OBJECTIVE To explore the risk factors for acute kidney injury （AKI） in children with steroid-resistant nephrotic syndrome （SRNS） during tacrolimus treatment and construct a predictive model. METHODS A retrospective selection was made of 155 children diagnosed with SRNS and treated with tacrolimus at Xuzhou Children’s Hospital from January 1， 2022， to December 31， 2023， serving as the study subjects. Various clinical data of the children were collected by reviewing the medical record system. Children who developed AKI during medication were assigned to the AKI group （n＝26）， and those who did not develop AKI were assigned to the control group （n＝129）. Univariate and multivariate Logistic regression analyses were used to screen independent risk factors. A clinical predictive model was constructed based on significant variables， and nomogram， calibration curve， receiver operator characteristic curve， and decision curve were drawn to evaluate the model’s performance. RESULTS Univariate analysis showed that blood urea nitrogen （BUN）， serum creatinine （Scr）， estimated glomerular filtration rate （eGFR）， the maximum trough concentration （cmin） of tacrolimus， CYP3A5*3/*3 genotype， concurrent infection， concurrent hypertension， and the use of non-steroidal anti-inflammatory drugs were influencing factors for AKI in children with SRNS during tacrolimus treatment （P＜0.05）. Multivariate Logistic regression analysis revealed that BUN≥9.58 mmol/L， Scr≥125 μmol/L， eGFR＜37 mL/（min·1.73 m2）， tacrolimus maximum cmin≥11.26 ng/mL，CYP3A5*3/*3 genotype， concurrent infection， and concurrent hypertension were independent risk factors for AKI in children with SRNS during tacrolimus treatment （P＜0.05）. The constructed clinical predictive model had an area under the curve of 0.747， showing good agreement between predicted and actual AKI occurrence and demonstrating favorable clinical net benefit in predicting AKI in children. CONCLUSIONS Impaired baseline renal function （elevated BUN， elevated Scr， and decreased eGFR）， elevated maximum cmin of tacrolimus， CYP3A5*3/*3 genotype， concurrent infection， and hypertension during treatment are independent risk factors for AKI in children with SRNS during tacrolimus treatment. The established clinical predictive model provides a scientific basis for implementing risk stratification management.

OBJECTIVE To explore the construction of selection system for drug directory of the county-level medical community based on multi-criteria decision analysis， and provide decision-making basis for the selection of drug directory of medical community. METHODS Taking county-level medical community in Chongqing as an example，Delphi method and analytic hierarchy process were employed to construct the selection system for drug directory of the county-level medical community. Selected drugs were quantitatively scored based on the constructed index system， and the drug directory was selected according to the drug’s comprehensive score. The implementation effect of the directory was then evaluated through questionnaire surveys one year after the implementation of the directory. RESULTS The expert authority coefficients of the two rounds of consultation were＞ 0.8， with Kendall’s W values of 0.213 and 0.196， respectively （P＜0.001）. Finally， the selection system for drug directory of the medical community was determined to include five evaluation dimensions： safety， effectiveness， economy， accessibility， and innovation， along with eight evaluation indicators. In the drug directory selected according to the above method， the proportions of centrally procured drugs， medical insurance drugs， and essential drugs had all increased compared to before the selection； the comprehensive scores of chemical drugs ranged from 50.25 to 96.31 scores， and the proportion of drugs scoring between 70 and 100 scores had increased from 78.06% before selection to 85.82%. Among them， antiparasitic drugs had the highest comprehensive scores， while drugs for the digestive tract and metabolism were the most numerous. The evaluation scores of each indicator and the comprehensive scores of drugs in the drug directory after the selection process increased significantly than before selection （P＜ 0.05）. CONCLUSIONS The selection system for drug directory of the county-level medical community constructed in this study is scientific， objective and operable. This process facilitates the promotion of standardized and unified management of drugs in the medical community.

BACKGROUND:Dysfunction of macrophage efferocytosis can induce local and systemic inflammatory damage and is associated with a variety of obesity-related metabolic diseases.Moreover,compounds targeting efferocytosis have shown good therapeutic effects. OBJECTIVE:By reviewing the effects of obesity on macrophage efferocytosis,to analyze the key mechanism by which obesity inhibits efferocytosis,to summarize the research progress in compounds targeting efferocytosis to treat obesity-related metabolic diseases,so as to provide new ideas for fully understanding efferocytosis and its relationship with metabolic diseases,aiming to provide new strategies for disease prevention and treatment. METHODS:The English search terms were"efferocytosis,metabolism,obesity,obese,atherosclerosis,non-alcoholic steatohepatitis,neurodegeneration,tumor,osteoarthritis,diabetes,compound,medicine,treatment,"which were used for literature retrieval in PubMed and Web of Science.The Chinese search term was"efferocytosis,"which was used for literature retrieval in CNKI,VIP and WanFang datebases.Ninety-nine papers were finally included in the review analysis after a rigorous screening process. RESULTS AND CONCLUSION:In the process of efferocytosis,the"Find me"and"Eat me"processes involving a large number of apoptotic cell derived factors are mainly regulated by apoptotic cells.The efferocytosis factor involved in cytoskeletal remodeling and digestion are mainly derived from macrophages,which are crucial for efferocytosis activity.These results suggest that the"Find me"and"Eat me"factors mainly reflect the condition of apoptosis,and it is more scientific to select the expression of factors involved in cytoskeletal remodeling and digestion when evaluating the efferocytosis activity of macrophages.Obesity inhibits efferocytosis,and shows an inhibitory effect on most digestive factors,but has a stress-induced activation effect on most"Find me,""Eat me"and cytoskeletal recombination factors,which further indicates the decisive effect of digestive stage on efferocytosis and suggests that it is not reliable for some studies to evaluate the efferocytosis based on the increased expression of"Find me"and"Eat me"factors.Targeting cytokines in the digestive phase may be more effective when discussing future intervention strategies targeting macrophages efferocytosis.The efferocytosis activators of macrophages are effective in the treatment of various metabolic diseases,but the efferocytosis inhibitors in tumor tissue show good anticancer effects,suggesting that the role of efferocytosis should be rationally evaluated according to the characteristics of tissue inflammation.Efferocytosis is a relatively new concept proposed in 2003,with a short research history and complex efferocytosis factors.Current studies on obesity and efferocytosis only involve a tip of the iceberg and most of them are at a superficial level and a large number of scientific experiments are needed to further validate the mechanisms.

Background Exposure to ozone (O₃) is closely associated with an increased risk of mortality in the population, but this association exhibits regional heterogeneity, and relevant research in northern and central-western China is limited. Hohhot, as a typical city in the northern and western region, has seen a significant upward trend in O₃ concentrations (an increase of 17.9 μg·m⁻³ in 2020 compared to 2016). Studies targeting this region can fill the regional research gap. Objective To evaluate the health effects of ground-level O₃ exposure on resident mortality in Hohhot from 2018 to 2023. Methods Air quality, meteorological, and mortality data in Hohhot from 2018 to 2023 were collected. A time-series analysis based on Quasi-Poisson generalized additive model (GAM) was employed, controlling for meteorological factors, day-of-week effects, and holiday effects, to assess the impact of O₃ on non-accidental mortality, mortality from circulatory system diseases (CSD), and mortality from respiratory system diseases (RSD). Results From 2018 to 2023, the non-accidental, CSD, and RSD mortalities in Hohhot amounted to 89721, 47394, and 11378 cases, respectively. The daily maximum 8-hour average O₃ concentration (O₃-8 h) was 90.00 μg·m⁻³. According to the Class I limit (100 μg·m⁻³) of GB 3095—2012 Ambient Air Quality Standard, the annual average number of days exceeding the standard was 144 d. For single-day lag effects, O₃ had the strongest health impact on non-accidental mortality and CSD mortality on the current day (lag0), with effect sizes of 0.78% (95%CI: 0.33%, 1.24%) and 1.10% (95%CI: 0.50%, 1.71%), respectively. The strongest impact on RSD mortality occurred on the second day (lag2), with an effect size of 1.61% (95%CI: 0.61%, 2.62%). The subgroup analyses showed that for every 10 μg·m⁻³ increase in O₃-8 h concentration, the risk of non-accidental mortality in females increased by 0.70% (95%CI: 0.01%, 1.41%); for CSD mortality, the risk in males and individuals aged ≥65 years increased by 0.73% (95%CI: 0.01%, 1.47%) and 0.76% (95%CI: 0.13%, 1.39%), respectively. During the warm season, statistically significant risks were observed for non-accidental, CSD, and RSD mortalities, with increases of 1.07% (95%CI: 0.54%, 1.60%), 1.31% (95%CI: 0.59%, 2.04%), and 2.27% (95%CI: 1.07%, 3.49%), respectively. In the two-pollutant models incorporating sulfur dioxide (SO₂), nitrogen dioxide (NO₂), carbon monoxide (CO), particulate matter with an aerodynamic diameter of 10 micrometers or less (PM₁₀), and fine particulate matter (PM_2.5), the effect estimates (excess risk) of O₃ remained stable and statistically significant (P<0.05), indicating model robustness. Conclusion Ground-level O₃ exposure in Hohhot increases mortalities due to non-accidental causes, CSD, and RSD, with more pronounced effects during the warm season. Females and individuals aged ≥65 years may be susceptible populations. Therefore, relevant authorities should prioritize the potential health risks of O₃ exposure, particularly to vulnerable groups, and promote targeted prevention and control strategies.

Alzheimer's disease (AD) is the major form of dementia in the elderly and is closely related to the toxic effects of microglia sustained activation. In AD, sustained microglial activation triggers impaired synaptic pruning, neuroinflammation, neurotoxicity, and cognitive deficits. Accumulating evidence has demonstrated that aberrant expression of deubiquitinating enzymes is associated with regulating microglia function. Here, we use RNA sequencing to identify a deubiquitinase YOD1 as a regulator of microglial function and AD pathology. Further study showed that YOD1 knockout significantly improved the migration, phagocytosis, and inflammatory response of microglia, thereby improving the cognitive impairment of AD model mice. Through LC-MS/MS analysis combined with Co-IP, we found that Myosin heavy chain 9 (MYH9), a key regulator maintaining microglia homeostasis, is an interacting protein of YOD1. Mechanistically, YOD1 binds to MYH9 and maintains its stability by removing the K48 ubiquitin chain from MYH9, thereby mediating the microglia polarization signaling pathway to mediate microglia homeostasis. Taken together, our study reveals a specific role of microglial YOD1 in mediating microglia homeostasis and AD pathology, which provides a potential strategy for targeting microglia to treat AD.

Cancer stem cells (CSCs) are proposed to account for the progression, metastasis, and recurrence of diverse malignancies. However, the disorganized vasculars in tumors hinder the accumulation and penetration of nanomedicines, posing a challenge in eliminating CSCs located distantly from blood vessels. Herein, a pair of twin-like small-sized nanoparticles, sunitinib (St)-loaded ROS responsive micelles (RM@St) and salinomycin (SAL)-loaded GSH responsive micelles (GM@SAL), are developed to normalize disordered tumor vessels and eradicate CSCs. RM@St releases sunitinib in response to the abundant ROS in the tumor extracellular microenvironment for tumor vessel normalization, which improved intratumor accumulation and homogeneous distribution of small-sized GM@SAL. Sequentially, GM@SAL effectively accesses CSCs and achieves reduction-responsive drug release at high GSH concentrations within CSCs. More importantly, RM@St significantly extends the window of vessel normalization and enhances vessel integrity compared to free sunitinib, thus further amplifying the anti-tumor effect of GM@SAL. The combination therapy of RM@St plus GM@SAL produces considerable depression of tumor growth, drastically reducing CSCs fractions to 5.6% and resulting in 78.4% inhibition of lung metastasis. This study offers novel insights into rational nanomedicines designed for superior therapeutic effects by vascular normalization and anti-CSCs therapy.

Hepatic osteodystrophy is a common complication in patients with chronic liver disease and is influenced by various risk factors， and it has become one of the important influencing factors for the prognosis of liver transplantation. By analyzing the influencing factors for bone health and bone metabolism during the perioperative period of liver transplantation， this article emphasizes the importance of a comprehensive assessment of bone health and necessary interventions at this stage， with an aim to reduce the risk of postoperative complications and improve the long-term prognosis of patients. A deeper exploration of the association between hepatic osteodystrophy and the prognosis of liver transplantation can help to reveal the key influencing factors for postoperative outcomes， thus providing a theoretical basis for optimizing postoperative management strategies. Furthermore， advances in this research field will offer new insights into the treatment of patients receiving liver transplantation， and it is expected to further improve quality of life and long-term survival rate.

Bitter taste receptors,also known as type 2 taste receptors(T2Rs),are found not only in the mouth's taste bud cells but also in various tissues and cells,including macrophages.Macrophages,known for their re-markable plasticity,play a crucial role in regulating innate immunity,managing inflammation,and orchestrating immune responses to antigens,pathogens,and environmental factors.Recently,the study of the expression and function of bitter taste receptors within macrophages has garnered significant interest.This review summarizes the expression levels and dis-tribution characteristics of bitter taste receptors in macrophages and examines their effects on macrophage polarization,phagocytosis,and chemotaxis,as well as their potential molecular mechanisms.The purpose of this review is to provide in-sight and perspectives for research on the regulatory role of T2Rs in macrophage functions.

Objective:To carry out a scoping review on characteristics and effects of intervention program for promoting motor behavior among older adults in the community based on transtheoretical model (TTM), so as to explore the mechanism and connotation of TTM guiding strategy selection in the intervention program.Methods:The literature on the intervention program for promoting motor behavior among older adults in the community based on TTM was systematically searched in PubMed, Embase, CINAHL, Cochrane Library, PsycINFO, China National Knowledge Infrastructure and Wanfang Data. The search period was from database establishment to October 11, 2023. Two researchers conducted a summary and data analysis of the included literature.Results:A total of 15 articles were included, and the intervention framework included two types according to behavior change stages and behavior change patterns. The intervention strategy mainly included 17 items, such as emphasizing the benefits of exercise and drawbacks of no-exercise, establishing family support relationships, sharing exemplary experiences, rewarding, setting reminders, and signing commitments. The intervention strategies mainly involved 14 forms such as health lectures, one-on-one communication, exercise commitment letters, exercise logs, group communication meetings, and material/honor. The outcome measures consisted of feasibility (safety, retention, attendance, satisfaction) and effectiveness (exercise compliance, behavioral stage changes, physical function, self-efficacy, decision balance and so on) .Conclusions:The stages of change in TTM can guide the design of intervention frameworks for promoting motor behavior among older adults in the community, and the change program can guide the intervention strategies and design of application forms. The characteristic of the TTM based intervention program for promoting motor behavior among older adults in the community is that it contains intervention strategies that are suitable for each stage of behavior, and has short-term effectiveness and feasibility in terms of results. It is necessary to further clarify the details of the intervention program to explore its long-term effectiveness, and conduct follow-up.

Objective:To conduct a scoping review on gamified exercise interventions for elderly patients with cognitive impairment to provide insights for the application of gamification design in exercise programs for this population.Methods:Guided by the scoping review framework proposed by Arksey and O'Malley, a systematic search was conducted in databases including China National Knowledge Infrastructure, Wanfang, VIP, SinoMed, PubMed, Cochrane Library, CINAHL, Web of Science, Scopus, ProQuest, and Wiley Online Library. The search covered the period from the establishment of the databases to June 12, 2024. An integrative analysis was performed on the included literature.Results:A total of 12 studies were included. The most commonly used gamification elements were achievement- and progress-oriented features, while the most frequently applied behavior change theories were behavior change techniques and social cognitive theory.Conclusions:Gamification-based exercise interventions can improve adherence to exercise programs in elderly patients with cognitive impairment, promote physical activity, and enhance cognitive function. Future research should focus on combining various theories with different gamification elements to encourage proactive exercise behavior in elderly individuals with cognitive impairment.