The excessive accumulation of advanced glycosylation end products(AGEs), the end products of non-enzymatic glycosylation reactions, can be involved in the pathological processes of various ocular diseases through mechanisms such as oxidative stress, inflammatory responses and apoptosis. In this paper, we systematically reviewed the key role of AGEs in diabetic keratopathy, cataract, glaucoma, age-related macular degeneration(ARMD)and diabetic retinopathy(DR). It was found that AGEs activate signalling pathways such as NADPH oxidase, MAPK and NF-κB by binding to the receptor RAGE, leading to reactive oxygen species(ROS)generation, release of inflammatory factors, and vascular endothelial dysfunction, which in turn induces delayed corneal healing, cross-linking of lens proteins, optic nerve degeneration, formation of choroidal neovascularisation(CNV), and blood-retinal barrier(BRB)disruption. For example, in diabetic keratopathy, AGEs delay wound healing via the ROS/NLRP3 inflammatory vesicle axis; in cataract, ascorbic acid-mediated cross-linking of lens proteins due to AGEs directly impairs lens transparency; and in DR, AGEs exacerbate microvascular damage by regulating vasucular endothelial growth factor(VEGF)expression and pericyte apoptosis. In addition, this article discusses the advances and limitations of AGEs detection techniques, such as the potential application of lens AGEscan fluorescence assay in screening for diabetic complications, and the need to develop tissue-specific assays for aqueous humour and vitreous. For therapeutic strategies, the research directions of inhibiting AGEs production, blocking RAGE signalling pathway and developing anti-glycosylation drugs are proposed to emphasise their clinical value in delaying disease progression. This review not only integrates the molecular mechanisms and clinical associations of AGEs in ocular diseases, but also provides a theoretical basis for targeted interventions, which is of great significance in exploring novel diagnostic and therapeutic strategies.

Objective To preliminarily investigate the anti-tumor effects of phytosphingosine(PHS)and the involvement of inducing apoptosis of leukemia cells.Methods Cellular model of leukemia was established in leukemia cell lines K562 and SUP-B15.CCK-8 assay and EdU assay were used to measure the viability and DNA synthesis of K562 and SUP-B15 cells.RNA-seq was carried out to verify the differentially expressed genes(DEGs)after PHS treatment.Gene Ontology(GO)enrichment and Kyoto Encyclopedia of Genes and Genomes(KEGG)enrichment analyses were applied to analyze the involved functions and signaling pathways.Comparative Toxicogenomics Database(CTD)and Discovery Studio software were employed to predict the underlying targets of PHS and molecular docking.Cell apoptosis was detected by flow cytometry,mitochondrial membrane potential was evaluated by JC-1 probe,and protein expression of key molecules was validated by Western blotting.Results PHS inhibited the proliferation of K562 and SUP-B15 cells in a time-and dose-dependent manner.The half-maximal inhibitory concentration(IC50)of K562 cells was 17.67 and 12.52 pmol/L for 24 and 48 h,respectively,and the IC50 value of SUP-B15 cells was 17.58 and 14.86 μmol/L for 24 and 48 h,respectively.PHS treatment at a dose of 20 μmol/L for 48 h resulted in significant inhibition of DNA synthesis.GO enrichment analysis of the K562 cells showed that PHS might be involved in positive regulation of apoptotic process,plasma membrane and its integral components,and protein kinase binding and activity.Reverse predictive analysis showed that BCL-2 protein was the most likely target of PHS.PHS significantly increased the apoptotic rate of leukemia cells(P＜0.05)in a dose-dependent manner,reduced the mitochondrial membrane potential,and down-regulated BCL-2 level(P＜0.05)and up-regulated the levels of Cleaved caspase-3 and Cleaved caspase-9(P＜0.05).Conclusion PHS may inhibit the proliferation of leukemia cells by inducing mitochondria-dependent apoptosis,possibly through PHS and BCL-2 interaction.

bjective　To analyze the drug resistance screening status and drug resistance influencing factors of high-risk groups of drug-resistant pulmonary tuberculosis in Qingdao, and to understand the inclusion of rifampicin patients in treatment, so as to provide a reference for the prevention and treatment of drug-resistant pulmonary tuberculosis. Methods　The medical records of 726 cases of drug-resistant pulmonary tuberculosis among high-risk populations registered in Qingdao from 2018 to 2022 were obtained from the National Health Insurance Information System of the China Center for Disease Control and Prevention. The drug resistance to five anti-tuberculosis drugs, namely isoniazid (INH), rifampicin (RFP), ethambutol (EMB), levofloxacin (Lfx), and amikacin (Am), in the high-risk populations of drug-resistant pulmonary tuberculosis was analyzed. Univariate and multivariate logistic regression were used toidentify factors influencing rifampicin resistance, and the detection and inclusion of treatment for rifampicin-resistant patients were evaluated. Results　Of the 726 subjects, 278 were drug-resistant, with a total drug resistance rate of 38.29%. The drug resistance for the five anti-tuberculosis drugs in descending order was: INH 25.90%(188/726), RFP 22.87%(166/726), Lfx 14.19%(103/726), EMB 11.29%(82/726), Am 2.48%(18/726). Analysis of the drug resistance spectrum showed that among those resistant to one drug, RFP was most common, accounting for 13.67% (38/278); among those resistant to two drugs, INH+RFP was predominant, accounting for 15.83% (44/278); among those resistant to three drugs, INH+RFP+Lfx was most frequent, at 7.19% (22/278); and among those resistant to four drugs, INH+RFP+EMB+Lfx was highest, at 6.12% (17/278). Multivariate logistic regression analysis of rifampicin resistance showed that compared with patients under 25 years of age, the risk of developing rifampicin resistance was lower in the groups aged 45 to under 65 and those aged 65 and above (OR=0.356, 95%CI: 0.181-0.700; OR=0.352, 95%CI: 0.170-0.729). Compared with migrant patients in other provinces, local patients from within the same county or district had a lower risk of developing rifampicin resistance (OR=0.599, 95%CI:0.383-0.962). Compared with patients who were smear-positive at the end of the second month of initial treatment, the risk of developing rifampicin resistance was higher in patients with relapse/return, failure of retreatment/chronic, and other categories of patients (OR=9.380, 95%CI:3.717-23.671;OR=25.749, 95%CI:8.037-82.490; OR=36.651, 95%CI:8.438-159.201). Conclusions　The situation of drug-resistant pulmonary tuberculosis in Qingdao cannot be ignored. Individuals under 25 years old, migrants from other provinces, and patients with relapse/return, failure of retreatment/chronic, and other categories are significant risk factors for developing rifampicin resistance in the high-risk groups of drug-resistant pulmonary tuberculosis.

Objective To investigate the effects of Gli2 on the proliferation,growth,migration,and invasion of oral cancer cells(Tca8113)at the cellular level,and to clarify the molecular mechanism of how Gli2 regulation affects the migration and invasion of oral cancer cells.Methods Small interfering(si)RNA was used to inhibit Gli2 expression in Tca8113 cells.The effects of Gli2 on the proliferation,growth,migration,and invasion of Tca8113 cells were examined by CCK-8,platb cloning,and transwell chamber assay.Further qRT-PCR and Western blot assays were used to explore the mechanism of how Gli2 regulation effects the malignant proliferation and metastasis of Tca8113 cells.Results The mRNA and protein expression of Gli2 in oral cancer cells(Tca8113)increased.Interference of Gli2 expression inhibited the proliferation,growth,migration,and invasion of Tca8113 cells.Further experiments showed that interfering with Gli2 expression inhibited the mRNA and protein expression of key factors in the Hedgehog(Hh)pathway.In addition,interference of Gli2 expression significantly affected the mRNA and protein expression of key factors in epithelial mesenchymal transformation(EMT)pathways.Conclusions Gli2 is abnormally activated during oral cancer,and interference of Gli2 expression significantly inhibits the proliferation,growth,migration,and invasion of oral cancer cells.Gli2 influences the migration and invasion of oral cancer cells by regulating the Hh and EMT pathways.This study has provided a new way to elucidate the pathogenesis of oral cancer and new perspectives on the clinical treatment of oral cancer.

AIM:From the perspective of regulating mitochondrial complex I activity by DJ-1 protein,this study aims to explore the mechanism of DJ-1-mediated resveratrol(RES)preconditioning in protecting against oxidative stress injury induced by myocardial ischemia-reperfusion(I/R)in rats.METHODS:After intramyocardial injection of lentivirus carrying DJ-1 shRNA(sh-DJ-1)or negative control(NC)shRNA,the myocardial I/R model was constructed by ligating the left anterior descending branch of the rat coronary artery.Sprague-Dawley(SD)rats were randomly divided in-to 6 groups:sham group,I/R group,RES+I/R group,NC+RES+I/R group,sh-DJ-1+RES+I/R group,and IACS-010759(mitochondrial complex I inhibitor)+RES+I/R group,with 10 rats in each group.The rats in RES treatment groups were given RES(20 mg/kg)via gavage for 7 d prior to the myocardial I/R modeling,once daily.Moreover,the rats in sham and I/R groups received an equivalent volume of normal saline via gavage.Myocardial infarction area and cardiac function were assessed by TTC staining and echocardiography,respectively.The MitoSOX fluorescent probe was used to detect levels of mitochondrial reactive oxygen species(ROS)in the myocardium.The levels of malondialdehyde(MDA),superoxide dis-mutase(SOD)and lactate dehydrogenase(LDH)in the serum were detected using kits.Western blot and co-immunopre-cipitation assays were used to observe the interaction between DJ-1 and the two subunits,ND-1 and NDUFA4,of the mito-chondrial complex I.RESULTS:Compared with I/R group,RES pretreatment significantly reduced the myocardial in-farction area,mitochondrial ROS levels,serum LDH activity,and serum MDA content(P＜0.01).It also elevated left ventricular ejection fraction,left ventricular fractional shortening and serum SOD activity(P＜0.01).Pretreatment with RES increased the expression and mitochondrial translocation of DJ-1(P＜0.01),promoted the interaction between DJ-1 and ND-1/NDUFA4,which in turn protected the activity of mitochondrial complex I(P＜0.01).However,when the ex-pression of DJ-1 was suppressed,the protective effects of RES against myocardial I/R injury were significantly inhibited compared with RES+I/R group(P＜0.05 or P＜0.01).CONCLUSION:Pretreatment with RES increases the expression and mitochondrial translocation of DJ-1,and facilitates the interaction of DJ-1 with ND1 and NDUFA4 subunits of mito-chondrial complex I,thus preserving the activity of mitochondrial complex I and attenuating myocardial I/R-induced oxida-tive stress damage.

Objective To investigate biomechanical differences of two posterior occipitocervical internal fixation techniques for treating basilar invagination with atlantoaxial dislocation (BI-AAD). Methods Intra-articular cage + posterior occipital plate+C2 pedicle screw (Cage+C2PS+OP), and intra-articular cage+C1 lateral mass screw+C2PS (Cage+C1LMS+C2PS) models were established based on occipitocervical CT data of the BI-AAD and clinical operation scheme, and the stability of atlantoaxial joint and stress distribution characteristics of C2 endplate and implanted instruments under different motion states were analyzed. Results Compared with the Cage+C1LMS+C2PS model, the atlantoaxial range of motion ( ROM) under flexion, extension, lateral bending and axial rotation in the Cage+C2PS+OP model were reduced by 5. 26% , 33. 33% , 43. 75% , -5. 56% , and stress peak of screw-rod fixation system were reduced by 47. 81% , 60. 90% , 48. 45% , 39. 14% , respectively. Under two internal fixation modes, stresses of C2 endplate and cage were mainly distributed on the compressive side during the motion, and both the screw-bone interface and the caudal side of screw subjected to large loading. Conclusions Two internal fixation methods could provide similar stability. However, the stress concentration of screw-rod system was more obvious and the possibility of screw loosening and fracture was greater under Cage+ C1LMS+C2PS fixation.

Primary aldosteronism (PA) is a kind of disease caused by excessive aldosterone secretion from the adrenal cortex, the reason of which include bilateral adrenal hyperplasia, aldosteronoma, unilateral adrenal hyperplasia, etc. Surgical treatment is the first choice for unilateral adrenal lesions. In this article, we report a patient who underwent left adrenal surgery but did not achieve the expected results. This case suggests that clinicians need to further improve the level of diagnosis and treatment of primary aldosteronism, especially the surgical methods.

Objective:To summarize the morphological characteristics and clinical experience of pulmonary artery sling(PAS) combined with anomalous bronchial branching, and provide new considerations for surgically treating PAS.Methods:A retrospective review of surgical experience of all patients with anomalous bronchial branching from January 2012 to December 2018 at Shanghai Children's Medical Center was conducted. There are 4 types according to the morphology of anomalous bronchial branching: tracheal bronchus, bronchial trifurcation, bridging bronchus, tracheal bronchus combined with bronchial trifurcation. The proportion of patients with anomalous bronchial branching combined with PAS was counted. The rate of tracheoplasty for four types was determined. We measured the interbronchial and subcarinal/subpseudocarinal angles before and after tracheoplasty.Results:140 patients were included in our study. The tracheal diameter of 11(21%, 11/53) patients with tracheal bronchus and 4(9%, 4/44) patients with bronchial trifurcation was normal. Among these patients, 125 patients had congenital tracheal stenosis(CTS). 115 patients underwent tracheoplasty. The rate of tracheoplasty of bridging bronchus was higher than tracheal bronchus(100% vs. 60%, P=0.000). One-stage surgery was performed in 76(61%) patients who had PAS. The interbronchial and subcarinal/subpseudocarinal angles were significantly reduced postoperatively( P=0.000). Conclusion:It is difficult to explain merely with vascular compression in patients with PAS with CTS and anomalous bronchial branching. One-stage slide tracheoplasty is currently the optimal option.

Objective: To explore the relationship between childhood abuse and cyberbullying among college students and to provide theoretical support for early intervention of cyberbullying among college students. Methods: A total of 3 850 sophomores and juniors from 6 universities in Shanxi Province, randomly selected by stratified cluster sampling method, were investigated by using the Questionnaire on Cyberbullying and the Chinese Version of the Child Abuse Questionnaire. Results: Male students reported higher rates of sexual abuse, emotional neglect and physical neglect than female students(χ2=5.22, 4.39, 7.53 P<0.05). The child abuse report rate of college students whose parents divorced was higher than that of those whose parents were not divorced(χ2=86.80, 134.06, 130.18, 175.64, 118.46，P<0.05). In addition to physical neglect, childhood abuse rate of only children was higher than that of non-only children, with statistically significant differences(χ2=9.44, 12.44, 21.18, 21.26, all P<0.05). The scores of all factors and total scores of cyberbullying implemented by male students were higher than those by female students(t=9.35, 5.59, 5.83, 7.57，P<0.05); the scores of all factors and total scores of cyberbullying implemented by only-child students were higher than those by non-only-child students(t=2.79, 3.74, 4.78, 4.40，P<0.05); the scores of all factors and total scores of cyberbullying implemented by students whose parents were divorced were higher than those by students whose parents were not divorced, with statistically significant differences(t=6.99,6.78, 8.04，11.33, P<0.05). Multiple linear regression model showed that there was a positive correlation between the childhood abuse of college students and the implementation of cyberbullying, and regression coefficient differences of all factors were statistically significant(β=0.10, 0.11, 0.05, 10.08,0.06, P<0.05). Conclusion Childhood abuse experiences increase the risk of college students practicing cyberbullying.

Objective: To explore the relationship between childhood maltreatment and suicide ideation of college students,so as to provide basis for physical and mental health of college students. Methods: Students from 6 universities in Shanxi Province(3 854 college students provided eligible questionniare for childhood abuse and 3 882 for suicidal ideation) were selected by multi-stage random cluster sampling from May to July 2018, the Chinese Version of the Childhood Trauma Questionnaire and the Self-rating Idea of Suicide Scale were used in the survey. Results: Of all subjects,42.4% had at least one kind of abuse experience in childhood and 3.9% had suicidal ideation in the past week. By chi square test,the detection rate of suicidal ideation of college students who suffered physical abuse,emotional abuse,sexual abuse,physical neglect,emotional neglect in childhood was higher than that of college students without maltreatment (χ2=13.78，12.97，17.10，56.56，66.58，P<0.01)；Spearman correlation analysis showed that there was a positive correlation between each type of maltreatment in childhood and college students’ suicidal ideation(r=0.06，0.06，0.07，0.12，0.13，P<0.01)；Multivariate Logistic regression model found that after controlling other influencing factors,physical neglect and emotional neglect in childhood were independent risk factors for suicide ideation of college students (OR=2.18,2.07,P<0.05). Conclusion Physical neglect and emotional neglect in childhood can increase the risk of college students’ suicidal ideation. Paying enough attention and care to them in early childhood may help to prevent their suicidal ideation in adulthood.