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 evaluate the value of perfusion imaging mismatch and low perfusion ratio(HIR)based on CT perfusion imaging in predicting acute intracranial large vessel occlusion(LVO)associated with intracranial atherosclerotic stenosis(ICAS).Methods A total of 82 pa-tients with acute intracranial LVO who underwent emergency thrombectomy in our hospital from February 2019 to December 2020 were enrolled in this study.According to the etiology,they were divided into ICAS-related LVO group(ICAS-LVO,65 cases)and cardiogenic embolism group(17 cases).ROC curve was plotted to analyze the predictive value of CT perfusion imaging parame-ters.Results Compared with the cardiogenic embolism group,the ICAS-LVO group had signifi-cantly larger male ratio,higher BMI and TG level,more severe progression of disease,longer time from onset to surgery,larger proportion of ischemic penumbra and higher mismatch ratio,and ob-viously less ratio of atrial fibrillation,lower BNP and HDL levels,smaller infarct volume,and lower HIR(P＜0.05,P＜0.01).ROC curve analysis showed that HIR and mismatch ratio had good predictive value for the etiology of ICAS-LVO.The optimal cut-off value of HIR was 0.26,with an AUC value of 0.74,a specificity of 0.88,and a sensitivity of 0.54.The optimal cutoff for the mismatch ratio was 3.84,with an AUC value of 0.84,a specificity of 0.75,and a sensitivity of 0.90.Generalized linear model revealed that HIR and cerebral blood volume index had no signifi-cant difference in prognostic performance(P=0.175).Conclusion HIR and mismatch ratio are helpful to identify the pathogenesis earlier and formulate surgical strategies more accurately,thereby reducing iatrogenic injury to a greater extent,increasing the effective reperfusion rate,re-ducing the disability and mortality,and improving the prognosis of clinical outcomes.

Children and adults differ significantly in physiology,biochemistry and immune function,which leads to sig-nificant differences in blood transfusion strategies between children and adults.To guide the clinical transfusion practice of pediatric patients and improve the prognosis of children,the National Health Commission organized the formulation and re-lease of the health industry standard Guideline for Pediatric Transfusion(WS/T 795-2022).This paper will briefly introduce some concepts that help understand of the Standard and the preparation process of the Standard,and explain and interpret the preparation of the"scope","general provisions"and"factors to consider"of the Standard,hoping to contribute to the understanding and implementation of the Standard.

The leukocyte immunoglobulin-like receptor LILRB4(ILT3 or CD85k),a member of the immunosuppressive re-ceptor family,is expressed predominantly on the cell membranes of immune cells of myeloid origin,and exerts an immunosuppressive effect in immune regulation by activating either the autoinhibitory motif(ITIM)or by inhibiting Fc receptor activation motif(ITAM).In tumors,activation of LILRB4 receptor generates an immunosuppressive tumor microenvironment that assists in tumor invasion and metastasis,and in inflammatory diseases,LILRB4 is expressed on a variety of cells,such as monocytes,macrophages,mast cells,etc.,and attenuates inflammatory responses.Currently,LILRB4 has become a therapeutic target for tumors and various inflammatory diseases,and anti-LILRB4 monoclonal antibodies against acute myeloid leukemia(AML)have entered clinical trials.This review dis-cusses LILRB4 in terms of its structural distribution,signaling,therapeutic targets,and new drug development.

Background There is a lack of research evidence on the association between sugar-sweetened beverage (SSB) consumption and gestational diabetes mellitus (GDM) in China. Objective To explore the association between frequency of SSB consumption before pregnancy and risk of GDM in pregnant women in Shaanxi Province, and to provide a scientific basis for targeted interventions to control maternal blood glucose. Methods The recruitment to the China Birth Cohort study started in October 2020. Pregnant women at 6-16 weeks who had their first prenatal examination at five hospitals in Shaanxi Province were recruited. A maternal health questionnaire was used to collect basic information about pregnant women. A semi-quantitative food frequency questionnaire was used to collect the consumption of carbonated beverages, fruit and vegetable juice beverages, coffee beverages, and milk tea beverages in one year before pregnancy, which were summed to obtain the SSB consumption. Pregnant women were divided into three groups according to SSB consumption, namely <1 serving·week⁻¹, 1-4 servings·week⁻¹, and ≥5 servings·week⁻¹. GDM was confirmed by oral glucose tolerance test (OGTT) between 24-28 weeks of gestation. A binary logistic regression model was applied to explore the association between SSB consumption and risk of GDM. Multiple linear regression was applied to investigate the associations between SSB consumption (per 1-serving·d⁻¹ increase) and OGTT fasting plasma glucose, 1-hour glucose, and 2-hour glucose. Results A total of 3811 pregnant women were finally enrolled in this study, of which 752 developed GDM, with an incidence rate of 19.7%. The incidence rates of GDM in pregnant women with SSB consumption frequency of <1 serving·week⁻¹, 1-4 servings·week⁻¹, and ≥5 servings·week⁻¹ were 18.0%, 21.1%, and 26.8%, respectively. After adjusting for maternal age, pre-pregnancy body mass index (BMI), education, number of children born, family history of diabetes, smoking, alcohol consumption, physical activity level, and total energy intake, the risk of GDM increased by 26% (OR=1.26, 95%CI: 1.05, 1.50) in the 1-4 servings·week⁻¹ group and by 76% (OR=1.76, 95%CI: 1.31, 2.38) in the ≥5 servings·week⁻¹ group compared to the <1 serving·week⁻¹ SSB consumption group, respectively. Further stratified analysis revealed no interaction effect (P_interaction>0.05) between SSB consumption and maternal age, pre-pregnancy BMI, or first labor or not. For each additional SSB consumption per day, the risk of GDM increased by 94% (OR=1.94, 95%CI: 1.37, 2.75); and the maternal OGTT 1-hour glucose and 2-hour glucose increased by 0.33 mmol·L⁻¹ and 0.18 mmol·L⁻¹, respectively (P<0.05), and no significant increase in fasting plasma glucose was found (P>0.05). Conclusion Higher SSB consumption before pregnancy increases the risk of GDM in pregnant women.

Objective : To explore whether the NLRP3 inflammasome is activated after Newcastle disease virus (NDV) exposure to esophageal cancer ECA109 cells , whether its activation is related to K + efflux , and the effect of ATP/P2X7 axis on the activation of NLRP3 inflammasome. Methods: The expression of NLRP3 and IL⁃1β was detected by Western blot; the content of IL⁃1β in the supernatant was detected by ELISA ; the formation of ASC spots was detected by fluorescence immunoassay; the change of intracellular K + concentration was detected by fluorescent probe technology; Interventions with ATPase , ATP and P2X7 receptor inhibitors were used to investigate their role in NLRP3 inflammasome activation. Results: Compared with the control group , the expression of NLRP3 , IL⁃1β and ASC protein in cells was up⁃regulated after NDV F3 infection ; the intracellular potassium concen tration decreased with the prolongation of infection time (P < 0. 05) . After the intervention of P2X7 receptor inhibitor, the efflux of intracellular K + was blocked. With the increase of inhibitor concentration , the efflux of K + was maximally inhibited at 10 μmol/L (P < 0. 05) . The results of ATPase and ATP intervention showed that ATPase inhibited K + efflux , while ATP promoted K + efflux. Western blot results showed that compared with the control group , P2X7 receptor was inhibited , and the expressions of NLRP3 and IL⁃1β were down⁃regulated ; after ATPase intervened cells , the expressions of NLRP3 and IL⁃1β decreased ; After ATP intervention in cells , the protein expressions of NLRP3 and IL⁃1β were up⁃regulated (P < 0. 05) . Conclusion NDV F3 infection of ECA109 cells can activate the NLRP3 inflammasome , the mechanism may be related to the ATP/P2X7 axis.

Objective:To investigate the effects of compound matrine injection on the proliferation of bladder cancer cell line BIU-87 and bladder orthotopic transplantated tumor in nude mice.Methods:BIU-87 cells in logarithmic growth phase were divided into experimental group (adding 300.00, 150.00, 75.00, 37.50, 18.75 μl/ml compound matrine injection 200μl) and negative control group (adding equal volume of culturing medium). The proliferation inhibition rate and the half inhibitory concentration ( IC50) of BIU-87 cells were detected and calculated by methyl thiazole tetrazolium (MTT) method. Twenty BALB/c-nu female nude mice were injected with 100 μl of BIU-87 cell suspension with a cell density of 2×10 7/ml in the bladder to establish an animal model of bladder orthotopic transplanted tumor. After 24 hours of perfusion of BIU-87 cell suspension, intravesical perfusion administration (100 μl per nude mouse) was started, and the mice were divided into compound matrine injection group (intravesical perfusion of matrine solution) and pirarubicin group (intravesical perfusion of 1 mg/ml pirarubicin), model control group (intravesical perfusion of the same volume of sterile water), blank control group (without intravesical perfusion of BIU-87 cell suspension or administration). The observation time was 90 d. The survival status and bladder wet weight of the animals were observed and recorded, and the tumor formation rate, tumor inhibition rate and life prolongation rate were calculated. Results:Different concentrations of compound matrine injection acted on BIU-87 cells for 48 hours, and the absorbance ( A) values ??of 300.00, 150.00, 75.00, 37.50, 18.75 μl/ml compound matrine injection group and negative control group were 0.027±0.006, 0.065±0.010, 1.695±0.105, 2.387±0.017, 2.427±0.134 and 2.721±0.080 ( F = 742.67, P < 0.05), the A values ??of each concentration of compound matrine injection group were compared with the negative control group, and the differences were statistically significant (all P < 0.05). The IC50 of compound matrine injection on BIU-87 cells was 70.05 μl/ml. On the 90th day of observation, the bladder wet weights of nude mice in blank control group, model control group, pirarubicin group and compound matrine injection group were (0.018±0.004) mg, (0.422±0.130) mg, (0.219±0.136) mg and (0.237±0.113) mg ( F = 14.01, P < 0.001), and the survival time of nude mice was (90±0) d, (54±12) d, (72±4) d and (69±8) d ( F = 18.53, P < 0.001). The inhibition rates of bladder cancer in the pirarubicin group and compound matrine injection group were 48.10% and 43.84%, and the life prolongation rates of the nude mice were 34.95% and 29.53%. Conclusions:Compound matrine injection can inhibit the proliferation of BIU-87 cells in a concentration-dependent manner. Compound matrine injection can increase the tumor inhibition rate and prolong the survival time of nude mice models of bladder orthotopic transplanted tumor.

Computed tomography (CT) examination is the major measure for detecting and diagnosis of foreign bodies in human body. Although CT has high sensitivity in diagnosis of foreign body, some interference factors may still lead to missed diagnosis or misdiagnosis. Here we report a rare case that a bamboo stick accidentally pierced into the left chest of a young man who was drunk and unware of this hurt. The patient experienced cough, chest pain, fever, hemoptysis, and was misdiagnosed as primary and secondary tuberculosis based on chest CT examinations at a local hospital, although no tubercular bacillus detected by sputum smear. He subsequently received anti-tuberculous treatments in the following three years, but no improvement of his symptoms was observed. Until one month before his death, the bamboo stick was detected by spiral CT examination as well as three-dimensional image reconstruction at another hospital. Postmortem examination revealed pneumonia, pulmonary infarction, and abscess as the causes of his death. We analyze the potential reasons of misdiagnosis in this case, aiming to provide reference for the diagnosis and treatment of pulmonary inflammation associated with foreign body in the future.
Abscess ; Diagnostic Errors ; Humans ; Male ; Pneumonia ; Pulmonary Infarction ; Tuberculosis, Pulmonary

AIM: To observe the effect of osthole on tricalcium phosphate (TCP) particles-induced calvarial osteolysis in vivo.METHODS:Male ICR mice were randomly divided into sham group , TCP group and osthole group .A mouse calvarial model of osteolysis was established by TCP particles .On the second postoperative day , osthole (20 mg/kg) was locally injected into the calvarium under the periosteum 3 times a week.Two weeks after osthole treatment , blood and calvaria were collected to determine the level of bone turnover markers such as alkaline phosphatase ( ALP) , osteocalcin and tartrate-resistant acid phosphatase ( TRACP) .The periosteum was performed to examine the release of tumor necrosis factor-α(TNF-α), interleukin-6 (IL-6) and IL-1βby ELISA.The calvaria was obtained for histological and molecular analyses.RESULTS:Data from HE and TRACP staining revealed that osthole prevented TCP particles-induced obvious increase in osteoclastogenesis and resorption area in the metaphysis of mouse calvaria .Osthole treatment increased ALP ac-tivity and osteocalcin level , and dncreased the activity of TRACP in the mouse serum compared with TCP group .Further-more, TCP particles-induced the releases of TNF-α, IL-6 and IL-1βwere significantly suppressed by osthole treatment .In addition, Western blot demonstrated that endoplasmic reticulum ( ER) stress markers such as glucose-regulated protein 78 (GRP78) and CAAT/enhancer binding protein homologous protein (CHOP) were significantly up-regulated in TCP parti-cles-implanted calvarial mice , indicating that TCP particles triggered an ER stress response in the mouse calvarial osteolysis model , which obviously attenuated by osthole .CONCLUSION:Osthole inhibits TCP particles-induced calvarial osteolysis in mice, which is mediated by inhibition of ER stress signaling pathway .

The tumor multidrug resistance reversal effect of NPB304, a novel taxane, was studied. MTT assay was used to determine the IC50 of chemotherapy drugs. Western blotting assay was applied to analyze the expression of P-glycoprotein (P-gp). The effect of compounds on the P-gp function and P-gp ATPase activity was determined by rhodamine 123 (Rh123) accumulation assay and analysis kit, respectively. Molecular docking was employed to predict the binding force between compounds and P-gp. Transmembrane transport of NPB304 was analyzed using MDCK II and MDR1-MDCK II cell model. NPB304 displayed multidrug resistance reversal effect on KBV cells and MCF-7/paclitaxel cells, NPB304 collaborative with P-glycoprotein (P-gp) inhibitors verapamil enhanced the reversal activity, specifically, 10 μmol x L(-1) verapamil in combination with paclitaxel reversed resistance by 56.5-fold, while combined with NPB304 increased the reversal fold; NPB304 synergistically increased Rh123 accumulation in the resistant cells when combined with verapamil, and NPB304 at 0-1 μmol x L(-1) enhanced the ATPase activity activated by verapamil was observed. NPB304 existed the hydrophobic interactions with the TM regions of P-gp, and the binding force between NPB304 and the A chain of the TM region was stronger. P-gp ATPase activity assay demonstrated NPB304 at lower concentrations (0-1.5 μmol x L(-1)) could activate the P-gp ATPase, playing a role on inhibition of P-gp function. However, NPB304 did not have an obvious feature of P-gp substrate. NPB304 exerted itself and synergy with verapamil activity on reversing tumor resistance via inhibiting the P-gp function.