Objective To explore the application effect of opioid-free postoperative patient-controlled analgesia strategy in thoracic endoscopic resection of lung lesions. Methods This study is a single center, double-blind, prospective, open label, randomized controlled trial. Ninety patients with lung surgery under thoracic endoscope in the Second Affiliated Hospital of Chongqing Medical University were selected from November 2021 to April 2023, and divided into three groups, according to the random number table method including esketamine and dexmedetomidine (esKDex group, n=30), sufentanil and dexmedetomidine (sFDex group, n=30) and tramadol and dexmedetomidine (TraDex group, n=30). The incidence of postoperative nausea and vomiting (PONV), vital signs related indicators, visual analogue scale (VAS) score, Ramsay sedation (RSS) score, Bruggrmann comfort scale (BCS) score and mini-mental state examination (MMSE) score were compared among the 3 groups within 48 hours after surgery. Results Within 48 h after surgery, the incidence of PONV in esKDex group was lower than that in sFDex group and TraDex group [10.0%(3/30) vs. 20.0%(6/30) vs. 20.0%(6/30), P<0.001]. The VAS scores in esKDex group and sFDex group at 2 h and 4 h after surgery were lower than those in TraDex group (2 h after surgery: P=0.001, 0.001; 4 h after surgery: P=0.027, 0.024). The VAS scores at 24 h and 48 h after surgery were higher than those in TraDex group (24 h after surgery: P=0.008, 0.029; 48 h after surgery: P=0.005, 0.005). The BCS scores of esKDex group and sFDex group at 24 h and 48 h after surgery were lower than those in TraDex group (24 h after surgery: P=0.017, 0.007; 48 h after surgery: P=0.005, 0.007). There was no significant difference between Ramsay scores and MMSE scores among the three groups within 48 h after surgery (P>0.05). Conclusion The strategy of opioid-free postoperative patient-controlled analgesia (esketamine and dexmedetomidine) can reduce the incidence of PONV under the premise of satisfying the sedation and analgesia of patients after thoracic endoscopic surgery.

Objective To investigate the effect of varying blood pressure stratification on renal function in the diabetic population. Methods A prospective cohort study was conducted, enrolling 9 489 diabetic patients from a total of 101 510 Kailuan Group employees who underwent health examinations between July 2006 and October 2007. The follow-up period was (8.6±4.0) years. Participants were categorized into four groups based on their baseline blood pressure levels: normal blood pressure (systolic blood pressure <120 mmHg and diastolic blood pressure <80 mmHg), elevated blood pressure (systolic blood pressure 120-130 mmHg and diastolic blood pressure <80 mmHg), stage 1 hypertension (systolic blood pressure 130-140 mmHg and/or diastolic blood pressure 80-90 mmHg), and stage 2 hypertension (systolic blood pressure ≥140 mmHg and/or diastolic blood pressure ≥90 mmHg). The incidence density of chronic kidney disease (CKD) was compared among these groups. A multivariate Cox proportional hazards regression model was employed to assess the effects of different blood pressure levels on renal function in diabetic patients, with the stability of the results confirmed using a multivariate time-dependent Cox proportional hazards model. Sensitivity analysis was conducted after excluding cases of cardiovascular disease (CVD) during follow-up, and cases using antihypertensive and antidiabetic medications at baseline. Results (1) At baseline, stage 1 hypertension patients demonstrated statistically significant higher differences with age and body mass index (BMI) compared to normal blood pressure group (P<0.05). (2) By the end of the follow-up, 2 294 cases of CKD were identified, including 1 117 cases of estimated glomerular filtration rate (eGFR) decline and 1 575 cases of urinary protein. The incidences density of CKD, eGFR decline and urinary protein for stage 1 hypertension group were 39.4, 16.3 and 25.5 per thousand person-years, respectively, all of which were statistically significant different from normal blood pressure group (log-rank test, P<0.01). (3) Multivariate Cox regression analysis revealed that, compared to the normal blood pressure group, stage 1 hypertension was associated with a 29% increased risk of CKD (HR=1.29, 95%CI 1.09-1.52) and a 40% increased risk of eGFR decline (HR=1.40, 95%CI 1.08-1.80) in diabetic individuals. Conclusion Stage 1 hypertension significantly increases the risk of CKD and eGFR decline in diabetic individuals, with a particularly notable effect on the risk of eGFR decline.

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 effect of vascular endothelial growth factor (VEGF) on the expression of genes related to ovarian steroid synthesis in mice and its underlying mechanism. Methods A transgenic mouse model with tetracycline -reversible regulation of VEGF expression was used, and the genotype of mice was identified by polymerase chain reaction (PCR). Twenty mice were divided into normal VEGF expression group (Dox⁺, n=10) and VEGF expression inhibition group (Dox^-, n=10) by feeding them doxycycline. Western blotting was used to detect the expression of VEGF protein in ovarian tissues. Fluorescence quantitative PCR was used to detect the mRNA expression of VEGF, KDR and genes known to play roles in follicle development, such as follicle-stimulating hormone (FSH) and inhibin B (INHBB). HE staining was used to observe changes in ovarian tissue. Total RNA was extracted from mouse ovarian tissues for transcriptome sequencing, and the relevant differential genes were analyzed by FPKM and log₂FC values. Results Compared with the Dox⁺ group, the mRNA and protein levels of VEGF in the Dox^- group significantly reduced, and the mRNA levels of KDR also significantly decreased (P<0.05). HE staining results showed that compared with the Dox⁺ group, follicular development was impaired and atresia follicles appeared in the Dox^- group. Sequencing analysis identified that significant differences in follicular development-related genes and steroid synthesis-related genes between the two groups (P<0.05). Enrichment analysis showed that VEGF in mouse ovaries mainly regulates ovarian steroidogenesis and other pathways. Fluorescence quantitative PCR results demonstrated that compared with the Dox⁺ group, the follicular development-related genes (INHBB and FSHR) in the ovarian tissues of the Dox^- group were significantly up-regulated (P<0.05), whereas the key genes of steroid synthesis (StAR, CYP11A1, 3β-HSD) were significantly down-regulated (P<0.05).The quantitative results were basically consistent with the sequencing results. Conclusion Mice with inhibited VEGF exhibited ovarian follicular dysplasia, potentially due to the mechanism whereby VEGF inhibition downregulated the expression of genes associated with steroid synthesis, such as FSH and INHBB, thereby obstructing cholesterol metabolism.

Objective To explore the effects of 1α,25-dihydroxyvitamin D₃ on airway inflammation in asthmatic mice and the potential mechanisms. Methods Twenty-four female BALB/c mice in SPF grade were randomly divided into three groups (n=8): control group, asthma group, and asthma+VD₃ group. On the 1st, 8th, and 15th day, asthma group and asthma+VD₃ group were given 0.2 ml ovalbumin (OVA) suspension for sensitization, while control group received 0.2 ml normal saline. On the 22-28th day, asthma group and asthma+VD₃ group were challenged with 1% OVA atomization inhalation, while control group received an equal amount of normal saline atomization, for 30 minutes each time, once a day, for a continuous 7 days. Asthma+VD₃ group was given intraperitoneal injection of 1α,25-dihydroxyvitamin D₃ injection (4 μg/kg) 30 minutes before each atomization, while control group and asthma group were given an equal dose of normal saline. After the last challenge, all mice were anesthetized, and serum, bronchoalveolar lavage fluid (BALF) and lung tissue samples were collected. HE staining and Periodic Acid Schiff (PAS) staining were used to observe the pathological changes in lung tissue and changes in airway mucus levels. ELISA was employed to detect serum IgE and inflammatory cytokines IL-4, IL-5 and IL-13 in BALF. Immunohistochemical technique and Western blotting were used to detect the expressions of SIRT1 and GATA-3 in mouse lung tissue. Results Compared with control group, asthma group had a significant increase in inflammatory cell infiltration around lung tissue, bronchia and accompanying perivascular, mainly characterized by eosinophils. Bronchial lumen stenosis, airway mucosal epithelial hyperplasia, and increased tracheal mucus secretion were also observed. The above changes in asthma+VD₃ group were reduced compared with asthma group. Compared with control group, serum levels of IgE, and IL-4, IL-5, IL-13 inflammatory factors in BALF and GATA-3 in lung tissue were increased in asthma group (P<0.05), and SIRT1 level in lung tissue was significant decreased (P<0.05). Compared with asthma group, IgE level in serum, inflammatory factors of IL-4, IL-5 and IL-13 in BALF, and GATA-3 in lung tissue in asthma+VD₃ group were decreased (P<0.05), and SIRT1 level in lung tissue was increased (P<0.05). Correlation analysis showed that the expression level of lung tissue SIRT1 was negatively correlated with the expression of GATA-3, serum IgG, and the levels of IL-4, IL-5, and IL-13 in BALF (P<0.05); the expression level of lung tissue GATA-3 was positively correlated with serum IgG and the levels of IL-4, IL-5, and IL-13 in BALF (P<0.05). Conclusion 1α,25-dihydroxyvitamin D₃ can alleviate airway inflammation in asthmatic mice, possibly by upregulating the expression of SIRT1 in lung tissue and inhibiting the expression of GATA-3, thereby inhibiting inflammatory factors (IL-4, IL-5, IL-13).

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.

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.

Takeda G protein-coupled receptor 5 (TGR5) is a bile acid receptor located on the surface of cell membrane, widely distributed in many tissues and cells in the body, and can be directly activated by most bile acids in vivo. TGR5 plays an important role in various physiological and pathophysiological processes, including cellular Ca²⁺ transport, oxidative stress, cell proliferation, inflammatory responses, and mitochondrial metabolism, thereby maintaining mitochondrial homeostasis and vascular endothelial function, and inhibiting the progression of cardiovascular diseases such as atherosclerosis, myocardial hypertrophy, and cardiac remodeling after myocardial infarction. Currently, with the gradual clinical application of numerous bile acid and bile acid derivatives drugs, it is necessary to further investigate the role of TGR5 in the cardiovascular system, which is an important basis for clinical application of these new drugs. This review discusses the relationship between TGR5 and cardiovascular system from five perspectives: TGR5's involvement in regulating macrophages, endothelial function, vascular smooth muscle cells, cardiomyocytes, and mitochondrial metabolism. It summarizes the recent research progress, aiming to provide the theoretical basis for TGR5 as a novel therapeutic target for cardiovascular diseases.

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.

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.