphysis, and bony end of phalanges and metacarpal and carpal bones). Two trained researchers independently read the films. Inter-rater reliability was assessed using weighted Kappa and percentage agreement. We fitted logistic regression model to examine the association of age, sex, and altitude of residential village with prevalence of KBD. We examined association between site involvement and severity of KBD using chi-square test. RESULTS: We recruited 13,573 children (mean age = 9.3 years, 48.40% girls) with a response rate of 95.81%. The overall prevalence of radiographic KBD was 0.26%. Luolong County had the highest prevalence (0.69%), followed by Bianba (0.26%), Basu (0.24%), Mangkang (0.14%), Zuogong (0.14%), Dingqing (0.07%), and Chaya (0.00%). A higher risk of radiographic KBD was associated with older age (P for trend <0.001) and girls (OR=1.86, 95% CI: 0.94, 3.70), but not the altitude of residential village (P for trend=0.957). Metaphysis was involved in all cases of KBD while lesions in epiphysis and bony end of phalanges and metacarpals were only observed in severe cases. CONCLUSIONS: The prevalence of radiographic KBD among children aged 7-12 years was low in Changdu compared with previous census data, suggesting the effectiveness of preventative measures. Key Points • In this study, 13,573 Tibetan children were taken X-ray films of their hands and wrists. • The prevalence of radiographic KBD among children aged 7-12 years was low in Changdu of Tibet. • The preventative measures against KBD launched by Chinese government were effective in decreasing new onsets of KBD among Tibetan children.

The prevalence and economic burden of pain on middle-aged and elderly Chinese people: results from the China health and retirement longitudinal study.

BACKGROUND: To estimate the prevalence of pain among people aged 45 years and older in China, to analyze the effect factors of pain and pain related economic burden. METHODS: Nationally representative sample was derived from China Health and Retirement Longitudinal Study (CHARLS). Pain data, medical cost data were obtained, as well as information of demographic characteristics, social structure, social-economic status, other health needs and health behaviors. The prevalence of pain in 2011, 2013, and 2015 was calculated. Univariate analysis and multivariate analysis were used to find the effect factors of pain. An optimization two-part model was used to calculate the range of the direct medical costs caused by pain. RESULTS: The prevalence of pain among people 45 years or older in China was 31.73% in 2011, 37.27% in 2013 and 28.62% in 2015. When evaluating factors lead a higher prevalence of pain, the results of the multi-variable after one-way analysis were older age, female, lower education, rural residents, without insurance status, abstained from alcohol and lower body mass index (BMI). Through the optimization of two-part model, the direct medical costs caused by pain was 898.9-1563.0 yuan in 2011, 2035.8-2568.7 yuan in 2013 and 2628.8-3945.7 yuan in 2015 (129.9US$ - 225.9US$ in 2011, 294.2 US$ - 371.2US$ in 2013 and 379.9US$ - 570.2US$ in 2015, converted to 2010 RMB). CONCLUSION: The prevalence of pain among middle-aged and elderly Chinese is high. Residents with older age, female, lower education, rural residents, without insurance status, abstained from alcohol and lower BMI seem to have a higher pain prevalence. Pain can cause extra direct medical costs and will cause more economic loss with the progress of time. Future research should pay more attention to effective treatment, management and prevention of pain to decrease its burden.

Burden of osteoarthritis in China, 1990-2017: findings from the Global Burden of Disease Study 2017.

BACKGROUND: China has seen a remarkable epidemiological and demographic transition during the past three decades. We aimed to describe the prevalence of osteoarthritis as well as years lived with disability (YLDs) due to osteoarthritis in China, according to age, sex, and geographical location, from 1990 to 2017. METHODS: Data were obtained from systematic reviews of symptomatic osteoarthritis of the knee and hip in the Global Burden of Diseases, Injuries, and Risk Factors Study 2017 (GBD 2017). Three categories of sequelae (mild, moderate, and severe) of osteoarthritis were defined to indicate the degrees of severity and functional loss associated with the condition. A Bayesian meta-regression tool was applied to estimate the prevalence of osteoarthritis and the distribution of its severity. YLDs were calculated by multiplying the prevalence of osteoarthritis sequelae by their corresponding disability weights. All data were analysed by age-sex-province-year groups in China. FINDINGS: Around 26·1 million individuals in China had osteoarthritis in 1990, and this number rose to 61·2 million in 2017. The age-standardised prevalence of osteoarthritis increased from 2·9% (95% uncertainty interval 2·5-3·3) in 1990 to 3·1% (2·7-3·4) in 2017. The total YLDs due to osteoarthritis increased from 0·84 million (0·42-1·69) in 1990 to 1·97 million (0·98-3·94) in 2017, while the age-standardised YLD rate increased from 92·5 (45·7-185·6) per 100 000 people to 98·8 (49·4-197·6) per 100 000. Osteoarthritis prevalence and YLDs were higher in females than in males, and YLD rate increased with age. Osteoarthritis was the 24th most common cause of YLDs in China in 2017, accounting for 1·08% (0·64-2·02) of all YLDs. INTERPRETATION: Osteoarthritis is prevalent in China. Between 1990 and 2017, disease burden increased and varied greatly according to geographical location. Appropriate prevention and treatment strategies, predominantly those targeted at women, older people, and underdeveloped areas, must be developed to reduce the burden of the disease. FUNDING: National Natural Science Foundation of China, China National Key Research and Development Programme.

Imaging features in incident radiographic patellofemoral osteoarthritis: the Beijing Shunyi osteoarthritis (BJS) study.

BACKGROUND: The present study aims to describe the imaging features in incident radiographic patellofemoral osteoarthritis (RPFOA) population in a Chinese suburban area. METHODS: The Beijing Shunyi osteoarthritis (BJS) study was a population-based, longitudinal and prospective study. Residents were recruited by randomized cluster sampling in 2014 and were followed 3 years later. Home interviews and clinical examinations were performed; weight-bearing posterior-anterior semi-flexed (45-degree) views of the tibiofemoral (TF) joints and skyline (45-degree) views of the patellofemoral (PF) joints were included. For each batch of study films (n = 100), 20 films from the year 2014 and 20 previously read PF radiographs were fed back to test inter-/intra-reader repeatability. The imaging features of incident RPFOA were analyzed. Narrative statistics, independent-sample t-tests, and nonparametric tests were performed. RESULTS: A total of 1295 participants (2590 knees) were recruited at baseline in 2014, and 967 (74.7%) residents were followed in 2017. Of all the knees (n = 1537) without RPFOA at baseline, 139 knees (13.3%) across 119 people developed incident RPFOA. Compared with the whole population, age (p = 0.031), body mass index (BMI, p = 0.042), and incidence of knee pain symptoms (p < 0.01) were significantly different in the incident RPFOA population, while range of motion (ROM, p = 0.052) and gender (0/1, p = 0.203) showed no significance. In the incident population, the changes of each imaging indicator grade were evaluated-lateral patellofemoral osteophyte (LPOST, increased by 1.02), medial patellofemoral osteophyte (MPOST, increased by 0.49), lateral joint space narrowing (LJSN, increased by 0.30), medial joint space narrowing (MJSN, increased by 0.06); indicator grade progress decreases, respectively. The progress of LPOST was the fastest among the four indicators (p < 0.01). CONCLUSIONS: In this population-based longitudinal study, among the incident RPFOA population, the imaging indicators show that marginal patellofemoral osteophyte is more pronounced than patellofemoral joint space narrowing. LPOST is the fastest-progressing indicator among all the radiographic features, which is also the most common imaging manifestation of RPFOA. In the incident RPFOA population, the proportion of elders, women, higher-BMI individuals, and people suffering knee pain is more than the normal population.

Clinical characteristics and genetic analysis of gene mutations in a Chinese pedigree with Peutz-Jeghers syndrome.

The genome-wide sequencing information of PJS is still lacking. Our result demonstrates that c.862+2T>C variant on STK11 as an important foundation of molecular mechanism in this familial PJS. Variants in KDR and MLL3 may play important roles in the initiation and development of this familial PJS polyps.

Metal-Organic Framework-Assisted Nanoplatform with Hydrogen Peroxide/Glutathione Dual-Sensitive On-Demand Drug Release for Targeting Tumors and Their Microenvironment.

A hydrogen peroxide (H2O2)/glutathione (GSH) dual-sensitive nanoplatform holds great promise to alleviate the side effects of chemo drugs and improve their therapeutic efficacy against cancer. The site-specific release of chemo drugs with a low premature release still remains a challenge in the field of chemotherapy. In the present work, a novel and multifunctional drug delivery system (DDS) based on a polymethylacrylic acid core with a cross-linked structure of disulfide bond (PMAABACy), metal-organic framework (MOF) interlayer and biologically inspired polydopamine (PDA) coating was developed, serving as a vehicle for on-demand drug release. The dual-responsive nanoplatform not only prevents the premature leakage of a chemotherapeutic drug but also is sensitive to biologically relevant GSH and H2O2 for the precise delivery of chemotherapeutic drug. Considering the transmission route to DDS at the tumor site, the DDS might first respond to the extracellular H2O2 and then to the intracellular GSH, exhibiting a tunable release of chemotherapeutic drug. Through incubation using tumor cells, the growth of tumor cells could be significantly inhibited. Overall, by integrating these different building modules, this research demonstrates the advantages of the MOF-assisted regulate strategy to DDS for a precise site-specific release against tumor cells with a greatly reduced side effect on normal tissues.

Charge reversible and biodegradable nanocarriers showing dual pH-/reduction-sensitive disintegration for rapid site-specific drug delivery.

Dual pH-/reduction-sensitive biodegradable poly(methacrylic acid-co-N,N-bis(acryloyl)cystamine)/chitosan/dimethylmaleic anhydride-modified chitosan (PMAABACy/CS/CS-DMMA) nanoparticles with PMAABACy cores as carriers and dimethylmaleic anhydride-modified chitosan as charge reversible shells were rationally designed. PMAABACy cores using N,N-Bis(acryloyl)cystamine (BACy) as a crosslinker and methacrylic acid (MAA) as a monomer were fabricated via a mild and facile one-pot distillation-precipitation polymerization. After that, CS and CS-DMMA were alternately adsorbed on the surface of PMAABACy cores through a mild self-assembly. The results from TEM and DLS reveal that the PMAABACy/CS/CS-DMMA nanoparticles with desired size and hydrodynamic diameter. And then the nanoparticles exhibit the excellent drug-loading capacity and encapsulation efficiency toward anti-cancer agent doxorubicin (DOX), whereas be rapidly triggered to realize the GSH-sensitive site-specific release via the destruction of sulfide cross-linked structure in response to the intracellular environment of tumor cells. Furthermore, their surface charges could transfer from negative in neutral or basic medium to positive in acidic medium to enhance cellular uptake. Most importantly, the excellent anticancer activity has been also revealed using confocal laser scanning microscope (CLSM) analysis, namely successfully delivering DOX molecules to the cell nucleus. These experimental results indicate that such the novel dual pH-/reduction-sensitive biodegradable PMAABACy/CS/CS-DMMA with surface charge reversal have great potential as a desired anticancer drug carrier for cancer therapy.

Design and Development of Graphene Oxide Nanoparticle/Chitosan Hybrids Showing pH-Sensitive Surface Charge-Reversible Ability for Efficient Intracellular Doxorubicin Delivery.

A novel graphene oxide nanoparticle (GON)-based drug delivery system containing GONs as carriers of anticancer drugs and chitosan/dimethylmaleic anhydride-modified chitosan (CS/CS-DMMA) as surface charge-reversible shells is fabricated via the classic self-assembly of the deprotonated carboxyl of GONs and the protonated amine of the CS backbone by electrostatic interaction, and CS-DMMA serves as the outmost layer. In this GON-based drug delivery system, the GON cores as desired carriers might adsorb doxorubicin hydrochloride (DOX) via the π-π stacking interaction between the large π conjugated structures of GO and the aromatic structure of DOX. Meanwhile, the chitosan-based polyelectrolyte shells served as a smart protection screen to evade the premature release of the as-loaded DOX in normal extracellular condition, and then, the release of DOX was accelerated because of the detachment of chitosan coating at low pH. Furthermore, the re-exposure of amino groups after hydrolysis of CS-DMMA endowed the drug delivery system with positive surface charge by taking advantage of the pH difference between physiological conditions and the tumor microenvironment to enhance the cellular uptake. Then, the pH-dependent site-specific drug release was realized. The in vitro investigations confirmed that these promising GON/CS/CS-DMMA hybrids with the charge-reversible character possessed various merits including excellent encapsulation efficiency, high stability under physiological conditions, enhanced cellular uptake by HepG2 cells, and tunable intracellular chemotherapeutic agent release profiles, proving its capability as an intelligent anticancer agent nanocarrier with enhanced therapeutic effects. This smart GON/CS/CS-DMMA vehicle with the surface charge-reversible character may be used as a significant drug delivery system for cancer treatment.