BACKGROUND:Circadian rhythms are closely related to the life activities of most mammals and insects.Timless gene plays a crucial role in the generation of circadian rhythms as key components encoding the Timeless/Period gene complex.However,its specific mechanism in circadian rhythms is still unclear.OBJECTIVE:To study the relationship between Timless protein gene,Period gene,circadian rhythm,environment and cryptochrome gene,so as to have a more comprehensive understanding of the nucleation and accumulation mechanism of circadian cycle and the influence of environment on circadian rhythm.METHODS:Literature retrieval was conducted in the Web of science Core Collection database,PubMed and CNKI,and the relevant literature was searched,consulted and screened after the keyword was set as"Timless,Period,circadian rhythm,environment"in English and Chinese.Non-relevant literature was progressively excluded through full-text reading,and 126 papers were finally included for the review.RESULTS AND CONCLUSION:In the circadian clock,the circadian spontaneous output of the cyclins kaput and CYCLE activate the Timeless/Period gene,Timeless gene regulates the nucleation mechanism and stability of Period gene,and Period gene can also be nucleated individually by a number of mechanisms.Casein kinase 2,Shaggy protein kinase and double time genes can regulate circadian rhythms and participate in transcription by phosphorylating Timeless gene/Period gene.Cryptochrome gene-mediated degradation of Timeless gene has a very important role in transcriptional integrity.External factors such as environmental factors and dietary patterns can influence circadian rhythms through the Timeless gene/Period gene.Interestingly,time-restricted eating can be used as an effective way to improve circadian rhythm disturbances.

OBJECTIVE To explore the efficacy and safety of pegylated recombinant human granulocyte colony-stimulating factor(PEG-rhG-CSF)in prevention of infections in the children with acute lymphoblastic leukemia(ALL)after chemotherapy.METHODS The clinical data were retrospectively collected from the children with ALL who received vincristine+daunorubicin+pegaspargase+prednisone acetate(VDLP)induction chemo-therapy in pediatrics department of the First Medical Center of Chinese PLA General Hospital from Jan.2018 to Oct.2024,the children were respectively treated with PEG-rhG-CSF or recombinant human granulocyte colony-stimulating factor(rhG-CSF)during the chemotherapy.The incidence of grade Ⅲ/Ⅳ agranulocytosis,the lowest absolute value of neutrophils,duration of grade Ⅳ agranulocytosis,incidence of agranulocytosis accompanied by fever,incidence of infections,use of antibiotics and length of hospital stay were observed and compared between the two groups.RESULTS Totally 47 children with ALL were enrolled in the study and were assigned as the PEG-rhG-CSF group with 24 cases and the rhG-CSF group with 23 cases.There were no significant differences in the incidence rates of grade Ⅲ/Ⅳ agranulocytosis and musculoskeletal soreness between the two groups.The low-est absolute value of neutrophils of the PEG-rhG-CSF group[(0.88±0.87)× 109/L]was higher than that of the rhG-CSF group;the duration of grade Ⅳ agranulocytosis of the PEG-rhG-CSF group[2.50(0.00,6.50)d]was shorter than that of the rhG-CSF group;the incidence of agranulocytosis accompanied by fever(41.67％),inci-dence of infections(41.67％)and the percentage of children treated with antibiotics were lower in the PEG-rhG-CSF group than in the rhG-CSF group;the length of hospital stay of the PEG-rhG-CSF group was shorter than that of the rhG-CSF group;there were significant differences between the two groups(P＜0.05).CONCLUSION The prophylactic use of PEG-rhG-CSF may raise the lowest value of neutrophils,shorten the duration of agranulo-cytosis,decrease the incidence of hospital-associated infections in the ALL children during the induction chemo-therapy,and reduce the use of antibiotics,with the safety favorable.

BACKGROUND:Circadian rhythms are closely related to the life activities of most mammals and insects.Timless gene plays a crucial role in the generation of circadian rhythms as key components encoding the Timeless/Period gene complex.However,its specific mechanism in circadian rhythms is still unclear.OBJECTIVE:To study the relationship between Timless protein gene,Period gene,circadian rhythm,environment and cryptochrome gene,so as to have a more comprehensive understanding of the nucleation and accumulation mechanism of circadian cycle and the influence of environment on circadian rhythm.METHODS:Literature retrieval was conducted in the Web of science Core Collection database,PubMed and CNKI,and the relevant literature was searched,consulted and screened after the keyword was set as"Timless,Period,circadian rhythm,environment"in English and Chinese.Non-relevant literature was progressively excluded through full-text reading,and 126 papers were finally included for the review.RESULTS AND CONCLUSION:In the circadian clock,the circadian spontaneous output of the cyclins kaput and CYCLE activate the Timeless/Period gene,Timeless gene regulates the nucleation mechanism and stability of Period gene,and Period gene can also be nucleated individually by a number of mechanisms.Casein kinase 2,Shaggy protein kinase and double time genes can regulate circadian rhythms and participate in transcription by phosphorylating Timeless gene/Period gene.Cryptochrome gene-mediated degradation of Timeless gene has a very important role in transcriptional integrity.External factors such as environmental factors and dietary patterns can influence circadian rhythms through the Timeless gene/Period gene.Interestingly,time-restricted eating can be used as an effective way to improve circadian rhythm disturbances.

OBJECTIVE To explore the efficacy and safety of pegylated recombinant human granulocyte colony-stimulating factor(PEG-rhG-CSF)in prevention of infections in the children with acute lymphoblastic leukemia(ALL)after chemotherapy.METHODS The clinical data were retrospectively collected from the children with ALL who received vincristine+daunorubicin+pegaspargase+prednisone acetate(VDLP)induction chemo-therapy in pediatrics department of the First Medical Center of Chinese PLA General Hospital from Jan.2018 to Oct.2024,the children were respectively treated with PEG-rhG-CSF or recombinant human granulocyte colony-stimulating factor(rhG-CSF)during the chemotherapy.The incidence of grade Ⅲ/Ⅳ agranulocytosis,the lowest absolute value of neutrophils,duration of grade Ⅳ agranulocytosis,incidence of agranulocytosis accompanied by fever,incidence of infections,use of antibiotics and length of hospital stay were observed and compared between the two groups.RESULTS Totally 47 children with ALL were enrolled in the study and were assigned as the PEG-rhG-CSF group with 24 cases and the rhG-CSF group with 23 cases.There were no significant differences in the incidence rates of grade Ⅲ/Ⅳ agranulocytosis and musculoskeletal soreness between the two groups.The low-est absolute value of neutrophils of the PEG-rhG-CSF group[(0.88±0.87)× 109/L]was higher than that of the rhG-CSF group;the duration of grade Ⅳ agranulocytosis of the PEG-rhG-CSF group[2.50(0.00,6.50)d]was shorter than that of the rhG-CSF group;the incidence of agranulocytosis accompanied by fever(41.67％),inci-dence of infections(41.67％)and the percentage of children treated with antibiotics were lower in the PEG-rhG-CSF group than in the rhG-CSF group;the length of hospital stay of the PEG-rhG-CSF group was shorter than that of the rhG-CSF group;there were significant differences between the two groups(P＜0.05).CONCLUSION The prophylactic use of PEG-rhG-CSF may raise the lowest value of neutrophils,shorten the duration of agranulo-cytosis,decrease the incidence of hospital-associated infections in the ALL children during the induction chemo-therapy,and reduce the use of antibiotics,with the safety favorable.

OBJECTIVE To explore the efficacy of using tragus perichondrium under otoscope without filling to repair small perforation of tympanic membrane.METHODS A retrospective analysis was conducted on the clinical data of 32 patients who underwent surgery for small perforation of tympanic membrane in the Department of Otolaryngology,the First Hospital of Jiaxing from July 2020 to December 2022.All patients were treated with endoscopic implantation of the tragus perichondrium for tympanic membrane repair.During the operation,the tympanic cavity and external auditory canal were completely unsupported by fillers,and the patient was followed up for 6 months postoperatively.Analyze the gas conduction hearing threshold and gas bone conduction difference before and after surgery,postoperative perforation healing rate,perforation healing time,VAS score,and incidence of complications.RESULTS Thirty-two cases of small perforation of tympanic membrane were successfully treated with surgery,and the postoperative perforation healing rate was 96.88%.The average healing time was(20.1±7.61)days,and the healing morphology was good.The postoperative average hearing threshold of air conduction[(19.84±5.55)dB HL]was significantly lower than the preoperative average hearing threshold of air conduction(31.56±6.69)dB HL,and the difference was statistically significant(t=14.77,P<0.05);The postoperative average air bone conduction difference[(8.87±3.64)dB]was significantly lower than the preoperative average air bone conduction difference[(20.50±3.27)dB],and the difference was statistically significant(t=14.41,P<0.05).The postoperative VAS score of 0-3 points accounts for 93.75%.There were 2 cases of postoperative tympanitis,1 case of unhealed tympanic membrane,and no secondary cholesteatoma or facial paralysis.CONCLUSION The minimally invasive treatment of small perforation of tympanic membrane using endoscopic implantation of the tragus perichondrium without filling is a minimally invasive and effective surgical method with high postoperative healing rate,good hearing rehabilitation effect,mild pain,and few complications.

Objective To investigate the predictive value of systemic immune-inflammation index(SII)and N-terminal pro-brain natriuretic peptide(NT-proBNP)level in elderly patients with acute ST-segment elevation myocardial infarction(STEMI)developing contrast-induced acute kidney injury(CIAKI)after PCI.Methods A total of 1085 elderly STEMI patients undergoing emergency PCI in the Affiliated Hospital of Xuzhou Medical University from January 2018 to March 2023 were consecutively recruited as a training set,and another 287 elderly STEMI pa-tients receiving emergency PCI in the East Branch of the Affiliated Hospital from January 2021 to June 2023 were included as a verification set.According to the diagnostic criteria of CIAKI,they were divided into CIAKI group(n=95)and non-CIAKI group(n=990).Based on the results of restricted cubic spline(RCS)analysis,the patients from the training set were assigned into low-risk subgroup(n=292),moderate-risk group(n=515)and high-risk group(n=278).Multivari-ate logistic regression analysis was used to analyze the independent risk factors of CIAKI in elder-ly STEMI patients after PCI,and ROC curve was plotted to analyze the predictive value of combi-nation of SII and NT-proBNP.The risk of CIAKI was compared among the patients at different risk grades.Results Age,SII,baseline serum creatinine,NT-proBNP,fasting blood glucose and use of diuretics were independent risk factors for CIAKI after primary PCI in elderly STEMI patients(P＜0.05,P＜0.01).The AUC value of SII combined with NT-proBNP in predicting CIAKI was 0.801(95％CI:0.761-0.842,P＜0.01),with a sensitivity of 83.2％and a specificity of 67.5％,both superior to that of SII or NT-proBNP alone.RCS analysis revealed an increased risk of CIAKI at SII ≥1084.97 × 109/L and NT-proBNP ≥296.12 ng/L.The incidence of CIAKI was increased with the increase of risk grades(1.71％vs 6.41％vs 20.50％).Conclusion SII and NT-proBNP are independent risk factors for CIAKI after emergency PCI in elderly STEMI pa-tients.And their combination has better predictive value for CIAKI.

Objective:To investigate the expression and role of DEAD-box RNA helicases 5(DDX5 helicases)in head and neck squamous carcinoma(HNSCC).Methods:Tissue microarray microarray was used to assess relevant mRNA expression profile data,and R software was used to screen differential mRNAs(DEGs).The expression level of DDX5 was predicted using GEPIA 2,TCGA databases,and detected by immunohistochemistry,western blot and RT-qPCR in the HNSCC tissue and cell lines.Based on high-throughput sequencing data of DECs,differentially expressed miRNAs(DEMIs)relevant DDX5 competitive endogenous RNA network(ceRNA)was constructed.The software cytoscape was used to visualize the ceRNA network map and further screen the regulatory ax-is.Results:The results of microarray screening revealed that DDX5 expression in HNSCC was upregulated.Immunohistochemistry ver-ified that DDX5 was stronger expressed in the nuclei of squamous carcinoma cells.qPCR results suggested that significant expression of DDX5 mRNA at the tissue and cellular levels(P＜0.05).Western blot results showed high expression of DDX5 protein in the tissues.The ceRNA network was constructed,from which the relevant HNSCC axis circRNA-039626-miR-222-5p-DDX5 was identified.Con-clusion:DDX5 is highly expressed in HNSCC,and the circRNA-039626-miR-222-5p-DDX5 axis may be a potential regulatory axis for the development of HNSCC.

DDX5 helicase (DEAD box helicases 5), also known as P68, is an important member of an ATP dependent RNA helicase.Studies have shown that DDX5 is abnormally expressed in a variety of cancers, targeting a variety of tumor related signal pathways, regulating upstream and downstream factors to affect the occurrence, invasion and migration of tumor cells. This article describes the biological role of DDX5 in malignant tumors and provides prospects for targeted treatment of tumors.

Objective:To explore the predictive value of systemic immune-inflammation index (SII) and small and dense low-density lipoprotein-cholesterol (sdLDL-C) on contrast-induced acute kidney injury (CI-AKI) in patients with acute ST-segment elevation myocardial infarction (STEMI) undergoing emergency percutaneous coronary intervention (PCI).Methods:This retrospective analysis included 674 STEMI patients who underwent emergency PCI in Affiliated Hospital of Xuzhou Medical University from November 2019 to October 2021, all patients were divided into a training cohort ( n=450) and validation cohort ( n=224) at a ratio of 2∶1 according to the chronological sequence. The patients in the training cohort were further divided into CI-AKI group ( n=92) and non-CI-AKI group ( n=358). Information at admission and emergency blood biochemical indexes were collected, and the SII was calculated. Multifactorial logistic regression analysis was used to explore the independent factors influencing the occurrence of CI-AKI in STEMI patients undergoing emergency PCI in the training cohort and a predictive model was established. Receiver operating characteristic (ROC) curve and Hosmer-Lemeshow test were used to evaluate the model discrimination and calibration. Results:The prevalence of CI-AKI was 20.4% (92/450). Age, proportion of women, sdLDL-C, urea, baseline creatinine, uric acid, neutrophil count, neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR) and SII were significantly higher in the CI-AKI group than in the non-CI-AKI group (all P<0.05), and left ventricular ejection fraction (LVEF), high-density lipoprotein cholesterol, estimated glomerular filtration rate (eGFR) and lymphocyte count were significantly lower in the CI-AKI group than in the non-CI-AKI group (all P<0.05). The results of multifactorial logistic regression analysis showed that age ( OR=1.046, P=0.001), LVEF ( OR=0.916, P<0.001), sdLDL-C ( OR=4.754, P<0.001), uric acid ( OR=1.012, P=0.007), eGFR ( OR=0.994, P=0.002), and lnSII ( OR=2.471, P<0.001) were independent determinants of CI-AKI after emergency PCI in STEMI patients. ROC curve analysis showed that area under the curve (AUC) for the diagnosis of CI-AKI was 0.688 with a sensitivity of 73.9% and specificity of 61.5% for the SII cut-off point of 1 179.07×10 9/L. The AUC for the diagnosis of CI-AKI was 0.709 with a sensitivity of 65.2% and specificity of 77.4% for the sdLDL-C cut-off point of 1.147 mmol/L. The AUC for the diagnosis of CI-AKI was 0.847 with a sensitivity of 88.0% and a specificity of 70.6% for the combination of SII and sdLDL-C with age, LVEF, uric acid and eGFR. The Hosmer-Lemeshow test (χ2=6.913, P=0.546) proved the goodness of fit of the model. Conclusions:SII and sdLDL-C have significant clinical value in the prediction of CI-AKI. SII and sdLDL-C combined with age, LVEF, uric acid and eGFR could further improve the predictive efficacy of CI-AKI.

PURPOSE: The aim of this study was to investigate the association of telomere length with breast cancer risk. We simultaneously explored the association between telomerase reverse transcriptase gene polymorphisms and telomere length. METHODS: We used real-time quantitative polymerase chain reaction to measure relative telomere length (RTL) in genomic DNA extracted from peripheral blood from 183 breast cancer cases and 191 healthy controls. Genotyping was performed using the Sequenom MassARRAY platform. RESULTS: Our results show that breast cancer patients had significantly shorter RTLs than control subjects (p < 0.05). When the RTLs were categorized into tertiles, we found that the lowest RTL was significantly associated with increased breast cancer risk compared with the highest RTL (odds ratio [OR], 2.33; 95% confidence interval [CI], 1.40–3.90; p=0.001). Subgroup analyses indicated that risk of breast cancer was also significantly increased in the lowest RTL compared with the highest RTL in age >40 years (OR, 2.41; 95% CI, 1.31–4.43; p=0.005), body mass index ≤24 kg/m2 (OR, 2.81; 95% CI, 1.55–5.10; p=0.001), and postmenopausal women (OR, 3.94; 95% CI, 1.63–9.51; p=0.002), respectively. In addition, individuals with the AA genotype of rs2853677 have longer telomeres than those of breast cancer patients with the AG genotype (p=0.011). CONCLUSION: Our results suggest that shorter RTL was associated with an increased risk of breast cancer. An association was found between the AA genotype of rs2853677 and longer RTLs in the case group. Functional studies are warranted to validate this association and further investigate our findings.
Asian Continental Ancestry Group* ; Body Mass Index ; Breast Neoplasms* ; Breast* ; Case-Control Studies* ; DNA ; Female ; Genotype ; Humans ; Polymerase Chain Reaction ; Real-Time Polymerase Chain Reaction ; Telomerase ; Telomere*