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

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Humans ; Adolescent ; Acne Vulgaris/therapy* ; Skin Care ; Surveys and Questionnaires ; Cognition ; China ; Skin

Objective To analyze the influencing factors and management of benign anastomotic stenosis in patients with colorectal cancer after concurrent prophylactic ileostomy.Methods The clinical data of 74 colorectal cancer patients undergoing preventive ileostomy admitted to Quanzhou First Hospital Affiliated to Fujian Medical University from April 2018 to June 2022 were selected,according to the presence or absence of anastomotic stenosis after surgery,patients were divided into anastomotic stenosis group and anastomotic normal group.The influencing factors of stenosis were analyzed using statistical methods,and the management methods for anastomotic stenosis were summarized.Results 15 cases of anastomotic stenosis occurred after surgery,with an incidence rate of 20.3%.Compared with anastomotic normal group,patients in anastomotic stenosis group had a higher proportion of preoperative radiation therapy,preoperative neoadjuvant chemotherapy,and a higher incidence of postoperative anastomotic leakage/pelvic infection,with statistical significance(P<0.05);Multivariate analysis suggests that preoperative radiotherapy,anastomotic leakage/pelvic infection are independent risk factors for anastomotic stenosis.Conclusion Patients with colorectal cancer who undergo preoperative radiotherapy,neoadjuvant chemotherapy,and postoperative anastomotic leakage/pelvic infection should pay attention to the occurrence of anastomotic stenosis after undergoing ileostomy;Postoperative anastomotic stenosis should be treated according to the characteristics of the stenosis.

【Objective】 To study the genotypes of ABO ambiguous blood group samples(n=20) and identify their molecular biological characteristics. 【Methods】 The serological phenotype of the samples was analyzed by serological techniques. Seven exons of ABO gene were amplified by polymerase chain reaction (PCR) and the PCR products were directly sequenced; the genotypes and sequences of ABO subtypes were analyzed. 【Results】 The serological phenotypes of 20 samples presenting ABO ambiguous blood group were as follows: weak A antigen (n=5), weak A antigen combined with anti-A1 antibody (n=5), normal A antigen combined with anti-A1 antibody (n=2), weak B antigen (n=8). The genotypes of them were as follows: Ax02/O01 (n=3), Ael07/O01 (n=2), B313/O01 (n=2), A204/O02 (n=1), A220/O01 (n=1), Ael07/O02 (n=1), Ael02/O01 (n=1), Ael02/O02 (n=1), Ax03/O01 (n=1), Ax03/O02 (n=1), B313/O02 (n=1), B302/O01 (n=1), B302/O02 (n=1), Bw19/O02 (n=1), A102/B313 (n=1) and A101/Bw37 (n=1). 【Conclusion】 ABO genotyping technology can accurately identify the ambiguous blood group of samples, provide definite genetic information of blood group and ensure the safety of clinical transfusion.

OBJECTIVE Alzheimer's disease(AD)is the most common neurodegenerative disease worldwide.Neuroinflammation is a potential target for the patients with AD.It is attributed to activated microglia and the release of various inflammatory mediators from infec-tion,ischemia and toxin accumulation.Accumulating evi-dence has indicated that the cGAS-STING pathway driven neuroinflammation in neurological disease.TSG is a main natural active ingredient that derived from polyg-onum multiflorum.Previous research from our group found that TSG has beneficial effects of anti-aging,anti-inflammatory action and improving memory function in APP/PS1 transgenic AD mice.Here,we investigated the effects of TSG on cognitive impairment and neuroinflam-mation in APP/PS1-AD mice and explore the underly-ing mechanism by which TSG ameliorates memory func-tion in the cGAS-STING-mediated inflammatory response.METHODS The Morris water mace test and the novel object recognition test were performed to test the effects of TSG on spatial learning and cognitive and memory abil-ity in APP/PS1 double transgenic AD mice model.In addi-tion,real-time quantitative PCR,Western blotting,ELISA analysis,and flow cytometry to examine gene and pro-tein expression of cGAS-STING related pro-inflammatory cytokines and chemokines.Statistical analyses were ana-lyzed using the SPSS 25.0 package by analysis of vari-ance(ANOVA).Neuman-Keuls or Tukey's multiple-com-parisons test were conducted as ANOVA justified post hoc comparisons between group means.RESULTS We demonstrated that AD transgenic mice exhibited cognitive deficits accompanied by the elevated serum and brain inflammation.The expressions of serum inflammatory cytokines and the activation of microglia in cerebral cor-tex and hippocampus were suppressed after TSG treat-ment,which was probably attributable to the decrease of cyclic GMP-AMP synthase(cGAS)and stimulator of interferon genes(STING)triggered immune response.Additionally,the data showed that TSG treatment reduced the expression level of inflammatory cytokines(IL-1β,TNF-α,IFN-β,IFN-α)in microglial cells BV2 primed with LPS and IFN-γ.CONCLUSION TSG implicated the health benefits in preventing cognitive disorders by inhib-iting neuroinflammation via cGAS-STING signalling path-way in AD.

Objective:To investigate the clinical phenotype and gene mutation in a child with developmental disorders caused by CTNNB1 gene mutation. Methods:Clinical data of a child with CTNNB1 gene mutation who was admitted to Xiamen Hospital of Fudan University Affiliated Pediatric Hospital in May 2017 were collected, whole exome sequencing technology was applied to verify the family lineage of the child, and the pathogenicity of mutation site was analyzed. Results:The patient was a 6 years and 1 month old male, with a clinical phenotype including mental retardation, motor developmental disorders, speech disorders, visual disorders (internal strabismus), microcephaly, and behavioral problems (social withdrawal, overdependence, etc.), as well as panic syndrome (i.e., sudden shrieking in response to auditory and visual stimuli, extensional rigidity of the body, etc., followed by short periods of general extensional rigidity). The whole exome sequencing results showed the presence of a de novo mutation c.283(exon4)C>T in the CTNNB1 gene, and the c.283(exon4)C>T mutation was interpreted as pathogenic (PVS1+PS2+PS1+PM2+PM) according to the American College of Medical Genetics and Genomics variant classification criteria and guidelines. No relevant genetic variants were found in the parental family verification. Conclusion:CTNNB1 gene mutation c.283(exon4)C>T can cause neurodevelopmental disorders, including mental retardation, motor developmental disorders, speech disorders, visual disorders, microcephaly and behavioral abnormalities.

Objective:To compare the differences in lung function between sanitation workers and the general population undergoing routine physical examinations, and to analyze the risk factors for restricted airflow and severity of the condition in sanitation workers.Methods:This study is a large cross-sectional study called "Shanxin Respiratory Health Screening for Ten Thousand People". A total of 1 036 sanitation workers (sanitation group) and 6 701 individuals from the general population undergoing routine physical examinations (control group) were selected as the original study subjects from June 2021 to April 2022 (before matching). Both groups underwent pre-bronchodilator lung function tests, and the differences in lung function characteristics between the two groups were compared. The sanitation group also completed a questionnaire survey. Multivariate and ordinal multinomial logistic regression analysis were used to analyze the risk factors for airflow limitation and its severity.Results:A total of 1 027 individuals from the sanitation group and 999 individuals from the control group were included in the study. There were no significant differences in age, gender, height, weight, and body mass index (BMI) between the two groups (all P>0.05). The rate of airflow restriction was significantly higher in the sanitation group compared to the control group (22.88% vs 8.81%, P<0.001). In the sanitation group, there was no statistically significant difference in a self-assessment test for chronic obstructive pulmonary disease (CAT) scores between individuals with airflow restriction (235 cases) and those without airflow restriction (792 cases) [(1.50±2.50) vs (1.15±2.03) points, P=0.084]. There were no statistically significant differences in forced vital capacity (FVC) as a percentage of predicted value (FVC%pred) between the two groups. However, the sanitation group had significantly lower %pred for forced expiratory volume in one second (FEV 1%pred), FVC/FEV 1 ratio (FEV 1/FVC%pred), forced expiratory flow at 50% of FVC (FEF 50%%pred), forced expiratory flow at 75% of FVC (FEF 75%%pred), and maximal mid-expiratory flow (MMEF%pred) compared to the control group (all P<0.05). The rates of abnormal FEF 50%%pred, FEF 75%%pred, and MMEF%pred were significantly higher in the sanitation group compared to the control group (17.62% vs 10.31%, 17.04% vs 10.01%, 27.26% vs 18.41%, all P<0.001). Small airway parameters and the rate of airflow restriction were significantly higher in past and current smokers of the sanitation group compared to never smokers (all P<0.05). Multifactorial analysis showed that high BMI ( OR=0.929, 95% CI: 0.885-0.974) was a protective factor for airflow restriction, while high smoking index was a risk factor ( OR=1.020, 95% CI: 1.011-1.030). Ordered multinomial logistic regression analysis showed that high BMI ( OR=0.925, 95% CI: 0.882-0.971) was a protective factor for the severity of airflow restriction, while high smoking index ( OR=1.020, 95% CI: 1.011-1.029) was a risk factor for the severity of airflow restriction. Conclusions:The incidences of airflow limitation and small airway abnormalities in sanitation workers are higher than that in general physical examination population. High smoking index and low BMI are independent risk factors for airflow limitation and its severity.

Objective:To retrieve and analyze the evidence related to perioperative blood glucose management in patients with coronary heart disease (CHD) complicated by diabetes undergoing percutaneous coronary intervention (PCI) , and provide clinical guidance for glucose management.Methods:Systematic searches were conducted on domestic and international guideline websites, evidence-based databases, primary research databases, and related association websites for evidence concerning perioperative blood glucose management for this patient group. The search included clinical decisions, guidelines, expert consensus, evidence summaries, and systematic reviews, covering the time span from database inception to February 2022. Two evidence-trained researchers independently conducted literature quality assessments and evidence extraction, with disputes resolved by a third party.Results:Eighteen articles were included: one clinical decision, nine guidelines, and eight expert consensuses. The findings were summarized into eight aspects: team formation and training, admission assessment and treatment, blood glucose control targets, preoperative glucose management, intraoperative glucose management, postoperative glucose management, perioperative abnormal glucose management, and discharge management, totaling 35 evidence points.Conclusions:This study consolidates evidence related to perioperative blood glucose management for patients with CHD complicated by diabetes undergoing PCI. However, during the evidence translation and application process, conditions of the application site, medical resources, and patient preferences should be fully considered. After assessing the feasibility and applicability of the evidence, a personalized blood glucose management plan should be developed for the patient, aiming to improve blood glucose levels and prognosis.

Objective:To evaluate clinical efficacy and safety of topical compound oleum lithospermi in the treatment of mild to moderate diaper dermatitis.Methods:A multicenter, randomized, positive-drug parallel-controlled clinical trial was conducted in 19 hospitals from July 2019 to August 2020. Children aged 0 - 12 months with mild to moderate diaper dermatitis were enrolled and randomly divided into 2 groups using a random number table: test group topically treated with compound oleum lithospermi, and control group topically treated with zinc oxide cream. The treatment was carried out 6 - 8 times a day for 7 days. Visits were scheduled on days 0 and 7, and total response rate and clinical healing time were evaluated. Changes in the dermatitis family impact (DFI) score were compared between the test group and control group, and adverse events were recorded. Statistical analysis was carried out by using independent-sample t test for normally distributed continuous data, Wilcoxon rank sum test for non-normally distributed continuous data, and chi-square test or Fisher′s exact test for unordered categorical data; survival curves were drawn, and log-rank test was used for comparisons between two groups. Results:A total of 343 children with diaper dermatitis were enrolled in this study. Among them, 31 children violated the protocol, so 312 were included in the per protocol set, including 157 in the test group and 155 in the control group, and all completed the visits on days 0 and 7. The total response rate was significantly higher in the test group (87.26%, 137/157) than in the control group (78.71%, 122/155; χ2 = 4.04, P = 0.044) . The clinical healing time was significantly shorter in the test group (5.33 days) than in the control group (6.13 days; χ2 = 4.67, P = 0.025) . After 7-day treatment, the DFI score significantly decreased in both the 2 groups compared with that before the treatment, but there was no significant difference in the DFI score between the 2 groups (test group: 4.02 ± 6.96, control group: 3.58 ± 5.90, Z = -0.39, P = 0.686) . The incidence of adverse events was 2.92% (5/171) and 5.45% (9/165) in the test group and control group respectively, and there was no significant difference between the 2 groups ( χ2 = 0.03, P = 0.865) . Conclusion:Compound oleum lithospermi can markedly reduce the clinical severity of diaper dermatitis, improve the total response rate, shorten the clinical treatment period, and improve the quality of life of children′s families with a favorable safety profile.