Objective To investigate the inhibitory effects of erianin on human gastric cancer AGS and HGC27 cells and the underlying mechanism. Methods Human gastric cancer AGS and HGC27 cells were cultured in vitro. The MTT assay was used to determine the effects of erianin at different final concentrations (0, 10, 20, 40, 60, and 80 nmol/L) on the viability of the two cell lines after 48 h of treatment. AGS and HGC27 cells were divided into groups A1-D1 and A2-D2, respectively, and treated with erianin at concentrations of 0, 10, 20, and 40 nmol/L for 48 h. AGS and HGC27 cells were further divided into groups E1-H1 and E2-H2, respectively, in which groups E1 and E2 were transfected with negative control siRNA, groups F1 and F2 with ribosomal protein L27 (RPL27) siRNA, groups G1 and G2 with ne-gative control plasmid, and groups H1 and H2 with an RPL27 overexpression plasmid. Colony formation and wound healing assays were used to assess the proliferative and migratory abilities of cells in groups A1-H1 and A2-H2. DCF staining, DHE staining, and JC-1 staining were used to detect reactive oxygen species levels and mitochondrial membrane potential in cells in groups A1-D1 and A2-D2. Western blot was used to detect the expression levels of proteins related to epithelial-mesenchymal transition (EMT), cell cycle, and apoptosis in cells in groups A1-D1 and A2-D2, as well as the relative expression level of RPL27 protein in cells in groups A1-H1 and A2-H2. Differentially expressed genes between groups A1 and B1 were identified by transcriptome sequencing, followed by GO functional annotation and KEGG pathway enrichment analysis. Venn diagram analysis and statistical comparison were performed between the identified differentially expressed genes and mitochondria-related metabolic genes identified in the GeneCards database to analyze the possibility of RPL27 as a target of erianin. AutoDock 4.2.6 software was used to predict the molecular docking affinity and binding energy between erianin and RPL27. Results The MTT assay showed that the viability of AGS and HGC27 cells decreased with increasing erianin concentration (F=85.62,89.61,t_LSD=2.36~28.72,P<0.05). Colony formation and wound healing assays showed that the number of colonies formed and the cell migration rate in groups A1-D1 and A2-D2 decreased with increasing concentration (F=22.37-102.31,t_LSD=5.52-41.57,P<0.05). DCF staining, DHE staining, and JC-1 staining showed that, compared with group A1 and group A2, respectively, groups B1-D1 and groups B2-D2 exhibited increased intracellular reactive oxygen species levels and decreased mitochondrial membrane potential with increasing concentration (F=98.20-189.20,t_LSD=3.24-38.89,P<0.05). Western blot showed that, compared with group A1 and group A2, respectively, groups C1-D1 and groups C2-D2 had significantly reduced relative expression levels of EMT-related proteins (Vi-mentin and N-cadherin), cell cycle-related proteins (Cyclin D1 and CDK2), and apoptosis-related proteins (Bcl-2 and Bcl-xL), whereas the relative expression levels of the EMT-related protein E-cadherin and the apoptosis-related proteins Bad, Bax, and PARP1 p25 were significantly increased (F=78.90-150.20,t_LSD=2.89-19.73,P<0.05). GO functional annotation and KEGG pathway enrichment analysis showed that the differentially expressed genes between groups A1 and B1 were significantly enriched in DNA replication, cell cycle, PI3K-AKT signaling pathway, and mitochondria-related biological processes (P<0.05), among which RPL27 showed a significant decrease (P<0.05). Molecular docking analysis showed that the binding energy between erianin and RPL27 was-4.84 kcal/mol. Western blot showed that, compared with group A1 and group A2, respectively, groups C1-D1 and groups C2-D2 had significantly decreased relative expression levels of RPL27 (F=112.10,138.80,t_LSD=4.56-22.32,P<0.05). Compared with groups E1, G1, F2, and H2, respectively, groups F1, H1, E2, and G2 showed significantly decreased relative expression levels of RPL27 (F=78.21,77.35,t_LSD=3.56-5.94,P<0.05), as well as significantly decreased numbers of colonies formed and cell migration rates (F=88.58-100.25,t_LSD=14.38-150.30,P<0.05). Conclusion Erianin has significant inhibitory effects on the proliferation and migration of human gastric cancer cells. The mechanism may involve targeted inhibition of RPL27 expression, thereby impairing mitochondrial function and activating the apoptotic program.

Objective To investigate the effect of DUSP9 on the proliferation and metastasis of hepatoblastoma and its mechanism. Methods Single-cell transcriptomic analysis for HB and pan-cancer analysis for DUSP9 were performed based on public tumor databases, and RT-qPCR and immunohistochemical staining were used to measure the mRNA and protein expression levels of DUSP9 in HB tumor tissue and paracancerous tissue. HepG2 cells were divided into groups A1 and B1, and Huh6 cells were divided into groups A2 and B2. The cells in groups A1 and A2 were transfected with shNC, and those in groups B1 and B2 were transfected with shDUSP9. CCK-8 assay, colony formation assay, wound healing assay, and Transwell assay were used to measure the proliferation and migration abilities of cells in each group. A xenograft nude mouse model was used to observe the effect of DUSP9 on the proliferation and tumorigenic abilities of HB cells in vivo. Western blotting was used to measure the expression levels of DUSP9 and MAPK/ERK pathway-related proteins in each group. Immunoprecipitation-mass spectrometry (IP-MS) was used to identify the potential interacting proteins of DUSP9, and enrichment analyses were performed to explore their potential molecular mechanisms. Results The single-cell transcriptomic analysis showed that DUSP9 was significantly highly expressed in malignant epithelial cells of the liver, and the pan-cancer analysis showed significantly high expression of DUSP9 in various malignant tumors such as bladder urothelial carcinoma, hepatocellular carcinoma, and lung squamous cell carcinoma. Immunohistochemical staining and RT-qPCR showed that compared with paracancerous tissue, the expression level of DUSP9 was significantly upregulated in tumor tissue of HB patients (t=5.719,5.273,P<0.05). CCK-8 assay showed that at 48-96 hours of cell culture, there was a significant difference in proliferation rate between HepG2 cells (groups A1 and B1) and Huh6 cells (groups A2 and B2) (F=13.64-179.23,P<0.05); the colony formation assay, wound healing assay, and Transwell assay showed that compared with groups A1 and A2, groups B1 and B2 had significantly lower number of cell colonies and cell migration rate (t=5.26-20.86,P<0.05). The xenograft nude mouse model experiment showed that compared with group A, group B showed significant reductions in the proliferative capacity and tumorigenic ability of tumor cells (P<0.05). Western blotting showed that there were significant differences in the relative protein expression levels of DUSP9, p-ERK, and p-MEK between groups A1 and B1 and between groups A2 and B2 (t=3.77-13.27,P<0.05). The results of IP-MS showed that DUSP9 could interact with various proteins including PA2G4, AFP, and SMARCC1, and such interacting proteins were mainly involved in the biological processes such as ribosomal function, translational regulation, and cell adhesion. Conclusion Abnormally high expression of DUSP9 is observed in HB. DUSP9 can promote tumor proliferation and metastasis by regulating the MAPK pathway and binding to various interacting proteins, it is a potential oncogene and therapeutic target for HB.

Objective To investigate the effects of Piwi-interacting RNA piR-0585 on doxorubicin (DOX)-induced cardiotoxicity and the underlying mechanism. Methods HL-1 mouse cardiomyocytes were treated with 0, 0.25, 0.50, 1.00, 2.00, and 5.00 μmol/L DOX, respectively. The expression level of piR-0585 in each group of cells was detected by RT-qPCR. HL-1 cells were then divided into groups M1-M4 and I1-I4. Cells in group M2 were transfected with piR-0585 mimics, and cells in group M1 were transfected with mimics negative control. Cells in group I2 were transfected with piR-0585 inhibitor, and cells in group I1 were transfected with inhibitor negative control. Cells in groups M3, M4, I3, and I4 received an additional 2 μmol/L DOX based on the treatments used for groups M1, M2, I1, and I2, respectively. Cell viability of each group was detected by MTT assay. Intracellular levels of malondialdehyde (MDA) and ferrous ion (Fe²⁺) in each group were measured using MDA and Fe²⁺ assay kits, respectively. Intracellular reactive oxygen species (ROS) and lipid peroxidation levels were detected using DCFH-DA and C11-BODIPY probes, respectively. Protein expression levels of transferrin receptor (TFRC) and ferritin heavy chain (FTH1) were detected by Western blot. Results Compared with the 0 μmol/L DOX group, the relative expression level of piR-0585 in HL-1 cells was significantly increased after treatment with 2.00 and 5.00 μmol/L DOX (F=1 366.00,q=19.32, 92.56,P<0.05). Two-way ANOVA showed significant interaction effects between piR-0585 mimics/inhibitor treatment and DOX treatment on cell viabi-lity and the levels of MDA, Fe²⁺, ROS, lipid peroxidation, TFRC, and FTH1 in each group (F=5.39-90.25,P<0.05). Compared with group M3, group M4 exhibited significantly decreased cell viability and significantly increased levels of MDA, Fe²⁺, ROS, lipid peroxidation, TFRC, and FTH1 (P<0.05). Compared with group I3, group I4 showed significantly increased cell viability and significantly decreased levels of MDA, Fe²⁺, ROS, lipid peroxidation, TFRC, and FTH1 (P<0.05). Conclusion DOX stimulation can upregulate piR-0585 expression in cardiomyocytes. piR-0585 may participate in the pathological process of DOX-induced cardiotoxicity by promoting ferroptosis in cardiomyocytes.

Objective To investigate the role of glucosaminyl (N-acetyl) transferase 3 (GCNT3) in the proliferation and metastasis of cholangiocarcinoma (CCA) cells. Methods The Cancer Genome Atlas (TCGA) database and immunohistochemistry (IHC) were used to analyze and detect the expression levels of GCNT3 mRNA and protein in CCA tumor tissues and adjacent normal tissues, respectively. Human CCA QBC939 cells were divided into groups A and B, and human CCA HUCCT1 cells were divided into groups C and D, which were transfected with negative control lentivirus and GCNT3-overexpressing lentivirus, respectively. QBC939 cells were further divided into groups E and F, and HUCCT1 cells were divided into groups G and H, which were transfected with siNC and siGCNT3, respectively. Reverse transcription quantitative polymerase chain reaction (RT-qPCR) and Western blot assay were used to detect the expression levels of GCNT3 mRNA and protein in each group. The proliferation and migration abilities of CCA cells were evaluated using CCK-8 assays, colony formation assays, scratch assays, and Transwell assays. Results TCGA analysis showed that GCNT3 mRNA expression in CCA tissues was significantly higher than that in adjacent normal tissues (t=9.46,P<0.05). IHC results indicated that GCNT3 expression in CCA tissues was significantly higher than that in adjacent normal tissues. RT-qPCR and Western blot assay showed that the relative expression levels of GCNT3 mRNA and protein were significantly increased in group B compared with group A, and in group D compared with group C (t=2.96-32.77,P<0.05); the relative expression levels of GCNT3 mRNA and protein were significantly decreased in group F compared with group E, and in group H compared with group G (t=10.06-243.80,P<0.05). Cell functional experiments showed that the proliferation and migration abilities of CCA cells were significantly increased in group B compared with group A, and in group D compared with group C (t=3.52-8.94,P<0.05); the proliferation and migration abilities of cells were significantly reduced in group F compared with group E, and in group H compared with group G (t=3.07-12.87,P<0.05). Conclusion GCNT3 is highly expressed in CCA tissues and can promote the proliferation and migration of CCA cells.

Objective To investigate the expression and potential role of ATP synthase α-subunit (ATP5A1) in gemci-tabine-resistant bladder cancer cells. Methods Human bladder transitional cell carcinoma cell lines T24 and 5637 were used to establish gemcitabine-resistant cell lines (T24R and 5637R) through a stepwise increase in gemcitabine concentration. Western blot and RT-qPCR were used to measure the protein and mRNA expression levels of ATP5A1 in these cells, and the cells were treated with oligomycin (an inhibitor of oxidative phosphorylation) or 2-DG (an inhibitor of glycolysis) to observe the dependence of ATP synthesis on oxidative phosphorylation and glycolysis in these cells. T24R and 5637R cells were divided into T24R-si-NC group, T24R-si-ATP5A1 group, 5637R-si-NC group, and 5637R-si-ATP5A1 group; the cells in the T24R-si-ATP5A1 group and the 5637R-si-ATP5A1 group were transfected with small interfering RNA (si-ATP5A1) to knockdown ATP5A1, while those in the T24R-si-NC group and the 5637R-si-NC group were transfected with a blank vector control (si-NC). ATP, glucose, and lactate assay kits were used to measure the content of ATP, glucose consumption, and lactate production in each cell group; MTT assay was used to observe the sensitivity of cells to gemcitabine; colony formation assay was used to measure the proliferative capacity of cells under gemcitabine treatment. Results The resistance indices of T24R and 5637R cells to gemcitabine were 46.21 and 5.64, respectively. Compared with their respective parental cells, T24R and 5637R cells had significantly higher relative mRNA and protein expression levels of ATP5A1, as well as a significant increase in the dependence on oxidative phosphorylation and a reduction in the dependence on glycolysis (t=5.12-18.52,P<0.01). Compared with the corresponding T24R-si-NC group and 5637R-si-NC group, the T24R-si-ATP5A1 group and the 5637R-si-ATP5A1 group had a significant increase in relative ATP content, significant reductions in glucose consumption and lactate production, a significantly lower IC50 for gemcitabine, and a significant reduction in the number of colonies (F=23.97-45.23,q=6.58-12.73,t=4.23-56.55,P<0.05). Conclusion ATP5A1 is highly expressed in gemcitabine-resistant bladder cancer cells, and highly expressed ATP5A1 may contribute to the development of gemcitabine resistance in bladder cancer cells by maintaining mitochondrial oxidative phosphorylation function.

Objective To investigate the role and mechanism of angiotensin Ⅱ (Ang Ⅱ) in inducing senescence in SH-SY5Y cells. Methods Firstly, senescence-associated β-galactosidase (SA-β-gal) staining was performed to observe the effect of Ang Ⅱ treatment for 24 h at concentrations of 0, 5, 10, and 50 μmol/L on the senescence of SH-SY5Y cells (groups A1-D1), as well as the effect of Ang Ⅱ treatment at a concentration of 10 μmol/L for 24, 48, and 72 h on the senescence of SH-SY5Y cells (groups B2-D2, group A2 does not add Ang Ⅱ). Western blotting was used to measure the protein expression levels of p16 and p21 in SH-SY5Y cells treated with 0 and 10 μmol/L Ang Ⅱ (groups a and b) for 48 h. CCK-8 assay was used to observe the effect of Ang Ⅱ treatment for 48 h at concentrations of 0, 5, 10, and 50 μmol/L on the viability of SH-SY5Y cells (groups A3-D3), as well as the effect of 10 μmol/L Ang Ⅱ treatment for 24, 48 and 72 h on the viability of SH-SY5Y cells (groups B4-D4, group A4 does not add Ang Ⅱ). Results SA-β-gal staining showed that among groups A1-C1, group C1 had the highest percentage of SA-β-gal-positive cells (F=7.021,t=2.880,3.087,P<0.05), and among groups A2-C2, group C2 had the highest percentage of SA-β-gal-positive cells (F=26.080,t=4.023,6.658,P<0.05), with the most significant cell senescence. Western blotting showed that compared with group a, group b had significant increases in the relative protein expression levels of p16 and p21 (t=6.662,18.340,P<0.05). CCK-8 assay showed that there was no significant difference in cell viability across groups A3-D3 and groups A4-D4 (P>0.05). Conclusion Ang Ⅱ treatment can significantly induce senescence in SH-SY5Y cells without causing cell damage, which may be associated with the functional expression of specific Ang Ⅱ receptors on the cell surface.

Objective To investigate the protective effect of herbacetin (HBT) on neurological function in a mouse model of cerebral ischemia/reperfusion injury induced by transient middle cerebral artery occlusion (tMCAO) and the underlying mechanism. Methods C57BL/6 mice were randomly divided into groups A, B, and C, which underwent sham operation, tMCAO induction, and tMCAO induction+HBT treatment (intraperitoneal injection of 30 mg/kg HBT), respectively. After 24 h of treatment, the modified neurological severity score was used to evaluate the degree of neurological impairment in mice. The percentage of cerebral infarction volume in each group of mice was measured by TTC staining. The mRNA expression levels of tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β), and IL-6 in the ischemic brain tissue were detected by RT-qPCR. Immunofluorescence staining with an anti-Iba-1 antibody was used to label microglia in brain tissues to evaluate their activation status. BV-2 microglial cells were divided into groups a-f. Groups a to c were subjected to conventional culture, oxygen-glucose deprivation/reoxygenation treatment, and oxygen-glucose deprivation/reoxygenation+HBT treatment, respectively. Groups d-f were subjected to conventional culture, lipopolysaccharide treatment, and lipopolysaccharide+HBT treatment, respectively. RT-qPCR was used to detect the expression levels of pro-inflammatory cytokines TNF-α, IL-1β, and IL-6 in BV-2 cells of groups a-f. Western blot was used to detect the expression levels of NF-κB P65 (P65) and phospho-NF-κB P65 (p-P65) in BV-2 cells of groups a-c. Results Compared with group B, group C showed significantly decreased modified neurological severity score, cerebral infarction volume percentage, and mRNA expression levels of TNF-α, IL-1β, and IL-6 (F=15.20-249.10,t_LSD=4.71-12.93,P<0.05). Compared with group B, group C showed significantly decreased relative fluorescence intensity of Iba-1 in microglia (F=52.30,t_LSD=6.93,P<0.05). Compared with group b, group c showed significantly decreased mRNA expression levels of pro-inflammatory cytokines (F=65.42-172.90,t_LSD=6.71-11.75,P<0.05). Compared with group e, group f showed significantly decreased mRNA expression levels of pro-inflammatory cytokines (F=61.34-67.97,t_LSD=4.34-7.19,P<0.05). Compared with group a, group b showed significantly increased relative expression level of p-P65 and the p-P65/P65 ratio, whereas those in group c were significantly decreased compared with group b (F=11.97,12.75,t_LSD=3.18-10.44,P<0.05). Conclusion HBT has a protective effect on neurological function in mice with cerebral ischemia/reperfusion injury. The underlying mechanism may be associated with reducing the level of p65 phosphorylation in microglia to inhibit the NF-κB pathway, reducing microglial activity and inhibiting the release of pro-inflammatory cytokines, thereby alleviating neuroinflammatory responses.

Objective To investigate the effect of the isolevuglandins scavenger 2-hydroxybenzylamine (2-HOBA) on the repair of cardiomyocytes with ischemia/reperfusion (I/R) injury and its mechanism. Methods Primary rat cardiomyocytes were isolated and randomly divided into groups A-D: Conventional culture was performed for the cardiomyocytes in group A; hypoxia/reoxygenation (H/R) treatment was performed for group B; the cardiomyocytes in group C were treated with 2-HOBA solution; the cardiomyocytes in group D were given H/R treatment after the addition of 2-HOBA solution. CCK-8 assay was used to measure cell viability; A malondialdehyde (MDA) assay kit was used to measure the level of lipid peroxidation, a lactate dehydrogenase (LDH) assay kit was used to measure cell injury, and a reactive oxygen species (ROS) assay kit was used to measure the level of ROS in cells; Western blotting was used to measure the relative protein expression levels of B-cell lymphoma 2 (Bcl-2), Bcl-2-associated X protein (Bax), and 4-hydroxynonenal (4-HNE)-modified protein adducts in cells. Results CCK-8 assay showed that group B had a significantly lower cell viability than group A, and group D had a significantly higher cell viability than group B (F=182.70,q=27.94,15.88,P<0.05). Measurement of biochemical parameters showed that compared with group A, group B had significant increases in the levels of MDA, LDH, and ROS, and compared with group B, group D had significant reductions in these parameters (F=48.27-214.50,q=4.47-21.41,P<0.05). Western blotting showed that compared with group A, group B had significant increases in the relative protein expression levels of Bax and 4-HNE-modified protein adducts and a significant reduction in the relative protein expression level of Bcl-2, and compared with group B, group D had significant reductions in the relative protein expression levels of Bax and 4-HNE-modified protein adducts and a significant increase in the relative protein expression level of Bcl-2 (F=7.28-130.50,q=3.63-22.51,P<0.05). Conclusion This study shows that 2-HOBA can alleviate myocardial I/R injury by inhibiting oxidative stress, lipid peroxidation, and apoptotic processes in cardiomyocytes.

Objective To investigate the etiology and ocular features of ophthalmic patients with cranial nerve Ⅲ, Ⅳ, and Ⅵ palsy, and to provide a reference for clinical diagnosis and treatment. Methods A retrospective analysis was performed on the clinical data of 2 165 patients with cranial nerve Ⅲ, Ⅳ, and Ⅵ palsy who attended Department of Strabismus, Amblyopia, and Pediatric Ophthalmology, Nanjing Southeast Eye Hospital, from January 1987 to December 2024, and their etiologies and ocular features were summarized. Results Among the 2 165 patients, the patients with congenital palsy accounted for the highest proportion of 74.2%, with a predominance of male patients; among the patients with acquired palsy, the patients with idiopathic causes accounted for 48.7%, and those with traumatic causes accounted for 31.9%, while approximately 66.9% of the trauma cases were male patients aged 20-50 years. As for the features of the affected cranial nerves and eyes, the patients only with trochlear nerve (cranial nerve Ⅳ) palsy accounted for 74.7%, and among the 2 165 patients, 803 had unilateral left eye palsy and 708 had bilateral palsy, both with relatively high incidence rates. In terms of accompanying symptoms, 29.4% of patients had compensatory head posture, and diplopia was more common in the acquired palsy group. Conclusion Ophthalmic patients with cranial nerve Ⅲ, Ⅳ, and Ⅵ palsy have complex etiologies and diverse clinical manifestations, and multidisciplinary comprehensive evaluation is required to avoid misdiagnosis and missed diagnosis and to formulate individualized diagnosis and treatment regimens.

Objective To investigate the common etiologies of vocal cord motion impairment (VCMI), and to provide a reference for the prevention, diagnosis, and treatment of this disease in clinical practice. Methods A retrospective analysis was performed on the clinical data of 547 patients who were diagnosed with VCMI by electronic fiberoptic laryngoscopy in Department of Otolaryngology Head and Neck Surgery, The Affiliated Hospital of Qingdao University, from January 2019 to December 2023. According to the side of involvement, the patients were divided into left-sided, right-sided, and bilateral groups, and according to sex, they were divided into male and female groups. Etiological composition was compared between the left-sided, right-sided, and bilateral groups and between the male and female groups, and then their etiologies and clinical features were summarized. Results Among the 547 patients, there were 307 male patients and 240 female patients. Of all patients, 328 (59.96%) had left-sided VCMI, 177 (32.36%) had right-sided VCMI, and 42 (7.68%) had bilateral VCMI. The main etiologies of VCMI were pulmonary malignancy (17.6%), idiopathic vocal cord paralysis (16.8%), and thyroid tumor (13.5%). The proportion of patients with left-sided or right-sided VCMI was significantly higher than that of patients with bilateral VCMI (χ²=336.806,P<0.05), and compared with the left-sided and right-sided groups, the bilateral group had a significantly higher proportion of patients with the etiology of cervical surgery-related injury (χ²=9.938,P<0.05), with no significant difference between the left-sided group and the right-sided group (P>0.05). Compared with the male group, the female group had a significantly higher proportion of patients with the etio-logy of thyroid tumor or cervical surgery-related injury (χ²=21.952,11.911,P<0.05) and a significantly lower proportion of patients with the etiology of pulmonary malignancy or esophageal malignancy (P<0.05). Conclusion The etiologies of VCMI are complex and diverse, with differences in etiological composition between male and female patients, and at present, extralaryngeal tumor has become the leading cause of VCMI and should be taken seriously in clinical practice.

Objective To investigate the clinical effect of core stability training combined with proprioceptive neuromuscular facilitation (PNF) in promoting clinical rehabilitation of patients with knee osteoarthritis (KOA). Methods A total of 82 patients who were diagnosed with KOA at the outpatient service of our hospital from October 2022 to October 2023 were enrolled and randomly divided into core group with 27 patients, PNF group with 27 patients, and combination group with 28 patients. The patients in the core group received conventional training combined with 30 minutes of core stability training, those in the PNF group received conventional training combined with 30 minutes of PNF training, and those in the combination group received conventional training combined with 15 minutes of core stability training and 15 minutes of PNF training. The three groups were observed and compared in terms of Lysholm knee score, multifidus muscle thickness, and peak torque of knee extension and flexion before treatment and after 4 weeks of treatment. Results After 4 weeks of treatment, all three groups had significant improvements in Lysholm knee score, multifidus muscle thickness, and peak torque of knee extension and flexion (t=8.98-70.01,P<0.05). The combination group had a significantly greater change in Lysholm knee score than the core group and the PNF group, the combination group and the core group had a significantly greater change in multifidus muscle thickness than the PNF group, and the PNF group and the combination group had a significantly greater change in peak torque of knee extension and flexion than the core group (F=39.08-370.80,t_LSD=6.11-24.12,P<0.05). Conclusion Core stability training combined with PNF can effectively improve knee joint function and trunk stability in patients with KOA, showing a favorable effect in promoting the rehabilitation of KOA.

Objective To investigate the association of triglyceride-total cholesterol-body mass index (TCBI) with the risk of cardiometabolic multimorbidity (CMM) in middle-aged and elderly Chinese adults. Methods Related data were collected from the China Health and Retirement Longitudinal Study from 2011 to 2018. A total of 6 074 subjects aged ≥45 years were enrolled, and their data were collected, including socio-demographic characteristics, lifestyle behaviors, chronic diseases, and blood biochemical parameters. Logarithmic transformation was performed for TCBI to obtain lgTCBI, and the subjects were divided into Q1-Q4 groups based on the quartiles of lgTCBI. The Cox proportional-hazards regression model with stepwise adjustment for confounding factors was used to investigate the association between lgTCBI and CMM, and subgroup analyses were used to explore the regulatory role of demographic features and health status in the association between lgTCBI and the risk of CMM. A sensitivity analysis was performed by excluding the subjects with dyslipidemia at baseline and those who developed CMM within the first two years of follow-up. Results There were significant differences between the Q1-Q4 groups in sex, age, marital status, place of residence, current status of smoking, body mass index, waist circumference, hypertension, dyslipidemia, renal disease, fasting plasma glucose, glycated hemoglobin, high-density lipoprotein cholesterol, serum uric acid, and serum creatinine (P<0.05). The number of patients with incident CMM increased significantly with the increase in TCBI (χ²=8.72-223.66,H=1 437.89,F=13.76-452.52,P<0.05). The Cox proportional-hazards regression model analysis showed that for every unit increase in lgTCBI, the risk of CMM was increased by 42% (HR=1.42,95%CI=1.03-1.98,P<0.05), and with the increase in lgTCBI, the risk of CMM gradually increased across the Q1-Q4 groups (HR=1.39-1.66,95%CI=1.04-2.25,P<0.05). Subgroup analyses revealed a significant interaction effect of hypertension status on the association between lgTCBI and the risk of CMM (P_interaction<0.05). The sensitivity analysis yielded consistent results and confirmed the robustness of the main findings. Conclusion In middle-aged and elderly Chinese adults, high TCBI is an independent risk factor for the onset of CMM. The increase in TCBI can lead to the increase in the risk of CMM, and this association is more significant in the non-hypertensive population.

Objective To investigate the potential mechanism by which chitinase-3-like protein 1 (YKL-40) in cerebrospinal fluid (CSF) affects cognitive function in patients with Parkinson’s disease (PD). Methods A total of 185 newly diagnosed PD patients from the Parkinson’s Progression Markers Initiative (PPMI) were enrolled. Basic demographic features were collected from all subjects, as well as the levels of YKL-40, β-amyloid 42 (Aβ₄₂), total tau (t-tau), phosphorylated tau (p-tau), and α-synuclein (α-syn) in CSF at baseline and during follow-up, and related cognitive function scores were collected and analyzed. Accor-ding to the Montreal Cognitive Assessment (MoCA) score at baseline, the patients were divided into Parkinson’s disease cognitive normal (PD-CN) group (MoCA≥26) and Parkinson’s disease mild cognitive impairment (PD-MCI) group (22<MoCA<26), and clinical data were compared between the two groups. A multiple linear regression model was used to investigate the association of CSF YKL-40 with the levels of Aβ₄₂, t-tau, p-tau, and α-syn and related cognitive function scores. The linear mixed-effects model was used to calculate the rates of change in the above indicators, and the correlation between baseline CSF YKL-40 level and the rates of change of the above indicators was analyzed. According to the me-dian baseline level and rate of change of CSF YKL-40, the patients were divided into high-baseline CSF YKL-40 group, low-baseline CSF YKL-40 group, high-rate-of-change group, and low-rate-of-change group. The Kaplan-Meier curve and the Cox proportional-hazards regression model analysis were used to analyze and compare the cumulative risk of Parkinson’s disease dementia (PD-D) and cognitive decline during follow up between groups. The me-diation analysis was used to investigate the mediating role of CSF t-tau, p-tau, and Aβ₄₂ in the association between CSF YKL-40 and cognitive function. Results Compared with the PD-CN group, the PD-MCI group had a significantly older age, a significantly higher baseline YKL-40 level in CSF, and significantly lower scores of MoCA, Hopkins Verbal Learning Test (HVLT) total recall, HVLT delayed recall, HVLT recognition memory, LNS, and SFT (t=-2.932-19.782, P<0.05). The multiple linear regression model analysis showed that in the PD-CN group, baseline CSF YKL-40 level was significantly negatively correlated with baseline Symbol Digit Modalities Test score (P<0.05) and was significantly positively correlated with baseline Aβ₄₂, t-tau, p-tau, and α-syn levels in CSF (P<0.05); in the PD-MCI group, baseline CSF YKL-40 level was significantly positively correlated with baseline HVLT retention memory score and the levels of t-tau, p-tau, and α-syn in CSF (P<0.05). The linear mixed-effects model analysis showed that baseline CSF YKL-40 level was positively correlated with the rates of change of HVLT total recall, HVLT delayed recall, HVLT retention memory, and SFT scores (P<0.05). The Kaplan-Meier curve analysis showed significant differences in the cumulative probability of PD-D and cognitive decline between the high- and low-baseline CSF YKL-40 groups and between the high- and low-rate-of-change groups (P<0.05). The Cox proportional-hazards regression model analysis showed that both the high baseline CSF YKL-40 level and the high rate of change of YKL-40 level could increase the risk of cognitive decline in PD patients (P<0.05). The mediation analysis showed that the effect of CSF YKL-40 on cognitive function scores in PD patients was partially mediated by CSF t-tau, p-tau, and Aβ₄₂. Conclusion The high level of CSF YKL-40 at baseline and the high rate of change of YKL-40 level can increase the risk of cognitive decline in PD patients, possibly by affecting CSF t-tau, p-tau, and Aβ₄₂ levels.

Objective To investigate the efficacy and safety of ultrasound-guided popliteal sciatic nerve block (PSNB) in endovascular intervention for lower extremity arteriosclerosis obliterans (LEAO). Methods A total of 80 patients with LEAO were enrolled at The Affiliated Hospital of Qingdao University and randomly assigned to a block group and a local anesthesia group, with 40 patients in each group. The block group received ultrasound-guided PSNB, whereas the local anesthesia group received local anesthesia. The Numerical Rating Scale (NRS) scores of patients in both groups were documented preoperatively and at 8, 24, and 48 hours postoperatively. The Quality of Recovery-40 (QOR-40) scores at postoperative days 0, 1, and 3 were recorded. Physician satisfaction, patient satisfaction, length of hospital stay, and analgesic dosage were recorded and compared between the two groups. Results Compared with the local anesthesia group, the block group had a significantly lower NRS score at 8 hours postoperatively, significantly higher QOR-40 scores at postoperative days 0 and 1, physician satisfaction, and patient satisfaction, a significantly shorter length of hospital stay, and a significantly lower analgesic drug dosage (Z=-6.67--1.77,P<0.05). However, there were no significant between-group differences in NRS scores at 24 and 48 hours postoperatively or QOR-40 score at postoperative day 3 (P>0.05). Conclusion PSNB exhibits significant advantages in early postoperative analgesia and promoting patient recovery following endovascular intervention for LEAO. While ensuring physician and patient satisfaction, it also reduces the dosage of opioids and other analgesics, and is worthy of clinical promotion and application.

Objective To investigate the clinical efficacy of endoscope-assisted functional rhinoplasty in children and adolescents with deviated nose complicated by nasal septal deviation. Methods Clinical data of 25 pediatric and adolescent patients with deviated nose and nasal septal deviation who underwent endoscope-assisted functional rhinoplasty at The Affiliated Hospital of Qingdao University between July 2011 and November 2022 were analyzed. Nasal deviation value, nasal appearance Visual Analog Scale (VAS) score, Rhinoplasty Outcome Evaluation score, nasal breathing VAS score, and Nasal Obstruction Symptom Evaluation score were collected for all patients preoperatively and at 6 months postoperatively. Results Nineteen patients were cured and six patients showed improvement. Compared with preoperative values, the postoperative deviation value was significantly reduced (t=8.32,P<0.05), nasal appearance VAS and Rhinoplasty Outcome Evaluation scores were significantly increased (t=-21.70,-25.33,P<0.05), and nasal breathing VAS and Nasal Obstruction Symptom Evaluation scores were significantly decreased (t=12.64,10.39,P<0.05). During a follow-up period of 2 to 12 years, patients exhibited good nasal development posto-peratively, and no complications such as nasal synechiae or dorsal nasal collapse were observed. Conclusion Endoscope-assisted functional rhinoplasty has good clinical efficacy in pediatric and adolescent patients with deviated nose complicated by nasal septal deviation. The procedure is safe and highly feasible, with no related complications observed postoperatively, and it can markedly improve subjective and objective outcome measures.

Indole-2,3-dione is a bioactive substance derived from the marine organism lobster and can help to maintain its survival and protect its reproduction. Indole-2,3-dione also has a high concentration and specific distribution in the male reproductive organs of mammals, and such asymmetry in tissue distribution indicates that it should have a special biological significance for reproduction during the long process of biological evolution. This article reviews the antioxidant, anti-inflammatory, anti-infective, and anti-aging activities of indole-2,3-dione and its role in combating reproductive system-related diseases such as prostatic hyperplasia, spermatogenesis disorder, sperm abnormality, and vaginitis, in order to provide ideas for revealing that indole-2,3-dione may be an endogenous reproductive protection factor in animals, as well as for developing new drugs for reproductive protection.