The circadian clock is a highly conserved timekeeping system in organisms, which maintains physiological homeostasis by precisely regulating periodic fluctuations in gene expression. Substantial clinical and experimental evidence has established a close association between circadian rhythm disruption and the development of various malignancies. Research has revealed characteristic alterations in the circadian gene expression profiles in tumor tissues, primarily manifested as a dysfunction of core clock components (particularly circadian locomotor output cycles kaput (CLOCK) and brain and muscle ARNT-like 1 (BMAL1)) and the widespread dysregulation of their downstream target genes. Notably, CLOCK demonstrates non-canonical oncogenic functions, including epigenetic regulation via histone acetyltransferase activity and the circadian-independent modulation of cancer pathways. This review systematically elaborates on the oncogenic mechanisms mediated by CLOCK/BMAL1, encompassing multidimensional effects such as cell cycle control, DNA damage response, metabolic reprogramming, and tumor microenvironment (TME) remodeling. Regarding the therapeutic strategies, we focus on cutting-edge approaches such as chrononutritional interventions, chronopharmacological modulation, and treatment regimen optimization, along with a discussion of future perspectives. The research breakthroughs highlighted in this work not only deepen our understanding of the crucial role of circadian regulation in cancer biology but also provide novel insights for the development of chronotherapeutic oncology, particularly through targeting the non-canonical functions of circadian proteins to develop innovative anti-cancer strategies.
Humans ; ARNTL Transcription Factors/physiology* ; Neoplasms/therapy* ; CLOCK Proteins/physiology* ; Circadian Clocks/genetics* ; Animals ; Circadian Rhythm/genetics* ; Tumor Microenvironment ; Epigenesis, Genetic ; Gene Expression Regulation, Neoplastic

Objective: To investigate whether differences exist in attention deficit hyperactivity disorder (ADHD) and intelligence between children born by cesarean delivery and those born by vaginal delivery. Methods: This retrospective study included singleton children that were born between January 2013 and December 2014. The Chinese version of the Conners’ Parent Rating Scale–Revised (CPRS-48) was required on the probability of psychological and behavioral problems. The China–Wechsler Intelligence Scale for Children (C-WIRS) was used for evaluation of crystallized intelligence and Raven’s Standard Progressive Matrices for evaluation of fluid intelligence. Results: A total of 10,568 valid questionnaires were obtained. CPRS-48 ADHD index and detection rate were higher in cesarean delivery group than those in vaginal delivery group. Cesarean delivery groups had a lower performance intelligence quotient score according to C-WISC. Conclusion Children born by cesarean delivery were more likely to have a risk of ADHD and a lower performance intelligence quotient compared with those born by vaginal delivery.

Objective:To investigate the depression status of adolescents of 12 to 16 years old at school and to analyze its influencing factors.Methods:From March to June 2018, 3 544 students of 12 to 16 years old from 12 schools in Zhenjiang were selected according to the method of clustering, stratification and random selection. The General Condition Questionnaire and Achenhach's Child Behavior Check1ist (CBCL) were used to evaluate depression factors. Logistic regression analysis was used to investigate the influencing factors of adolescent depression.Results:A total of 4 268 questionnaires were distributed, and 3 544 valid questionnaires were recovered. This study included 3 544 students aged 12 to 16 from 12 primary and middle schools in Zhenjiang, among whom 214 were diagnosed with depressive factors, with a total detection rate of 6.04% (214/ 3 544) , among them, the detection rate of boys was 5.14% (87/1 691) , and the detection rate of girls was 6.85% (127/1 853) , the different was statistically significant (χ 2=4.550, P=0.032) . There were statistically significant among adolescents with different genders, learning situations, family upbringing methods, parental relationships, family relationships, relationships with other people and parental expectations ( P<0.05) . Logistic regression analysis showed that learning condition, family parenting style, relationship between parents, relationship with family members, relationship with people around them and parents' expectation of children were the influencing factors of adolescent depression ( P<0.05) . Conclusions:Learning conditions, disharmony with people around them and disharmony with family members are important causes of adolescent depression.

Objective:To explore the application and effects of the self-management-oriented network platform in depression rehabilitation.Methods:Totally 118 patients with depression discharged from a municipal mental health center and the communities that it governs between January and December 2017 were selected by convenient sampling and divided into the study group and the control group by Excel sheets, with 59 cases in each group, of which 2 cases dropped out from the study group. Patients in the control group received routine disease management, while patients in the study group received self-management and education via the depression network management platform after a personalized management plan was formulated upon discharge on this basis. After 6 months of intervention, the improvements in satisfaction, self-efficacy and suicidal risks were compared between the two groups.Results:After intervention, the satisfaction scores of visit time, visit attitude, visit content, and humanistic care of the study group were higher than those of the control group, and the differences were statistically significant ( P<0.05) ; the General Self-Efficacy Scale score of the study group was higher than that of the control group, and the difference was statistically significant ( P<0.05) ; the scores of despair, optimism, and sleep factors in suicidal ideation in the study group were lower than those of the control group, and the differences were statistically significant ( P<0.05) . Conclusions:The self-management-oriented network platform management model for discharged patients with depression can improve patient satisfaction, enhance their sense of self-efficacy, reduce the risk of suicide, and strengthen their self-management capabilities.

Objective To investigate the expression of glucose-regulated protein 78(GRP78)and cysteine aspartic acid protease 12(Caspase-12) and evaluate the endoplasmic reticulum stress (ERS) in rats with contrast-induced nephropathy (CIN),and observe the protective effects of hydroxytyrosol on CIN rats.Methods Eighty-four Wistar rats,(220±20) g,were randomly divided into control group,CIN group,hydroxytyrosol treated group (group C+H).At 12th,24th,48th,72th day after the rats model were established,BUN and Scr were detected.ELISA were used to detect the expression of methane dicarboxylic aldehyde (MDA),superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px).HE staining were used to evaluate the pathological change of kidney.TUNEL were used to detect the apoptosis of tubular ceils.Real-time PCR were used to detect the expression of GRP78 mRNA and Caspase-12 mRNA in tubular cells.Immunohistochemistry and Western blotting were used to detect the expression of GRP78 and Caspase-12 protein in tubular cells.Results BUN,Scr,the mRNA and protein expression of GRP78,Caspase-12 in hydroxytyrosol treated group were higher than that in control group(P ＜ 0.05),but were significantly lower than that in CIN group (P ＜ 0.05).Pathological changes and the apoptosis of tubular cells in CIN group were more serious than that in hydroxytyrosol treated group (P ＜ 0.05).Conclusions Endoplasmic reticulum stress may be associated with contrast-induced nephropathy.Hydroxytyrosol can protect kidney from contrast medium via reducing the endoplasmic reticulum stress.

Objective To investigate the expression of 4-hydroxynonenal (4-HNE) in the kidney of diabetic rats and the effect of probucol.Methods The rats were being intraperitoneal injected with STZ (60 mg/kg) to establish diabetic models.Then diabetic rats were randomly divided into diabetic group (group D,n =24),probucol treated group (group P,n =24).Normal rats were taken as control group (group C,n =24).Rats in group P were treated by probucol (110 mg·kg-1·d-1); rats in group D and group C were given equal volume water instead.Scr,BUN,triglyceride (TG),total cholesterol (TC) and 24-hour urinary proteinin were measured at the 4th,8th and 12th week.PAS staining and HE staining were used to evaluate the pathological changes of the kidney.The immunohistochemistry and Western blotting were used to detect the expression of 4-HNE in renal tissue.Results Levels of Scr,BUN,TG,TC and 24-hour urinary protein in group D were higher than those in group C at the 4th,8th and 12th week(all P ＜ 0.05); Levels of Scr,BUN,TG,TC and 24-huor urinary protein in group P were lower than those in group D at 4th,8th and 12th week (all P ＜ 0.05).The pathological changes of the kidney in group D were more serious than that in group P.The expression of 4-HNE in group D were higher than group C at the 4th,8th and 12th week (all P ＜ 0.05);The expression of 4-HNE in the kidneys of group P decreased significantly compared to that of group D at the same time (P ＜ 0.05).Conclusions As an indicator of lipid peroxidation,the expression of 4-HNE significantly increases in the kidney of diabetic rat.Probucol may protect the diabetic kidney through decreasing the expression of 4-HNE and the level of lipid peroxidation.