BACKGROUND: Chronic kidney disease (CKD) is associated with common pathophysiological processes, such as inflammation and fibrosis, in both the heart and the kidney. However, the underlying molecular mechanisms that drive these processes are not yet fully understood. Therefore, this study focused on the molecular mechanism of heart and kidney injury in CKD. METHODS: We generated an microRNA (miR)-26a knockout (KO) mouse model to investigate the role of miR-26a in angiotensin (Ang)-II-induced cardiac and renal injury. We performed Ang-II modeling in wild type (WT) mice and miR-26a KO mice, with six mice in each group. In addition, Ang-II-treated AC16 cells and HK2 cells were used as in vitro models of cardiac and renal injury in the context of CKD. Histological staining, immunohistochemistry, quantitative real-time polymerase chain reaction (PCR), and Western blotting were applied to study the regulation of miR-26a on Ang-II-induced cardiac and renal injury. Immunofluorescence reporter assays were used to detect downstream genes of miR-26a, and immunoprecipitation was employed to identify the interacting protein of LIM and senescent cell antigen-like domain 1 (LIMS1). We also used an adeno-associated virus (AAV) to supplement LIMS1 and explored the specific regulatory mechanism of miR-26a on Ang-II-induced cardiac and renal injury. Dunnett's multiple comparison and t -test were used to analyze the data. RESULTS: Compared with the control mice, miR-26a expression was significantly downregulated in both the kidney and the heart after Ang-II infusion. Our study identified LIMS1 as a novel target gene of miR-26a in both heart and kidney tissues. Downregulation of miR-26a activated the LIMS1/integrin-linked kinase (ILK) signaling pathway in the heart and kidney, which represents a common molecular mechanism underlying inflammation and fibrosis in heart and kidney tissues during CKD. Furthermore, knockout of miR-26a worsened inflammation and fibrosis in the heart and kidney by inhibiting the LIMS1/ILK signaling pathway; on the contrary, supplementation with exogenous miR-26a reversed all these changes. CONCLUSIONS Our findings suggest that miR-26a could be a promising therapeutic target for the treatment of cardiorenal injury in CKD. This is attributed to its ability to regulate the LIMS1/ILK signaling pathway, which represents a common molecular mechanism in both heart and kidney tissues.
Animals ; MicroRNAs/metabolism* ; Angiotensin II/toxicity* ; Mice ; Renal Insufficiency, Chronic/chemically induced* ; Mice, Knockout ; Disease Models, Animal ; Male ; Signal Transduction/genetics* ; LIM Domain Proteins/genetics* ; Mice, Inbred C57BL ; Cell Line ; Humans

OBJECTIVE: To elucidate the specific mechanisms by which electroacupuncture (EA) alleviates anxiety and fear behaviors associated with posttraumatic stress disorder (PTSD), focusing on the role of lipocalin-2 (Lcn2). METHODS: The PTSD mouse model was subjected to single prolonged stress and shock (SPS&S), and the animals received 15 min sessions of EA at Shenmen acupoint (HT7). Behavioral tests were used to investigate the effects of EA at HT7 on anxiety and fear. Western blotting and enzyme-linked immunosorbent assay were used to quantify Lcn2 and inflammatory cytokine levels in the prefrontal cortex (PFC). Additionally, the activity of PFC neurons was evaluated by immunofluorescence and in vivo electrophysiology. RESULTS: Mice subjected to SPS&S presented increased anxiety- and fear-like behaviors. Lcn2 expression in the PFC was significantly upregulated following SPS&S, leading to increased expression of the proinflammatory cytokines tumor necrosis factor-α and interleukin-6 and suppression of PFC neuronal activity. However, EA at HT7 inhibited Lcn2 release, reducing neuroinflammation and hypoexcitability in the PFC. Lcn2 overexpression mitigated the effects of EA at HT7, resulting in anxiety- and fear-like behaviors. CONCLUSION EA at HT7 can ameliorate PTSD-associated anxiety and fear, and its mechanism of action appears to involve the inhibition of Lcn2-mediated neural activity and inflammation in the PFC. Please cite this article as: Yang YD, Zhong W, Chen M, Tang QC, Li Y, Yao LL, et al. Electroacupuncture alleviates behaviors associated with posttraumatic stress disorder by modulating lipocalin-2-mediated neuroinflammation and neuronal activity in the prefrontal cortex. J Integr Med. 2025; 23(5):537-547.
Electroacupuncture ; Stress Disorders, Post-Traumatic/metabolism* ; Animals ; Lipocalin-2/metabolism* ; Prefrontal Cortex/physiopathology* ; Male ; Mice ; Neurons/physiology* ; Disease Models, Animal ; Fear ; Behavior, Animal ; Mice, Inbred C57BL ; Neuroinflammatory Diseases/metabolism* ; Anxiety/therapy* ; Acupuncture Points

Objective To analyze the magnetic resonance images (MRI) of patients with spinal epidural lipomatosis (SEL) in high-altitude areas and to determine the optimal cut-off value for diagnosis with epidural fat thickness. Methods This retrospective study included patients who underwent lumbosacral MRI examination for lumbosacral pain in Ping’an District Hospital of Traditional Chinese Medicine, Haidong City, China from January 1, 2021 to December 31, 2022. The epidural fat thickness in vertebral segments T12/L1 to L5/S1 was compared between the SEL group and the non-SEL group. The diagnostic efficacy with different cut-off values at each vertebral segment was evaluated. Between-group comparisons were performed using the t-test, Mann-Whitney U test, chi-square test, or modified chi-square test. The area under the receiver operating characteristic (AUC) was used to evaluate the diagnostic efficiency. The DeLong test was used to compare AUC between the two groups. Results A total of 370 patients were included (60 in the SEL group and 310 in the non-SEL group). There were no significant differences in age, sex, height, body weight, and body mass index between the two groups (all P > 0.05). At different vertebral segments, the epidural fat thickness was significantly higher in the SEL group than in the non-SEL group (all P < 0.05). The cut-off values for SEL diagnosis with epidural fat thickness in segments T12/L1 to L5/S1 were 2.23, 4.25, 4.85, 5.57, 7.21, and 8 mm, respectively. The AUC of MRI SEL diagnosis with epidural fat thickness in segment L5/S1 was the highest (0.945, 95% confidence interval [CI]: 0.916-0.966, P < 0.001). SEL diagnosis with epidural fat thickness > 8 mm in segment L5/S1 was the most accurate, with an AUC of 0.931 (95% CI: 0.901-0.955, P < 0.001), a sensitivity of 95.0%, and a specificity of 91.3%; this AUC was significantly higher than those of diagnosis with other cut-off values (all P < 0.05). Conclusion SEL patients have significantly increased epidural fat in the spinal canal. Epidural fat thickness > 8 mm in segment L5/S1 can be used for diagnosis of SEL with improved efficiency and accuracy.

Objective To explore the effect of propranolol on femoral fracture healing in mice through regulation of microRNA-92a-3p(miR-92a-3p)and its mechanism.Methods C57BL/6J male mice were randomly divided into sham group(equal amount of 0.9％NaCl),model group(equal amount of 0.9％NaCl),experimental group(50 mg·kg-1 propranolol administration),inhibitor group(mice were injected with 100 mg·kg-1 miR-92a-3p inhibitor via tail vein on the basis of the experimental group).Femur was severed and molded in all mice except sham operation group.X-ray was used to observe bone healing.Quantitative real time polymerase chain reaction was used to detect the expression of miR-92a-3p in femur tissues.The expression level of bone formation and bone metabolism markers was detected by enzyme linked immunosorbent assay.Western blot was used to detect the expression of pathway-related proteins.Results The X-ray scores of femur in sham group,model group and experimental group were 11.20±2.60,4.70±1.50 and 9.60±2.40,respectively;the relative expression levels of miR-92a-3p in sham operation group,model group,experimental group and inhibitor group were 1.00±0.09,0.73±0.06,0.90±0.07 and 0.78±0.06;alkaline phosphatase levels were(35.21±2.63),(43.16±3.29),(67.58±5.37)and(49.62±4.05)U·L-1,respectively;crosslaps levels were(4.57±0.52),(8.41±0.91),(4.26±0.67)and(5.73±0.84)ng·mL-1,respectively;the relative expression levels of brain derived neurotrophic factor were 1.00±0.14,0.58±0.05,0.83±0.09 and 0.71±0.06,respectively;the relative expression levels of phospho-tyrosine kinase receptor B were 1.00±0.12,0.62±0.05,0.89±0.08 and 0.76±0.07,respectively;the relative expression levels of phospho-extracellular regulated protein kinases were 1.00±0.11,0.54±0.04,0.78±0.07 and 0.65±0.05,respectively.The above indexes in the model group were compared with those in the sham group,those in the experimental group were compared with those in the model group,and those in the inhibitor group were compared with those in the experimental group,and the differences were statistically significant(P＜0.05,P＜0.001).Conclusion Propranolol can promote femoral fracture healing in mice,which may be achieved by up-regulating miR-92a-3p activation of brain derived neurotrophic factor/tyrosine kinase receptor B/extracellular regulated protein kinases signaling pathway.

Objective The aim of this study was to assess the impact of bisphenol A (BPA) and its substitute, bisphenol F (BPF), on the colonic fecal community structure and function of mice.Methods We exposed 6-8-week-old male C57BL/6 mice to 5 mg/(kg·day) and 50 μg/(kg·day) of BPA or BPF for 14 days. Fecal samples from the colon were analyzed using 16S rRNA sequencing. Results Gut microbiome community richness and diversity, species composition, and function were significantly altered in mice exposed to BPA or BPF. This change was characterized by elevated levels of Ruminococcaceae UCG-010 and Oscillibacter and decreased levels of Prevotella 9 and Streptococcus. Additionally, pathways related to carbohydrate and amino acid metabolism showed substantial enrichment. Conclusion Mice exposed to different BP analogs exhibited distinct gut bacterial community richness, composition, and related metabolic pathways. Considering the essential role of gut bacteria in maintaining intestinal homeostasis, our study highlights the intestinal toxicity of BPs in vertebrates.

Ankylosing spondylitis (AS) combined with lower cervical fracture is often categorized into unstable fracture, with a high incidence of neurological injury and a high rate of disability and morbidity. As factors such as shoulder occlusion may affect the accuracy of X-ray imaging diagnosis, it is often easily misdiagnosed at the primary diagnosis. Non-operative treatment has complications such as bone nonunion and the possibility of secondary neurological damage, while the timing, access and choice of surgical treatment are still controversial. Currently, there are no clinical practice guidelines for the treatment of AS combined with lower cervical fracture with or without dislocation. To this end, the Spinal Trauma Group of Orthopedics Branch of Chinese Medical Doctor Association organized experts to formulate Clinical guidelines for the treatment of ankylosing spondylitis combined with lower cervical fracture in adults ( version 2024) in accordance with the principles of evidence-based medicine, scientificity and practicality, in which 11 recommendations were put forward in terms of the diagnosis, imaging evaluation, typing and treatment, etc, to provide guidance for the diagnosis and treatment of AS combined with lower cervical fracture.

BACKGROUND:Pulsed electromagnetic fields,as an important physical therapy,are exactly effective in the treatment of osteoarthritis,but the mechanism has not been fully clarified. OBJECTIVE:To observe the effect of pulsed electromagnetic field on the degeneration of knee joint cartilage in aged rats. METHODS:Eight 6-month-old Sprague-Dawley rats were selected as the young group and were subjected to normal diet with no treatment.Sixteen 22-month-old Sprague-Dawley rats were randomly divided into old group(n=8)and pulsed electromagnetic field group(n=8).The rats in the pulsed electromagnetic field group were subjected to a pulsed electromagnetic field intervention,once a day,5 days per week for continuous 8 weeks.The rats in the old group were given no treatment.All rats were anesthetized and executed after 8 weeks for the detection of relevant indexes. RESULTS AND CONCLUSION:Compared with the young group,serum type Ⅱ collagen C-terminal peptide level was increased in the old group(P<0.05);compared with the old group,serum type Ⅱ collagen C-terminal peptide level was decreased in the pulsed electromagnetic field group(P<0.05).Micro-CT showed that the bone volume fraction,bone mineral density,and number of bone trabeculae decreased(P<0.05)and the trabecular separation increased(P<0.05)in the tibia of rats in the aged group compared with the young group;and the bone volume fraction,bone density,and number of trabeculae increased(P<0.05)and the trabecular separation decreased(P<0.05)in the tibia of rats in the pulsed electromagnetic field group compared with the aged group.The tibial plateau Safranin O-fast green staining showed that the articular cartilage structure of rats in the aged group was disorganized,and the number of chondrocytes was obviously reduced,and the tidal line could not be distinguished.The above results were improved in the pulsed electromagnetic field group.RT-qPCR and western blot assay showed that the mRNA and protein expression levels of matrix metalloproteinase 1,matrix metalloproteinase 13,P53 and P21 in the articular cartilage and subchondral bone of rats were elevated in the aged group compared with the young group(P<0.05)and decreased in the pulsed electromagnetic field group compared with the old group(P<0.05).To conclude,pulsed electromagnetic fields may improve osteoarthritis in aged rats by inhibiting chondrocyte senescence,alleviating articular cartilage degradation and inhibiting subchondral bone osteoporosis through suppressing the expression of P53/P21.

Atrial fibrillation(AF)is the most common arrhythmia in the world and is closely related to mortality of patients.So far,number of patients in China has approached 10 million.Identifying manageable risk factors for AF and developing appropriate prevention strategies possess critical significance in reducing occurrence of fatal AF and costs on healthcare system.Risk factors for AF include obesity,hypertension,diabetes,obstructive sleep apnea,etc.Alcohol consumption,smoking and a sedentary lifestyle have also been recognized as important factors in occur-rence and development of AF.The present article makes a review on role of modifiable risk factors of AF in occur-rence,development and treatment of AF and mechanisms of each potential risk factor associated with AF.

Objective:Non-alcoholic fatty liver disease(NAFLD)is a common metabolic disorder in overweight and obese children,and its etiology and pathogenesis remain unclear,lacking effective preventive and therapeutic measures.This study aims to explore the association between whole blood copper,zinc,calcium,magnesium and iron levels and NAFLD in overweight and obese children aged 6 to 17 years,providing a scientific basis for the prevention and intervention of early NAFLD in overweight and obese children. Methods:A cross-sectional study design was used to collect relevant data from overweight and obese children who visited the Hunan Children's Hospital from January 2019 to December 2021 through questionnaire surveys.Fasting blood samples were collected from the subjects,and various indicators such as blood glucose,blood lipid,and mineral elements were detected.All children were divided into an overweight group(n=400)and a NAFLD group(n=202).The NAFLD group was divided into 2 subgroups according to the ALT level:A non-alcoholic fatty liver(NAFL)group and a non-alcoholic steatohepatitis(NASH)group.Logistic regression analysis was used to analyze the association between minerals(copper,zinc,calcium,magnesium,and iron)and NAFLD,NAFL and NASH. Results:A total of 602 subjects were included,of whom 73.6%were male,with a median age of 10(9,11)years,and a body mass index(BMI)of 24.9(22.7,27.4)kg/m2.The intergroup comparison results showed that compared with the overweight group,the NAFLD group had higher levels of age,BMI,diastolic blood pressure(DBP),systolic blood pressure(SBP),triglyceride(TG),low density lipoprotein(LDL),alanine transaminase(ALT)and aspartate aminotransferase(AST),and lower level of high density lipoprotein(HDL).The NAFL group had higher levels of age,BMI,DBP,SBP,ALT,and AST,and lower levels of HDL compared with the overweight group.The levels of age,BMI,DBP,SBP,TG,LDL,ALT,and AST of NASH were higher than those in the overweight group,while the level of HDL was lower than that in overweight group(all P<0.017).After adjusting for a variety of confounders,the OR of NAFLD for the highest quantile of iron was 1.79(95%CI 1.07 to 3.00)compared to the lowest quantile,and no significant association was observed between copper,zinc,calcium,and magnesium,and NAFLD.The subgroup analysis of NAFLD showed that the OR for the highest quantile of iron in children with NAFL was 2.21(95%CI 1.26 to 3.88),while no significant association was observed between iron level and NASH.In addition,no significant associations were observed between copper,zinc,calcium,and magnesium levels and NAFL or NASH. Conclusion:High iron level increases the risk of NAFLD(more likely NAFL)in overweight and obese children,while copper,zinc,calcium,magnesium,and other elements are not associated with the risk of NAFLD in overweight and obese children.