Objective To explore the effects of standardized environmental enrichment (EE) on cognitive function and serum brain-derived neurotrophic factor (BDNF) levels in patients with post-stroke dementia. Methods A prospective study was conducted, including 80 patients with post-stroke dementia admitted to Department of Traditional Chinese Medicine Rehabilitation, 910th Hospital of the Joint Logistics Support Force of Chinese PLA from January 2021 to May 2023. Patients were randomly divided into control group, cognitive training (COG) group, aerobic exercise training (AE) group and environmental enrichment (EE) group, with 20 cases in each group. All patients received routine treatment, with COG group receiving additional cognitive function training (30 minutes each time), AE group receiving additional aerobic exercise training (30 minutes each time), and EE group receiving both aerobic exercise and cognitive function training (15 minutes of aerobic exercise training and 15 minutes of cognitive training each time). The training was conducted once a day, 5 days a week, for a total of 8 weeks. The patients' mini-mental state scale (MMSE), modified Barthel index (MBI), Hamilton depression scale (HAMD), stroke-specific quality of life (SS-QOL) score and serum levels of BDNF were assessed before treatment, at 4 weeks and 8 weeks of treatment, respectively. Results Before treatment, there were no significant differences in general information, MMSE, MBI, HAMD, SS-QOL scores, and serum levels of BDNF among the four groups (P>0.05). After 4 and 8 weeks of treatment, the above indicators of the four groups were improved compared with those before treatment, with all differences being statistically significant (P<0.05). Inter-group comparison showed that after 4 and 8 weeks of treatment, MMSE, MBI, SS-QOL scores, and serum BDNF levels in COG, AE and EE groups were significantly higher than those in control group, and HAMD scores were significantly lower than those in control group (P<0.05). In addition, MMSE, MBI, SS-QOL scores and BDNF levels of group EE were better than those of other 3 groups, while HAMD scores were lower than those of other 3 groups, with all differences being statistically significant (P<0.05). There was no significant difference in above outcome indicators between COG group and AE group after 4 and 8 weeks of treatment (P>0.05). Conclusion Standardized enrichment environment can significantly enhance cognitive function, daily living abilities of post-stroke dementia patients, alleviate depression symptoms, and improve the quality of life, which may be related to the increase in serum BDNF levels.

Objective To analyze the prevalence, disease burden, and trends of diabetes in China from 1999 to 2019, providing reference for diabetes prevention and control as well as health resource allocation to alleviate the disease burden. Methods Data on the disease burden of diabetes in China from 1999 to 2019 were collected from the Global Burden of Disease (GBD) 2019 database. Indicators such as incidence rate, prevalence rate, mortality rate, disability-adjusted life years (DALYs), years of life lost due to premature mortality (YLLs) and years lived with disability (YLDs) were used to analyze the diabetes burden in China by gender, age and year. The estimated annual percentage change (EAPC) was used to measure the temporal trend of standardized rates over a specified period, and the rank sum test was used to assess the gender differences in disease burden. Results In 2019, 3.78×10⁶ cases of diabetes and 1.73×10⁵ deaths were reported in China. Compared with 1999, the standardized rates of incidence and prevalence increased by 5.80% and 17.12%, respectively, while the standardized mortality rate decreased by 2.82%. Compared with 1999, the standardized rates of DALYs and YLDs increased by 2.86% and 16.06%, respectively, while the standardized YLL rate decreased by 14.39%. The EAPC for diabetes incidence, prevalence, YLDs, and DALYs in the 20-40 age group all exceed 0, indicating an annually upward trend in disease burden of diabetes. Additionally, the disease burden in males was significantly higher than that in females (P<0.05), and the gap is continuously widening. Conclusions The disease burden of diabetes in China is severe, particularly in term of life loss due to disability. The population with diabetes onset is becoming increasingly younger. Males constitute a high-risk population for diabetes-related morbidity and mortality. Diabetes prevention and control efforts should continue to enhance behavioral interventions, appropriately tilt health resource allocation towards high-risk population, and focus on improving the rehabilitation capabilities and promoting rehabilitation technology at grass-roots unit.

Objective To investigate the role and underlying mechanisms of miR-34a/SIRT1 in intensive care unit acquired weakness (ICU-AW). Methods (1) C2C12 mouse skeletal muscle cells were induced to differentiate into myotubes, and were divided into two groups: model group [ICU-AW group, treated with lipopolysaccharides (LPS) for 12 hours] and normal control group (treated with the same amount of sterile water for 12 hours). Western blotting was used to detect the protein expression level of Muscle ring finger 1 (MuRF-1), atrophy gene 1 (Atrogin-1) and Sirtuin-1 (SIRT1). RT-qPCR was used to assess the mRNA expression level of microRNA-34a (miR-34a), MuRF-1, Atrogin-1 and SIRT1, and light microscope was used to observe the growth and differentiation of C2C12 skeletal muscle cells in each group. (2) ICU-AW cells were further subdivided into control group (treated with siRNA transfection agent intervention), Scra siRNA group (treated with transfection agent and non-specific siRNA), miR-34a siRNA group (treated with transfection agent and specific siRNA intervention), vehicle group (treated with agonist solvent dimethyl sulfoxide) and SRT1720 group (treated with SIRT1 agonist SRT1720). Western blotting was used to detect the protein expression level of SIRT1, Atrogin-1 and MuRF-1 in each group. RT-qPCR was used to detect the miR-34a and the mRNA expression level of SIRT1, Atrogin-1 and MuRF-1 in each group. (3) In addition, another group of ICU-AW cells were divided into control group (treated with siRNA transfection), miR-34a siRNA group (treated with transfection agent and specific siRNA intervention), miR-34a siRNA+vehicle group (treated with transfection agent, specific siRNA and Dimethyl sulfoxide intervention) and miR-34a siRNA+EX-527 group (treated with transfection agent, specific siRNA and SIRT1 inhibitor EX-527). Western blotting was used to detect the protein expression level of Atrogin-1 and MuRF-1. RT-qPCR was used to assess the mRNA expression level of Atrogin-1 and MuRF-1. Results Myotube differentiation was observed on the 4th day. Compared with control group, myotube atrophy was obvious in ICU-AW group. RT-qPCR and Western blotting results revealed that, compared with normal control group, in ICU-AW group, the mRNA and protein expression levels of Atrogin-1 and MuRF-1 significantly increased (P<0.05), and the expression level of miR-34a significantly increased (P<0.05), while the mRNA and protein expression levels of SIRT1 significantly decreased (P<0.05). RT-qPCR results showed that, compared with control group (treated with siRNA transfection agent intervention) and Scra siRNA group, the expression of miR-34a and mRNA expression of Atrogin-1 and MuRF-1 in miR-34a siRNA group significantly decreased (P<0.05), while the mRNA expression of SIRT1 significantly increased (P<0.05), meanwhile the protein expression of Atrogin-1 and MuRF-1 decreased significantly (P<0.01), and the protein expression of SIRT1 significantly increased (P<0.05). RT-qPCR results also showed that, compared with vehicle group, the mRNA expression of Atrogin-1 and MuRF-1 in SRT1720 group decreased significantly (P<0.05), while SIRT1 increased significantly (P<0.05). Western blotting results demonstrated that, compared with control group and Scra siRNA group, the protein expression of Atrogin-1 and MuRF-1 in miR-34a siRNA group decreased significantly (P<0.05), while SIRT1 increased significantly (P<0.05). RT-qPCR and Western blotting results indicated that, compared with miR-34a siRNA+vehicle group, the mRNA and protein expression of Atrogin-1 and MuRF-1 in miR-34a siRNA+EX-527 group increased significantly (P<0.05). Conclusion Overactivation of miR-34a in ICU-AW contributes to skeletal muscle atrophy by inhibiting the expression of SIRT1, which may play an important role in the pathogenesis of ICU-AW.

Objective To analyze the correlation of malondialdehyde (MDA), advanced oxidation protein products (AOPP), nuclear factor erythroid-2 related factor 2 (Nrf2), glutathione (GSH) levels with postoperative acute kidney injury (AKI) among patients undergoing laparoscopic partial nephrectomy (LPN). Methods A total of 110 patients with renal cell carcinoma who were admitted to the Department of Urology, the Third Medical Center of Chinese PLA General Hospital from February to August 2022 were included in the study. Patients were divided into AKI group (n=30) and non-AKI group (n=80) based on the Kidney Disease: Improving Global Outcomes (KDIGO) criteria, and then divided into elderly AKI (>65 years old, n=14), middle-aged AKI (50-65 years old, n=16), elderly non-AKI (>65 years old, n=30), and middle-aged non-AKI (50-65 years old, n=50) four sub-groups based on age. Clinical characteristics and laboratory examination data were recorded. Venous blood was collected from the patients before the operation (T₁), immediately after the surgery (T₂), and 24 h after surgery (T₃), and MDA, AOPP, Nrf2 and GSH levels were measured. MDA, AOPP, Nrf2 and GSH levels were compared between the four subgroups at different time points, and their correlation with the occurrence of AKI after LPN were explored. The risk factors for AKI after LPN were analyzed using the univariate and multivariate logistic regression. Results Spearman correlation analysis revealed that AKI was not associated with the MDA level at each time point (P>0.05), was positively associated with AOPP-T₃ level (r=0.315, P=0.037), was negatively associated with the Nrf2-T₃ level (r=-0.365, P=0.015) and GSH-T₂ level (r=-0.338, P=0.025) in elderly patients after LPN. AKI was not associated with MDA, AOPP, Nrf2, and GSH levels (P>0.05) in middle-aged patients after LPN. Multivariate logistic regression analysis showed that BMI (OR=2.724, P=0.040) and surgically resected kidney volume (OR=1.309, P=0.049) were independent risk factors for AKI in elderly patients after LPN, GSH-T₂ (OR=0.271, P=0.042) was an independent protective factor for AKI in elderly patients after LPN. Intraoperative colloid fluid intake (OR=1.006, P=0.007) was an independent risk factor for AKI in middle-aged patients after LPN, intraoperative urine output (OR=0.104, P=0.007) was an independent protective factor for AKI in middle-aged patients after LPN. Conclusions The AKI after LPN may be related to the increase of AOPP level and the decrease of Nrf2 and GSH levels in elderly patients, and the postoperative GSH is an independent protective factor for AKI in elderly patients after LPN. The correlation of AKI after LPN is not significant with the levels of MDA, AOPP, Nrf2 and GSH in the middle-aged patients.

Objective To investigate the mechanism of nootkatone (NKT) in mitigating depression-like behavior caused by blast traumatic brain injury (TBI). Methods The rat bTBI depression-like model was established by simulating the shock wave parameters of blast overpressure (BOP of 60 kPa, 90 kPa, and 120 kPa) with a biological shock wave tube. After 14 days of exposure, we evaluated the depression-like behavior of rats using the tail suspension test and forced swimming test. We identified that the BOP (120 kPa) condition caused the most noticeable depressive behavior and used this condition for subsequent experiments. Thirty male SD rats were randomly divided into sham operation group, bTBI group (BOP of 120 kPa), and bTBI+NKT group [at 1 d after exposure to BOP of 120 kPa, giving NKT 10 mg/(kg·d) orally for 14 days], 10 in each group. After 14 days of exposure, the depression-like behavior of rats was evaluated by tail suspension test and forced swimming test. The expression levels of protein kinase A (PKA), phosphorylated cyclic adenosine monophosphate effector binding protein (pCREB), and brain-derived neurotrophic factor (BDNF) in the hippocampus of rat were determined by Western blotting. Immunohistochemistry was used to detect the generation of proliferating cell nuclear antigen (PCNA)-labeled neurons in the hippocampal dentate gyrus (DG). Results BOP of 90 kPa can cause depression-like in rats and BOP of 120 kPa can cause the most noticeable depressive behavior (P<0.05). Therefore, we selected the BOP exposure of 120 kPa for subsequent experiments. After 14 days of BOP exposure, compared with sham operation group, the immobility time of tad suspension test in bTBI group was prolonged (P<0.05), the latency of for ced swimming test was shortened, the immobility time was prolonged (P<0.05), the expression levels of PKA, pCREB and BDNF protein in hippocampus were lowered (P<0.05), and the number of PCNA-labeled neurons in hippocampal DG area was reduced (P<0.05); compared with the bTBI group, the immobility time of tail suspension test in bTBI+NKT group was shortened (P<0.05), the latency of forced swimming test was prolonged, the immobility time was shortened (P<0.05), the expression levels of PKA, pCREB and BDNF protein in hippocampus were increased (P<0.05), and the number of PCNA-labeled neurons in hippocampal DG area was increased (P<0.05). Conclusions Early treatment with NKT can improve depression-like behavior in mild bTBI rats. The mechanism may be related to the up-regulation of the PKA-CREB-BDNF signaling pathway and increased expression levels of pCREB and BDNF in the hippocampus, which results in increased neuron numbers in the DG region of the hippocampus.

Hepatic fibrosis refers to repeated or persistent inflammation and necrosis of liver parenchymal cells and excessive deposition of liver fibrous connective tissue caused by various etiologies, which is a necessary stage for chronic liver disease to develop into cirrhosis. Etiological treatment as antiviral therapy can reduce the inflammation of the liver tissues to a certain degree, but cannot completely stop the process of liver fibrosis. In recent years, researchers have found that intrahepatic macrophages play an important role in the occurrence and progression of hepatic fibrosis, among which M1/M2 macrophages have become the key to exploring macrophages to regulate hepatic fibrosis. This article will focus on the role and mechanism of intrahepatic M1/M2 macrophages in hepatic fibrosis.

Objective To investigate the differentially expressed genes (DEGs) and their molecular interactions in unstable carotid atherosclerotic plaques. Methods Gene expression datasets related to carotid atherosclerotic plaques (GSE41571, GSE118481, and E-MTAB-2055) were downloaded from Gene Expression Omnibus (GEO) and European Bioinformatics Institute (EBI) ArrayExpress databases. The co-regulated DEGs in at least two datasets of unstable carotid plaques were merged and analyzed using Gene Ontology Biological Process (GO-BP), Kyoto Encyclopedia of Genes and Genomes (KEGG), Protein-Protein Interaction (PPI) Networks and subnetwork analysis, relationships between miRNAs/transcription factors and target genes, and drug-gene interaction database. Quantitative real-time PCR (qRT-PCR) and enzyme-linked immunosorbent assay (ELISA) were used to detect the expression levels of some DEGs in carotid plaques and plasma from 58 patients with carotid atherosclerosis. Results GO enrichment analysis showed that DEGs in unstable carotid atherosclerotic plaques were mainly enriched in genes related to inflammatory response and extracellular matrix structure genes. KEGG enrichment analysis indicated that upregulated DEGs in unstable carotid plaques were enriched in extracellular matrix receptor (ECM-receptor) interaction, PI3K-Akt, Hippo and transforming growth factor-β (TGF-β) signaling pathways, while downregulated DEGs were primarily enriched in lysosomes, phagosomes, and chemokines processes. PPI network analysis suggested that COL1A2, COL4A2, insulin-like growth factor binding protein 6 (IGFBP6), COL4A5, C1QA, CXCL10, CXCL2, CXCR4, and CSF1R may play important roles in PPI networks. Prediction of drug-gene interactions revealed that CSF1R had the most drug interaction, CXCL2 was most antagonized by drugs, and IGFBP6 was most activated by drugs. qRT-PCR showed that the expression level of IGFBP6 in unstable carotid plaques group was significantly lower than that in stable carotid plaques group (P<0.001). ELISA results showed that plasma concentration of IGFBP6 in unstable carotid plaques group was significantly lower than that in stable carotid plaques group (P<0.0001). Receiver operating characteristic (ROC) suggested that the area under the curve (AUC) for plasma IGFBP6 levels to identify unstable plaques was 0.894 (95%CI 0.810-0.977), with a cutoff value of 142.08 ng/ml. Conclusion IGFBP6 may become an important biomarker for predicting unstable carotid atherosclerotic plaques.

Objective To elucidate the clinical significance of high expression levels of endonuclease meiosis 1 (EME1) in the prognosis of hepatocellular carcinoma (HCC). Methods The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) databases were used to screen and analyze differential gene expression between HCC and non-tumor tissues. A retrospective collection of liver tissue samples from 80 HCC patients who underwent hepatectomy in the Fifth Medical Center of Chinese PLA General Hospital between January 2010 and December 2014 was performed. Immunohistochemistry analysis was employed to detect the EME1 expression levels. Survival analysis was then conducted to assess the impact of EME1 expression on 5-year postoperative survival rate of HCC patients. Additionally, gene enrichment analysis was applied to predict the function of EME1 in HCC. Results A total of 371 HCC tissue samples and 50 non-tumor liver tissue samples from TCGA database were analyzed, revealing significantly higher EME1 expression in HCC tissues. Microarray analysis of 107 samples within the GEO database (70 HCC tissues and 37 non-tumor tissues) confirmed that EME1 mRNA expression was markedly elevated in HCC tissues compared with non-tumor tissues (P<0.05). The 5-year overall survival (OS) rate was notably lower in high EME1 expression group than that in low expression group (44.1% vs. 53.0%, P<0.05). Semi-quantitative immunohistochemistry analysis demonstrated that patients with high EME1 expression had a significantly lower OS rate than those with low EME1 expression (32.8% vs. 45.0%, P<0.05). Multivariate COX regression analysis identified that high EME1 expression (HR=2.234, 95%CI 1.073-4.649, P=0.032) and advanced China liver caner (CNLC) staging (HR=4.317, 95%CI 1.799-10.359, P=0.001) were independent risk factors for the 5-year OS of post-operation patients with HCC. Conclusion Elevated EME1 expression in HCC tissues correlates with an adverse prognosis of HCC and suggests that EME1 could serve as a potential therapeutic target for HCC.

As a novel tumor treatment, photodynamic therapy (PDT) has been widely used in clinical treatment of a variety of tumors due to its advantages, such as fewer adverse reactions, precise targeting and repeatability of treatment. Unlike conventional treatments, such as surgery, chemotherapy and radiotherapy, PDT not only eliminates the primary tumor but also effectively inhibits metastatic tumors by activating the body's immune response. However, the PDT-activated immune response is influenced by multiple factors, including the localization and dose of photosensitizer in the cells, light parameters, oxygen concentration in the tumor, and the integrity of immune function. This review summarizes the mechanisms behind the PDT-activated anti-tumor immune response, systematically examines the key influencing factors on the immune effect of PDT, and discusses the future development direction of PDT in cancer treatment.

Objective To investigate the risk factors for early neurological deterioration (END) following intravenous thrombolysis with recombinant tissue plasminogen activator (rt-PA) acute mild ischemic stroke (AMIS) patients. Methods Eighty-six patients with AMIS who underwent intravenous thrombolysis with rt-PA in the Department of Neurology, Civil Aviation General Hospital between January 2019 and October 2022 were retrospectively analyzed. Patients were categorized into END group (n=8) and non-END group (n=78) based on the presence of END within 24 hours after thrombolysis (NIHSS score increased by ≥2 points within 24 hours after intravenous thrombolysis). Baseline characteristics, including age, gender, past medical history (hypertension, diabetes, hyperlipidemia, etc.), smoking history, pre-thrombolysis NIHSS score, homocysteine level, fibrinogen level, and post-thrombolysis bleeding transformation were documented for each patient. A multivariate logistic regression analysis was conducted to access the risk factors associated with END following intravenous thrombolysis in AMIS. Results There were significant differences in homocysteine and fibrinogen levels, as well as bleeding transformation after thrombolysis between the two groups (P<0.05). In contrast, other factors such as age, gender, past medical history, pre-thrombolysis NIHSS score, and other imaging features were not statistically significant (P>0.05). Multivariate logistic regression analysis revealed that elevated homocysteine level was independently linked to risk of END after intravenous thrombolysis in AMIS, with an odds ratio of 1.074(95%CI 1.011-1.142, P=0.021). Conclusions Hyperhomocysteinemia emerges as an independent risk factor for END following intravenous thrombolysis in patients with AMIS.