OBJECTIVES: Osteoarthritis (OA) and sarcopenia are significant health concerns in the elderly, substantially impacting their daily activities and quality of life. However, the relationship between them remains poorly understood. This study aims to uncover common biomarkers and pathways associated with both OA and sarcopenia. METHODS: Gene expression profiles related to OA and sarcopenia were retrieved from the Gene Expression Omnibus (GEO) database. Differentially expressed genes (DEGs) between disease and control groups were identified using R software. Common DEGs were extracted via Venn diagram analysis. Gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses were conducted to identify biological processes and pathways associated with shared DEGs. Protein-protein interaction (PPI) networks were constructed, and candidate hub genes were ranked using the maximal clique centrality (MCC) algorithm. Further validation of hub gene expression was performed using 2 independent datasets. Receiver operating characteristic (ROC) curve analysis was used to evaluate the predictive value of key genes for OA and sarcopenia. Mouse models of OA and sarcopenia were established. Hematoxylin-eosin and Safranin O/Fast Green staining were used to validate the OA model. The sarcopenia model was validated via rotarod testing and quadriceps muscle mass measurement. Real-time reverse transcription PCR (real-time RT-PCR) was employed to assess the mRNA expression levels of candidate key genes in both models. Gene set enrichment analysis (GSEA) was conducted to identify pathways associated with the selected shared key genes in both diseases. RESULTS: A total of 89 common DEGs were identified in the gene expression profiles of OA and sarcopenia, including 76 upregulated and 13 downregulated genes. These 89 DEGs were significantly enriched in protein digestion and absorption, the PI3K-Akt signaling pathway, and extracellular matrix-receptor interaction. PPI network analysis and MCC algorithm analysis of the 89 common DEGs identified the top 17 candidate hub genes. Based on the differential expression analysis of these 17 candidate hub genes in the validation datasets, AEBP1 and COL8A2 were ultimately selected as the common key genes for both diseases, both of which showed a significant upregulation trend in the disease groups (all P<0.05). The value of area under the curve (AUC) for AEBP1 and COL8A2 in the OA and sarcopenia datasets were all greater than 0.7, indicating that both genes have potential value in predicting OA and sarcopenia. Real-time RT-PCR results showed that the mRNA expression levels of AEBP1 and COL8A2 were significantly upregulated in the disease groups (all P<0.05), consistent with the results observed in the bioinformatics analysis. GSEA revealed that AEBP1 and COL8A2 were closely related to extracellular matrix-receptor interaction, ribosome, and oxidative phosphorylation in OA and sarcopenia. CONCLUSIONS AEBP1 and COL8A2 have the potential to serve as common biomarkers for OA and sarcopenia. The extracellular matrix-receptor interaction pathway may represent a potential target for the prevention and treatment of both OA and sarcopenia.
Sarcopenia/genetics* ; Osteoarthritis/genetics* ; Computational Biology/methods* ; Humans ; Protein Interaction Maps/genetics* ; Animals ; Mice ; Gene Expression Profiling ; Gene Ontology ; Transcriptome ; Male ; Signal Transduction/genetics* ; Gene Regulatory Networks

OBJECTIVES: Osteoarthritis (OA) is one of the most common chronic degenerative diseases, with chondrocyte apoptosis and extracellular matrix (ECM) degradation as the major pathological changes. The mechanical stimulation can attenuate chondrocyte apoptosis and promote ECM synthesis, but the underlying molecular mechanisms remain unclear. This study aims to investigate the role of primary cilia (PC) in mediating the effects of mechanical stimulation on OA progression. METHODS: In vivo, conditional knockout mice lacking intraflagellar transport 88 (IFT88^flox/flox IFT88 knockout; i.e., primary cilia-deficient mice) were generated, with wild-type mice as controls. OA models were established via anterior cruciate ligament transection combined with destabilization of the medial meniscus, followed by treadmill exercise intervention. OA progression was evaluated by hematoxylin-eosin staining, safranin O-fast green staining, and immunohistochemistry; apoptosis was assessed by TUNEL staining; and limb function by rotarod testing. In vitro, primary articular chondrocytes were isolated from mice and transfected with lentiviral vectors to suppress IFT88 expression, thereby constructing a primary cilia-deficient cell model. Interleukin-1β (IL-1β) was used to induce an inflammatory environment, while cyclic tensile strain (CTS) was applied via a cell stretcher to mimic mechanical loading on chondrocytes. Immunofluorescence and Western blotting were used to detect the protein expression levels of type II collagen α1 chain (COL2A1), primary cilia, IFT88, and caspase-12; reverse transcription polymerase chain reaction was performed to assess COL2A1 mRNA levels; and flow cytometry was used to evaluate apoptosis. RESULTS: In vivo, treadmill exercise significantly reduced Osteoarthritis Research Society International (OARSI) scores and apoptotic cell rates, and improved balance ability in wild-type OA mice, whereas IFT88-deficient OA mice showed no significant improvement. In vitro, CTS inhibited IL-1β-induced ECM degradation and apoptosis in primary chondrocytes; however, this protective effect was abolished in cells with suppressed primary cilia expression. CONCLUSIONS Mechanical stimulation delays OA progression by mediating signal transduction through primary cilia, thereby inhibiting cartilage degeneration and chondrocyte apoptosis.
Animals ; Chondrocytes/cytology* ; Apoptosis/physiology* ; Mice ; Cilia/metabolism* ; Osteoarthritis/pathology* ; Extracellular Matrix/metabolism* ; Mice, Knockout ; Disease Progression ; Interleukin-1beta ; Male ; Cells, Cultured

[This corrects the article DOI: 10.1016/j.apsb.2018.08.009.].

Radiotherapy is a crucial component of the treatment of tumors. In addition to directly causing DNA damage in tumor cells and inducing cell apoptosis, radiotherapy is also involved in the regulation of systemic immune status. Increasing evidence indicates that radiotherapy can remodel the tumor immune microenvironment (TIME) and reverse the immunosuppressive state, thereby enhancing anti-tumor effects and demonstrating stronger immune responses and therapeutic benefits when combined with immune checkpoint inhibitors. Taking lung cancer as an example to explore the impacts and potential mechanisms of radiotherapy on the TIME and anti-tumor immunity, which can provide a scientific basis for optimizing the treatment strategies of lung cancer.

Objective : To explore the effect of esketamine on anxiety-depressive-like behavior in mice and its rela- tionship with inflammation． Methods : SPF grade healthy adult male C57BL/6J mice，weighing 20 －24 g，were used in the exprement．The random number table method was used to divide into 5 groups (n = 8) : control group ( Con group) ，esketamine group (ESK group) ，model group ( LPS group) ，model + esketamine prevention group (LPS + ESK1 group) and model + esketamine treatment group ( LPS + ESK2 group) ．An inflammation-induced anxiety-depression model was prepared by intraperitoneal injection of LPS 0. 83 mg / kg．The ESK group was injec- ted with esketamine 10 mg / kg ; LPS group was injected with LPS 0. 83 mg / kg ; LPS + ESK1 group was injected with LPS 0. 83 mg / kg before 24 hours intraperitoneal injection of esketamine 10 mg / kg ; and the LPS + ESK2 group was injected with LPS 0. 83 mg / kg and 30 minutes later with esketamine 10 mg / kg．24 h after intraperitoneal injec- tion of LPS，the anxiety-depression-like behaviors of mice were measured using behavioral experiments．At the end of behavioral experiments，the spleen was taken immediately ; hippocampal tissues were taken and enzyme-linked immunosorbent assay (ELISA) was used to detect the contents of interleukin-1 β (IL-1 β) ，tumor necrosis factor al- pha (TNF-α) and interleukin 6 (IL-6) and neuronal pathological changes in hippocampal tissues were observed by HE staining. Results : Compared with the Con group，mice in the LPS group showed increased anxiety and depres- sion-like behavior (P＜0. 05) ，increased spleen weight / body weight (P ＜0. 05 ) ，increased hippocampal tissue concentrations of IL-1 β , TNF-α and IL-6 (P＜0. 05) ，and increased neuronal degeneration necrosis，there was no statistically significant difference in these indicators in the ESK group compared with the Con group．Compared with the LPS group，mice in the LPS + ESK1 and LPS + ESK2 groups showed reduced anxiety-depression-like behavior (P＜0. 05) ，decreased splenic weight / body weight (P ＜0. 05) ，hippocampal tissue IL-1 β , TNF-α , IL- 6 con- centrations were reduced (P＜0. 05) ，and neuronal degeneration necrosis was reduced．Compared with the LPS + ESK1 group，the LPS + ESK2 group showed an increase in the distance travelled in the central area of the open field experiment and the distance into the open arm of the elevated cross maze experiment (P＜0. 05) ，a decrease in IL-6 and TNF-α concentrations (P＜0. 05) ，and a reduction in the degree of neuronal damage． Conclusion Esketamine ameliorates LPS-induced anxiety-depression-like behavior and neuronal damage in mice by a mechanism that may be related to reduced inflammation.

Objective: To evaluate the intervention effectiveness of broken window effect combined with narrative nursing on non-suicidal self-injury (NSSI) in adolescents, so as to provide the basis for NSSI prevention in adolescents. Methods: Totally 134 adolescents with NSSI admitted to Mental Health Center of the Affiliated Hospital of Anhui West Health Vocational College from January 2022 to December 2023 were enrolled and randomly assigned into the control and treatment group. All were given narrative nursing and routine care, and the adolescents in the treatment group were given additional intervention based on broken window effect. The effects were evaluated using Self-Rating Depression Scale (SDS), Hamilton Depression Scale (HAMD), Self-Rating Idea of Suicide Scale (SIOSS), Ottawa Self-injury Inventory-Functions (OSI-F) and Nursing Satisfaction Scale, and the two groups were compared before and after intervention. Results: The treatment and control groups comprised 67 cases each, had a median age of 14.12 (interquartile range, 2.01) years and 14.10 (interquartile range, 1.52) years, included 71.64% and 68.66% girls, and 79.10% and 74.63% junior high school students, respectively. There were no statistically significant differences between the treatment and control groups in terms of gender, age or educational level (all P>0.05). The results of analysis of variance for repeated measures showed that there were interactions between time and group for SDS, HAMD and SIOSS scores (all P<0.05), and the decrease in scores before and after intervention was greater in the treatment group than in the control group. After intervention, the SDS, HAMD, SIOSS score and incidence of suicidal behaviors in the treatment group were all lower than the control group [SDS: (32.54±1.27) vs. (44.25±2.23); HAMD: (10.54±1.83) vs. (18.73±1.89); SIOSS: (10.37±2.20) vs. (15.76±1.62); incidence of suicidal behavior: 14.93% vs. 32.84%; all P<0.05]. The nursing satisfaction rate was significantly higher in the treatment group than in the control group (98.51% vs. 88.06%, P<0.05). Conclusion The broken window effect combined with narrative nursing would improve the depressive symptoms in adolescents with NSSI, and reduce the suicidal ideation and self injury.

Objective To compare the analgesic effect and the effect on the success rate of reduc-tion of three doses of remifentanil combined with dexmedetomidine in the clamping reduction of cricoarytenoid joint dislocation.Methods Fifty-one patients with cricoarytenoid joint dislocation,30 males and 21 females,aged 18-80 years,BMI 18.5-30.0 kg/m2,ASA physical status Ⅰ-Ⅲ,were selected from April 2021 to December 2022 in the department of otolaryngology,head and neck surgery.The patients were randomly divided into three groups according to remifentanil dose:remifentanil 0.5 μg·kg-1·min-1 group(group A,n=17),remifentanil 1.0 μg·kg-1·min-1 group(group B,n=18),and remifentanil 1.5 μg·kg-1·min-1 group(group C,n=16).After admission,dexmedetomidine 0.6 μg·kg 1·h-1 was injected intravenously,and an ear,nose and throat anesthetic spray(2％lidocaine 2 ml)was used to administer surface anesthesia to the base of the tongue.A second surface anesthesia was administered to the throat at 5 minutes,and dexmedetomidine was stopped at 10 minutes.The supraglottic and periarticular cri-coarytenoid joints were subjected to superficial anesthesia for a third time under visual laryngoscope,and then remifentanil at corresponding doses was injected intravenously in three groups for 5 minutes,and the reduction operation began after the pumping was stopped.The success of the first reduction,the anesthesia quality satisfaction score of the surgeon and the recovery of remifentanil during the operation were recorded.VAS pain scores were recorded at the time of entry,3 minutes,30 minutes,and 6 hours after operation.The adverse reactions during operation and recovery were recorded.Results Compared with group B,the success rate of first reduction and the score of anesthesia quality satisfaction were significantly decreased in groups A and C(P＜0.05).Compared with group A,the ratio of additional remifentanil supplementation in groups B and C was significantly reduced,and the VAS pain score 3 minutes after surgery was significant-ly decreased(P＜0.05).Compared with group C,the proportion of mandibular manipulation ventilation in groups A and B was significantly reduced(P＜0.05).There was no significant difference in the incidence of bradyheart rate,nausea and vomiting,agitation,delirium and laryngeal spasm between the three groups.Conclusion Compared with remifentanil 0.5 and 1.5 μg·kg-1·min-1,remifentanil 1.0 μg·kg-1·min-1 combined with dexmedetomide sequential pumping provided good analgesic effect for the clamping reduction of cricoarytenoid joint dislocation,improved the success rate of the first reduction,more stable respiratory circulation and fewer perioperative adverse reactions.

Purpose The aim of this study is to investigate the relationship between the expression of kinesin family member C1(KIFC1)in endometrioid carcinoma and clinicopathological features and prognosis of endometrioid carcinoma patients.Methods The expression of KIFC1 in 30 cases of paracancer-ous endometrium and 95 cases of endometrioid carcinoma was detected by immunohistochemical SP method.qRT-PCR and Western blot were used to detect the expression level of mRNA and protein of KIFC1 in 30 pairs of fresh cancer tissues and ad-jacent non-cancer tissues.Furthermore,the relationship between KIFC1 protein expression and survival time was analyzed by TC-GA database,and their clinicopathologic features were analyzed.Results The immunohistochemistry results showed the positive rate of KIFC1 in endometrioid carcinoma(61.05％)was signifi-cantly higher than that in the neighboring noncancerous tissue(13.33％),and the difference was statistically significant(P＜0.05).The expression of KIFC1 was correlated with myometrial invasion,FIGO stage and lymphatic metastasis(all P＜0.05).The relative expression of KIFC1 mRNA in endometrioid carci-noma(2.99±0.59)was significantly higher than that in the neighboring noncancerous tissue(1.00±0.29),and there was significant difference(P＜0.05).The relative expression of KIFC1 protein in endometrioid carcinoma(1.70±0.36)was significantly higher than that in the neighboring noncancerous tissue(0.72±0.17),and there was significant difference(P＜0.05).Furthermore,elevated KIFC1 expression was positive-ly correlated with a poorer prognosis.Conclusion KIFC1 is upregulated in endometrioid carcinoma and associated with poor prognosis of patients,KIFC1 was expected to be a potential ther-apeutic target and prognostic indicator for endometrioid carcino-ma.

BACKGROUND:microRNA-26b(miR-26b)plays an important regulatory role in a variety of stem cell functions,but its effects on the biological properties of stem cells from human exfoliated deciduous teeth and human umbilical cord mesenchymal stem cells are unknown. OBJECTIVE:To investigate the effects of miR-26b on the proliferation,migration and osteogenic differentiation of stem cells from human exfoliated deciduous teeth and human umbilical cord mesenchymal stem cells. METHODS:Stem cells from human exfoliated deciduous teeth and human umbilical cord mesenchymal stem cells were cultured and identified.miR-26 mimics(experimental group)and miRNAs mimics control(control group)were used to transfect above mentioned two kinds of cells and construct overexpressed models for subsequent experiments.CCK-8 assay was applied to detect the proliferation ability of overexpressed miR-26b cells.Transwell and scratch assay were employed to analyze the migration ability of overexpressed miR-26b cells.RT-qPCR was utilized to examine the expression of osteogenic markers after osteogenic induction of overexpressed miR-26b cells. RESULTS AND CONCLUSION:(1)Transfection of miR-26b mimics increased miR-26b expression in the two kinds of cells and promoted the proliferation of stem cells from human exfoliated deciduous teeth,with no significant effect on the amplification of human umbilical cord mesenchymal stem cells.(2)Compared with the control group,the migration ability was enhanced after two types of cells overexpressing miR-26b.(3)miR-26b expression decreased during osteogenic differentiation of the two kinds of cells.(4)Compared with the control group,the levels of osteogenesis-related genes osteocalcin,osteopontin,alkaline phosphatase,and human type I collagen mRNA were downregulated after overexpression of miR-26b in the two kinds of cells.The results showed that overexpression of miR-26b promoted the proliferation and migration of stem cells from human exfoliated deciduous teeth and inhibited their osteogenic differentiation;it promoted the migration of human umbilical cord mesenchymal stem cells and inhibited their osteogenic differentiation,but had no significant effects on their proliferation.

Objective:To investigate the association between congenital hypothyroidism (CH) and the adverse outcomes during hospitalization in very low birth weight infants (VLBWI).Methods:This prospective, multicenter observational cohort study was conducted based on the data from the Sino-northern Neonatal Network (SNN). Data of 5 818 VLBWI with birth weight <1 500 g and gestational age between 24-<37 weeks that were admitted to the 37 neonatal intensive care units from January 1 st, 2019 to December 31 st, 2022 were collected and analyzed. Thyroid function was first screened at 7 to 10 days after birth, followed by weekly tests within the first 4 weeks, and retested at 36 weeks of corrected gestational age or before discharge. The VLBWI were assigned to the CH group or non-CH group. Chi-square test, Fisher exact probability method, Wilcoxon rank sum test, univariate and multivariate Logistic regression were used to analyze the relationship between CH and poor prognosis during hospitalization in VLBWI. Results:A total of 5 818 eligible VLBWI were enrolled, with 2 982 (51.3%) males and the gestational age of 30 (29, 31) weeks. The incidence of CH was 5.5% (319 VLBWI). Among the CH group, only 121 VLBWI (37.9%) were diagnosed at the first screening. Univariate Logistic regression analysis showed that CH was associated with increased incidence of extrauterine growth retardation (EUGR) ( OR=1.31(1.04-1.64), P<0.05) and retinopathy of prematurity (ROP) of stage Ⅲ and above ( OR=1.74(1.11-2.75), P<0.05). However, multivariate Logistic regression analysis showed no significant correlation between CH and EUGR, moderate to severe bronchopulmonary dysplasia, grade Ⅲ to Ⅳ intraventricular hemorrhage, neonatal necrotizing enterocolitis in stage Ⅱ or above, and ROP in stage Ⅲ or above ( OR=1.04 (0.81-1.33), 0.79 (0.54-1.15), 1.15 (0.58-2.26), 1.43 (0.81-2.53), 1.12 (0.70-1.80), all P>0.05). Conclusion:There is no significant correlation between CH and in-hospital adverse outcomes, possibly due to timely diagnosis and active replacement therapy.