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

LIN28 is an RNA binding protein with important roles in early embryo development, stem cell differentiation/reprogramming, tumorigenesis and metabolism. Previous studies have focused mainly on its role in the cytosol where it interacts with Let-7 microRNA precursors or mRNAs, and few have addressed LIN28's role within the nucleus. Here, we show that LIN28 displays dynamic temporal and spatial expression during murine embryo development. Maternal LIN28 expression drops upon exit from the 2-cell stage, and zygotic LIN28 protein is induced at the forming nucleolus during 4-cell to blastocyst stage development, to become dominantly expressed in the cytosol after implantation. In cultured pluripotent stem cells (PSCs), loss of LIN28 led to nucleolar stress and activation of a 2-cell/4-cell-like transcriptional program characterized by the expression of endogenous retrovirus genes. Mechanistically, LIN28 binds to small nucleolar RNAs and rRNA to maintain nucleolar integrity, and its loss leads to nucleolar phase separation defects, ribosomal stress and activation of P53 which in turn binds to and activates 2C transcription factor Dux. LIN28 also resides in a complex containing the nucleolar factor Nucleolin (NCL) and the transcriptional repressor TRIM28, and LIN28 loss leads to reduced occupancy of the NCL/TRIM28 complex on the Dux and rDNA loci, and thus de-repressed Dux and reduced rRNA expression. Lin28 knockout cells with nucleolar stress are more likely to assume a slowly cycling, translationally inert and anabolically inactive state, which is a part of previously unappreciated 2C-like transcriptional program. These findings elucidate novel roles for nucleolar LIN28 in PSCs, and a new mechanism linking 2C program and nucleolar functions in PSCs and early embryo development.
Animals ; Cell Differentiation ; Embryo, Mammalian/metabolism* ; Embryonic Development ; Mice ; Pluripotent Stem Cells/metabolism* ; RNA, Messenger/genetics* ; RNA, Ribosomal ; RNA-Binding Proteins/metabolism* ; Transcription Factors/metabolism* ; Zygote/metabolism*

Clostridioides difficile is a key pathogen of antibiotic related diarrhea and hospital associated infection, causing several outbreaks in Europe and North Americans and resulting in severe disease burden. However, the standardized diagnostic principle and detection specifications in C. difficile infection (CDI) survey are limited in China, and the infection rate and disease burden of CDI in China are unclear. Therefore, National Institute for Communicable Disease Control and Prevention,National Institute for Communicable Disease Control and Prevention, Chinese Center for Disease Control and Prevention, together with another 11 institutions, draft the group standard entitled "Diagnosis of Clostridium difficile infection (T/CPMA 008-2020)" of Chinese Preventive Medicine Association. Based on the principle of "legality, scientificity, advancement, and feasibility", this standard clarifies risk factors, diagnosis principles, diagnoses and differential diagnoses in order to improve the accuracy of CDI diagnosis in clinical practice, guide the surveillance for CDI, and understand the infection rate and disease burden of CDI in China .

Objective: To study the feasibility, safety and aesthetics of laparoscopic cholecystectomy using a single-port through the umbilicus in patients with chronic cholecystitis with cholecystolithiasis. Methods: From Jan 2007 to Jun 2017, the clinical data of 4790 patients who underwent single-port, 4 426 patients conventional three-ports, and 3 304 patients two-ports laparoscopic cholecystectomy were retrospectively studied. Results: There were no death in all the three groups. There were no significant differences in the incidences of postoperative bleeding, bile leakage, biliary tract injury and other significant short-term complications (all P>0.05). The operation time of transumbilical single-port laparoscopic cholecystectomy was significantly longer than that of two-ports and three-ports laparoscopic cholecystectomy [(35.3±9.0)min vs. (28.4±7.2)min vs. (23.3±6.4)min, P<0.05]. Looking only in a single year, there was no significant difference in the operation time of the three groups in the year 2017 (P>0.05). There were no significant differences among the three groups in intraoperative blood loss, first postoperative passing of flatus, postoperative pain, and length of hospital stay (all P>0.05). The satisfaction score of surgical scar in the single-port group was higher than that in the two-ports and three-ports groups [(9.6±1.6) vs. (7.6±1.9) vs. (6.7±2.0), P<0.05]. Conclusions Transumbilical single-port laparoscopic cholecystectomy was safe and feasible, with good aesthetics and other advantages. It was more difficult than the traditional laparoscopic technique. After the learning curve, the operation time could be comparable to the three-ports technique.

Objective To investigate the prevalence rate of healthcare-associated infection(HAI)in Xiangya Hospital,and provide reference for preventing and controlling HAI.Methods The cross sectional surveys on preva-lence rates of HAI,cross-sectional antimicrobial use,and bacterial detection among all hospitalized patients on the given days in 2000-2014 (except 2006)were carried out by combination of bedside investigation and medical record reviewing.Results The prevalence rates of HAI in 2000-2014 decreased from 6.30% to 3.91%,difference was statistically significant (χ2 = 35.14,P < 0.001 );prevalence rates of community-associated infection(CAI)were 15.61%-15.76%,there was no significant difference among each year.General intensive care unit (ICU)had the highest prevalence rate;respiratory tract was the most common site of both HAI and CAI;urinary catheterization rate showed a decreased tendency,arteriovenous catheterization rate showed a increased tendency,difference were both significant(χ2 = 5.21,96.24,respectively,both P <0.001).In 2008 - 2014,pathogenic detection rates for specimens from patients receiving therapeutic antimicrobial agents were 36.37%-44.51%,from patients with HAI were 34.00%-44.99%,detection rate of pathogens causing HAI were 41.57%-68.48%,all showed a increased tendency,difference was significant (χ2 = 22.78,10.03,26.49,respectively,all P < 0.001 ).Gram-negative bacteria were the main pathogens causing infection;both cross sectional and combination antimicrobial usage rates declined (P < 0.05 ).Conclusion Prevention and control of HAI,and antimicrobial management has achieved preliminary success,prevalence rate of HAI and cross sectional antimicrobial usage rate declined obviously,the main pathogen is gram-negative bacteria,and the major infection site is lower respiratory tract.

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 status of awareness of hand hygiene(HH)knowledge and compliance among health care workers (HCWs)in China,and provide scientific basis for further improvement of HH practice. Methods A multi-centre retrospective survey on awareness of HH knowledge and compliance was conducted in 200 nationwide hospitals in 2015.Results The awareness rates of HH methods and HH indications among HCWs were 86.5% and 82.5% respectively;cleaning staff had the lowest awareness rate of HH indications(69.9%),followed by the other interns and advanced-study students (70.2%),as well as medical technicians (79.8%);attendants had the lowest awareness rate of HH methods(76.9%),followed by advanced-study students and interns(81.0%),and cleaning staff (82.4%);HH knowledge awareness rate among HCWs in secondary hospitals was lower than tertia-ry hospitals,and the district-level hospitals had the lowest awareness rate of HH.HH compliance rate and correct rate were 70.1% and 74.9% respectively;the interns and advanced-study students were at a low level of compliance and correct rates (61.4% and 60.9% respectively);the municipal hospitals had the lowest compliance and correct rates,non-teaching hospitals were lower than teaching hospitals.Conclusion HH in primary hospitals is weak,HH of interns,advanced-study students,as well as attendants and cleaning staffs are not enough,HH management should be strengthened,awareness and compliance of HH should be improved.

Objective To investigate the status and risk factors of surgical site infection (SSI)in hospitals in Chi-na,so as to provide theoretical basis for the prevention and treatment of SSI.Methods Four types of surgeries (colorectal surgery,abdominal hysterectomy,femoral neck repair surgery,and vascular surgery)in 29 hospitals were monitored prospectively,risk factors for SSI were analyzed.Results A total of 6 309 surgical procedures were investigated,incidence of SSI was 1 .60%.Incidences of SSI in patients receiving colorectal surgery,abdominal hys-terectomy,femoral neck repair surgery,and vascular surgery were 4.47%(74/1 655 ),1 .03%(22/2 139),0.21 %(5/2 372),and 0.00% (0/143 )respectively.The incidences of SSI were different among different regions (χ2 =114.213,P <0.05).The most common SSI was superficial incisional infection,the next was deep incisional infec-tion.The major pathogens causing SSI were Escherichia coli ,Enterococcus spp .,coagulase negative staphylococ-cus ,Staphylococcus aureus ,and Klebsiella pneumoniae .The independent risk factors for SSI were male patients, long duration of surgery,and high NNIS score.Conclusion The risk of SSI is varied with different types of surger-ies.Male,long duration of surgery,and high NNIS score can increase the risk of postoperative SSI.

Objective To explore the incidence of surgical site infection (SSI)and compliance to bundled interven-tion measures,and evaluate the effect of bundled interventions on controlling SSI.Methods From October 2013 to September 2014,three types of surgeries (colorectal surgery,abdominal hysterectomy,and femoral neck repair sur-gery)in 29 hospitals in China were monitored,October 2013 to March 2014 was baseline investigated stage,April 2014 to September 2014 was intervention stage.Results A total of 6 166 episodes of surgeries were monitored,the incidence of SSI was 1 .64%,incidence of SSI following colorectal surgery,abdominal hysterectomy,and femoral neck repair surgery were 4.47%,1 .03%,and 0.21 % respectively.The P 75 time of three types of surgeries were 3,2,and 2 hours respectively.Compared with the baseline stage,the compliance to most intervention measures im-proved after intervention,the largest increase in the compliance to interventions was disinfection with chlorhexidine-containing disinfectant at surgical sites of colorectal surgery (increased by 29.09%),followed by preoperative shower of femoral neck repair surgery (increased by 26.24%),preoperative shower of colorectal surgery(increased by 22.95%),and skin preparation on the day of operation (increased by 20.75%).Incidences of SSI in three types of surgeries were not significantly different before and after intervention(all P >0.05).Conclusion The incidences of SSI are different among different types of surgeries,the compliance to most bundled intervention measures has im-proved to some extent after intervention,but effectiveness of intervention measures needs to be further observed.