Distribution of Nosocomial Pathogens and Antimicrobial Resistance among Patients with Burn Injuries in China: A Comprehensive Research Synopsis and Meta-Analysis.

INTRODUCTION: Over the past decade, numerous studies have described the types of pathogens and their antibiotic resistance patterns in patients with burn injuries in China; however, the findings have generally been inconsistent. We conducted a literature search and meta-analysis to summarize the infection spectra and antimicrobial resistance patterns in patients with burn injuries. METHODS: We searched the PubMed, Embase, Web of Science, China National Knowledge Infrastructure, China Biomedical Literature, Wanfang, and Weipu databases for relevant articles published between January 2010 and December 2023. The DerSimonian-Laird random-effects model was used to estimate the proportions and 95% confidence intervals (CIs) of pathogens among Chinese patients with burn injuries. Meta-regression analyses were performed to explore differences in the proportions of pathogens among different subgroups and their resistance patterns. This study was registered with PROSPERO (CRD42024514386). RESULTS: The database searches yielded 2017 records; after removing duplicates and conducting initial screening, 219 articles underwent full-text screening. Ultimately, 60 studies comprising a total of 62,819 isolated strains reported the proportions of pathogens in patients with burn injuries and were included in this meta-analysis. Meta-analyses were conducted on 18 types of pathogens. The most common pathogens causing infections in Chinese patients with burn injuries were Staphylococcus aureus, Pseudomonas aeruginosa, Acinetobacter baumannii, Klebsiella pneumoniae, and Staphylococcus epidermidis. Similar results were observed in the subgroup analysis focusing on wound infections. Since 2015, there has been a significant decrease in the proportion of Pseudomonas aeruginosa (R2 = 4.89%) and a significant increase in the proportion of Klebsiella pneumoniae (R2 = 9.60%). In terms of antibiotic resistance, there has been a significant decrease in the resistance of Staphylococcus aureus to multiple antibiotics and an increasing trend in the resistance of Klebsiella pneumoniae. CONCLUSIONS: We systematically summarized the epidemiological characteristics and antibiotic resistance patterns of pathogens among individuals suffering from burns in China, thus providing guidance for controlling wound infections and promoting optimal empirical antimicrobial therapy. The observed high levels of antibiotic resistance underscore the need for ongoing monitoring of antibiotic usage trends.

Proportions of Pseudomonas aeruginosa and Antimicrobial-Resistant P aeruginosa Among Patients With Surgical Site Infections in China: A Systematic Review and Meta-analysis.

Background: Pseudomonas aeruginosa is one of the most common pathogens in surgical site infections (SSIs). However, comprehensive epidemiological and antibiotic resistance details for P aeruginosa in Chinese SSIs are lacking. We evaluated the proportions and antimicrobial resistance of P aeruginosa among patients with SSIs in China. Methods: Relevant papers from January 2010 to August 2022 were searched in databases including PubMed, Embase, Web of Science, China Biomedical Literature Database, China National Knowledge Infrastructure, Wanfang, and Weipu. A meta-analysis was performed to analyze the proportions and 95% confidence interval (CIs) of P aeruginosa among patients with SSIs. Meta-regression analysis was used to investigate the proportion difference among different subgroups and antimicrobial resistance. Results: A total of 72 studies met inclusion criteria, involving 33 050 isolated strains. The overall proportion of P aeruginosa among patients with SSIs was 16.0% (95% CI, 13.9%-18.2%). Subgroup analysis showed higher proportions in orthopedic (18.3% [95% CI, 15.6%-21.0%]) and abdominal surgery (17.3% [95% CI, 9.9%-26.2%]). The proportion in the central region (18.6% [95% CI, 15.3%-22.1%]) was slightly higher than that in other regions. Antibiotic resistance rates significantly increased after 2015: cefoperazone (36.2%), ceftriaxone (38.9%), levofloxacin (20.5%), and aztreonam (24.0%). Notably, P aeruginosa resistance to ampicillin and cefazolin exceeded 90.0%. Conclusions: The proportion of P aeruginosa infection among patients with SSIs was higher than the data reported by the Chinese Antimicrobial Resistance Surveillance System, indicating rising antimicrobial resistance. The existing antimicrobial drug management plan should be strengthened to prevent a hospital epidemic of drug-resistant P aeruginosa strains.

Multiobjective Combinatorial Optimization Using a Single Deep Reinforcement Learning Model.

This article proposes utilizing a single deep reinforcement learning model to solve combinatorial multiobjective optimization problems. We use the well-known multiobjective traveling salesman problem (MOTSP) as an example. Our proposed method employs an encoder-decoder framework to learn the mapping from the MOTSP instance to its Pareto-optimal set. Specifically, it leverages a novel routing encoder to extract information for both the entire multiobjective aspect and every individual objective from the MOTSP instance. The global embeddings and each objective's embeddings are adaptively aggregated via a routing network to form the subproblems' embedding that can well represent the MOTSP features. Using a modified context embedding, the subproblems' embeddings are fed into a decoder to produce a set of approximate Pareto-optimal solutions in parallel. Additionally, we develop a Top-k baseline to enable more efficient data utilization and lightweight training for our proposed method. We compare our method with heuristic-based and learning-based ones on various types of MOTSP instances, and the experimental results show that our method can solve MOTSP instances in real-time and outperform the other algorithms, especially on large-scale problem instances.

MT4MTL-KD: A Multi-Teacher Knowledge Distillation Framework for Triplet Recognition.

The recognition of surgical triplets plays a critical role in the practical application of surgical videos. It involves the sub-tasks of recognizing instruments, verbs, and targets, while establishing precise associations between them. Existing methods face two significant challenges in triplet recognition: 1) the imbalanced class distribution of surgical triplets may lead to spurious task association learning, and 2) the feature extractors cannot reconcile local and global context modeling. To overcome these challenges, this paper presents a novel multi-teacher knowledge distillation framework for multi-task triplet learning, known as MT4MTL-KD. MT4MTL-KD leverages teacher models trained on less imbalanced sub-tasks to assist multi-task student learning for triplet recognition. Moreover, we adopt different categories of backbones for the teacher and student models, facilitating the integration of local and global context modeling. To further align the semantic knowledge between the triplet task and its sub-tasks, we propose a novel feature attention module (FAM). This module utilizes attention mechanisms to assign multi-task features to specific sub-tasks. We evaluate the performance of MT4MTL-KD on both the 5-fold cross-validation and the CholecTriplet challenge splits of the CholecT45 dataset. The experimental results consistently demonstrate the superiority of our framework over state-of-the-art methods, achieving significant improvements of up to 6.4% on the cross-validation split.

Trends and patterns in stroke incidence, mortality, DALYs and case-fatality by sociodemographic index worldwide: an age-period-cohort analysis using the Global Burden of Disease 2019 study.

OBJECTIVES: Stroke is a significant public health burden worldwide. This study aimed to explore the trends and patterns of stroke incidence, mortality, disability-adjusted life years (DALYs) and case-fatality percent (CFP) worldwide from 1990 to 2019. STUDY DESIGN: Age-period-cohort analysis. METHODS: Trends in stroke burden worldwide were evaluated using data from the Global Burden of Disease 2019 study. In addition, the relationship between the burden of stroke and sociodemographic index (SDI) was examined by quantile regression. Age, period and cohort patterns in stroke burden across different SDI groups were estimated using age-period-cohort analysis. RESULTS: Between 1990 and 2019, the age-standardised rates (ASRs) of stroke incidence, mortality and DALYs declined significantly worldwide, with decreases of -16.89% (95% uncertainty interval [UI]: -18.41 to -15.29), -36.43% (95% UI: -41.65 to -31.20) and -35.23% (95% UI: -40.49 to -30.49), respectively. Regions with ASRs in the 75th percentile and below experienced significant decreases in ASRs with increasing SDI. After 2014, there was a stable or slightly increased period effect for stroke incidence in all groups, while mortality, DALYs and CFP increased only in the high SDI group. The cohort effect of stroke incidence remained constant in the high SDI group from the 1960-1964 cohort onwards. CONCLUSIONS: Although high SDI regions had a lower stroke burden and a faster overall decline in burden, the recent relative risk data suggest a potential deceleration in the progress of reducing stroke burden in these areas. There is a need for more active measures to reduce the stroke burden in areas with the highest incidence, mortality and DALYs, as increasing SDI alone cannot lower the burden in these regions.

CholecTriplet2022: Show me a tool and tell me the triplet - An endoscopic vision challenge for surgical action triplet detection.

Formalizing surgical activities as triplets of the used instruments, actions performed, and target anatomies is becoming a gold standard approach for surgical activity modeling. The benefit is that this formalization helps to obtain a more detailed understanding of tool-tissue interaction which can be used to develop better Artificial Intelligence assistance for image-guided surgery. Earlier efforts and the CholecTriplet challenge introduced in 2021 have put together techniques aimed at recognizing these triplets from surgical footage. Estimating also the spatial locations of the triplets would offer a more precise intraoperative context-aware decision support for computer-assisted intervention. This paper presents the CholecTriplet2022 challenge, which extends surgical action triplet modeling from recognition to detection. It includes weakly-supervised bounding box localization of every visible surgical instrument (or tool), as the key actors, and the modeling of each tool-activity in the form of triplet. The paper describes a baseline method and 10 new deep learning algorithms presented at the challenge to solve the task. It also provides thorough methodological comparisons of the methods, an in-depth analysis of the obtained results across multiple metrics, visual and procedural challenges; their significance, and useful insights for future research directions and applications in surgery.

EVA1A regulates hematopoietic stem cell regeneration via ER-mitochondria mediated apoptosis.

Excessive protein synthesis upon enhanced cell proliferation frequently results in an increase of unfolded or misfolded proteins. During hematopoietic regeneration, to replenish the hematopoietic system, hematopoietic stem cells (HSCs) are activated and undergo a rapid proliferation. But how the activated HSCs respond to the proliferation pressure is still ambiguous; The proper control of the functional reservoir in the activated HSCs remains poorly understood. Here, we show a significant upregulation of EVA1A protein associated with the increase of ER stress during hematopoietic regeneration. Deletion of Eva1a significantly enhances the regeneration capacity of HSCs by inhibiting the ER stress-induced apoptosis. Mechanistically, the expression of EVA1A protein was upregulated by CHOP, and thereby promoted the ER-mitochondria interlinking via MCL1, which resulted in mitochondria-mediated apoptosis. These findings reveal a pathway for ER stress responses of HSCs by the EVA1A mediated apoptosis, which play an important role in HSCs regeneration.

Choose Appropriate Subproblems for Collaborative Modeling in Expensive Multiobjective Optimization.

In dealing with the expensive multiobjective optimization problem, some algorithms convert it into a number of single-objective subproblems for optimization. At each iteration, these algorithms conduct surrogate-assisted optimization on one or multiple subproblems. However, these subproblems may be unnecessary or resolved. Operating on such subproblems can cause server inefficiencies, especially in the case of expensive optimization. To overcome this shortcoming, we propose an adaptive subproblem selection (ASS) strategy to identify the most promising subproblems for further modeling. To better leverage the cross information between the subproblems, we use the collaborative multioutput Gaussian process surrogate to model them jointly. Moreover, the commonly used acquisition functions (also known as infill criteria) are investigated in this article. Our analysis reveals that these acquisition functions may cause severe imbalances between exploitation and exploration in multiobjective optimization scenarios. Consequently, we develop a new acquisition function, namely, adaptive lower confidence bound (ALCB), to cope with it. The experimental results on three different sets of benchmark problems indicate that our proposed algorithm is competitive. Beyond that, we also quantitatively validate the effectiveness of the ASS strategy, the CoMOGP model, and the ALCB acquisition function.

Road to entire insulation for resonances from a forced mechanical system.

The effective solution to avoid machinery damage caused by resonance has been perplexing the field of engineering as a core research direction since the resonance phenomenon was discovered by Euler in 1750. Numerous attempts have been performed to reduce the influence of resonance since the earlier of last century, by introducing a nonlinear structure or a closed-loop control system. However, the existed methodologies cannot eliminate resonance completely even extra problems were introduced inevitably, which means the technical choke-point of resonance-free remains unsolved. Here we propose a designable archetype model, which establishes a mapping between the mechanical properties and its structure. A general inverse method for structure construction is proposed based upon the required property for the system with quasi-zero stiffness of any designed finite order and the zero-stiffness properties. It is shown that an ellipse trajectory tracking of the designed model is the sufficient and necessary condition to satisfy the zero-stiffness property. Theoretical analysis shows that no resonant response happens in a zero-stiffness system to the full-band frequency excitation, or equivalently, the system can completely isolate the energy transfer between the load and environment, when the damping ratio approaches zero. Finally, an experimental rig for the prototype structure is built up according to the sufficient and necessary condition of the zero-stiffness system, for which the special dynamic behaviours are verified through experiments of frequency-sweep and random-vibration as well. Experimental results show that the prototype of the initial vibration isolation frequency of zero-stiffness system is much lower than 0.37 Hz, and the vibration attenuation of the proposed model is about 16.86 dB, 45.63 dB, and 112.37 dB at frequencies of 0.37 Hz, 1 Hz, and 10 Hz, respectively. The distinguished geometric structure of the zero-stiffness system leads to a new inspiration for the design of resonance-free in metamaterial unit and the inverse method can even adapt the design for a more targeted applications based on an arbitrary complex dynamic requirement.

Green stocks, crypto asset, crude oil and COVID19 pandemic: Application of rolling window multiple correlation.

The COVID-19 pandemic disrupted almost all spares of global social, psychological, and economic life. The emergence of various variants and corresponding variations in daily infection asymmetrically influenced economic indicators. This study extends the existing literature by exploring the hedging potential of crude oil, carbon efficiency index of green firms, and bitcoin during this pandemic. This objective is realized by employing the recently advanced rolling window multiple correlation of Polanco-Martínez (2020). This approach is based on the new p-value corrected method, which has advantages over other correlation methods. The sample observations are based on daily data from 1/22/2020 to 12/20/2021. In the bivariate case, we find a significant positive correlation between COVID-19 and CEI, while a negative impact is observed between COVID-19 and WTI. Similarly, we observe a significant and nonlinear association between COVID-19 and BTC. However, our findings show positive and significant correlations among variables in the multivariate case. The overall findings show that CEI and BTC can be safe havens for investors during this worse pandemic. The study's robust findings can be used to derive important policy implications worldwide during the COVID-19 pandemic.

Umbilical Cord Mesenchymal Stem Cell-Derived Small Extracellular Vesicles Deliver miR-21 to Promote Corneal Epithelial Wound Healing through PTEN/PI3K/Akt Pathway.

Objective: Rapid restoration of corneal epithelium integrity after injury is particularly important for preserving corneal transparency and vision. Mesenchymal stem cells (MSCs) can be taken into account as the promising regenerative therapeutics for improvement of wound healing processes based on the variety of the effective components. The extracellular vesicles form MSCs, especially exosomes, have been considered as important paracrine mediators though transferring microRNAs into recipient cell. This study investigated the mechanism of human umbilical cord MSC-derived small extracellular vesicles (HUMSC-sEVs) on corneal epithelial wound healing. Methods: HUMSC-sEVs were identified by transmission electron microscopy, nanoparticle tracking analysis, and Western blot. Corneal fluorescein staining and histological staining were evaluated in a corneal mechanical wound model. Changes in HCEC proliferation after HUMSC-sEVs or miR-21 mimic treatment were evaluated by CCK-8 and EdU assays, while migration was assessed by in vitro scratch wound assay. Full-length transcriptome sequencing was performed to identify the differentially expressed genes associated with HUMSC-sEVs treatment, followed by validation via real-time PCR and Western blot. Results: The sEVs derived from HUMSCs can significantly promote corneal epithelial cell proliferation, migration in vitro, and corneal epithelial wound healing in vivo. Similar effects were obtained after miR-21 transfection, while the beneficial effects of HUMSC-sEVs were partially negated by miR-21 knockdown. Results also show that the benefits are associated with decreased PTEN level and activated the PI3K/Akt signaling pathway in HCECs. Conclusion: HUMSC-sEVs could enhance the recovery of corneal epithelial wounds though restraining PTEN by transferring miR-21 and may represent a promising novel therapeutic agent for corneal wound repair.

Memory-based variable neighborhood search for green vehicle routing problem with passing-by drivers: a comprehensive perspective.

A business delivery model with professional vehicles as well as occasional passing-by vehicles is investigated in this paper. The drivers deliver parcels from the distribution center to customers and the passing-by driver can get a certain amount of compensation in return. To give a satisfactory solution from the perspective of platform owner, customers, professional drivers, occasional drivers, and authority, a multi-layer comprehensive model is proposed. To effectively solve the proposed model, we introduce an improved variable neighborhood search (VNS) with a memory-based restart mechanism. The new algorithm is evaluated on instances derived from Solomon's benchmark and real-life beer delivery instances. Taguchi experiment is used to tune parameters in the proposed VNS, followed by component analysis and real-life experiments. Experimental results indicate that the proposed strategies are effective and the new delivery model in this paper has some advantages over traditional and single-delivery ones from the comprehensive perspectives of stakeholders in the crowdsourcing logistics system.

Membrane dynamics of ATG4B and LC3 in autophagosome formation.

The biogenesis of autophagosomes provides the basis for macroautophagy to capture and degrade intracellular cargoes. Binding of the autophagy-related protein ATG8/LC3 to autophagic membranes is essential to autophagosome formation, which involves the specific and dynamic processing of ATG8/LC3 by cysteine protease ATG4. However, to date, the mechanism whereby ATG4 is recruited to the membranes, the interaction of ATG4 and ATG8/LC3 on the membranes, and its role in the growth of phagophore are not completely understood. Here, we used fluorescence recovery after photobleaching to monitor the turnover of GFP-tagged ATG4B and LC3B in living animal cells. The data show that ATG4B localizes to early autophagic membranes in an LC3B-dependent manner. During autophagy, ATG4B and LC3B undergo rapid cytosol/isolation membrane exchange but not at the cytosol/completed autophagosome. In addition, ATG4B activity controls the efficiency of autophagosome formation by impacting the membrane binding/dissociation of LC3B. These data suggest that ATG4 and LC3 play interdependent roles in the formation of autophagosomes.

Multiobjective Optimization-Aided Decision-Making System for Large-Scale Manufacturing Planning.

This work is geared toward a real-world manufacturing planning (MP) task, whose two objectives are to maximize the order fulfillment rate and minimize the total cost. More important, the requirements and constraints in real manufacturing make the MP task very challenging in several aspects. For example, the MP needs to cover many production components of multiple plants over a 30-day horizon, which means that it involves a large number of decision variables. Furthermore, the MP task's two objectives have extremely different magnitudes, and some constraints are difficult to handle. Facing these uncompromising practical requirements, we introduce an interactive multiobjective optimization-based MP system in this article. It can help the decision maker reach a satisfactory tradeoff between the two objectives without consuming massive calculations. In the MP system, the submitted MP task is modeled as a multiobjective integer programming (MOIP) problem. Then, the MOIP problem is addressed via a two-stage multiobjective optimization algorithm (TSMOA). To alleviate the heavy calculation burden, TSMOA transforms the optimization of the MOIP problem into the optimization of a series of single-objective problems (SOPs). Meanwhile, a new SOP solving strategy is used in the MP system to further reduce the computational cost. It utilizes two sequential easier SOPs as the approximator of the original complex SOP for optimization. As part of the MP system, TSMOA and the SOP solving strategy are demonstrated to be efficient in real-world MP applications. In addition, the effectiveness of TSMOA is also validated on benchmark problems. The results indicate that TSMOA as well as the MP system are promising.

Systematic Analysis of the Global, Regional and National Burden of Cardiovascular Diseases from 1990 to 2017.

BACKGROUND: Previous studies on the burden of cardiovascular diseases (CVDs) were mainly based on limited data of the study period or area, or did not include detailed risk factor analysis. OBJECTIVE: To investigate up-to-date temporal and regional trends and risk factors of mortality and disability-adjusted life years (DALYs) attributed to CVDs by age, sex, and disease throughout the world. METHODS: Data for the disease burden of CVDs in 195 countries and territories from 1990 to 2017, including mortality, DALYs, age-standardized mortality rates, and age-standardized DALY rates, were estimated from the Global Burden of Disease Study 2017. Risk factors attributable to deaths and DALYs for CVDs were also estimated using the comparative risk assessment framework. RESULTS: The number of deaths from CVDs increased by 48.62%, from 11.94 (95% UI 11.78-12.18) million in 1990 to 17.79 (17.53-18.04) million in 2017. However, the age-standardized mortality rate decreased by an average of - 1.45% (- 1.72% to - 1.18%) annually. After fluctuation in the expected age-standardized mortality rate of CVDs in most of the socio-demographic index (SDI) scale, these rates decrease rapidly for SDI values of 0.7 and higher. In 2017, metabolic risks accounted for 73.48% of deaths and 73.25% of DALYs due to CVDs, behavioral factors accounted for 63.23% of deaths and 66.71% of attributable DALYs. CONCLUSION: CVDs remain a major global health burden due to the increment in death numbers and DALYs. Aging and the main risk factors are the main drivers of mortality and health loss. More attention to main risk factors should be paid with supportive health policies.

[Effect of Laptm4b Deletion on Hematopoietic Stem and Progenitor Cells Homeostasis in Mice].

OBJECTIVE: To investigate the effect of lysosomal-associated protein transmembrane-4 Beta(Laptm4b) deletion on hematopoietic stem/progenitor cells (HSPCs) homeostasis in mice. METHODS: The hematopoietic system specific Laptm4b-deficient mice were constructed. The number and proportion of HSPCs (LSK, LT, ST, MPP, etc) in Laptm4b-deficient mice were analyzed by flow cytometry. Single SLAM-HSC cell was sorted by flow sorter and cultured in vitro to measure the effect of Laptm4b deletion on the colony forming ability of hematopoietic stem cells (HSCs). The effect of Laptm4b-deficient on the reconstitution ability of HSCs in mice was detected by competitive transplantation experiment of SLAM-HSC cells. RESULTS: Laptm4b deficiency could moderately upregulate the proportion of T cells in the peripheral blood of the mice, but showed no significant effect on the proportion and number of HSPCs. Laptm4b deletion showed no effect on the reconstruction ability of HSCs after competitive transplantation, but it could inhibit the colony formation of HSCs in vitro. CONCLUSION: LAPTM4B may play a role in HSCs under the proliferation stress. Laptm4b-deficient in mice hematopoietic system showed no significant effect on the HSPCs homeostasis maintenance and reconstruction ability.

Trends and age-period-cohort effects on mortality of the three major gynecologic cancers in China from 1990 to 2019: Cervical, ovarian and uterine cancer.

BACKGROUND: Gynecologic cancers seriously threaten women's life and health. This study aims to assess the long-term trends of mortality from the three major gynecologic cancers in China and to examine the age-, period-, and cohort-specific effects behind them during the period 1990 to 2019. METHODS: The mortality data of cervical, ovarian, and uterine cancer in China were obtained from the Global Burden of Disease Study 2019 and were analyzed with the age-period-cohort framework. RESULTS: It was found that the net drift for cervical cancer mortality was -0.19% (95% CI, -0.46% to 0.08%) per year, for ovarian cancer was 0.76% (95% CI, 0.57% to 0.95%) per year, and for uterine cancer was -3.09% (95% CI, -3.44% to -2.76%) per year from 1990 to 2019. During this period, while cervical cancer remained the most common cause of death among gynecologic cancers among Chinese women, ovarian cancer replaced uterine cancer as the second leading cause of death in gynecologic cancers after about 2005. Significant age, cohort, and period effects were found for the mortality trends of all three major gynecologic cancers. CONCLUSIONS: The secular trends of mortality from the three major gynecologic cancers in China and their underlying age, period, and cohort effects are likely to reflect the progress of diagnosis and treatment, rapid socio-economic transitions, and the accompanying lifestyle and behavior changes. More priorities of further epidemiology studies and efforts on the prevention and control should be given to three major gynecologic cancers.

The Effects of Age, Period, and Cohort on the Mortality of Cervical Cancer in Three High-Income Countries: Canada, Korea, and Italy.

BACKGROUND: As the second most common gynecologic cancer worldwide, cervical cancer has led to morbidity and mortality in thousands of women. Our study is aimed at comparing the long-term trends of mortality rates for cervical cancer in three high-income countries-Canada, Korea, and Italy-and analyzing the detached effects of chronological age, time period, and birth cohort by age-period-cohort (APC) analysis. METHODS: Joinpoint regression was used in this study, and the age-period-cohort model combined with the intrinsic estimator method was also applied to estimate the detached effect of each age, time period, and birth cohort on cervical cancer mortality. RESULTS: For the overall trends of ASMRs for cervical cancer, the rates for Canada and Italy generally decreased during the whole observation periods while the rate for Korea exhibited a significant increase from 1986 to 2003. The APC analysis suggested that the cancer mortality risks consistently increased with age in the age groups including women aged 20 to 50 years in all areas. The period effect exhibited a general upward trend for both Korea and Italy, while a decreased trend was observed for Canada during the whole observation period. The mortality risk generally decreased with birth cohort, except there was a slight increase for younger generations in the three countries. CONCLUSIONS: Our study shows that the overall decrease in the cohort effect may have contributed to the reduced mortality rate for Italy and Canada, and the increased period effects and cohort effect in younger generations may have led to the increase in cancer mortality rate for Korea.

Long-Term Trends in Unintentional Fall Mortality in China: A Population-Based Age-Period-Cohort Study.

Background: Unintentional falls seriously threaten the life and health of people in China. This study aimed to assess the long-term trends of mortality from unintentional falls in China and to examine the age-, period-, and cohort-specific effects behind them. Methods: This population-based multiyear cross-sectional study of Chinese people aged 0-84 years was a secondary analysis of the mortality data of fall injuries from 1990 to 2019, derived from the Global Burden of Disease Study 2019. Age-standardized mortality rates of unintentional falls by year, sex, and age group were used as the main outcomes and were analyzed within the age-period-cohort framework. Results: Although the crude mortality rates of unintentional falls for men and women showed a significant upward trend, the age-standardized mortality rates for both sexes only increased slightly. The net drift of unintentional fall mortality was 0.13% (95% CI, -0.04 to 0.3%) per year for men and -0.71% (95% CI, -0.96 to -0.46%) per year for women. The local drift values for both sexes increased with age group. Significant age, cohort, and period effects were found behind the mortality trends of the unintentional falls for both sexes in China. Conclusions: Unintentional falls are still a major public health problem that disproportionately threatens the lives of men and women in China. Efforts should be put in place urgently to prevent the growing number of fall-related mortality for men over 40 years old and women over 70 years old. Gains observed in the recent period, relative risks (RRs), and cohort RRs may be related to improved healthcare and better education.

Construction of CII-Specific CAR-T to Explore the Cytokine Cascades Between Cartilage-Reactive T Cells and Chondrocytes.

Cytokine cascades exist in many autoimmune disorders which amplify and sustain the autoimmune process and lead to chronic inflammatory injury to the host tissues. Increasing evidence indicates that chondrocytes can interact with T cells, which may be a crucial event in inflammatory arthritis. To address the reciprocal influences of cartilage-reactive T cells and chondrocytes, we constructed cartilage-reactive T cells by developing a type II collagen-specific chimeric antigen receptor (CII-CAR). An in vitro co-culture model of CII-CAR-T cells and fresh cartilage was developed, in which CII-CAR-T displayed specific proliferative capacity and cytokine release against fresh cartilage samples, and chondrocytes could respond to CII-CAR-T cells by secreting IL-6. The proposed model will help us to explore the possible cytokine cascades between cartilage-reactive T cells and cartilage.