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 investigate the postoperative renal function and oncologic outcomes of cystic renal cell carcinoma with partial nephrectomy,and to compared the single-center data on surgical out-comes with the Surveillance,Epidemiology,and End Results(SEER)database.Methods:This was a retrospective study that included the patients with cystic renal cell carcinoma who underwent partial ne-phrectomy in the Department of Urology,Peking University Third Hospital(PUTH)from 2010 to 2023.The clinical data and depicting baseline characteristics were collected.Renal dynamic imaging and the Chinese Coefficients for Chronic Kidney Disease Epidemiology Collaboration(C-CKD-EPI)formulae were used to calculate the estimated glomerular filtration rate(eGFR).The renal function curves over time were then plotted,and the patients were followed-up to record their survival status.Cases of cystic renal cell carcinoma in the SEER database between 2000 and 2020 were included,propensity score matching(PSM)was performed to balance the differences between SEER cohort and PUTH cohort,and the cancer-specific survival(CSS)curves for both groups were plotted and statistical differences were calcu-lated by the Kaplan-Meier method.Results:A total of 38 and 385 patients were included in the PUTH cohort and SEER cohort,respectively,and 31 and 72 patients were screened in each cohort after PSM.Of the baseline characteristics,only tumor size(P=0.042)was found to differ statistically between the two groups.There was no statistically significant difference between the two cohorts in terms of CSS after PSM(P=0.556).The median follow-up time in the SEER cohort was 112.5(65,152)months and a 10-year survival rate of 97.2％,while the PUTH cohort had a median follow-up of 57.0(20,1 172)months and a 10-year survival rate of 100.0％.There was no statistically significant difference between eGFR determined by preoperative renal dynamic imaging and the results of the C-CKD-EPI formulae based on creatinine estimation(P=0.073).There was a statistically significant difference in eGFR among the preoperative,short-term postoperative,and long-term postoperative(P＜0.001),which was characterized by the presence of a decline in renal function in the short-term postoperative period and the recovery of renal function in the long-term period.Conclusion:Partial nephrectomy for cystic renal cell carcinoma is safe and feasible with favorable renal function and oncologic outcomes.

Objective:To investigate the treatment efficacy of adjuvant anti-VEGF/VEGFR targeted therapy in patients with non-metastatic (cM 0) non-clear cell renal cell carcinoma and tumor thrombus (nccRCC-VTT). Methods:This retrospective study enrolled 26 patients who underwent radical nephrectomy combined with inferior vena cava tumor thrombectomy at Peking University Third Hospital from January 2014 to July 2021. Patients were divided into adjuvant therapy group (10 cases) and control group (16 cases)based on the use of postoperative targeted therapy. The distribution of baseline clinical characteristics in the adjuvant therapy group and the control group were as follows: gender (6 males and 4 females in the adjuvant therapy group, 12 males and 4 females in the control group, P=0.66), age (56.2±18.5 years old in the adjuvant therapy group; 54.6±14.5 years old in the control group; P=0.80), BMI(24.0±3.5 in the adjuvant therapy group; 24.3±3.3 in the control group; P=0.80), presence of clinical symptoms (8 cases in the adjuvant therapy group; 15 cases in the control group; P=0.54), tumor laterality(6 cases on the left and 4 cases on the right in the adjuvant therapy group; 6 cases on the left and 10 cases on the right in the control group; P=0.42), location of tumor thrombus (2 cases with renal vein tumor thrombus and 8 cases with inferior vena cava tumor thrombus in the adjuvant therapy group; 2 cases with renal vein tumor thrombus and 14 cases with inferior vena cava tumor thrombus in the control group; P=0.67), ASA classification (2 cases in ASA class 1 and 8 cases in ASA class 2 in the adjuvant therapy group; 2 cases in ASA class 1 and 14 cases in ASA class 2 in the control group; P=0.63), surgical approach (7 minimally invasive surgeries and 3 open surgeries in the adjuvant therapy group; 9 minimally invasive surgeries and 7 open surgeries in the control group; P=0.68), conversion to open surgery (2 cases in the adjuvant therapy group; 2 cases in the control group; P=0.63), operation time [287.5(222.2, 456.0) minutes in the adjuvant therapy group; 344.0(287.8, 482.5) minutes in the control group; P=0.34), blood loss [400.0(250.0, 600.0)ml in the adjuvant therapy group; 575.0(175.0, 800.0)ml in the control group; P=0.63), Clavien-Dindo classification of postoperative complications (8 cases with no postoperative complications, 2 cases with level 1-2 complications, and 0 cases with level ≥3 complications in the adjuvant therapy group; 10 cases with no postoperative complications, 4 cases with level 1-2 complications, and 2 cases with level ≥3 complications in the control group; P=0.68), postoperative hospital stay (8.5 [5.5, 11.5] days in the adjuvant therapy group; 7.5 [6.0, 13.0] days in the control group; P=1.00), maximum tumor diameter[ (9.2±2.7)cm in the adjuvant therapy group; (8.9±3.3)cm in the control group; P=0.81], sarcomatoid differentiation (0 cases in the adjuvant therapy group; 1 case in the control group; P=1.00), perinephric fat invasion (2 cases in the adjuvant therapy group; 7 cases in the control group; P=0.40), tumor necrosis (6 cases in the adjuvant therapy group; 5 cases in the control group; P=0.23), pathological subtype (1 case of PRCC type 1, 6 cases of PRCC type 2, and 3 cases of TFE3 rearrangement RCC in the adjuvant therapy group; 2 cases of PRCC type 1, 10 cases of PRCC type 2, and 1 case each of oncocytic PRCC, TFE3 rearrangement RCC, FH-deficient RCC, and unclassified RCC in the control group; P=0.72), WHO/ISUP nuclear grade (10 cases of grades 3-4 in the adjuvant therapy group; 4 cases of grades 1-2 and 12 cases of grades 3-4 in the control group; P=0.14), invasion of tumor thrombus into the vessel wall (5 cases in the adjuvant therapy group; 5 cases in the control group; P=0.43), T stage (1 case of T 3a, 3 cases of T 3b, 5 cases of T 3c, and 1 case of T 4 in the adjuvant therapy group; 1 case of T 3a, 4 cases of T 3b, 10 cases of T 3c, and 1 case of T 4 in the control group; P=1.00), and positive lymph nodes metastasis(3 cases in the adjuvant therapy group; 0 cases in the control group; P<0.05). The recommended doses for sunitinib, axitinib, and pazopanib are 50mg qd, 5mg q12h, and 800mg qd, respectively. The primary endpoint of this study was disease-free survival (DFS), and the secondary endpoint was overall survival (OS). Statistical analyses were performed using R v4.2.2. Confounding factors were adjusted using propensity score weighting. Results:The median follow-up time for DFS was 29 months in the adjuvant therapy group and not reached in the control group, while median follow-up time for OS was 28 and 26 months, respectively. In the univariate Cox regression analysis, there were no statistically significant difference in the impact of all baseline characteristics and exposure factors on DFS and OS between the two groups. In survival analysis, there were no significant difference between DFS and OS curves of patients in the adjuvant therapy group and the control group (DFS, P=0.62; OS, P=0.74). The median DFS of patients in the adjuvant therapy group and the control group were 17 and 19 months, respectively, while the median OS was 43 and 27 months. After adjusting for confounding factors, the median DFS of patients in the adjuvant therapy group and the control group were 26 and 12 months, respectively, and the median OS remained 43 and 27 months, with no significant difference (DFS, P=0.81; OS, P=0.40). Conclusion:There is currently a lack of definitive evidence for survival benefit from adjuvant anti-VEGF/VEGFR targeted therapy in patients with cM0 nccRCC-VTT after surgery.

Objective:To evaluate and compare the outcomes of maxillary protraction treatment assisted by temporary anchorage devices (TADs) and removable biteplate in cleft lip and palate patients using cephalometric analysis.Methods:Fifty-four cleft lip and palate patients were divided into 3 groups based on different maxillary protraction treatments: bitepalate removable appliance group (group A), maxillary protraction treatment assisted by TADs group (group B) and control group (group C). Lateral cephalograms were taken at the start and the end of maxillary protraction. Skeletal, dental and soft tissue changes were measured using Dolphin software and compared between groups.Results:The average protraction time of groups A and B were (8.51±1.33) and (9.20±1.45) months ( P=0.146), respectively. A point moved forward by 4.08 mm in group A and 4.83 mm in group B were noted, without significant differences between the two groups. Compared to group C, ANB and wits was highly improved after protraction in groups A and B. U6-VRmx increased by 0.46 mm and U1-pp increased by 0.63 mm in group B, both of which were significantly smaller than those of group A (both P<0.05), suggesting that maxillary protraction treatment assisted by TADs could reduce molar advancement and upper incisor protrusion. Conclusions:Both maxillary protraction treatment assisted by TADs and removable biteplate could significantly improve skeletal class Ⅲ malocclusion in unilateral cleft and palate patients. Maxillary protraction treatment assisted by TADs could reduce molar advancement and upper incisor protrusion.

Preservation of erectile function is an important goal of radical prostatectomy. The neurovascular bundles (NVBs), which is closely related to erectile function, are quite susceptible to intraoperative injury because it is difficult to be identified and localized during surgical process. As a result, long-term postoperative potency rate is not satisfying. Techniques of monitoring pro-erectile neurovascular bundles, such as electrical stimulation, ultrasound and MRI have significant limitations in the context of real-time identification during operation. Advances of fluorescence imaging in the surgical navigation field has made it possible to achieve real-time visualization of NVBs in vivo. At present, there have already been many fluorescent agents worldwide targeting different structures within nerves, such as the axon, myelin, perineurium and vaso nervorum, and they varied in their affinity to nerves and imaging efficacies. Some lipophilic molecules, oxazine dyes and peptide-dye conjugates have successfully visualized in periprostatic autonomic nerves in rodents or in human prostate specimen. Indocyanine Green (ICG), a non-specific neurovascular dye, has already been used in clinical setting to guide during nerve-sparing radical prostatectomy. This review focused on fluorescent nerve imaging technique and its application in research on real-time imaging of NVBs in radical prostatectomy.

In recent years, peptide self-assembly has received much attention because of its ability to form regular and ordered structures with diverse functions. Self-assembled peptides can form aggregates with defined structures under specific conditions. They show different characteristics and advantages (e.g., good biocompatibility and high stability) compared with monomeric peptides, which form the basis for potential application in the fields of drug delivery, tissue engineering, and antiseptics. In this paper, the molecular mechanisms, types and influencing factors of forming self-assembled peptides were reviewed, followed by introducing the latest advances on fibrous peptide hydrogels and self-assembled antimicrobial peptides. Furthermore, the challenges and perspectives for peptide self-assembly technology were discussed.
Drug Delivery Systems ; Hydrogels ; Peptides ; Tissue Engineering

Objective:To explore the clinical value of point-of-care ultrasonography(PoCUS) in the diagnosis of acute pulmonary embolism(PE).Methods:Consecutive 196 patients suspected of acute PE were enrolled in East Branch, the Second Hospital of Hebei Medical University from January 2017 to November 2017. All the patients were categorized into no PE group( n=143) and PE group( n=53) based on CTPA results. PoCUS was performed and considered diagnostic for PE if one or more right ventricular dysfunction (right ventricular dilation, right ventricular free wall hypokinesia, increased tricuspid regurgitation velocity or decreased tricuspid annular plane systolic excursion), deep venous thrombosis(DVT) or subpleural infarcts were detected. Results:With CTPA as the gold standard for diagnosis, the sensitivity (94.34%), Youden index (0.531) and the area under the ROC curve(AUC) (0.765) of the combined diagnosis of PE by transthoracic echocardiography(TTE), lower limb vein compression ultrasonography(CUS) and lung ultrasonography (LUS) were the highest. The specificity (94.41%) and accuracy (81.63%) of LUS in the diagnosis of PE were the highest, and the misdiagnosis rate (5.59%) of LUS the lowest. The sensitivity of the combined triple PoCUS (TTE, CUS, and LUS) diagnosis of PE was higher than TTE and CUS combined diagnosis ( P=0.016), and the sensitivity and specificity were higher than TTE and CUS combined diagnosis as a whole ( P<0.005). Conclusions:The combined triple PoCUS (TTE, CUS, and LUS) has the highest accuracy in the diagnosis of PE, while LUS has a high specificity and a low misdiagnosis rate in the diagnosis of PE. Therefore, it is recommended to apply the combined triple PoCUS in clinical practice.

To provide guidance for quality control and variety breeding of Gastrodia elata f. glauca cultivated form in Zhaotong, nine agronomic traits of G. elata f. glauca cultivation form were measured and the traits were analyzed using multiple comparison,correlation analysis, multiple stepwise regression analysis and path analysis. The results of multiple comparison and analysis showed that the number of dot ring and the length-width ratio of tuber were no different in G. elata f. glauca cultivation form. The coefficient of variation about the single tuber fresh weigh, ring spacing and belly button diameter was about 20%. The coefficient of variation about the length of the tuber, the width of the tuber, the thickness of the tuber, the length-width ratio of tuber and the number of dot ring was near 10%. The correlation analysis results showed that the single tuber fresh weigh and the length,the width and the thickness of the tuber were extremely significant positive correlated. The results of multiple stepwise regression analysis and path analysis showed that the length, the width and the thickness of the tuber were the main factors affecting the fresh weight of single tuber,which were the best agronomic traits on high yield of G. elata f. glauca. The length of the tuber,the width of the tuber and the thickness of the tuber, which would be used as indicators of the characteristics of high yield varieties in Zhaotong. The number of dot ring and the length-width ratio of tuber, which would be selected as quality control indicators of the genuine Chinese medicinal materials in Zhaotong.

Objective:To investigate the current situation of basic knowledge and diagnosis and treatment behavior for chronic obstructive pulmonary disease (COPD) among physicians of South Henan area .Methods:Questionnaire was designed for a research ,which was conducted among physicians from 15 hospitals located in 9 counties ,and the data were analyzed by using SAS 6 .12 software .Results:A total of 135 valid questionnaires were collected .And 80 .7% (109/135)of the physicians understood the epidemiology of COPD ,while 31 .8% (43/135) of them understood the disease characteristics .The proportion of physicians who understood the disease characteristics in respiratory professional group was 44 .4% (20/45) ,which was significantly higher than that (25 .5% ,23/90) in non‐respiratory professional group (P<0 .05) .Furthermore ,66 .6% (90/135) of the physicians diagnosed disease by clinical symptoms ,while 33 .3% (45/135) of them diagnosed disease by clinical symptoms and pulmonary function .The proportion of physicians who diagnoses disease by clinical symptoms and pulmonary function in respiratory professional group was 60 .0% (27/45) ,which is significantly higher than that 20 .0% (18/90) in non‐respiratory professional group (P< 0 .05) .Therapy for acute exacerbation of COPD was nearly conformed to the treatment guidelines ,however ,50 .3% (68/135)of physicians did not completely understand mechanical ventilation .For therapy of stable COPD ,57 .7% (78/135) of physicians recommended inhaled glucocorticosteroids combined with beta‐2‐receptor agonist .The proportion of physicians who recommended inhaled glucocorticosteroids combined with beta‐2‐receptor agonist in respiratory professional group was 88 .8% (40/45) ,which was significantly higher than that 42 .2% (38/90) in non‐respiratory professional group (P<0 .05) .Non‐respiratory professional group were lack of knowledge of home oxygen therapy ,respiratory exercises , and nutritional support .Only 11 .1% (10/90) physicians in the non‐respiratory professional group understood the knowledge comprehensively .Conclusions:It is key to enhance the education of COPD and popularize the treatment guideline among the physicians ,especially non‐respiratory physicians ,in South Henan area .