Objective To explore the related risk factors of osteosarcopenia (OS) in elderly patients with type 2 diabetes mellitus (T2DM) and to evaluate their predictive value. Methods We selected 409 elderly patients with T2DM from our hospital between June 2021 and December 2024 as the study subjects, and divided them into an OS occurrence group and a non-occurrence group based on whether they were diagnosed with OS. Results Among the 409 elderly patients with T2DM included, 93 were diagnosed with OS, yielding a prevalence rate of 22.73%. Spearman correlation analysis revealed a significant association between lumbar spine BMD and T-scores with age, history of previous fractures, fasting plasma glucose (FPG), procollagen type I N-terminal propeptide (PINP), osteocalcin (OC), and 25-hydroxyvitamin D (25(OH)D). Gender (OR=0.193), Body Mass Index (BMI) (OR=0.254), history of previous fractures (OR=8.883), FPG (OR=0.543), Total Cholesterol (TC) (OR=3.684), High-Density Lipoprotein Cholesterol (HDL-C) (OR=86.024), PINP (OR=0.818), and OC (OR=0.526) are identified as influential factors for the occurrence of OS in elderly patients with T2DM. The combined prediction of these variables yields a sensitivity of 96.5%, a specificity of 97.8%, and an area under the curve (AUC) of 0.992 for the occurrence of OS in elderly patients with T2DM, indicating an excellent predictive performance. Conclusion The following factors—gender, BMI, history of previous fractures, FPG, TC, HDL-C, PINP, and OC—are influential in the occurrence of OS among elderly patients with T2DM. Formulating intervention measures based on these influencing factors can provide assistance in preventing and treating the occurrence of OS.

Purpose: In this study, the neural communication patterns between hypothalamic structures and cortical areas in girls diagnosed with central precocious puberty (CPP) were explored. Endocrine profiles were incorporated to clarify the pathophysiological interactions between cerebral networks and hormonal regulation. The hypothalamus was designated as the key focus area for connectivity analysis. Methods: Fifty-seven girls (37 CPP, 20 non-CPP) were recruited from the Pediatric Development Clinic at the Second Affiliated Hospital of Anhui Medical University. The collected data included demographic information, gonadotropin-releasing hormone stimulation tests, and magnetic resonance imaging scans. Hypothalamic functional connectivity (FC) was analyzed using predefined region of interest coordinates, and correlations between hormone levels and FC values were assessed. Results: Compared to the non-CPP group, the CPP group exhibited elevated baseline follicle-stimulating hormone (FSH), baseline luteinizing hormone (LH), peak FSH, peak LH, and peak LH/FSH ratios. Patients with CPP exhibited enhanced neural synchronization linking the right lateral hypothalamic effector zone to the right superior frontal gyrus (displaying a borderline significant correlation with peak LH concentrations), concurrent with diminished functional coupling of the right lateral hypothalamic efferent to the right fusiform/supramarginal gyri. The left lateral hypothalamic projections demonstrated amplified connectivity with the right cuneus. No FC differences were observed in the medial hypothalamus. Conclusion Abnormal lateral hypothalamus FC patterns were identified in CPP girls and were particularly linked to peak LH levels. The findings offer novel insights into the neuroendocrine mechanisms underlying CPP.

Microplastics are emerging pollutants of increasing concern, which can enter the human body through pathways such as diet, respiration and skin contact, inducing oxidative stress and inflammatory responses and posing a potential risk on the formation and development of mineralized tissues in the body. Early life is a critical period for the formation and development of mineralized tissues. Microplastics can pass though the placental barrier during early life to affect the fetus directly by accumulating in the bone marrow and interfering with the development of the growth plate, leading to abnormal bone growth. Additionally, microplastics can act as carriers to release bisphenol A (BPA), synergistically enhancing the toxicity of pollutants such as lead and zinc oxide, thereby affecting the development of mineralized tissues. Therefore, exposure to microplastics during early life may be a significant environmental factor contributing to the abnormal development of mineralized tissues. Future researches are needed to explore the specific impacts and mechanisms of microplastics on maxillofacial and tooth development, to provide insights and theoretical foundations for the prevention and treatment of diseases related to the development of mineralized tissues.

Objective:To evaluate the efficacy and safety of nebulized inhalation of recombinant human interferon (IFN) α1b injection in the treatment of respiratory syncytial virus (RSV) associated lower respiratory tract infections (pneumonia and bronchiolitis) in children.Methods:A randomized, double-blind, parallel, placebo-controlled add-on design was used.Children with pneumonia or bronchiolitis aged 2 months to 5 years who tested positive for RSV antigen within 72 hours of onset from 30 clinical trial sites including Beijing Children′s Hospital, Capital Medical University between February 2021 and December 2022 were included in this study and randomly divided into 2 groups at a ratio of 1∶1 based on a stratified-block method.Both groups received basic treatments such as cough control, asthma relieving, expectorant treatment, fever reduction, oxygen therapy, etc.The experimental group received additional nebulized inhalation of IFN α1b injection at a dose of 2.0 μg/(kg·time), twice a day.The control group received nebulized inhalation of placebo twice a day.Clinical efficacy was evaluated based on indicators such as the duration of clinical symptoms and signs, and the Kaplan-Meier method was used to calculate the median and 95% CI of the duration of clinical symptoms and signs.The Log-rank test was used to compared data between groups.Safety was assessed through the incidence of adverse reactions and laboratory tests, and the Chi-square test was used to analyze the difference between groups. Results:There were 123 children in the experimental group and 122 children in the control group.The median durations of all the 5 clinical symptoms and signs [including shortness of breath, wheezing, dyspnea (visible retractions), decreased transcutaneous oxygen saturation, and abnormal mental state] in the experimental group after treatment were slightly shortened than those in the control group [2.7 d(95% CI: 1.9-3.0 d)] vs.[2.9 d(95% CI: 2.6-3.6 d), P=0.027].The improvement in dyspnea (retractions) was especially pronounced in the experimental group, with a relief rate of 50.0% (0, 100%) on the first day of administration[compared with 0 (0, 50.0%) in the control group ( Z=2.002, P=0.025)].The median duration of dyspnea in the experimental group was nearly 1 day shorter than that in the control group [1.0 d(95% CI: 0.7-1.7 d) vs.1.8 d(95% CI: 1.0-2.5 d), P=0.046].There were no significant difference in hospital stay [6.0(5.0, 8.0) d vs.6.5(5.0, 8.0) d, Z=0.675, P=0.500], oxygen therapy duration [32.0(14.0, 96.3) h vs.39.0 (24.0, 83.2) h, Z=0.094, P=0.925], the recovery rate from clinical symptoms during treatment [(105/106, 99.1%) vs.(96/101, 95.0%)], and recurrence rate [(0/106, 0) vs.(2/101, 2.0%)] between the 2 groups (all P>0.05).However, the above-mentioned four indicators in the experimental group showed a trend of clinical benefits.The quantitative virus detection results showed that the RSV viral load in both groups decreased after treatment compared to before treatment.After 2 days of treatment, the decline rate of RSV viral load from the baseline was 0.90 lg copies/(mL·d) in the experimental group and 0.25 lg copies/(mL·d)in the control group, with a statistically significant difference ( P<0.05).Furthermore, there was no statistically significant difference in the incidence of adverse reactions between the 2 groups ( P>0.05).Importantly, no drug-related serious adverse reactions occurred in both groups. Conclusions:The nebulized inhalation therapy of IFN α1b demonstrates efficacy and safety in treating pediatric RSV associated lower respiratory tract infections.It particularly offers outstanding clinical therapeutic value for severe children.

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.

OBJECTIVES: To explore the mechanism of Gandou Fumu Decoction (GDFMD) for improving Wilson's disease (WD) in tx-J mice. METHODS: With 6 syngeneic wild-type mice as the control group, 30 tx-J mice were randomized into WD model group, low-, medium- and high-dose GDFMD treatment groups, and Fer-1 treatment group. Saline (in control and model groups) and GDFMD (3.48, 6.96 or 13.92 g/kg) were administered by gavage, and Fer-1 was injected intraperitoneally once daily for 14 days. Oil red and HE staining were used to observe lipid deposition and pathological conditions in the liver tissue; ALT, AST, albumin, AKP levels were determined to assess liver function of the mice. Western blotting and RT-qPCR were used to detect hepatic protein and mRNA expressions of GPX4, ACSL4, ALOX15, FTH1, FLT, TFR1, FAS, SCD1, and ACOX1, and Fe²⁺, MDA, ROS, SOD, GSH and 4-HNE levels were analyzed to assess oxidative stress. RESULTS: The mouse models of WD showed obvious fatty degeneration in the liver tissue significantly increased serum levels of ALT, AST and AKP, decreased albumin level, increased Fe²⁺, MDA, ROS, 4-HNE levels, decreased SOD and GSH levels (P<0.05), lowered protein expressions of ACOX1, GPX4, FTH1, FLT, FAS, and SCD1, and increased protein contents of TFR1, ACSL4 and ALOX15 in the liver. Treatment with GDFMD and Fer-1 improved liver histopathology and liver function of the mouse models, decreased the levels of Fe²⁺, MDA and ROS, increased SOD and GSH levels, and reversed the changes in hepatic protein expressions. CONCLUSIONS GDFMD improves liver steatosis in mouse models of WD possibly by inhibiting hepatocyte ferroptosis through the GPX4/ACSL4/ALOX15 signaling pathway.
Animals ; Ferroptosis/drug effects* ; Mice ; Signal Transduction/drug effects* ; Drugs, Chinese Herbal/therapeutic use* ; Hepatolenticular Degeneration/drug therapy* ; Hepatocytes/metabolism* ; Phospholipid Hydroperoxide Glutathione Peroxidase ; Fatty Liver/metabolism* ; Arachidonate 15-Lipoxygenase/metabolism* ; Coenzyme A Ligases/metabolism* ; Liver/metabolism* ; Male

Objective:To deeply understand the real experiences of self-management in home-dwelling elderly patients with diabetic foot, explore the factors associated with management dilemmas, and reveal the diversity of coping strategies based on the theory of planned behavior, so as to provide a reference for development of targeted clinical nursing strategies.Methods:Purposive sampling was used to select 21 elderly patients with diabetic foot who attended the Fourth Medical Center of the Chinese PLA General Hospital from May 2023 to March 2024 for semi-structured interviews. Colaizzi 7-step analysis was used to analyze and refine the themes.Results:After collating, analyzing and summarizing the interview data, 3 themes and 9 sub-themes were extracted, namely, behavioral attitudes (lack of self-management awareness due to insufficient cognition, compromising and avoiding psychology restricting self-management behaviors, negative emotions generating and attacking confidence in self-management), subjective norms (lack of healthcare channels increasing the difficulty of accessing healthcare, increased economic burden delaying disease treatment, and poor treatment experience damaging physical and mental health) and perceived behavioral control (accumulation of knowledge to put into practice, experience of multiple management strategies, seeking external help and support) .Conclusions:The home-dwelling elderly patients with diabetic foot have multiple self-management dilemmas. Nursing staff should emphasize the patient's own and objective dilemmas, provide cognitive intervention strategies, multiple coping support, and long-term professional guidance to improve the patients' self-management ability.

Objective:To evaluate the effect of continuous theta burst stimulation (cTBS) on postoperative cognitive dysfunction (POCD) in mice and its association with the excitability of parvalbumin (PV) neurons in the medial prefrontal cortex (mPFC).Methods:Twenty-four specific pathogen-free healthy male C57BL/6 mice, aged 8 weeks, weighing 18-24 g, in which adeno-associated virus (AAV) for labeling PV neurons was injected into the mPFC using stereotaxic surgery, were used in this study. Three weeks later, the mice were divided into 3 groups ( n=8 each) using a random number table method: control group (group C), POCD group (group P) and cTBS group. Group C received no treatment. A mouse model of POCD was established by performing tibial fracture surgery under sevoflurane anesthesia and the mice received sham stimulation from postoperative day 0 to day 4 in group P. Group cTBS underwent POCD model establishment and received cTBS stimulation from postoperative day 0 to day 4. Cognitive function was assessed using contextual fear conditioning, Y-maze and novel object recognition tests on postoperative day 5. The spontaneous firing frequency of PV neurons in the mPFC was then measured using ex vivo patch-clamp electrophysiology. Results:The results of contextual fear conditioning test showed that compared to group C, the percentage of freezing time was significantly increased in group P ( P<0.05); compared to group P, the percentage of freezing time was significantly decreased in group cTBS ( P<0.05). The results of Y-maze test showed that compared to group C, the alternation accuracy was significantly decreased in group P ( P<0.05); compared to group P, the alternation accuracy was significantly increased in group cTBS ( P<0.05). The results of novel object recognition test showed that compared to group C, the percentage of time spent exploring the novel object was significantly decreased in group P ( P<0.05); compared to group P, this percentage of time spent exploring the novel object was significantly increased in group cTBS ( P<0.05). The results of ex vivo patch-clamp electrophysiology showed that compared to group C, the spontaneous firing frequency of PV neurons in the mPFC was significantly decreased in group P ( P<0.05); compared to group P, the spontaneous firing frequency of PV neurons in the mPFC was significantly increased in group cTBS ( P<0.05). Conclusions:cTBS can ameliorate POCD in mice, and the mechanism is related to the restoration of excitability of PV neurons in the mPFC.

Objective:To evaluate the role of the TANK-binding kinase 1 (TBK1)/receptor-interacting protein kinase 1 (RIPK1) signaling pathway in postoperative cognitive dysfunction (POCD) in aged mice.Methods:Fifty SPF healthy male C57BL/6 mice, aged 18 months, weighing 20-25 g, were divided into 5 groups ( n=10 each) using a table of random numbers: control group (group C), POCD group, dimethyl sulfoxide group, GSK group and GSK+ Nec-1 group. A mouse model of POCD was established by the closed reduction internal fixation of the left tibial fracture in anesthetized animals. Dimethyl sulfoxide, TBK1 inhibitor GSK8612 and RIPK1 inhibitor Nec-1 (0.5 μl/side) were stereotactically injected into the hippocampal CA1 region at 30 min before operation. Cognitive function was assessed using the contextual fear conditioning test before operation and at 3 days after operation. The mice were then anesthetized and sacrificed, and the hippocampal tissues were obtained for determination of the expression of TBK1, RIPK1, interleukin-lbeta (IL-1β), tumor necrosis factor-alpha (TNF-α), activator protein 1 (AP-1) and Nestin (by Western blot), the expression of Bcl-2, Bax and caspase-3 mRNA (by fluorescent quantitative real-time polymerase chain reaction) and for examination of TBK1/RIPK1 molecular interactions and neural stem cell proliferation in the hippocampal dentate gyrus (DG) region (by immunofluorescent staining). Results:Compared with C group, the percentage of freezing time was significantly decreased at 3 days after operation, the expression of Bax mRNA, caspase-3 mRNA, RIPK1, IL-1β, TNF-α and AP-1 was up-regulated, the expression of TBK1, Bcl-2 mRNA and Nestin was down-regulated, and the proliferation of neural stem cells in the hippocampal DG region was decreased in POCD group ( P<0.05 or 0.01). Compared with POCD group, the percentage of freezing time was significantly decreased at 3 days after operation, the expression of Bax mRNA, caspase-3 mRNA, IL-1β, TNF-α and AP-1 was up-regulated, the expression of TBK1, Bcl-2 mRNA and Nestin was down-regulated, and the proliferation of neural stem cells in the hippocampal DG region was decreased in GSK group ( P<0.05 or 0.01). Compared with GSK group, the percentage of freezing time was significantly increased at 3 days after operation, the expression of Bax mRNA, caspase-3 mRNA, IL-1β, TNF-α and AP-1 was down-regulated, the expression of TBK1, Bcl-2 mRNA and Nestin was up-regulated, and the proliferation of neural stem cells in the hippocampal DG region was increased in GSK+ Nec-1 group ( P<0.05 or 0.01). Conclusions:The TBK1/RIPK1 signaling pathway is involved in the pathogenesis of POCD in aged mice.