One of the basic questions in the aging field is whether there is a fundamental difference between the aging of lower invertebrates and mammals. A major difference between the lower invertebrates and mammals is the abundancy of noncoding RNAs, most of which are not conserved. We have previously identified a noncoding RNA Terc-53 that is derived from the RNA component of telomerase Terc. To study its physiological functions, we generated two transgenic mouse models overexpressing the RNA in wild-type and early-aging Terc-/- backgrounds. Terc-53 mice showed age-related cognition decline and shortened life span, even though no developmental defects or physiological abnormality at an early age was observed, indicating its involvement in normal aging of mammals. Subsequent mechanistic study identified hyaluronan-mediated motility receptor (Hmmr) as the main effector of Terc-53. Terc-53 mediates the degradation of Hmmr, leading to an increase of inflammation in the affected tissues, accelerating organismal aging. adeno-associated virus delivered supplementation of Hmmr in the hippocampus reversed the cognition decline in Terc-53 transgenic mice. Neither Terc-53 nor Hmmr has homologs in C. elegans. Neither do arthropods express hyaluronan. These findings demonstrate the complexity of aging in mammals and open new paths for exploring noncoding RNA and Hmmr as means of treating age-related physical debilities and improving healthspan.
Animals ; Mice ; RNA, Untranslated/metabolism* ; Aging/genetics* ; Mice, Transgenic ; Telomerase/metabolism* ; RNA/genetics* ; Hippocampus/metabolism* ; Humans ; Mice, Inbred C57BL

Objective:To analyze the distribution of tumor necrosis factor-alpha（TNF-α）308 gene loci polymorphism in children with febrile seizures（FS）and to explore the correlation between TNF-α 308 gene polymorphisms and FS in children.Methods:A total of 320 children diagnosed with FS in the Department of Emergency，Shanghai Children's Hospital from September 1st，2020 to June 30th，2021 were enrolled as the study subjects，which were divided into simple febrile seizures（SFS）group（232 cases）and complex febrile seizures（CFS）group（88 cases）based on their clinical characteristics，and the clinical characteristics and laboratory indexes of the two groups were compared. Children with no history of convulsions were selected as the control group（160 cases）. The high-resolution melting and gene sequencing technology were used to analyze the polymorphism of TNF-α 308 gene in each group and the distribution of different gene types and allele frequencies among the groups was compared. A multivariate Logistic regression model was constructed to analyze the relationship between TNF-α 308 gene polymorphism and FS.Results:The age，mean corpuscular volume，mean corpuscular hemoglobin and platelet distribution width of the CFS group were significantly higher than those in the SFS group，and the difference was statistically significant（all P<0.05）.There was no significant difference in gender distribution，family history of FS，history of FS，body temperature at time of convulsions，WBC，Hb，CRP and PLT between the two groups（all P>0.05）.The genotype frequency distribution of TNF-α 308 polymorphism in the three groups was in line with the Hardy-Weinberg equilibrium（ P>0.05）.The AA genotype of TNF-α 308 locus was not detected in the study.Compared with the control group［17 cases（10.6%）］，the distribution proportion of GA genotype in the CFS group［22cases（25.0%）］and the SFS group［52cases（22.4%）］was increased，and the difference was statistically significant（ χ2＝11.126， P＝0.004）；Compared with the control group［17 frequencies（5.3%）］，the frequency distribution proportion of allele A in the CFS group［22 frequencies（12.5%）］and SFS group［52 frequencies（11.2%）］was also increased，and the difference was statistically significant（ χ2＝9.960， P＝0.007）. Adding control factors such as gender，age，family history of FS，body temperature at time of convulsions and blood routine markers，the multivariate Logistic regression model was constructed to show that there was no statistically significant association between TNF-α 308 genotype and CFS in children（ OR＝1.805，95% CI：0.926~3.519， P＝0.083）. Conclusion:In this study，there was no significant correlation between TNF-α 308 gene loci polymorphism and CFS in children.

Objective To investigate the causes for the continuous detection of Pseudomonas fluorescens(P.fluo-rescens)from bronchoalveolar lavage fluid(BALF)in pediatric department of a hospital,formulate intervention measures and evaluate its effectiveness,and provide basis for improving the whole process infection control of fiber bronchoscopy.Methods Epidemiological investigation was conducted on three children from whose BALF P.fluorescens were detected in May 3-6,2024.The comprehensive methods were adopted,including case revie-wing,on-site process tracking,environmental hygiene monitoring,laboratory testing on disinfectant sterilization effect,fiber bronchoscope structure maintenance and checking,etc.Risks were identified and targeted interventions were implemented.Results Among the 5 pediatric patients who underwent fiber bronchoscopy within 4 days,P.fluorescens was detected from BALF of 3 cases,with a detection rate of 60.0％.The children were 5-8 years old and were admitted to the hospital due to lobar pneumonia.They underwent fiber bronchoscopy from the day of admission to the second day,and bacterial strains were clinically determined to be contaminated strains.Environ-mental sampling showed that the detection rate of P.fluorescens at sampling points such as fiber bronchoscope and enzyme solution storage tank was 15.7％(8/51).After implementing intervention,no target bacteria were detected again,and the difference was statistically significant(P＜0.05).From January 1 to May 2,2024,71 BALF from pediatric department were not detected P.fluorescens;From May 3 to 6,among 5 detected BALF,3 were detected P.fluorescens;After intervention(May 16 to December 31),no specimen was detected P.fluorescens.Conclusion This event is a pseudo-outbreak caused by fiber bronchoscope damage as well as improper cleaning and disinfection procedures.Through collaborative investigation and timely intervention by multiple departments,the event was ef-fectively controlled.

Objective To investigate the causes for the continuous detection of Pseudomonas fluorescens(P.fluo-rescens)from bronchoalveolar lavage fluid(BALF)in pediatric department of a hospital,formulate intervention measures and evaluate its effectiveness,and provide basis for improving the whole process infection control of fiber bronchoscopy.Methods Epidemiological investigation was conducted on three children from whose BALF P.fluorescens were detected in May 3-6,2024.The comprehensive methods were adopted,including case revie-wing,on-site process tracking,environmental hygiene monitoring,laboratory testing on disinfectant sterilization effect,fiber bronchoscope structure maintenance and checking,etc.Risks were identified and targeted interventions were implemented.Results Among the 5 pediatric patients who underwent fiber bronchoscopy within 4 days,P.fluorescens was detected from BALF of 3 cases,with a detection rate of 60.0％.The children were 5-8 years old and were admitted to the hospital due to lobar pneumonia.They underwent fiber bronchoscopy from the day of admission to the second day,and bacterial strains were clinically determined to be contaminated strains.Environ-mental sampling showed that the detection rate of P.fluorescens at sampling points such as fiber bronchoscope and enzyme solution storage tank was 15.7％(8/51).After implementing intervention,no target bacteria were detected again,and the difference was statistically significant(P＜0.05).From January 1 to May 2,2024,71 BALF from pediatric department were not detected P.fluorescens;From May 3 to 6,among 5 detected BALF,3 were detected P.fluorescens;After intervention(May 16 to December 31),no specimen was detected P.fluorescens.Conclusion This event is a pseudo-outbreak caused by fiber bronchoscope damage as well as improper cleaning and disinfection procedures.Through collaborative investigation and timely intervention by multiple departments,the event was ef-fectively controlled.

Ribosomopathies encompass a spectrum of disorders arising from impaired ribosome biogenesis and reduced functionality.Mutation or dysexpression of the genes that disturb any finely regulated steps of ribosome biogenesis can result in different types of ribosomopathies in clinic,collectively known as ribosomopathy genes.Emerging data suggest that ribosomopathy patients exhibit a significantly heightened susceptibility to cancer.Abnormal ribosome biogenesis and dysregulation of some ribo-somopathy genes have also been found to be intimately associated with cancer development.The cor-relation between ribosome biogenesis or ribosomopathy and the development of malignancies has been well established.This work aims to review the recent advances in the research of ribosomopathy genes among human cancers and meanwhile,to excavate the potential role of these genes,which have not or rarely been reported in cancer,in the disease development across cancers.We plan to establish a theoretical framework between the ribosomopathy gene and cancer development,to further facilitate the potential of these genes as diagnostic biomarker as well as pharmaceutical targets for cancer treatment.

OBJECTIVETo investigate the effect of electro-acupuncture on Toll-like receptor 4 (TLR4) nuclear factor κB (NF-κB) expressions in the liver of rats with non-alcoholic fatty liver disease (NAFLD).

METHODSSD rat models of NAFLD induced by feeding high-fat diet for 5 weeks were subjected to early or late intervention with electro-acupuncture at the acupoints Zusanli, Fenglong and Sanyinjiao for 20 min once daily for 21 consecutive days. The changes in serum ALT, AST, TC, and TG levels were determined in the rats and hepatic expressions of TLR4 and NF-κB detected with quantitative fluorescence PCR and Western blotting after treatments.

RESULTSSerum ALT, AST, TC, and TG levels and TLR4 and NF-κB levels increased significantly after NAFLD onset (P<0.05), and were markedly reduced by interventions with electro-acupuncture (P<0.05).

CONCLUSIONElectro-acupuncture at the acupoints Zusanli, Fenglong and Sanyinjiao can modify blood lipid and hepatic function to produce positive effect on NAFLD possibly by modifying lipid metabolism, lowering expressions of TLR4 and NF-κB in the liver, and reducing the impact of inflammation on NAFLD.

Animals ; Diet, High-Fat ; Disease Models, Animal ; Electroacupuncture ; Inflammation ; NF-kappa B ; metabolism ; Non-alcoholic Fatty Liver Disease ; metabolism ; therapy ; Rats ; Rats, Sprague-Dawley ; Toll-Like Receptor 4 ; metabolism

Objective To investigate the effect of electro-acupuncture on Toll-like receptor 4 (TLR4) nuclear factor κB (NF-κB) expressions in the liver of rats with non-alcoholic fatty liver disease (NAFLD). Methods SD rat models of NAFLD induced by feeding high-fat diet for 5 weeks were subjected to early or late intervention with electro-acupuncture at the acupoints Zusanli, Fenglong and Sanyinjiao for 20 min once daily for 21 consecutive days. The changes in serum ALT, AST, TC, and TG levels were determined in the rats and hepatic expressions of TLR4 and NF-κB detected with quantitative fluorescence PCR and Western blotting after treatments. Results Serum ALT, AST, TC, and TG levels and TLR4 and NF-κB levels increased significantly after NAFLD onset (P<0.05), and were markedly reduced by interventions with electro-acupuncture (P<0.05). Conclusion Electro-acupuncture at the acupoints Zusanli, Fenglong and Sanyinjiao can modify blood lipid and hepatic function to produce positive effect on NAFLD possibly by modifying lipid metabolism, lowering expressions of TLR4 and NF-κB in the liver, and reducing the impact of inflammation on NAFLD.

Objective To investigate the effect of electro-acupuncture on Toll-like receptor 4 (TLR4) nuclear factor κB (NF-κB) expressions in the liver of rats with non-alcoholic fatty liver disease (NAFLD). Methods SD rat models of NAFLD induced by feeding high-fat diet for 5 weeks were subjected to early or late intervention with electro-acupuncture at the acupoints Zusanli, Fenglong and Sanyinjiao for 20 min once daily for 21 consecutive days. The changes in serum ALT, AST, TC, and TG levels were determined in the rats and hepatic expressions of TLR4 and NF-κB detected with quantitative fluorescence PCR and Western blotting after treatments. Results Serum ALT, AST, TC, and TG levels and TLR4 and NF-κB levels increased significantly after NAFLD onset (P<0.05), and were markedly reduced by interventions with electro-acupuncture (P<0.05). Conclusion Electro-acupuncture at the acupoints Zusanli, Fenglong and Sanyinjiao can modify blood lipid and hepatic function to produce positive effect on NAFLD possibly by modifying lipid metabolism, lowering expressions of TLR4 and NF-κB in the liver, and reducing the impact of inflammation on NAFLD.

Objective To construct recombinant plasmids containing HPV18E7 gene ,and explore the optimization condition of its expression in Escherichia coli .Methods The genomic DNA extracted from HeLa cell line which served as a template to the HPV18 E7 gene was amplified using PCR method ;and the amplified product of HPV18E7 gene was connected to the pET-32a(+ ) vector ,which composed the pET-32a(+ )-HPV18E7 recombinant plasmid ;the positive recombinant plasmids were transformed into BL21-DE3-pLysS competent cells and the optimized expression condition was explored in order to obtain a large amount of HPV18E7 oncogenic protein .Results The fragment length of PCR products of HeLa cell genomic DNA was consistent with that of HPV18 E7 gene .In LB medium ,the expression level of the target protein was not high under such conditions as different concentra-tion of IPTG and lactose ,different temperatures and different induction starting amount .Therefore the ZYM-5052 auto-induction medium was tried in this experiment ,and the expression amount of the fusion protein was much higher than that induced with IPTG and lactose .Conclusion The amount of HPV18E7 fusion protein in ZYM-5052 automatic induction medium is much higher than that induced with IPTG and lactose .

Objective To investigate the effect of massage on quadriceps femoris repair after injury by external force and the expression of transforming growth factor β1 (TGF-β1) and collagen-Ⅰ (COL-Ⅰ) mRNA.To explore the molecular mechanisms inhibiting scar tissue formation and promoting muscle repair.Methods Forty New Zealand white rabbits weighing (2.0 ±0.5) kg were randomly divided into a normal control group (A) (n =4),a selfrepair group (B) (n =20,further divided into the 3rd,7th,11th,15th and 19th day time points),and a massage group (C) (n =16,further divided as in group B).In group A the rabbits were not treated,as normal controls.In groups B and C rabbit models of quadriceps femoris injury were prepared using a self-made beater.In group B no massage therapy was given as a natural recovery control; in group C,massage therapy was given after 5 days.Realtime quantitative PCRs were used to detect TGF-β1 and COL-Ⅰ mRNA expression.Resnlts There was no significant difference between groups B and C in the expression of TGF-β1 or COL-Ⅰ mRNA on day 7.At the later time points,expression of both mRNAs in group C was significantly less than in group B.Conclusion Massage can effectively reduce the expression of TGF-β1 and COL-Ⅰ mRNA,inhibit excessive scar formation and promote repair of injured tissue.