Loss of protein homeostasis is a hallmark of cellular senescence, and ribosome pausing plays a crucial role in the collapse of proteostasis. However, our understanding of ribosome pausing in senescent cells remains limited. In this study, we utilized ribosome profiling and G-quadruplex RNA immunoprecipitation sequencing techniques to explore the impact of RNA G-quadruplex (rG4) on the translation efficiency in senescent cells. Our results revealed a reduction in the translation efficiency of rG4-rich genes in senescent cells and demonstrated that rG4 structures within coding sequence can impede translation both in vivo and in vitro. Moreover, we observed a significant increase in the abundance of rG4 structures in senescent cells, and the stabilization of the rG4 structures further exacerbated cellular senescence. Mechanistically, the RNA helicase DHX9 functions as a key regulator of rG4 abundance, and its reduced expression in senescent cells contributing to increased ribosome pausing. Additionally, we also observed an increased abundance of rG4, an imbalance in protein homeostasis, and reduced DHX9 expression in aged mice. In summary, our findings reveal a novel biological role for rG4 and DHX9 in the regulation of translation and proteostasis, which may have implications for delaying cellular senescence and the aging process.
G-Quadruplexes ; Cellular Senescence ; Ribosomes/genetics* ; Humans ; Animals ; Mice ; DEAD-box RNA Helicases/genetics* ; Protein Biosynthesis ; RNA/chemistry* ; Neoplasm Proteins

Objective To investigate the relationship between Fat Mass- and obesity-associated gene (FTO) polymorphisms and the susceptibility of non-alcohol-related fatty liver disease (NAFLD) in a Han population from Qingdao region of China. Methods A total of 119 NAFLD patients were recruited from Qingdao Municipal Hospital and Chengyang District People's Hospital and 187 control individuals who received annual physical examination were also included. Their clinicopathological information and study questionnaire were collected. Their fasting venous blood was extracted for biochemical analyses and FTO polymorphism genotyping using the polymerase chain reaction combined with DNA sequencing. The data were statistically assessed. Results The data showed statistically significant differences in age, BMI, ALT, GGT, TG and Bil between NAFLD patients and normal controls (all P < 0.05). FTO polymorphism genotyping data showed three genotypes of FTO rs1421085 (TT, CT, and CC), rs8050136 (TT, CT, and CC) and rs9939609 (TT, AT, AA). However, there was no statistical difference in both allele frequency and genotype of FTO rs1421085, rs9939609, and rs8050136 between NAFLD and controls (all P > 0.05) and there was also no statistical difference in clinical parameters among these genotype carriers (all P > 0.05). Conclusion NAFLD patients showed significantly statistical differences in age, BMI, ALT, GGT, TG, and BIL vs. those of normal controls. However, this study did not find any association of FTO rs1421085, rs9939609, and rs8050136 polymorphisms with NAFLD susceptibility in this Qingdao region of Han Chinese population.

Objective: To evaluate the interobserver agreement, diagnostic value, and associated clinical factors of automated breastultrasound (ABUS) coronal features in differentiating breast lesions. Materials and Methods: This study enrolled 457 pathologically confirmed lesions in 387 female (age, 46.4 ± 10.3 years),including 377 masses and 80 non-mass lesions (NMLs). The unique coronal features, including retraction phenomenon,hyper- or hypoechoic rim (continuous or discontinuous), skipping sign, and white wall sign, were defined and recorded. Theinterobserver agreement on image type and coronal features was evaluated. Furthermore, clinical factors, including the lesionsize, distance to the nipple or skin, palpability, and the histological grade were analyzed. Results: Among the 457 lesions, 296 were malignant and 161 were benign. The overall interobserver agreement for imagetype and all coronal features was moderate to good. For masses, the retraction phenomenon was significantly associated withmalignancies (p < 0.001) and more frequently presented in small and superficial invasive carcinomas with a low histologicalgrade (p = 0.027, 0.002, and < 0.001, respectively). Furthermore, continuous hyper- or hypoechoic rims were predictive ofbenign masses (p < 0.001), whereas discontinuous rims were predictive of malignancies (p < 0.001). A hyperechoic rim wasmore commonly detected in masses more distant from the nipple (p = 0.027), and a hypoechoic rim was more frequently foundin large superficial masses (p < 0.001 for both). For NMLs, the skipping sign was a predictor of malignancies (p = 0.040). Conclusion The coronal plane of ABUS may provide useful diagnostic value for breast lesions.

Objective To investigate the effect of tacrolimus on the function of islet beta cells in mature SD rats.Methods 72 Healthy SD rats were divided into 4 groups by random number table:High dose group (group H),middle dose group (group M),low dose group (group L) and control group,18 for each group.Measured body weight every 3 days and monitored fasting blood glucose every month.Fasting serum insulin levels (FINS) was determined by enzyme-linked immunoasaay (ELISA) after 1 month and 4 months later.The histological structure of islets were observed by HE staining.Results The clinical symptoms of polydipsia and polyuria in rats after 4 months in group H and M group tacrolimus irrigation group were presented,and the weight growth rate was lower than earlier;There was no significant change in blood glucose within one month of each group,as the duration of drug administration was extended,the blood glucose levels of the experimental groups gradually increased significantly and were positively correlated with the concentration;In the early stage of insulin level,the insulin secretion was negatively correlated with the concentration of tacrolimus;After 1 month,HE staining the pancreatic structure was clear and the islet structure was intact,After 4 months,the pancreatic tissue structure of H and M group was destroyed.Conclusion The short-term use of tacrolimus will not cause damage to the function of beta cells of the islet,but long-term use may gradually lead to the damage of beta cell function,and these changes are closely related to the concentration of tacrolimus.

Objective To investigate the prevalence of healthcare-associated infection (HAI)in a hospital in 2013-2015,and provide reference for the improvement of HAI management.Methods Prevalence rates of HAI among patients in the First Affiliated Hospital of Zhengzhou University in 2013 -2015 were investigated with cross-sec-tional survey method,prevalence rates of HAI and constituent ratios of HAI sites in patients of different genders and different age groups were analyzed.Results In 2013 -2015,29 605 patients should be investigated,29 581 (99.92%)were actually investigated.Prevalence rates of HAI in 2013-2015 were 2.83%,2.14%,and 1 .73%,re-spectively,difference was significant(χ2 =27.521 ,P <0.01),which showed a downward trend year by year.Preva-lence rates of HAI in male was significantly higher than that of female (2.47% vs 1 .98%,χ2 =7.954,P <0.01). The prevalence rates of HAI in the age dimension was roughly U-shaped distribution in 2013 -2015.Prevalence rates of HAI in ≥70 age group was the highest(4.15%),in 0 -30 age group decreased with age,in > 30 age group increased with age.The top three sites for prevalence of HAI were lower respiratory tract (45.67%),upper respiratory tract (9.92%),and urinary tract (8.52%).Conclusion The prevalence rates of HAI decreased year by year in 2013-2015,which suggests that HAI prevention and control measures are effectively implemented.

Objective To explore the direct economic loss caused by healthcare-associated infection(HAI)in general hospitals in China.Methods 68 hospitals were selected,a retrospective 1:1 matched survey was conducted to compare the direct medical cost in patients with and without HAI between January 1,2015 and December 31,2015. Results A total of 2 123 pairs of patients with and without HAI were included in the survey.The average cost of hospitalization in HAI and non-HAI groups were ￥25 845.30 and ￥12 006.14 respectively,￥13 839.16 on average was increased due to HAI.The average economic loss in provincial and ministerial levels of hospitals were￥21 409.83.The average economic loss in different regional hospitals were ￥9 725.42-￥18 909.59,and north China ranked the first.Economic loss caused by bloodstream infection and lower respiratory tract infection were more than other sites,which were ￥23 190.09 and ￥18 194.50 respectively.Conclusion HAI resulted in considerable direct economic loss.Prevention and control of HAI,especially bloodstream infection and lower respiratory tract infection should be paid more attention.

Objective To understand the current situation of occupational exposure and protection among health care workers (HCWs ), and provide evidence for formulating preventive measures of occupational exposure. Methods From April 6,2016 to May 6,2016,questionnaire surveys were conducted in 158 different levels of hos-pitals in 13 provinces in China,occupational exposure,protection management,and monitoring of occupational expo-sure in the first year,2010,and 2015 was surveyed by cluster random sampling method.Results Occupational ex-posure in 81.65% (129/158)of hospitals was responsible by healthcare-associated infection management depart-ments;98.73%(156/158)of hospitals set up the relevant rules and regulations;77.22%(122/158)of hospitals had missing report of occupational exposure.A total of 11 116 times of occupational exposure occurred (1 542 cases in the first year,2 474 in 2010,and 7 100 in 2015).Of various types of occupational exposure,sharp injury accounted for 96.76%;among HCWs sustained occupational exposure,nursing staff accounted for 53.90%;the major de-partment that HCWs who sustained occupational exposure were general wards,operating rooms,and intensive care units;the main medical appliances related to occupational exposure were syringes,scalp needles,and surgical suture needles;high-risk behavior causing occupational exposure were intravenous injection,putting needles into the sharp con-tainers,and surgical suturing;among occupational exposure sources,HBV accounted for 58.69%.Conclusion HCWs in China face a high risk of occupational exposure,occurrence of occupational exposure should be reduced through gov-ernment legislation,application of safety appliances,standardizing behavior of HCWs,proper using of personal pro-tective equipment,strengthening education and training of HCWs,and establishing a sound occupational exposure report,evaluation and follow-up system.

Objective To realize the current situation of prevention and control of catheter-associated urinary tract infection (CAUTI)since the development of healthcare-associated infection(HAI)management in China in the re-cent 30 years.Methods Random cluster sampling was used to select 165 secondary and tertiary hospitals in 13 provinces and cities in China,questionnaires were filled in,the content included time,scope,method,data feed-back,and incidence of CAUTI monitoring.Results Of 165 hospitals,92.12% (152/165)have implemented targe-ted monitoring,the implementation rate in tertiary hospitals was higher than secondary hospitals (98.08% [102/104]vs 81.97%[50/61],χ2 =13.748,P <0.001).Most hospitals (82.24%[125/152])only implemented monito-ring in intensive care units(ICUs)or partial ICUs.HAI management professionals,HAI control doctors and nurses in 69.08%(105/152)of hospitals jointly took responsibility for CAUTI monitoring.95.39% (145/152)of hospitals diagnosed CAUTI by combination of clinical manifestations and laboratory examination results.98.68%(150/152) of hospitals have gradually implemented intervention measures,such as strictly mastering the indications of urinary indwelling catheters,hand hygiene of health care workers,non-frequent change of urinary indwelling catheters,and necessity for daily assessment of catheterization.75.66% (115/152)of hospitals conducted feedback of monitored results to the whole hospital.Incidences of CAUTI in pre-2010,2010,and 2015 were 3.10‰,4.72‰,and 1.89‰respectively.Conclusion In the recent 30 years,monitoring on CAUTI in China has obtained achievement,CAUTI monitoring is gradually standardized and scientific,but the development at all levels of medical institutions is still imbalance,which needs to be improved further.

Objective To understand the current situation and existing problems in the training of healthcare-asso-ciated infection(HAI)management,and provide scientific basis for strengthening the management of HAI preven-tion and control system.Methods A questionnaire survey was adopted to investigate situation of training on HAI in 15 provincial-level HAI training agencies in China during the past 30 years,and basic condition of training on HAI management in recent 5 years.Results Among 15 provincial-level training agencies,66.67%(n=10)were respon-sible by HAI management quality control centers,80.00% have already conducted training in each city,53.33%carried out training for 10 to 20 times,33.34% performed training for ≤2 times per year.Of 33 728 trainees in 2011-2015,41.30% were 41-50 years old,61.82% were nursing staff,50.56% had bachelor degree,43.96%were with the intermediate professional title.Most trainers were HAI prevention and control experts in their respec-tive province,accounting for 68.07%,the curriculums were mainly designed on professional course,and only 26.78% were involved in management.Conclusion Professional structure of HAI management personnel is not reasonable,faculty is imbalance,knowledge update is lacking,and HAI training and education system need to be improved further.

Objective To summarize the effectiveness in monitoring activities for healthcare-associated infection (HAI)in China in the past 30 years,explore the changing trend in HAI monitoring,find a new model for the moni-toring of HAI in China.Methods A total of 194 comprehensive hospitals and military hospitals in 13 provinces (au-tonomous regions,municipalities)were selected,questionnaire survey was adopted to investigate the situation of HAI monitoring.Results Of 194 hospitals,184 (94.85%)had available data after being checked,incidence of HAI in secondary and tertiary hospitals were 0.78% and 1.58% respectively,difference was significant (P <0.01).Monitoring was divided into two stages,cumulative percentage of each monitoring activity before 2006 and during 2006-2016 were respectively as follows:environmental hygiene were 73.91% and 100.00%,disinfection ef-ficacy 69.57% and 97.28%,overall comprehensive monitoring 64.67% and 98.91%,surgical site infection(SSI) 13.04% and 94.57%,ICU HAI 4.89% and 87.50%,neonatal HAI 1.75% and 60.82%,multidrug-resistant or-ganisms(MDROs)5.43% and 95.65%,hand hygiene compliance 2.17% and 93.48%,antimicrobial agents 15.22% and 87.50%.The reporting rate of HAI outbreak in tertiary hospitals was higher than secondary hospitals (33.33% [n=37]vs 16.44%[n=12],P =0.01).Conclusion The monitoring of HAI in China starts late,but develops rapidly,defects still exist in HAI monitoring system,reporting rate of HAI cases is still high,reporting rate of HAI outbreak is low.