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 analyze the pathogens distribution in patients with ventilator-associated pneumonia (VAP), and their association with anti-β-glucan receptor-1 (Dectin-1)/spleen tyrosine kinase (Syk) signaling pathway, and to provide scientific basis for formulating more effective treatment strategies and preventive measures. METHODS: A prospective study was conducted. 160 patients with VAP admitted to the department of critical care medicine of Xingtai People's Hospital from January 2021 to March 2023 were enrolled. The respiratory secretions of patients were collected for Candida colonization analysis, and then the bacteria in the respiratory secretions were identified by automatic microbial identification instrument. The expression levels of Dectin-1 and Syk in peripheral blood mononuclear cells were detected by fluorescent immunopolymerase chain reaction. Clinical pulmonary infection score (CPIS) was performed based on imaging, clinical and microbiological criteria. The basic data, pathogen distribution, Dectin-1 and Syk expression levels and CPIS score of the two groups were compared. Spearman test was used to analyze the correlation between the expression levels of Dectin-1 and Syk and respiratory Candida colonization and CPIS score. RESULTS: 160 VAP patients, 97 were Candida colonized (colonized group) and 63 were not (non-colonized group). There were significantly differences in gender (males: 57.73% vs. 41.27%, P = 0.042) and age (years: 57.98±12.46 vs. 62.09±10.61, P = 0.029) between the colonized group and the non-colonized group, while there were no significantly differences in the data of duration of mechanical ventilation, underlying diseases and primary diseases. The distribution of pathogenic bacteria showed that the infection rate of Staphylococcus aureus in the colonized group was significantly higher than that in the non-colonized group (24.74% vs. 7.94%, P < 0.05), and there was no significantly difference in the infection rate of other G-positive and G-negative bacteria between the two groups. The CPIS score in the colonized group was significantly higher than that in the non-colonized group (8.73±0.43 vs. 7.31±0.39, P < 0.01), and the expression levels of Dectin-1 and Syk in peripheral blood mononuclear cells were significantly higher than those in the non-colonized group (Dectin-1/U6: 0.86±0.22 vs. 0.47±0.16, Syk/U6: 0.77±0.18 vs. 0.42±0.11, both P < 0.01). The expression levels of Dectin-1 and Syk in peripheral blood mononuclear cells of VAP patients were significantly positively correlated with the colonization of respiratory Candida (r values were 0.754 and 0.631, respectively, both P < 0.05), and were significantly positively correlated with CPIS score (r values were 0.594 and 0.618, respectively, both P < 0.05). CONCLUSION The proportion of Staphylococcus aureus in VAP patients with respiratory Candida colonization is higher, and Dectin-1/Syk signaling pathway is significantly positively correlated with respiratory Candida colonization and CPIS score.
Humans ; Syk Kinase ; Lectins, C-Type/metabolism* ; Signal Transduction ; Pneumonia, Ventilator-Associated/metabolism* ; Prospective Studies ; Male ; Female ; Middle Aged ; Candida ; Aged

OBJECTIVE: To analyze the risk factors for ventilator-associated pneumonia (VAP) and its prognosis in patients with severe craniocerebral injury. METHODS: A prospective observational study was conducted. Patients with severe craniocerebral injury admitted to the Second Affiliated Hospital of Xingtai Medical College from January 2020 to December 2022 were enrolled as the study subjects. Patients were divided into VAP group and non-VAP group based on the occurrence of VAP. VAP patients were further stratified into low-risk group [sequential organ failure assessment (SOFA) score 0-5], moderate-risk group (SOFA score 6-8), and high-risk group (SOFA score ≥ 9). General data, serological indicators [interleukin-6 (IL-6), interleukin-1β (IL-1β), tumor necrosis factor-α (TNF-α), and signal transducer and activator of transcription 3 (STAT3)], and 28-day prognosis (with mortality as the endpoint event) were compared. Multivariate Logistic regression was used to identify risk factors for VAP and 28-day mortality. Linear regression was applied to analyze the correlations between risk factors and outcomes. RESULTS: A total of 140 patients with severe craniocerebral injury were enrolled, including 49 in the VAP group and 91 in the non-VAP group. The primary cause of injury was traffic accidents, followed by falls and heavy object impacts. Among VAP patients, 38 survived and 11 died within 28 days; 112 were classified as low-risk, 25 as moderate-risk, and 12 as high-risk. Significant differences were observed in age, body mass index (BMI), smoking history, hypertension, diabetes, hyperlipidemia, length of hospital stay, duration of mechanical ventilation, serum albumin levels, and frequency of sputum suction among different subgroups. Serologically, IL-1β, TNF-α, IL-6, and STAT3 mRNA expression levels in the VAP group were significantly higher than those in the non-VAP group. Deceased VAP patients exhibited higher IL-1β, TNF-α, IL-6, and STAT3 mRNA levels compared to survivors. These biomarkers progressively increased from low-risk to high-risk subgroups. Multivariate Logistic regression identified age [odds ratio (OR) were 0.328 and 0.318], BMI (OR were 0.340 and 0.268), hypertension (OR were 0.275 and 0.245), diabetes (OR were 0.319 and 0.307), hyperlipidemia (OR were 0.228 and 0.235), smoking history (OR were 0.255 and 0.240), length of hospital stay (OR were 0.306 and 0.230), duration of mechanical ventilation (OR were 0.247 and 0.219), frequency of sputum suction (OR were 0.325 and 0.228), IL-1β (OR were 0.231 and 0.259), TNF-α (OR were 0.308 and 0.235), IL-6 (OR were 0.298 and 0.277), and STAT3 (OR were 0.259 and 0.265) as independent risk factors for both VAP occurrence and 28-day mortality (all P < 0.05). Correlation analysis revealed that serum albumin levels were negatively correlated with VAP occurrence and mortality (all P < 0.01), while other factors showed positive correlations (all P < 0.01). CONCLUSIONS Age, BMI, length of hospital stay, duration of mechanical ventilation, frequency of sputum suction, hypertension, diabetes, hyperlipidemia, smoking history, IL-1β, TNF-α, and IL-6/STAT3 signaling pathway activation are significantly associated with VAP development and poor prognosis in patients with severe craniocerebral injury, providing a scientific basis for targeted clinical interventions.
Humans ; Risk Factors ; Pneumonia, Ventilator-Associated ; Prognosis ; Prospective Studies ; Craniocerebral Trauma/complications* ; Interleukin-6/blood* ; Male ; Female ; STAT3 Transcription Factor/blood* ; Interleukin-1beta/blood* ; Tumor Necrosis Factor-alpha/blood* ; Middle Aged ; Adult ; Logistic Models

To analyze potential adverse drug events(ADEs) associated with ustekinumab and upadacitinib in the treatment of inflammatory bowel disease(IBD) based on an international authoritative database, thereby providing evidence for clinical medication safety.

Objective To investigate the role of tongue diagnosis in the evaluation of airway mucus plug formation in mycoplasma pneumoniae pneumonia(MPP).Methods Totally 418 MPP children with MPP were included in this study.According to the formation of mucus plug under the microscope,the children with MPP were divided into mucus plug group(n=108)and non-mucus plug group(n=310).The purpose of this study was to compare the tongue features(tongue color,coating color,coating quality,tongue fluid)and levels of related inflammatory factors C-reactive protein(CRP),lactate dehydrogenase(LDH),interleukin(IL)-6,etc between the two groups,and to explore the role of tongue examination in evaluating the formation of mucus plugs in MPP.Results The tongue color of MPP mucus plug group was mainly crimson tongue,the coating color was mainly yellow fur,the coating quality was mainly thick greasy coating,and the tongue fluid was mainly fluid.The tongue image score of MPP mucus plug group was significantly higher than that of non-mucus plug group(P<0.05).Multivariate logistic regression analysis showed that CRP,IL-6,IL-17,γ interferon(IFN-γ),LDH and tongue total score were independent risk factors for mucus plug formation in MPP.The results of receiver operating characteristic(ROC)curve showed that the area under the curve(AUC)of CRP,tongue image score,LDH,IL-6,IL-17 and IFN-γ to predict the formation of mucus plug in MPP were 0.893,0.830,0.783,0.794,0.627 and 0.602,respectively.The optimal cut-off values were 37.445(mg/L),4.5(pionts),358.673(U/L),27.174(pg/mL),4.855(pg/mL)and 26.427(pg/mL),respectively.The AUC of MPP mucous plug formation was 0.930,the sensitivity was 0.907,and the specificity was 0.827.Conclusion There are differences in tongue image characteristics in MPP children with mucus plug formation.Total tongue image score can better predict mucus plug formation in MPP,and combined analysis has greater value in predicting MPP mucus plug formation.

Objective:To investigate the application of virtual reality (VR) technology on intraoperative pain in patients undergoing peritoneal dialysis (PD)-related procedures with local infiltration anesthesia and the satisfaction.Methods:It was a single-center, prospective, concurrent controlled study. Patients were divided into two groups: VR group and control group. In the VR group, patients wore a VR headset to watch soothing audio and video content during surgery, while the control group underwent routine procedures. Intraoperative pain and satisfaction were assessed using the visual analog scale (VAS) and a 5-point satisfaction scale within 30 minutes of surgery. In addition, tolerance of the VR experience in the VR group was assessed using the VR sickness questionnaire.Results:A total of 43 patients were included in the study, including 25 males (58.1%). Chronic glomerulonephritis [17 cases (39.5%)] and diabetic nephropathy [6 cases (14.0%)] were the main primary diseases. There were 23 cases in the control group and 20 cases in the VR group. There were no significant differences between the two groups in age, sex ratio, proportion of primary disease, diabetes, hypertension, distribution of operation methods, preoperative vital signs and operation time (all P>0.05). VAS pain score was significantly lower in the VR group than that in the control group (5.90±2.38 vs. 7.43±1.67, t=2.469, P=0.018). The percentage of patients who were satisfied was 89.5% (17/19) in the VR group and 78.3% (18/23) in the control group, but there was no significant difference (chi-square test for continuity correction, χ2=0.308, P=0.579). Three patients in the VR group withdrew from the study due to severe discomfort, while the remaining participants found the VR experience to be tolerable. Common adverse effects included fatigue and blurred vision. Conclusions:The application of VR technology in PD-related procedures has been effective in reducing intraoperative pain when combined with local infiltration anesthesia. Furthermore, the utilization of VR technology in PD-related procedures is associated with a safe and tolerable outcome, despite the observation of some adverse effects.

Objective:To explore the genetic characteristics of a child with comorbid 16p11.2 microdeletion syndrome and Rett syndrome (RTT).Methods:A male infant who was admitted to Gansu Provincial Maternity and Child Health Care Hospital in May 2020 was selected as the study subject. Clinical data of the infant was collected. Genomic DNA was extracted from peripheral blood samples from the infant and his parents, and subjected to whole exome sequencing (WES). Candidate variant was verified by Sanger sequencing.Result:The patient, a 4-day-old male infant, had presented with poor response, poor intake, feeding difficulties, and deceased at 8 months after birth. WES revealed that he has harbored a 0.643 Mb deletion in the 16p11.2 region, which encompassed key genes of the 16p11.2 microdeletion syndrome such as ALDOA, CORO1A, KIFF22, PRRT2 and TBX6. His father has carried the same deletion, but was phenotypically normal. The deletion was predicted to be pathogenic. The child was also found to harbor a maternally derived c. 763C>T (p.R255X) hemizygous variant of the MECP2 gene, which was also predicted to be pathogenic (PVS1+ PS4+ PM2_Supporting). Conclusion:The 16p11.2 deletion and the MECP2: c.763C>T (p.R255X) variant probably underlay the pathogenesis in this infant.

In recent years, the high temperature and heatwaves have seriously affected the health of Chinese residents, and there is an important need for public health protection guidelines for high temperature and heatwaves in China. The National Bureau of Disease Control and Prevention has organized experts to fully investigate the evidence from epidemiological research on the health of populations in high temperature and heatwaves globally and in China, analyze the health hazards and protection needs of different populations, and put forward practical and effective individual protection measures and health recommendations. For this reason, the "Guideline for Public Health Protection against High Temperature and Heatwaves" (referred to as the "Guideline") was officially issued in June 2023. This article interprets the background and significance of the Guideline, the principles of compilation, the main considerations, the main contents, the implementations and promotions and other aspects, to improve the understanding of the content of the Guideline and strengthen the publicity and implementations.

In recent years, the high temperature and heatwaves have seriously affected the health of Chinese residents, and there is an important need for public health protection guidelines for high temperature and heatwaves in China. The National Bureau of Disease Control and Prevention has organized experts to fully investigate the evidence from epidemiological research on the health of populations in high temperature and heatwaves globally and in China, analyze the health hazards and protection needs of different populations, and put forward practical and effective individual protection measures and health recommendations. For this reason, the "Guideline for Public Health Protection against High Temperature and Heatwaves" (referred to as the "Guideline") was officially issued in June 2023. This article interprets the background and significance of the Guideline, the principles of compilation, the main considerations, the main contents, the implementations and promotions and other aspects, to improve the understanding of the content of the Guideline and strengthen the publicity and implementations.

Objective:To investigate the correlation of the emm genotypes and virulence genes with the isolation sites of Group A Streptococcus (GAS). Methods:It was a retrospective study.The specimens were collected from children with impetigo in Beijing Children′s Hospital, Capital Medical University from 2006 to 2008 for GAS isolation and identification.A total of 24 GAS strains were isolated from 16 children with impetigo, among which 7 pairs of strains were isolated from the throat and skin of 7 children, and 1 pair of strains was isolated from the vulva and skin of one child, and the remaining 8 GAS strains were isolated from the skin pus samples of 8 children.Polymerase chain reaction was applied to detect the emm genotypes and 13 virulence genes ( speA, speB, speC, speF, speG, speH, speI, speJ, speK, speL, speM, smeZ and ssa). The correlation of the emm genotypes and virulence genes with the isolation sites of GAS strains was analyzed. Results:In this study, four emm genotypes were detected, including emm1.0 (15/24), emm12.0 (4/24), emm22.0 (2/24) and emm160.0 (1/24), and one subtype emm12.19 (2/24) was detected as well.The carrying rates of 13 virulence genes speA, speB, speC, speF, speG, speH, speI, speJ, speK, speL, speM, smeZ and ssa were 58.3%, 100%, 91.7%, 100%, 50.0%, 12.5%, 54.2%, 66.7%, 16.7%, 25.0%, 12.5%, 100% and 91.7%, respectively.All strains carried 5 to 11 virulence genes and they all carried speB, speF and smeZ.There were significant differences in the carrying rate of speA and speJ among the strains with different emm genotypes (all P<0.05). There was no significant difference in the distribution of virulence genes between skin isolates and pharyngeal isolates, including the 5 pairs of strains carrying the emm1.0 genotype (all P>0.05). Conclusions:The distribution of virulence gene of GAS in children with impetigo is significantly correlated with the emm genotype, rather than the isolation site.