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 develop a method for rapidly identifying Clostridioides difficile(C.difficile)and de-termining high-producing toxin strains,conduct clinical evaluation.Methods The loop-mediated isothermal amplifi-cation(LAMP)method was used to identify C.difficile based on the tcdC,tcdA,and tcdB genes.The sensitivi-ty,specificity,and overall consistency of the detection method were evaluated.Results Feces specimens from 499 hospitalized patients suspected of C.difficile-associated diarrhea were detected,with C.difficile detection rate of 12.8％(64/499),out of which the detection rate of toxin-producing C.difficile was 10.8％(54/499).The sensi-tivity,specificity,positive predictive value,and negative predictive value of the detection method for tcdA were 87.2％,98.9％,89.1％,and 98.6％,respectively,and 88.2％,99.6％,90.0％,and 98.73％for tcdB,respec-tively.The total toxin levels of different strains were different,but the average toxin production level of A+B+strains(1.79 μg/mL)was higher than those of A-B+strains(0.72 μg/mL)and A-B-strains(＜0.10 μg/mL).Conclusion The portable high-throughput LAMP detection method can rapidly and efficiently identify C.difficile and determine high-producing toxin strains.

Creutzfeldt-Jakob disease(CJD)is a rapidly progressive and fatal neurodegenerative disorder caused by prions,with certain infectivity and iatrogenic transmission risks.With the rapid progress and application of new dia-gnostic biomarkers and detection methods,as well as the construction and improvement of surveillance and reporting systems,the detection of CJD in patients domestically and internationally has shown an increasing trend year by year.Due to its long incubation period and heterogeneity of early symptoms,early identification and diagnosis of the disease is difficult,increasing the risk of transmission within medical institutions.Currently,there is a lack of con-sensus on the infection prevention and control of CJD.In order to timely identify and diagnose CJD as well as effec-tively block its transmission in medical institutions,this consensus summarizes 15 clinical concerns and formulates 24 specific recommendations based on the latest domestic and international research findings and clinical evidence,as well as combines with clinical practice,aiming to standardize healthcare-associated infection prevention and control measures for CJD and reduce its transmission risk in medical institutions.

Objective To analyze the risk factors of fluconazole resistance in Candida tropicalis(C.tropicalis)urinary tract infection(UTI),and evaluate the efficacy of different treatment regimens.Methods Patients with C.tropicalis UTI at Xiangya Hospital of Central South University from January 2021 to December 2023 were in-cluded for single center retrospective study.The minimum inhibitory concentration(MIC)of fluconazole was deter-mined by microbroth dilution.Patients were divided into a fluconazole-resistant group and a fluconazole-sensitive group based on fluconazole resistance.Risk factors for fluconazole resistance were analyzed based on clinical data,and therapeutic efficacy in patients in fluconazole-resistant group was analyzed.Results A total of 198 patients were included in the study.133(67.2％)C.tropicalis strains were detected to be sensitive to fluconazole,while 65(32.8％)strains were resistant,and 63.1％(n=41)had MIC values ≥128 μg/mL.Compared with fluconazole-sensitive group,fluconazole-resistant group had a higher proportion of pulmonary infection(P=0.019).Pulmonary infection(OR=3.282)was a risk factor for fluconazole resistance in C.tropicalis UTI,while urinary system ob-struction(OR=0.269)was a protective factor for fluconazole resistance in C.tropicalis UTI.There was no statis-tically significant difference in the usage rate of different antimicrobial agent types between the two groups(all P＞0.05).The therapeutic efficacy analysis showed that the effective rates of treatment with fluconazole dosage regi-mens of ≤200 mg/d,≥400 mg/d,and fluconazole monotherapy against fluconazole-resistant strains were 66.7％(6/9),83.3％(5/6),and 100％(6/6),respectively.For patients treated with monotherapy using other drugs or with multidrug sequential treatment regimens,the treatment effective rate was 60.0％(3/5).The proportion of pa-tients in the effective treatment group who removed their urinary catheters after detecting C.tropicalis was higher than that in the ineffective treatment group(P＜0.001).Conclusion The fluconazole resistance of C.tropicalis is related to urinary tract obstruction and concurrent pulmonary infection.When treating UTI caused by fluconazole-resistant strains,the catheter should be removed as early as possible.In addition to increasing the dosage of flucon-azole,other antifungal drugs such as flucytosine alone or sequential treatment with multiple drugs can also be con-sidered.

A 70-year-old male patient was admitted to a hospital on March 1,2024 due to"muscle soreness in his extremities for over a month".Diagnosis consideration:polymyalgia rheumatica(with a high likelihood,the possi-bility of a tumor needs to be excluded).The patient was treated with methylprednisolone.After discharge from the hospital,the patient's symptoms worsened due to self-withdrawal of medication(methylprednisolone treatment for 20 days),and developed fever and cough.He then revisited the hospital and was confirmed to have Legionella mar-ssiliensis infection through metagenomic sequencing of bronchoalveolar lavage fluid(nucleic acid of all microorga-nisms were extracted from the specimens and compared in the PMDB database to obtain species information of the suspected pathogenic microorganisms).Subsequently,the patient was treated with a combination of 0.75 g levo-floxacin intravenous infusion qd+0.1 g doxycycline enteric-coated capsules orally bid for anti-infective therapy.The patient's symptoms,such as cough and muscle pain,improved significantly after anti-inflammatory and anti-in-fective treatment,and he was discharged on March 18.As the first reported case of Legionella marssiliensis pulmo-nary infection in China,this case highlights that among the multiple species of Legionella,there is another bacte-rium that can infect the human body and cause disease.This case report is beneficial for improving medical staff's understanding on Legionella marssiliensis and providing reference for the diagnosis and treatment of future cases of Legionella marssiliensis infection.

Medical ultrasound technology is widely used for diagnosis and therapy in clinical practice.Ultrasound probes,which are directly contact with patients,pose a potential risk of pathogen transmission.This expert consen-sus was developed by a multidisciplinary team based on international guidelines,standards in China,and the results of a national survey,aiming to reduce the risk of healthcare-associated infection through standardizing reprocessing of medical ultrasound probes,and formulating consensus recommendations with the Delphi method.The consensus clarifies the reprocessing principles for three types of ultrasound probes of different infection risks:external-use ul-trasound probes,interventional percutaneous ultrasound probes,and internal-use ultrasound probes,puts forward systematic suggestions on the reprocessing standards and disinfection levels of ultrasound probe isolation covers and coupling agents,the reprocessing procedures and methods of ultrasound probes,as well as architectural layout and management of reprocessing,so as to provide a scientific prevention and control framework for ensuring ultrasound diagnosis and therapy safety.

Currently,aging is a major public health topic globally.Infectious diseases exhibit high incidence and mortality among the elderly,which seriously affect the quality of life of the elderly and cause a heavy economic bur-den.The changes of immune function in the elderly are complicated.Their immune response and clinical immune regulation methods after infection need further clarification.This expert consensus summarizes the immune charac-teristics of the elderly and the inherent connection with infections,the application of glucocorticoids,the use of re-lated immune modulators,as well as diagnosis and treatment under specific conditions,providing high-quality recommendations for clinical practice.

Hemodialysis patients exhibit compromised immune function and require long-term repeated vascular punctures as therapeutic approach,the risk of infection increases.Hospital-associated infection in hemodialysis de-partment(center)happens from time to time,which has already become a concern for the medical community,patients and social media.This paper outlines the task origin of China's"Standard for infection prevention and control in hemodialysis department(center)"(WS/T854-2025),the compilation basis and explanations for its key content,feasibility and implementation recommendations,as well as the clarifications on common issues encoun-tered during its promotion and enforcement.

Climate change has emerged as a focal point of global concern in the 21st century.This paper systema-tically summarizes the direct and indirect impacts of climate change on human health,including directly causing hu-man death and disability in the form of disasters,and increasing the risk of climate-sensitive diseases,including chronic non-infectious diseases,infectious diseases,mental and psychological problems,as well as allergic diseases and malnutrition through changes in temperature and humidity,air pollution,as well as changes in the geographical distribution of disease vectors.Based on these,within the global governance framework,this paper focuses on the challenges faced by medical institutions in the field of infection prevention and control,and explores in depth infec-tion control response strategies from five aspects,so as to provide reference for further enhancing the climate resi-lience capacity of the medical system and safeguarding public health.

A 70-year-old male patient was admitted to a hospital on March 1,2024 due to"muscle soreness in his extremities for over a month".Diagnosis consideration:polymyalgia rheumatica(with a high likelihood,the possi-bility of a tumor needs to be excluded).The patient was treated with methylprednisolone.After discharge from the hospital,the patient's symptoms worsened due to self-withdrawal of medication(methylprednisolone treatment for 20 days),and developed fever and cough.He then revisited the hospital and was confirmed to have Legionella mar-ssiliensis infection through metagenomic sequencing of bronchoalveolar lavage fluid(nucleic acid of all microorga-nisms were extracted from the specimens and compared in the PMDB database to obtain species information of the suspected pathogenic microorganisms).Subsequently,the patient was treated with a combination of 0.75 g levo-floxacin intravenous infusion qd+0.1 g doxycycline enteric-coated capsules orally bid for anti-infective therapy.The patient's symptoms,such as cough and muscle pain,improved significantly after anti-inflammatory and anti-in-fective treatment,and he was discharged on March 18.As the first reported case of Legionella marssiliensis pulmo-nary infection in China,this case highlights that among the multiple species of Legionella,there is another bacte-rium that can infect the human body and cause disease.This case report is beneficial for improving medical staff's understanding on Legionella marssiliensis and providing reference for the diagnosis and treatment of future cases of Legionella marssiliensis infection.