Sirolimus for the treatment of patients with refractory connective tissue disease-related thrombocytopenia: a pilot study.

OBJECTIVE: CTD-related immune thrombocytopenia (CTD-ITP) represents an unmet medical need because the drugs that are available are only partly effective and have considerable side-effects. The aim of this study was to assess the efficacy and safety of sirolimus in refractory CTD-ITP patients. METHODS: We did a single-arm, open-label, pilot study of sirolimus in patients with CTD-ITP unresponsive to, or intolerant of, conventional medications. Patients received oral sirolimus for 6 months at a starting dose of 0.5-1 mg per day, with dose adjusted according to tolerance and to maintain a therapeutic range of 6-15 ng/ml. The primary efficacy end point was changes in platelet count, and overall response assessed according to the ITP International Working Group Criteria. Safety outcomes included tolerance as assessed by the occurrence of common side-effects. RESULTS: Between November 2020 and February 2022, 12 consecutively hospitalized patients with refractory CTD-ITP were enrolled and prospectively followed. Of these, six patients (50%) achieved complete response, two (16.7%) achieved partial response, and four (33.3%) were no response under therapy. Three of four patients with primary Sjögren's syndrome and two of three patients with systemic lupus erythematosus achieved overall response. One of two patients with overlapping Sjögren's syndrome and systemic lupus erythematosus achieved complete response at 6 months. No severe drug-related toxicities were observed. CONCLUSION: Our results do support sirolimus as an alternative regimen for refractory CTD-ITP patients, including systemic lupus erythematosus and primary SS.

Management of Concomitant Inflammatory Bowel Disease or Uveitis in Patients with Psoriatic Arthritis: An Updated Review Informing the 2021 GRAPPA Treatment Recommendations.

OBJECTIVE: Several advanced therapies have been licensed across the related conditions of psoriatic arthritis (PsA), Crohn disease (CD), ulcerative colitis (UC), and noninfectious uveitis. We sought to summarize results from randomized controlled trials (RCTs) investigating the efficacy and safety of advanced therapies for these related conditions in patients with PsA. METHODS: We updated the previous systematic search conducted in 2013 with literature reviews of MEDLINE, Embase, and the Cochrane Library (from February 2013 to August 2020) on this subject; only those new studies are presented here. The quality of evidence was assessed using the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) framework. RESULTS: The number of RCTs meeting eligibility criteria were 12 for CD, 15 for UC, and 5 for uveitis. The tumor necrosis factor inhibitor (TNFi) class appears to be efficacious and safe across CD, UC, and uveitis, with the exception of etanercept. Interleukin 12/23 inhibitors (IL-12/23i) are efficacious for CD and UC. Phase II and III RCTs of Janus kinase inhibitors (JAKi) and IL-23i in CD and UC are promising in terms of efficacy and safety. IL-17i must be used with great caution in patients with PsA at high risk of inflammatory bowel disease (IBD). RCTs in uveitis have mainly studied adalimumab. CONCLUSION: We have identified 32 recent RCTs in IBD and uveitis and updated recommendations for managing patients with PsA and these related conditions. A multispecialty approach is essential to effectively, safely, and holistically manage such patients. Advanced therapies are not equally efficacious across these related conditions, with dosing regimens and safety varying.

Short-Term Patient Outcomes Using the Interlaminar Endoscopic Surgical System Ilessys® Delta System versus Bilateral Laminotomy: A Single-Center Study of 80 Patients with Degenerative Lumbar Spinal Stenosis.

BACKGROUND This study from a single center aimed to compare short-term patient outcomes from the Interlaminar Endoscopic Surgical System iLESSYS® Delta system vs bilateral laminotomy in 80 patients with degenerative lumbar spinal stenosis (DLSS). MATERIAL AND METHODS We selected 80 patients with DLSS for the study. Of these, 40 were treated with the iLESSYS® Delta system and 40 were treated with bilateral laminotomy. We followed these patients for 1 year. We recorded and compared data on incision length, operation time and intraoperative blood loss, hospitalization time, postoperative complications, the visual analog scale (VAS), and Oswestry Disability Index (ODI) before, 1 week, 3 months, 6 months, and 12 months after surgery, and the Modified Macnab evaluation criteria. RESULTS The incision length, intraoperative blood loss, and hospitalization time were significantly better in group A than in group B (P<0.05); however, the operation time in group B was shorter than that in group A, and the differences were statistically significant (P<0.05). The VAS and ODI in both groups improved significantly after surgery compared with before the operation. The VAS and ODI in group A patients after surgery were lower than those in group B, and only at 1 week after surgery,(P<0.05). The excellent rate of modified MacNab criteria was not statistically significant between groups A and B (P>0.05). CONCLUSIONS Use of the Interlaminar Endoscopic Surgical System iLESSYS® Delta system can effectively manage DLSS and speed patient recovery.

Pattern and trend of five major musculoskeletal disorders in China from 1990 to 2017: findings from the Global Burden of Disease Study 2017.

BACKGROUND: With increasing life expectancy in China, no large population-based studies have been done on the trend for musculoskeletal disorders in China. We have investigated the pattern and trend of five major musculoskeletal disorders in China from the Global Burden of Disease Study 2017 and its association with sociodemographic index (SDI). METHODS: The main outcome measures were incidence, prevalence, and disability-adjusted life years (DALYs) for rheumatoid arthritis, osteoarthritis, low back pain, neck pain, and gout. Average annual percent change (AAPC) and annual percent change (APC) between 1990 and 2017 were analyzed with Joinpoint regression. RESULTS: The age-standardized rate of incidence, prevalence, and DALYs for the five major musculoskeletal disorders increased with age. For SDI, the age-standardized rate of DALYs was zigzagged increasing for rheumatoid arthritis and curvilinear increasing for gout, curvilinear decreasing for low back pain, and reaching to the highest point for osteoarthritis and neck pain with an SDI value of 0.61. The AAPC in age-standardized rate of DALYs indicated an increasing trend for rheumatoid arthritis (0.20, 95% CI 0.07, 0.34), osteoarthritis (0.26, 95% CI 0.20, 0.31), neck pain (0.09, 95% CI 0.07, 0.12), and gout (0.25, 95% CI 0.23, 0.27), but a decreasing trend for low back pain (- 0.96, 95% CI - 0.98, - 0.93). The AAPC of risk factors indicated a decreasing trend in smoking (- 0.14, 95% CI - 0.24, - 0.04) for rheumatoid arthritis, smoking (- 0.22, 95% CI - 0.24, - 0.19) and occupational ergonomic factors (- 1.25, 95% CI - 1.29, - 1.21) for low back pain, and impaired kidney function (- 0.95, 95% CI - 1.00, - 0.90) for gout, but an increasing trend in high body-mass index for osteoarthritis (3.10, 95% CI 3.03, 3.17), low back pain (3.07, 95% CI 2.99, 3.14), and gout (3.12, 95% CI 3.04, 3.20). Comparing the burden of five musculoskeletal diseases in China with the 19 countries of G20, China ranked first to second in the number of DALYs, and 12th to 16th in age-standardized rate of DALYs. CONCLUSION: There are remarkably complex temporal patterns in disease burden and risk factors for five major musculoskeletal disorders across past three decades. Population-wide initiatives targeting high body-mass index may mitigate the burden of musculoskeletal disorders.

The causal effect of interleukin-17 on the risk of psoriatic arthritis: a Mendelian randomization study.

OBJECTIVE: To determine causal associations between genetically predicted TNF-α, IL-12p70 and IL-17 levels and risk of PsA. METHODS: The publicly available summary-level findings from genome-wide association studies (GWAS) was used to identify loci influencing normal physiological concentrations of TNF-α, IL-12p70 and IL-17 (n = 8293) among healthy individuals as exposure and a GWAS for PsA from the UK Biobank (PsA = 900, control = 462 033) as the outcome. A two-sample Mendelian randomization (MR) analysis was performed using the inverse-variance weighted (IVW), weighted median and MR-Egger regression methods. Sensitivity analysis and MR-Egger regression analysis were performed to evaluate the heterogeneity and pleiotropic effects of each variant. RESULTS: Single-nucleotide polymorphisms (SNPs) at genome-wide significance from GWASs on TNF-α, IL-12p70 and IL-17 were identified as the instrumental variables. The IVW method indicated a causal association between increased IL-17 level and risk of PsA (ß = -0.00186 per allele, s.e. = 0.00043, P = 0.002). Results were consistent in the weighted median method (ß = -0.00145 per allele, s.e. = 0.00059, P = 0.014) although the MR-Egger method suggested a non-significant association (ß = -0.00133 per allele, s.e. = 0.00087; P = 0.087). Single SNP MR results revealed that the C allele of rs117556572 was robustly associated with risk of PsA (ß = 0.00210, s.e. = 0.00069, P = 0.002). However, no evidence for a causal effect was observed between TNF-α, IL-12p70, decreased IL-17 levels and risk of PsA. CONCLUSION: Our findings provide preliminary evidence that genetic variants predisposing to higher physiological IL-17 level are associated with decreased risk of PsA.

Effect of biologics on radiographic progression of peripheral joint in patients with psoriatic arthritis: meta-analysis.

OBJECTIVES: To determine the efficacy of biologics in preventing radiographic progression in peripheral joints of PsA patients. METHODS: Studies were searched in MEDLINE, Web of Science, and abstracts from the last three EULAR and ACR meetings up to 31 December 2019. Primary and secondary endpoints were the proportion of patients without radiographic progression and the mean change in total radiographic score at week 24. RESULTS: Eleven studies, involving 5382 patients, 9 drugs and 18 treatments, were included. Patients receiving biologics were more likely to achieve radiographic non-progression compared with placebo [odds ratio: pooled: 2.40, 95% CI: 2.00, 2.87; TNF inhibitors (TNFi): 2.94, 95% CI: 2.38, 3.63; IL inhibitors (ILi): 2.15, 95% CI: 1.69, 2.74; abatacept: 1.54, 95% CI: 1.03, 2.28] and have significantly lower radiographic progression [standardized mean difference (SMD): pooled: -2.16, 95% CI: -2.91, -1.41; TNFi: -2.82, 95% CI: -4.31, -1.33; ILi: -1.60, 95% CI: -2.49, -0.72; abatacept: -0.40, 95% CI: -0.59, -0.21]. Concomitant MTX therapy was not superior to monotherapy (SMD: pooled: 0.01, 95% CI: -0.07, 0.08; biologics: 0.01, 95% CI: -0.09, 0.11; placebo: -0.01, 95% CI: -0.13, 0.12). The effect of ustekinumab and secukinumab on radiographic progression was not influenced by prior anti-TNF therapy (SMD: -0.08, 95% CI: -0.25, 0.10). CONCLUSION: Biologic agents may retard radiographic progression in PsA patients in terms of bone erosion and joint space narrowing compared with placebo. MTX seems to have no added effect. Prior anti-TNF therapy seems to not influence the radiographic efficacy of IL blockers.

Efficacy and safety of biologics targeting interleukin-6, -12/23 and -17 pathways for peripheral psoriatic arthritis: a network meta-analysis.

OBJECTIVE: To investigate the comparative efficacy, safety and tolerability of IL-6, IL-12/23 and IL-17 inhibitors for patients with active PsA. METHODS: Randomized controlled trials evaluating the efficacy, safety and tolerability of IL-6, IL-12/23 and IL-17 inhibitors were identified by a comprehensive systematic literature review. Pairwise meta-analyses and Bayesian network meta-analyses using the random effects model were performed to estimate pooled odds ratios (ORs) and 95% credible intervals of attaining a 20% or 50% improvement in ACR criteria (ACR20 and ACR50, respectively) across trials. RESULTS: Six trials were identified that included 2411 participants and 11 treatments. Pairwise meta-analysis showed that secukinumab, ustekinumab and ixekizumab demonstrated superior efficacy over placebo in achieving an ACR20 and ACR50 response. However, ixekizumab has a higher incidence of adverse events (AEs) than placebo. In contrast, ustekinumab has a higher tolerability (less likely to be discontinued due to AEs) than placebo. Network meta-analysis showed that secukinumab (300 mg monthly) had the highest efficacy in achieving ACR20 and ACR50, whereas clazakizumab (200 mg monthly), ustekinumab (45 mg 12 weekly) and secukinumab (150 mg monthly) had the lowest probability of having AEs, serious AEs and intolerability, respectively. Considering the overall risk-benefit profile, secukinumab (150 mg monthly) may offer an optimal balance for peripheral PsA patients. CONCLUSION: Secukinumab may be the safest and most efficacious short-term treatment for peripheral PsA among all the new biologics targeting IL-6, IL-12/23 and IL-17 pathways.

Association between asymptomatic hyperuricemia and risk of arthritis, findings from a US National Survey 2007-2018.

BACKGROUND: Arthritis is thought to be closely related to serum uric acid. The study aims to assess the association between asymptomatic hyperuricemia (AH) and arthritis. METHODS: A multistage, stratified cluster was used to conduct a cross-sectional study of adult US civilians aged≥20 years from the 2007-2018 National Health and Nutrition Examination Survey. Participants with hyperuricemia and without hyperuricemia prior to gout were included. A questionnaire was used to determine whether participants had arthritis and the type of arthritis. Logistic regression was used to investigate the association between hyperuricemia and arthritis. RESULT: During the past 12 years, the percentage of participants with arthritis changed from 25.95% (22.53%-29.36%) to 25.53% (21.62%-29.44%). The prevalence of osteoarthritis (OA) increased from 8.70% (95% CI: 6.56% to 10.85%) to 12.44% (95% CI: 9.32% to 15.55%), the prevalence of AH changed from 16.35% (95% CI: 14.01% to 18.40%) to 16.39% (95% CI: 13.47% to 19.30%). Participants with AH were associated with onset of arthritis (OR=1.34, 95% CI: 1.07 to 1.69), but the association was muted after adjusting demographic and socioeconomic factors. For participants aged 40-49 years, AH is associated with incident arthritis (OR=1.96, 95% CI: 1.23 to 2.99) and the relationship remained after adjusting for education level, income to poverty ratio, body mass index, diabetes, hypertension and smoking (OR=2.00, 95% CI: 1.94 to 3.36). Compared with male, female participants with AH are more likely to develop arthritis, especially in OA (OR=1.35, 95% CI: 1.14 to 1.60). CONCLUSION: Our data identified AH as the risk factor for incident arthritis, especially for OA, which might be exaggerated in aged population and female population.

Tocilizumab Successfully Treating Refractory Hearing Impairment in a Patient With Cogan Syndrome: A Case Report and Review of the Literature.

Cogan syndrome (CS) is a rare systemic vasculitis characterized primarily by nonsyphilitic interstitial keratitis and vestibular and auditory dysfunction. In this article, we report the case of a 31-year-old male diagnosed with CS for 1 year. He was admitted to the hospital with fever, dizziness, headache, tinnitus, and hearing loss. After being treated with glucocorticoids, cellular immunosuppressants, and infliximab therapy, his symptoms were greatly relieved except for hearing loss. Then, he attempted to use tocilizumab (TCZ) which was ultimately effective in controlling the auditory dysfunction. In addition, we found 4 cases of TCZ for CS through a literature review and compared them with our patient. Although glucocorticoids are still the first-line treatment for CS, TCZ therapy provides fresh hope for patients who have refractory hearing impairment with hormone resistance, or whose hormone dosages cannot be lowered to maintenance levels.

Association between the composite dietary antioxidant index and sarcopenia among United States adults: A cross-sectional study.

BACKGROUND: Diets high in antioxidants are associated with decreased prevalence of sarcopenia. This study aimed to investigate whether the composite dietary antioxidant index (CDAI) and sarcopenia have an underlying relationship. METHODS: We used the data from the National Health and Nutrition Examination Survey 2011-2018. According to dietary antioxidant intake, the CDAI was calculated for each individual. Appendicular skeletal muscle mass index was employed to determine sarcopenia. Multivariate weighted logistic models and restricted cubic spline regression analysis was undertaken to determine the association between CDAI and sarcopenia. RESULTS: A total of 7012 participants were enrolled in this study, including 473 with sarcopenia (weighted percentage, 5.6%). Compared with the lowest tertile, those in the highest tertile of the CDAI exhibited a greater likelihood of being male, with lower body mass index, higher education level and economic standard, and more chance of being single or separated. In multivariate weighted logistic models, model 3 revealed a noteworthy inverse association between the CDAI and sarcopenia (odds ratio = 0.94; 95% CI, 0.91-0.98; P = 0.003). Compared with the lowest tertile, the highest tertile of CDAI was associated with a 0.57-fold risk of sarcopenia (95% CI, 0.42-0.77; P < 0.001). The inverse association between CDAI and sarcopenia strengthened in the participants with elevated education levels (P for interaction = 0.003). CONCLUSION: The CDAI was inversely correlated with the prevalence of sarcopenia. As a comprehensive measurement representing antioxidant status, the CDAI may help manage and prevent sarcopenia.

Magnetic fibrin nanofiber hydrogel delivering iron oxide magnetic nanoparticles promotes peripheral nerve regeneration.

Peripheral nerve injury is a debilitating condition that have a profound impact on the overall quality of an individual's life. The repair of peripheral nerve defects continues to present significant challenges in the field. Iron oxide magnetic nanoparticles (IONPs) have been recognized as potent nanotools for promoting the regeneration of peripheral nerves due to their capability as biological carriers and their ability to template the hydrogel structure under an external magnetic field. This research used a fibrin nanofiber hydrogel loaded with IONPs (IONPs/fibrin) to promote the regeneration of peripheral nerves in rats. In vitro examination of PC12 cells on various concentrations of IONPs/fibrin hydrogels revealed a remarkable increase in NGF and VEGF expression at 2% IONPs concentration. The biocompatibility and degradation of 2% IONPs/fibrin hydrogel were assessed using the in vivo imaging system, demonstrating subcutaneous degradation within a week without immediate inflammation. Bridging a 10-mm sciatic nerve gap in Sprague Dawley rats with 2% IONPs/fibrin hydrogel led to satisfactory morphological recovery of myelinated nerve fibers. And motor functional recovery in the 2% IONPs/fibrin group was comparable to autografts at 6, 9 and 12 weeks postoperatively. Hence, the composite fibrin hydrogel incorporating 2% IONPs exhibits potential for peripheral nerve regeneration.

Prognostic value and association of the age-adjusted Charlson Comorbidity Index with sarcopenia within patients with gastric cancer after radical resection.

PURPOSE: The association between the age-adjusted Charlson Comorbidity Index (ACCI) and sarcopenia in patients with gastric cancer (GC) remains ambiguous. This study aimed to investigate the association between the ACCI and sarcopenia and the prognostic value in patients with GC after radical resection. In addition, this study aimed to develop a novel prognostic scoring system based on these factors. METHODS: Univariate and multivariate Cox regression analyses were used to determine prognostic factors in patients undergoing radical GC resection. Based on the ACCI and sarcopenia, a new prognostic score (age-adjusted Charlson Comorbidity Index and Sarcopenia [ACCIS]) was established, and its prognostic value was assessed. RESULTS: This study included 1068 patients with GC. Multivariate analysis revealed that the ACCI and sarcopenia were independent risk factors during the prognosis of GC (P = 0.001 and P < 0.001, respectively). A higher ACCI score independently predicted sarcopenia (P = 0.014). A high ACCIS score was associated with a greater American Society of Anesthesiologists score, higher pathologic TNM (pTNM) stage, and larger tumor size (all P < 0.05). Multivariate analysis demonstrated that the ACCIS independently predicted the prognosis for patients with GC (P < 0.001). By incorporating the ACCIS score into a prognostic model with sex, pTNM stage, tumor size, and tumor differentiation, we constructed a nomogram to predict the prognosis accurately (concordance index of 0.741). CONCLUSION: The ACCI score and sarcopenia are significantly correlated in patients with GC. The integration of the ACCI score and sarcopenia markedly enhances the accuracy of prognostic predictions in patients with GC.

Advancing Understanding of Childhood Asthma: Lessons Learned from Birth Cohort Studies.

Asthma and allergies are some of the most common chronic disorders affecting children, the prevalence of which has been increasing in countries and regions undergoing rapid development like China. To curb the rising tide of allergies and safeguard the health of future generations, it is of critical importance to understand how asthma inception is influenced by factors acting at different life stages. Birth cohorts represent a powerful tool to investigate the temporal sequence of exposures along the natural course of asthma. We examined recent evidence on birth cohort studies of asthma and allergic diseases and evaluated their strengths and weaknesses. Essential elements for a successful birth cohort are proposed to further elucidate asthma etiology and pathogenies. Initiating new cohorts in understudied populations with the application of advanced analytical approaches will be needed. Moreover, fostering collaborative networks using standardized methodologies should be prioritized to enable integration of findings across diverse cohorts. There remains an urgent and unmet need to further translate the seminal findings from asthma birth cohort studies into targeted primary prevention strategies to eradicate the disease.

Advanced TiO2/Al2O3 Bilayer ALD Coatings for Improved Lithium-Rich Layered Oxide Electrodes.

Surface modification is a highly effective strategy for addressing issues in lithium-rich layered oxide (LLO) cathodes, including phase transformation, particle cracking, oxygen gas release, and transition-metal ion dissolution. Existing single-/double-layer coating strategies face drawbacks such as poor component contact and complexity. Herein, we present the results of a low-temperature atomic layer deposition (ALD) process for creating a TiO2/Al2O3 bilayer on composite cathodes made of AS200 (Li1.08Ni0.34Co0.08Mn0.5O2). Electrochemical analysis demonstrates that TiO2/Al2O3-coated LLO electrodes exhibit improved discharge capacities and enhanced capacity retention compared with uncoated samples. The TAA-5/AS200 bilayer-coated electrode, in particular, demonstrates exceptional capacity retention (∼90.4%) and a specific discharge capacity of 146 mAh g-1 after 100 cycles at 1C within the voltage range of 2.2 to 4.6 V. The coated electrodes also show reduced voltage decay, lower surface film resistance, and improved interfacial charge transfer resistances, contributing to enhanced stability. The ALD-deposited TiO2/Al2O3 bilayer coatings exhibit promising potential for advancing the electrochemical performance of lithium-rich layered oxide cathodes in lithium-ion batteries.

Imaging in psoriatic arthritis: established methods and emerging techniques.

Psoriatic arthritis (PsA) is a heterogeneous, chronic, inflammatory musculoskeletal disease that can lead to peripheral and axial damage and loss of function. A clear difference between PsA and other forms of inflammatory arthritis is the different forms of bone remodeling seen in PSA which incorporates not only increased bone resorption with bone erosions, osteolysis, and loss of bone mineral density but also increased bone formation with periostitis, syndesmophytes, enthesiophytes, and ankylosis. PsA, if diagnosed late, will lead to significant structural damage, the most severe form of which is known as arthritis mutilans, and loss of physical function. Imaging plays a crucial role in diagnosing and monitoring both peripheral and axial conditions associated with PsA. Radiography is currently the main modality used to monitor structural damage in PsA though commonly used scoring systems do not include bony proliferation as a criterion. Besides, radiography is limited in determining the presence and cause of periarticular soft tissue thickening, which may arise from tendinosis, tenosynovitis, synovial proliferation, bursitis, or enthesitis. Recently, much more attention has been paid to determining the imaging characteristics of PsA, which enables more precise identification of disease and severity assessment. Newer imaging technologies also enable variations in normal bone microstructure to be distinguished from disease-related abnormality. This review discusses the current state of innovative imaging modalities in PsA, specifically concentrating on their roles in PsA diagnosis and treatment, improving the early detection of PsA, and identifying patients with skin psoriasis at risk of developing psoriatic arthritis.

Comparison of Delta Spinal Endoscopy and Bilateral Laminotomy for Short-term Patient Outcomes in Degenerative Lumbar Spinal Stenosis.

This prospective randomised controlled trial aimed to compare the clinical efficacy of Delta spinal endoscopy with bilateral laminotomy for degenerative lumbar spinal stenosis (DLSS). Eighty patients with DLSS were randomly assigned to two groups: 40 treatments by Delta spinal endoscopy named (A) and 40 treatments by bilateral laminotomy named (A). Patients were followed up for one year. The incision length, intraoperative bleeding, and hospitalisation time were lower in group A than in B (p <0.01); however, the operation time in group B was lower than in A (p <0.05). The VAS and ODI in both groups improved significantly after surgery, compared with the results before the surgery. The VAS and ODI in group A after surgery were lower than in B, but only for one week after the surgery, (p <0.05). The excellent rate of modified MacNab criteria was not statistically significant between groups A and B (p >0.05). Overall, Delta spinal endoscopy can effectively manage DLSS with faster patient recovery. Key Words: Delta spinal endoscopy, Spinal stenosis, Minimally invasive, Bilateral laminotomy.

Temporal trend of population structure, burden of diseases, healthcare resources and expenditure in China, 2000-2019.

OBJECTIVES: To explore the evolutionary trend of population structure, disease burden, healthcare resources and expenditure in China, and to identify key domains that are most in need of intervention. DESIGN: A cross-sectional and longitudinal analysis. DATA SOURCE: Population and healthcare data from China Statistical Yearbook, and disease burden attributable to causes and risk factors from the Global Burden of Diseases between 2000 and 2019. MEASURES AND METHODS: We used the Joinpoint Regression Program to measure trends in population composition, population change, dependency ratio, healthcare institution, personnel, expenditure and disease burden from 2000 to 2019. RESULTS: Regarding the population in China between 2000 and 2019, a decreasing trend was observed among youth aged 0-14 years (average annual percent change (AAPC): -1.17), a slow rising trend was observed among individuals aged 15-64 years (AAPC: 1.10) and a rapidly increasing trend was observed among individuals older than 65 years (AAPC: 3.67). Astonishing increasing trends in healthcare institutions (AAPC: 3.97), medical personnel (AAPC: 3.26) and healthcare expenditures (AAPC: 15.28) were also observed. Among individuals younger than 70 years, neoplasms (AAPC: 0.54) and cardiovascular diseases (AAPC: 0.67) remained among the top three causes, while tobacco (AAPC: 0.22) remained a top three risk factor. However, while musculoskeletal disorders (AAPC: 1.88) were not a top three cause in 2000, they are a top three cause in 2019. CONCLUSION: Comprehensive age/cause/risk factor-specific strategies are key to reconcile the tension among the triad of population ageing, disease burden and healthcare expenditure. The disease burden from cardiometabolic diseases, neoplasms and musculoskeletal disorders was identified as key domains that require intervention to reduce an increasing disease burden among individuals currently older than 70 years, as well as those approaching this age group.

Hydrothermal Extraction and Characterization of Natural Hydroxyapatite from Waste Bovine Femur Bone.

The management of large amounts of bio-wastes, such as bovine femurs from kitchens and slaughterhouses, has long been a challenging issue. However, through the utilization of a hydrothermal process, it is possible to transform these bio-wastes into valuable products. In this study, we focused on extracting hydroxyapatite (HAp), the primary inorganic component of bovine femurs, for potential use in bone tissue engineering scaffolds. By subjecting the femurs to hydrothermal treatment at varying times and solvents, we successfully decomposed and removed the organic matter present, resulting in the extraction of HAp. To comprehensively evaluate the properties of the extracted HAp, we employed several characterization techniques that provided valuable insights into the structure, morphology, and elemental composition of the extracted HAp. Furthermore, we conducted a Cell Counting Kit-8 assay, which confirmed the favorable biocompatibility of the extracted HAp. Overall, this study highlights the potential of hydrothermal treatment as an environmentally friendly and cost-effective method for handling bio-waste, specifically bovine femurs. The extracted HAp exhibits promising characteristics, making it suitable for a wide range of biomedical applications. This research contributes to the sustainable utilization of bio-waste and underscores the importance of resourceful exploitation for environmental protection.

Evaluation of causal associations between interleukin-18 levels and immune-mediated inflammatory diseases: a Mendelian randomization study.

BACKGROUND: Altered interleukin (IL)-18 levels are associated with immune-mediated inflammatory diseases (IMIDs), but no studies have investigated their causal relationship. This study aimed to examine the causal associations between IL-18 and IMIDs. METHODS: We performed a two-sample Mendelian randomization (MR) analysis. Genetic variants were selected from genome-wide association study datasets following stringent assessments. We then used these variants as instrumental variables to estimate the causal effects of IL-18 levels on the risk of developing five common IMIDs: rheumatoid arthritis (RA), systemic lupus erythematosus (SLE), inflammatory bowel disease (IBD), ankylosing spondylitis (AS), and psoriasis. We used the inverse variance-weighted (IVW) method as the primary analysis, with sensitivity analyses performed to avoid potential bias. Reverse-direction MR analyses were performed to rule out the possibility of reverse associations. RESULTS: We found that genetically determined higher circulating IL-18 levels were causally associated with a higher risk for SLE (PIVW = 0.009; OR, 1.214; 95% CI, 1.049 - 1.404) and IBD (PIVW < 0.001; OR, 1.142; 95% CI, 1.062 - 1.228), but found no significant associations of IL-18 with RA (PIVW = 0.496; OR, 1.044; 95% CI, 0.923 - 1.180), AS (PIVW = 0.021; OR, 1.181; 95% CI, 1.025 - 1.361), or psoriasis (PIVW = 0.232; OR, 1.198; 95% CI, 0.891 - 1.611). In the reverse direction, no causal relationship existed between SLE or IBD and IL-18 levels. Globally, sensitivity studies using alternative MR methods supported the results that were robust and reliable. The Cochran's Q test, MR-Egger intercept, and MR-Pleiotropy RESidual Sum and Outlier excluded the influence of heterogeneity, horizontal pleiotropy, and outliers. CONCLUSIONS: We have demonstrated that elevated IL-18 levels increase the risk of SLE and IBD but not RA, AS, or psoriasis. The results enhanced our understanding of IL-18 in the pathology of IMIDs.