Effect of Preoperative Carbohydrate Loading on Postoperative Recovery of Individuals Who Have Type 2 Diabetes After Total Knee Arthroplasty: A Randomized Controlled Trial.

BACKGROUND: Many individuals undergoing surgery involving general anesthesia are asked to fast for a prolonged period to ensure perioperative safety, yet this can initiate stress reactions and insulin resistance, harming postoperative recovery. Such fasting may be particularly problematic for those who have type 2 diabetes. Here, we assessed how giving such individuals' oral carbohydrates before total knee arthroplasty can affect outcomes. METHODS: We randomized 90 patients who had non-insulin-dependent type 2 diabetes mellitus who were scheduled for elective total knee arthroplasty at one medical center between April 2022 and January 2023 to receive oral carbohydrates at two or four hours before surgery or to receive a carbohydrate-free "placebo" drink at four hours before surgery. The three groups were compared in terms of postoperative blood glucose, insulin resistance, ß cell activity, postoperative wound complications, and other clinical outcomes. RESULTS: The group who received oral carbohydrates at two or four hours before surgery showed significantly lower insulin resistance than the placebo group (group at two hours, 9.0 ± 3.4; group at four hours, 15.8 ± 6.9 versus placebo, 30.9 ± 10.5, P < 0.001) and lower ß cell activity (207.7 ± 106.7%; group at four hours, 243.2 ± 114.9% versus 421.5 ± 209.3%, P < 0.001). Those groups were also significantly less likely than the placebo group to experience preoperative hunger or postoperative hyperglycemia. Among patients who received oral carbohydrates, those who received them two hours before surgery showed significantly lower insulin resistance and better glycemic control on postoperative day 1 than those who received carbohydrates four hours before surgery. None of the subjects developed intraoperative aspiration or experienced severe postoperative complications. CONCLUSION: Oral carbohydrates at two to four hours before total knee arthroplasty are safe and can significantly alleviate preoperative hunger while mitigating postoperative insulin resistance and improving glycemic control in patients who have non-insulin-dependent type 2 diabetes mellitus.

Janus-Structured Microgel Barrier with Tissue Adhesive and Hemostatic Characteristics for Efficient Prevention of Postoperative Adhesion.

Postoperative adhesion (POA) is a common and serious complication following various types of surgery. Current physical barriers either have a short residence time at the surgical site with a low tissue attachment capacity or are prone to undesired adhesion formation owing to the double-sided adhesive property, which limits the POA prevention efficacy of the barriers. In this study, Janus-structured microgels (Janus-MGs) with asymmetric tissue adhesion capabilities are fabricated using a novel bio-friendly gas-shearing microfluidic platform. The anti-adhesive side of Janus-MGs, which consists of alginate, hyaluronic acid, and derivatives, endows the material with separation, lubrication, and adhesion prevention properties. The adhesive side provided Janus-MGs with tissue attachment and retention capability through catechol-based adhesion, thereby enhancing the in situ adhesion prevention effect. In addition, Janus-MGs significantly reduced blood loss and shortened the hemostatic time in rats, further reducing adhesion formation. Three commonly used rat POA models with different tissue structures and motion patterns are established in this study, namely peritoneal adhesion, intrauterine adhesion, and peritendinous adhesion models, and the results showed that Janus-MGs effectively prevented the occurrence of POA in all the models. The fabrication of Janus-MGs offers a reliable strategy and a promising paradigm for preventing POA following diverse surgical procedures.

Cross-country inequalities in disease burden and care quality of chronic kidney disease due to type 2 diabetes mellitus, 1990-2021: Findings from the global burden of disease study 2021.

AIM: To explore the trend of burden and care quality of chronic kidney disease due to type 2 diabetes mellitus (CKD-T2DM) and their cross-country inequalities from 1990 to 2021. MATERIALS AND METHODS: Data were from the Global Burden of Disease 2021 study. Disease burden and care quality were quantified using the disability-adjusted life years rate and the quality-of-care index (QCI). Trend analyses of the age-standardized disability-adjusted life years rate (ASDR) and age-standardized QCI from 1990 to 2021 were conducted using the estimated annual percentage change. The associations of disease burden and care quality with the socio-demographic index (SDI) were explored. Cross-country inequalities in disease burden and care quality were assessed using the slope index of inequality (SII) and concentration index. RESULTS: From 1990 to 2021, the global ASDR for CKD-T2DM increased, while the age-standardized QCI slightly decreased, with an estimated annual percentage change of 0.81 [95% confidence interval (CI): 0.75, 0.87] and -0.08 (95% CI: -0.09, -0.07). The ASDR escalated with increasing SDI, reaching a peak at mid-level SDI, followed by a decrease. The age-standardized QCI was higher with increasing SDI. Globally, ASDR concentrated on countries/territories with a lower SDI. The SII of ASDR was -96.64 (95% CI: -136.94, -56.35) in 1990 and -118.15 (95% CI: -166.36, -69.94) in 2021,  with a concentration index of -0.1298 (95% CI: -0.1904, -0.0692) in 1990 and -0.1104 (95% CI: -0.1819, -0.0389) in 2021. In 1990 and 2021, countries/territories at higher SDI levels exhibited increased age-standardized QCI, indicated by an SII of 15.09 (95% CI: 10.74, 19.45) and 15.75 (95% CI: 10.92, 20.59), and a concentration index of 0.0393 (95% CI: 0.0283, 0.0503) and 0.0400 (95% CI: 0.0264, 0.0536). CONCLUSIONS: Our study highlights considerable disparities in the burden and care quality of CKD-T2DM. Regions experiencing an increasing burden and a declining care quality simultaneously underscore the need for further research and tailored health interventions.

Inequalities in disease burden and care quality of chronic obstructive pulmonary disease, 1990-2021: Findings from the Global Burden of Disease Study 2021.

Background: Chronic obstructive pulmonary disease (COPD) is one of the primary causes of significant morbidity and mortality worldwide. This study aimed to explore the cross-country inequalities by age, sex, and region in COPD's burden and care quality from 1990 to 2021. Methods: We obtained data from the Global Burden of Disease 2021. Using age-standardised disability-adjusted life years rate (ASDR) per 100 000 population and quality of care index (QCI), we quantified the COPD burden and care quality, respectively. Applying the principal component analysis method, we calculated QCI scores, ranging from 0 to 100, where higher values indicate better care quality. We quantified temporal trends from 1990 to 2021 for ASDR and QCI by estimated annual percentage change (EAPC). Finally, we assessed the absolute and relative disparities in ASDR and QCI across countries using the slope index of inequality (SII) and concentration index. Results: Between 1990 and 2021, there was a notable decline in ASDR of COPD globally (1990 = 1492.64; 2021 = 940.66; EAPC = -1.71), accompanied by an increase in QCI (1990 = 58.42; 2021 = 73.86; EAPC = 0.89). Regions with middle sociodemographic index (SDI) consistently demonstrated the highest ASDR and the lowest QCI in 1990 (ASDR = 2332.91; QCI = 31.70), whereas by 2021, low-middle SDI regions exhibited similar trends (ASDR = 1707.90; QCI = 57.50). In 2021, the highest ASDR was among individuals aged 95 years and above (16251.22), while the lowest QCI was among people aged 70-74 years (72.18). Papua New Guinea recorded the highest ASDR and the lowest QCI in 2021 (ASDR = 3004.36; QCI = 19.18). Compared to 1990, where the SII for ASDR was -612.44 and for QCI was 21.78, with concentration indices of -0.14 for ASDR and 0.11 for QCI, the absolute values of both SII and concentration index were smaller in 2021, with ASDR's SII at -555.90, QCI's at 16.72, ASDR's concentration index at -0.13, and QCI's at 0.04. Conclusions: The global burden of COPD decreases and care quality increases over time, with notable variations across ages, sexes and SDI regions. Countries with lower SDI had disproportionately higher burden and poorer care quality for COPD.

Temporal trends in cross-country inequalities of stroke and subtypes burden from 1990 to 2021: a secondary analysis of the global burden of disease study 2021.

Background: Stroke remains a significant global health challenge, with persistent disparities in burden across different countries and regions. This study aimed to assess the temporal trends in cross-country inequalities of stroke and its subtypes burden from 1990 to 2021. Methods: We conducted a secondary analysis of the Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2021. The age-standardised disability-adjusted life years (DALYs) rate (ASDR) was used to assess the burden of stroke and its subtypes (ischemic stroke, intracerebral haemorrhage, and subarachnoid haemorrhage) across 21 GBD regions and 204 countries. The slope index of inequality (SII) and the concentration index were calculated to quantify the absolute and relative cross-country inequalities in the burden of stroke and its subtypes, with negative values indicating a higher burden in lower socio-demographic index (SDI) countries, and positive values indicating a higher burden in higher SDI countries. Estimated annual percentage change (EAPC) was used to illustrate temporal trends at global and regional levels from 1990 to 2021. The inequality changing patterns from 1990 to 2021 were classified as worsening, improving, and shifting to higher burdens among higher or lower SDI countries. Findings: From 1990 to 2021, the ASDR of total stroke decreased from 3078.95 (95% uncertainty interval [UI]: 2893.58, 3237.34) to 1886.20 (95% UI: 1738.99, 2017.90) per 100,000 population globally. While both absolute and relative inequalities increased, with a disproportionately higher burden shouldered by countries with lower SDI. The SII of total stroke exhibited a worsening inequality among lower SDI countries, increasing by 286.97 units from -2329.47 (95% confidence interval [CI]: -2857.50, -1801.43) in 1990 to -2616.44 (95% CI: -2987.33, -2245.56) in 2021. Similarly, the concentration index of total stroke increased by 0.03 from -0.0819 (95% CI: -0.1143, -0.0495) in 1990 to -0.1119 (95% CI: -0.1478, -0.0759) in 2021. The changing patterns from 1990 to 2021 were diverse across regions, yet most regions exhibited a worsening inequality among lower SDI countries in both SII and concentration index. Southern Sub-Saharan Africa showed the largest worsening inequality in SII (EAPC: -2.15, 95% CI: -2.71, -1.57) while Central Europe showed the largest worsening inequality in concentration index (EAPC: -0.51, 95% CI: -0.58, -0.44). In 2021, the highest negative SII was observed in Oceania and the highest negative concentration index was in the Caribbean. In terms of subtypes, ischemic stroke reported a worsening inequality among lower SDI countries in SII (EAPC: -2.13, 95% CI: -2.20, -2.05) while intracerebral haemorrhage showed an improving inequality in SII (EAPC: 0.44, 95% CI: 0.40, 0.47). SII in subarachnoid haemorrhage (EAPC: -0.18, 95% CI: -0.19, -0.17) and concentration index in ischemic stroke (EAPC: -0.25, 95% CI: -0.27, -0.23) presented a shift to higher burden among lower SDI countries from 1990 to 2021. Interpretation: Although the burden of stroke and its subtypes decreased from 1990 to 2021, inequalities have persisted and even widened in some regions. Timely and effective prevention and management strategies for stroke and its subtypes are needed in specific areas to reduce the stroke burden and achieve equity in health outcomes. Funding: None.

Dose-Response Associations of Internet Use Time and Internet Addiction With Depressive Symptoms Among Chinese Children and Adolescents: Cross-Sectional Study.

Background: Children's lives are increasingly mediated by digital technologies, yet evidence regarding the associations between internet use and depression is far from comprehensive and remains unclear. Objective: This study aimed to investigate the dose-response association between internet use, including use time and addiction behaviors, and depressive symptoms among children and adolescents in Zhejiang Province. Methods: Data were collected from a school-based health survey China Common Disease and Risk Factor Surveillance Among Students, encompassing 21,336 students in Zhejiang Province. The daily internet use time, internet addiction (IA) behaviors, and depressive symptoms were assessed with questionnaires. Logistic regression models were used to explore the associations of internet use time and IA behaviors with depressive symptoms among children and adolescents. Restricted cubic spline curves were used to determine the dose-response associations. Results: A total of 6225 (29.2%) students had depressive symptoms. Compared to those reporting no internet use, boys using the internet for >2 hours/day (odds ratio [OR] 1.53, 95% CI 1.34-1.74) and girls using internet for 1.1-2 hours/day (OR 1.22, 95% CI 1.06-1.39) and >2 hours/day (OR 1.70, 95% CI 1.50-1.93) were at higher risks of depressive symptoms. A significant J-shaped association was identified between internet use time and depressive symptoms among children and adolescents, especially in boys and primary school students (nonlinear P values were .006, .003, and <.001, respectively). Increased IA behaviors were associated with a higher odd of depressive symptoms (1 IA behavior: OR 2.01, 95% CI 1.83-2.21; 2 IA behaviors: 2.91, 95% CI 2.57-3.29; and ≥3 IA behaviors: 4.72, 95% CI 4.26-5.22). A positive nonlinear association between the number of IA behaviors and depressive symptoms was found in total population, girls, and primary school students (nonlinear P values were .02, .002, .007, respectively). Conclusions: Findings suggested that excessive internet use time and IA behaviors were significantly associated with an increased risk of depressive symptoms, highlighting the importance of interventions to regulate and educate about adequate internet use during childhood and adolescence.

Prevalence of childhood hypertension and associated factors in Zhejiang Province: a cross-sectional analysis based on random forest model and logistic regression.

With childhood hypertension emerging as a global public health concern, understanding its associated factors is crucial. This study investigated the prevalence and associated factors of hypertension among Chinese children. This cross-sectional investigation was conducted in Pinghu, Zhejiang province, involving 2,373 children aged 8-14 years from 12 schools. Anthropometric measurements were taken by trained staff. Blood pressure (BP) was measured in three separate occasions, with an interval of at least two weeks. Childhood hypertension was defined as systolic blood pressure (SBP) and/or diastolic blood pressure (DBP) ≥ age-, sex-, and height-specific 95th percentile, across all three visits. A self-administered questionnaire was utilized to collect demographic, socioeconomic, health behavioral, and parental information at the first visit of BP measurement. Random forest (RF) and multivariable logistic regression model were used collectively to identify associated factors. Additionally, population attributable fractions (PAFs) were calculated. The prevalence of childhood hypertension was 5.0% (95% confidence interval [CI]: 4.1-5.9%). Children with body mass index (BMI) ≥ 85th percentile were grouped into abnormal weight, and those with waist circumference (WC) > 90th percentile were sorted into central obesity. Normal weight with central obesity (NWCO, adjusted odds ratio [aOR] = 5.04, 95% CI: 1.96-12.98), abnormal weight with no central obesity (AWNCO, aOR = 4.60, 95% CI: 2.57-8.21), and abnormal weight with central obesity (AWCO, aOR = 9.94, 95% CI: 6.06-16.32) were associated with an increased risk of childhood hypertension. Childhood hypertension was attributable to AWCO mostly (PAF: 0.64, 95% CI: 0.50-0.75), followed by AWNCO (PAF: 0.34, 95% CI: 0.19-0.51), and NWCO (PAF: 0.13, 95% CI: 0.03-0.30). Our results indicated that obesity phenotype is associated with childhood hypertension, and the role of weight management could serve as potential target for intervention.

Association between disease activity of rheumatoid arthritis and risk of complications following total hip arthroplasty: a retrospective cohort study.

BACKGROUND: Identifying rheumatoid arthritis patients at higher risk of complications after total hip arthroplasty could make perioperative management more effective. Here we examined whether disease activity is associated with risk of such complications. METHODS: We retrospectively analyzed data for 337 rheumatoid arthritis patients at our medical center who underwent primary total hip arthroplasty. Rheumatoid arthritis patients were categorized according to the simplified disease activity index (SDAI), the values of which at admission and follow-up were averaged together. Logistic regression was used to examine associations of mean SDAI with rates of dislocation, infection, periprosthetic fracture and aseptic loosening. As controls, 337 osteoarthritis patients who did not have systemic inflammation and who underwent the same procedure were matched across numerous clinicodemographic variables. RESULTS: Among the 337 rheumatoid arthritis patients, 38 (11.3%) had postoperative complications, the rates of which varied significantly from 0 to 17.5% (p = 0.003) among the four subgroups whose disease activity based on mean SDAI was categorized as high, moderate, low or in remission. Each 1-unit increase in mean SDAI was associated with a significant increase in risk of postoperative complications (OR 1.015, 95% CI 1.001-1.029, p = 0.035). Across all rheumatoid arthritis patients, rate of complications did not differ significantly between patients who received disease-modifying anti-rheumatic drugs or other treatments. Rates of dislocation, of infection or of all postoperative complications combined were significantly lower among osteoarthritis controls than among rheumatoid arthritis patients. CONCLUSION: Greater mean SDAI is associated with higher risk of dislocation, infection and composite postoperative complications after total hip arthroplasty in rheumatoid arthritis patients. These patients show a significantly higher rate of postoperative complications than osteoarthritis patients, likely reflecting the influence of systemic inflammation. Disease activity should be reduced as much as possible in rheumatoid arthritis patients before they undergo total hip arthroplasty.

Age at natural menopause and associated factors with early and late menopause among Chinese women in Zhejiang province: A cross-sectional study.

OBJECTIVES: Menopause is a significant life transition for women, impacting their physical and psychological health. The age at natural menopause (ANM) and its associated factors have differed by race and region. This study aimed to investigate ANM and associated factors of early and late menopause among Chinese women in Zhejiang province. METHODS: A cross-sectional study was conducted using a multi-stage stratified cluster sampling method to recruit 8,006 women aged 40-69 years who had resided in Zhejiang province for over 6 months between July 2019 and December 2021. Self-reported ANM and sociodemographics, lifestyle behaviors, reproductive history, and health-related factors were collected using questionnaires in face-to-face surveys. ANM were categorized into three groups: early menopause (<45 years), normal menopause (45-54 years), and late menopause (≥55 years). Kaplan-Meier survival analysis was utilized to calculate the median ANM. Multivariable multinomial logistic regression was employed to explore the associated factors of early menopause and late menopause. RESULTS: A total of 6,047 women aged 40-69 years were included for survival analysis, with 3,176 of them for the regression analysis. The overall median ANM was 51 years (Inter-quartile range [IQR]: 51-52). Women who were smokers (odds ratio [OR]:4.54, 95% confidence interval [CI]:1.6-12.84), had irregular menstrual cycles (OR:1.78, 95% CI:1.12-2.83) and hypertension (OR:1.55, 95% CI:1.09-2.21) had a higher odds ratio of early menopause, while central obesity (OR:1.33, 95% CI:1.03-1.73) and hyperlipidemia (OR:1.51, 95% CI:1.04-2.18) were factors associated with late menopause. CONCLUSIONS: This study revealed the associations between ANM and various factors among Chinese women. These factors included socio-demographic factors such as age; life behavior factors like current or prior smoking status; reproductive history factors such as irregular menstrual cycles, miscarriages, and breastfeeding; and health-related factors like central adiposity, hypertension, and hyperlipidemia. These findings provided a basis for understanding factors associated with ANM.

Genome-wide analysis of R2R3-MYB transcription factors in poplar and functional validation of PagMYB147 in defense against Melampsora magnusiana.

MAIN CONCLUSION: Transcription of PagMYB147 was induced in poplar infected by Melampsora magnusiana, and a decline in its expression levels increases the host's susceptibility, whereas its overexpression promotes resistance to rust disease. Poplars are valuable tree species with diverse industrial and silvicultural applications. The R2R3-MYB subfamily of transcription factors plays a crucial role in response to biotic stresses. However, the functional studies on poplar R2R3-MYB genes in resistance to leaf rust disease are still insufficient. We identified 191 putative R2R3-MYB genes in the Populus trichocarpa genome. A phylogenetic analysis grouped poplar R2R3-MYBs and Arabidopsis R2R3-MYBs into 33 subgroups. We detected 12 tandem duplication events and 148 segmental duplication events, with the latter likely being the main contributor to the expansion of poplar R2R3-MYB genes. The promoter regions of these genes contained numerous cis-acting regulatory elements associated with response to stress and phytohormones. Analyses of RNA-Seq data identified a multiple R2R3-MYB genes response to Melampsora magnusiana (Mmag). Among them, PagMYB147 was significantly up-regulated under Mmag inoculation, salicylic acid (SA) and methyl jasmonate (MeJA) treatment, and its encoded product was primarily localized to the cell nucleus. Silencing of PagMYB147 exacerbated the severity of Mmag infection, likely because of decreased reactive oxygen species (ROS) production and phenylalanine ammonia-lyase (PAL) enzyme activity, and up-regulation of genes related to ROS scavenging and down-regulation of genes related to PAL, SA and JA signaling pathway. In contrast, plants overexpressing PagMYB147 showed the opposite ROS accumulation, PAL enzyme activity, SA and JA-related gene expressions, and improved Mmag resistance. Our findings suggest that PagMYB147 acts as a positive regulatory factor, affecting resistance in poplar to Mmag by its involvement in the regulation of ROS homeostasis, SA and JA signaling pathway.

Perioperative Short-Term Glucocorticoids Do Not Increase Incidence of Complications after Total Joint Arthroplasty in Patients with Rheumatoid Arthritis.

OBJECTIVES: The safety and analgesic efficacy of perioperative glucocorticoids have been established for patients without rheumatoid arthritis. Therefore, our study aims to investigate whether similar benefits can be observed in patients with rheumatoid arthritis undergoing total joint arthroplasty. Specifically, we aim to explore the impact of perioperative glucocorticoid use on postoperative complications, opioid consumption, incidence of hypotension, hyperglycemia, 30-day mortality, and 90-day re-admission in this patient population. METHODS: Approval for the study protocol was obtained from the Medical Research Ethics Committee at Sichuan University, aligning with the principles outlined in the Declaration of Helsinki. We retrospectively analyzed a consecutive series of patients with rheumatoid arthritis who underwent total joint arthroplasty at our medical center between November 2009 and April 2021 and who were not on chronic glucocorticoid therapy before surgery. Those who received glucocorticoids at any time during hospitalization were compared to those who did not in terms of acute complications within 90 days after surgery as well as postoperative rescue opioid consumption, hypotension, and hyperglycemia during hospitalization. The two groups were also compared in terms of overall duration of hospitalization, all-cause mortality within 30 days, and readmission for any reason within 90 days. Continuous data were assessed for significance using the independent-samples t test. Categorical data were assessed using the Pearson chi-squared test. RESULTS: Of the 849 patients included in the analysis, 598 administered perioperative glucocorticoids and 251 did not. Prior to surgery, the two groups did not differ significantly in any clinicodemographic variable that we examined. The incidence of acute postoperative complications (2.3% vs. 4.0%, p = 0.187) and acute postoperative infection (2.0% vs. 2.8%, p = 0.482) was comparable between those who received perioperative glucocorticoids and those who did not, but the former group exhibited a significantly lower incidence of rescue opioid use (17.9% vs. 44.6%, p < 0.001) as well as significantly lower total rescue opioid consumption (4.7 ± 2.1 mg vs. 8.9 ± 4.6 mg, p < 0.001). However, the two groups showed similar incidences of postoperative hypotension, hyperglycemia, 30-day mortality, and 90-day re-admission. CONCLUSION: Perioperative glucocorticoids may reduce the need for rescue opioids after total joint arthroplasty of rheumatoid arthritis patients, without increasing the incidence of acute complications, hypotension or hyperglycemia.

A Composite Hydrogel Functionalized by Borosilicate Bioactive Glasses and VEGF for Critical-Size Bone Regeneration.

Critical-size bone defects pose a formidable challenge in clinical treatment, prompting extensive research efforts to address this problem. In this study, an inorganic-organic multifunctional composite hydrogel denoted as PLG-g-TA/VEGF/Sr-BGNPs is developed, engineered for the synergistic management of bone defects. The composite hydrogel demonstrated the capacity for mineralization, hydroxyapatite formation, and gradual release of essential functional ions and vascular endothelial growth factor (VEGF) and also maintained an alkaline microenvironment. The composite hydrogel promoted the proliferation and osteogenic differentiation of rat bone marrow mesenchymal stem cells (rBMSCs), as indicated by increased expression of osteogenesis-related genes and proteins in vitro. Moreover, the composite hydrogel significantly enhanced the tube-forming capability of human umbilical vein endothelial cells (HUVECs) and effectively inhibited the process of osteoblastic differentiation of nuclear factor kappa-B ligand (RANKL)-induced Raw264.7 cells and osteoclast bone resorption. After the implantation of the composite hydrogel into rat cranial bone defects, the expression of osteogenic and angiogenic biomarkers increased, substantiating its efficacy in promoting bone defect repair in vivo. The commendable attributes of the multifunctional composite hydrogel underscore its pivotal role in expediting hydrogel-associated bone growth and repairing critical bone defects, positioning it as a promising adjuvant therapy candidate for large-segment bone defects.

Socioeconomic disparities in the association of age at first live birth with incident stroke among Chinese parous women: A prospective cohort study.

Background: Stroke has become a significant public health issue in China. Although studies have shown that women's age at first live birth (AFLB) might be associated with incident stroke, there is limited evidence on this relationship among Chinese parous women. Likewise, the nature of this association across urban-rural socioeconomic status (SES) has yet to be explored. In this prospective study, we sought to investigate the associations of women's AFLB with the risk of incident stroke and its subtypes (ischaemic stroke, intracerebral haemorrhage, and subarachnoid haemorrhage) and to explore the differences of these associations as well as the population-level impacts across SES classes. Methods: We used data on 290 932 Chinese parous women from the China Kadoorie Biobank who were recruited in the baseline survey between 2004 and 2008 and followed up until 2015. We used latent class analysis to identify urban-rural SES classes and Cox proportional hazard regression to estimate hazard ratios (HRs) and 95% confidence intervals (CIs) for AFLB's association with incident stroke. We then calculated population attributable fraction (PAF) to demonstrate the population-level impact of later AFLB on stroke. Results: Around 8.9% of parous women developed stroke after AFLB. Compared with women with AFLB <22 years, those with older AFLB had a higher risk of total stroke, with fully adjusted HRs (95% CI) of 1.71 (95% CI = 1.65-1.77) for 22-24 years and 3.37 (95% CI = 3.24-3.51) for ≥25 years. The associations of AFLB with ischaemic stroke were stronger among rural-low-SES participants. We found the highest PAFs of ischaemic stroke (60.1%; 95% CI = 46.2-70.3) associated with later AFLB for urban-high-SES individuals. Conclusions: Older AFLB was associated with higher risks of incident stroke and its subtypes among Chinese parous women, with stronger associations between AFLB and ischaemic stroke among rural-low-SES participants. Targeted medical advice for pregnant women of different ages could have long-term benefits for stroke prevention.

The learning curve of a novel seven-axis robot-assisted total hip arthroplasty system: a randomized controlled trial.

BACGROUND: The aim of this study was to assess the learning curve of a novel seven-axis robot-assisted total hip arthroplasty (RaTHA) system. METHODS: A total of 59 patients who underwent unilateral total hip arthroplasty at our institution from June 2022 to September 2022 were prospectively included in the study. In this randomized controlled clinical trial, robot-assisted THA (RaTHA) and Conventional THA (CoTHA) were performed using cumulative sum (CUSUM) analysis to evaluate the learning curve of the RaTHA system. The demographic data, preopera1tive clinical data, duration of operation, postoperative Harris Hip Score (HHS), postoperative Western Ontario and McMaster Universities Arthritis Index (WOMAC) score, and duration of operation between the learning stage and the proficiency stage of the RaTHA group were compared between the two groups. RESULTS: The average duration of operation of the RaTHA group was increased by 34.73 min compared with the CoTHA group (104.26 ± 19.33 vs. 69.53 ± 18.38 min, p < 0.01). The learning curve of the RaTHA system can be divided into learning stage and proficiency stage, and the former consists of the first 13 cases by CUSUM analysis. In the RaTHA group, the duration of operation decreased by 29.75 min in the proficiency stage compared to the learning stage (121.12 ± 12.84 vs.91.37 ± 12.92, p < 0.01). CONCLUSIONS: This study demonstrated that the surgical team required a learning curve of 13 cases to become proficient using the RaTHA system. The duration of operation, total blood loss, and drainage gradually shortened (decreased) with the learning curve stage, and the differences were statistically significant. TRIAL REGISTRATION: Number: ChiCTR2200061630, Date: 29/06/2022.

The Long-term Efficacy of Total Knee Arthroplasty on End-stage Kashin-Beck Disease of the Knee in Highland Tibetan Areas Patients: A Retrospective Study with 10-Year Follow-up.

OBJECTIVE: Despite the established success of total knee arthroplasty (TKA) with end-stage osteoarthritis, there is a notable scarcity of research on its long-term outcomes in individuals suffering from end-stage Kashin-Beck disease (KBD). This retrospective study aimed to assess the long-term outcomes and effectiveness of clinical function, quality of life, and complications of TKA and end-stage KBD patients in Tibetan highland areas. METHODS: The retrospective cohort included 43 KBD patients, comprising a total of 59 knees, who had undergone TKA at West China Hospital, Sichuan University between 2008 and 2021. Patients were subsequently followed up for a minimum of 3 years, and received rigorous radiological and clinical assessments at 3, 6, and 12 months post surgery, followed by annual examinations thereafter. The evaluation included various efficacy indices, including visual analogue scale (VAS) scores, hospital for special surgery (HSS) scores, functional score for adult Tibetans with Kashin-Beck disease (FSAT-KBD), and radiographic findings. Comparison of indicators within the same group was conducted using one-way repeated-measures analysis of variance or paired sample t-tests, whereas between-group differences were compared using an independent t-test. RESULTS: Throughout the average follow-up duration of 10.8 years, patients experienced a substantial reduction in knee pain and noteworthy functional improvement. The VAS scores decreased significantly from 77.47 ± 4.12 mm before surgery to 10.91 ± 1.97 mm after surgery, indicating considerable alleviation of knee pain. The HSS scores improved markedly, increasing from 44.26 ± 4.95 preoperatively to 91.26 ± 4.37, indicating enhanced joint function. Similarly, the FSAT-KBD exhibited positive progression, increasing from 25.90 ± 3.12 to 36.95 ± 3.54. Importantly, at the last follow-up, none of the patients presented with periprosthetic infection, prosthesis loosening, or periprosthetic fracture. CONCLUSION: At long-term follow-up, compared with patients in the preoperative period, patients in Tibetan highland areas with KBD of the knee who underwent TKA benefited from a significant reduction in pain, improvement in joint function, and satisfactory improvement in quality of life.

Copper-Cystine Biohybrid-Embedded Nanofiber Aerogels Show Antibacterial and Angiogenic Properties.

Copper-cystine-based high aspect ratio structures (CuHARS) possess exceptional physical and chemical properties and exhibit remarkable biodegradability in human physiological conditions. Extensive testing has confirmed the biocompatibility and biodegradability of CuHARS under diverse biological conditions, making them a viable source of essential Cu2+. These ions are vital for catalyzing the production of nitric oxide (NO) from the decomposition of S-nitrosothiols (RSNOs) found in human blood. The ability of CuHARS to act as a Cu2+ donor under specific concentrations has been demonstrated in this study, resulting in the generation of elevated levels of NO. Consequently, this dual function makes CuHARS effective as both a bactericidal agent and a promoter of angiogenesis. In vitro experiments have shown that CuHARS actively promotes the migration and formation of complete lumens by redirecting microvascular endothelial cells. To maximize the benefits of CuHARS, they have been incorporated into biomimetic electrospun poly(ε-caprolactone)/gelatin nanofiber aerogels. Through the regulated release of Cu2+ and NO production, these channeled aerogels not only provide antibacterial support but also promote angiogenesis. Taken together, the inclusion of CuHARS in biomimetic scaffolds could hold great promise in revolutionizing tissue regeneration and wound healing.

DLP Fabrication of Multiple Hierarchical Biomimetic GelMA/SilMA/HAp Scaffolds for Enhancing Bone Regeneration.

Severe bone defects resulting from trauma and diseases remain a persistent clinical challenge. In this study, a hierarchical biomimetic microporous hydrogel composite scaffold was constructed by mimicking the hierarchical structure of bone. Initially, gelatin methacrylamide (GelMA) and methacrylic anhydride silk fibroin (SilMA) were synthesized, and GelMA/SilMA inks with suitable rheological and mechanical properties were prepared. Biomimetic micropores were then generated by using an aqueous two-phase emulsification method. Subsequently, biomimetic microporous GelMA/SilMA was mixed with hydroxyapatite (HAp) to prepare biomimetic microporous GelMA/SilMA/HAp ink. Hierarchical biomimetic microporous GelMA/SilMA/HAp (M-GSH) scaffolds were then fabricated through digital light processing (DLP) 3D printing. Finally, in vitro experiments were conducted to investigate cell adhesion, proliferation, and inward migration as well as osteogenic differentiation and vascular regeneration effects. In vivo experiments indicated that the biomimetic microporous scaffold significantly promoted tissue integration and bone regeneration after 12 weeks of implantation, achieving 42.39% bone volume fraction regeneration. In summary, this hierarchical biomimetic microporous scaffold provides a promising strategy for the repair and treatment of bone defects.

M2 macrophage-derived exosome-functionalized topological scaffolds regulate the foreign body response and the coupling of angio/osteoclasto/osteogenesis.

Designing scaffolds that can regulate the innate immune response and promote vascularized bone regeneration holds promise for bone tissue engineering. Herein, electrospun scaffolds that combined physical and biological cues were fabricated by anchoring reparative M2 macrophage-derived exosomes onto topological pore structured nanofibrous scaffolds. The topological pore structure of the fiber and the immobilization of exosomes increased the nanoscale roughness and hydrophilicity of the fibrous scaffold. In vitro cell experiments showed that exosomes could be internalized by target cells to promote cell migration, tube formation, osteogenic differentiation, and anti-inflammatory macrophage polarization. The activation of fibrosis, angiogenesis, and macrophage was elucidated during the exosome-functionalized fibrous scaffold-mediated foreign body response (FBR) in subcutaneous implantation in mice. The exosome-functionalized nanofibrous scaffolds also enhanced vascularized bone formation in a critical-sized rat cranial bone defect model. Importantly, histological analysis revealed that the biofunctional scaffolds regulated the coupling effect of angiogenesis, osteoclastogenesis, and osteogenesis by stimulating type H vessel formation. This study elaborated on the complex processes within the cell microenvironment niche during fibrous scaffold-mediated FBR and vascularized bone regeneration to guide the design of implants or devices used in orthopedics and maxillofacial surgery. STATEMENT OF SIGNIFICANCE: How to design scaffold materials that can regulate the local immune niche and truly achieve functional vascularized bone regeneration still remain an open question. Here, combining physical and biological cues, we proposed new insight to cell-free and growth factor-free therapy, anchoring reparative M2 macrophage-derived exosomes onto topological pore structured nanofibrous scaffolds. The exosomes functionalized-scaffold system mitigated foreign body response, including excessive fibrosis, tumor-like vascularization, and macrophage activation. Importantly, the biofunctional scaffolds regulated the coupling effect of angiogenesis, osteoclastogenesis, and osteogenesis by stimulating type H vessel formation.

Interpretable feature extraction and dimensionality reduction in ESM2 for protein localization prediction.

As the application of large language models (LLMs) has broadened into the realm of biological predictions, leveraging their capacity for self-supervised learning to create feature representations of amino acid sequences, these models have set a new benchmark in tackling downstream challenges, such as subcellular localization. However, previous studies have primarily focused on either the structural design of models or differing strategies for fine-tuning, largely overlooking investigations into the nature of the features derived from LLMs. In this research, we propose different ESM2 representation extraction strategies, considering both the character type and position within the ESM2 input sequence. Using model dimensionality reduction, predictive analysis and interpretability techniques, we have illuminated potential associations between diverse feature types and specific subcellular localizations. Particularly, the prediction of Mitochondrion and Golgi apparatus prefer segments feature closer to the N-terminal, and phosphorylation site-based features could mirror phosphorylation properties. We also evaluate the prediction performance and interpretability robustness of Random Forest and Deep Neural Networks with varied feature inputs. This work offers novel insights into maximizing LLMs' utility, understanding their mechanisms, and extracting biological domain knowledge. Furthermore, we have made the code, feature extraction API, and all relevant materials available at https://github.com/yujuan-zhang/feature-representation-for-LLMs.

Rapid Volumetric Bioprinting of Decellularized Extracellular Matrix Bioinks.

Decellularized extracellular matrix (dECM)-based hydrogels are widely applied to additive biomanufacturing strategies for relevant applications. The extracellular matrix components and growth factors of dECM play crucial roles in cell adhesion, growth, and differentiation. However, the generally poor mechanical properties and printability have remained as major limitations for dECM-based materials. In this study, heart-derived dECM (h-dECM) and meniscus-derived dECM (Ms-dECM) bioinks in their pristine, unmodified state supplemented with the photoinitiator system of tris(2,2-bipyridyl) dichlororuthenium(II) hexahydrate and sodium persulfate, demonstrate cytocompatibility with volumetric bioprinting processes. This recently developed bioprinting modality illuminates a dynamically evolving light pattern into a rotating volume of the bioink, and thus decouples the requirement of mechanical strengths of bioprinted hydrogel constructs with printability, allowing for the fabrication of sophisticated shapes and architectures with low-concentration dECM materials that set within tens of seconds. As exemplary applications, cardiac tissues are volumetrically bioprinted using the cardiomyocyte-laden h-dECM bioink showing favorable cell proliferation, expansion, spreading, biomarker expressions, and synchronized contractions; whereas the volumetrically bioprinted Ms-dECM meniscus structures embedded with human mesenchymal stem cells present appropriate chondrogenic differentiation outcomes. This study supplies expanded bioink libraries for volumetric bioprinting and broadens utilities of dECM toward tissue engineering and regenerative medicine.