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 review the clinicopathological features of TFE3-rearranged renal cell carcino-ma(TFE3-RCC)with venous tumor thrombus(VT)(TFE3-VT),to explore treatment strategies and to prognostic characteristics,and to provide diagnostic and therapeutic references for TFE3-VT patients.Methods:Patients who underwent surgery at Department of Urology,Peking University Third Hospital from January 2013 to January 2024 were enrolled,including three cohorts:Pathologically confirmed TFE3-VT patients,TFE3-RCC patients without VT(TFE3-non-VT),and non-TFE3-rearranged renal cell carcinoma patients with VT(non-TFE3-VT).Clinical history,imaging data,pathological data,and follow-up records were collected.Primary and secondary endpoints were progression-free survival(PFS)and overall survival(OS),respectively.(1)Baseline characteristics were compared between the TFE3-VT and TFE3-non-VT patients.Normally distributed continuous variables were expressed as mean±SD and compared using Student's t-test;non-normally distributed variables were expressed as M(P25,P75)and analyzed with Mann-Whitney U test;categorical variables were described as frequency and percentage[n(％)]and compared by x2 test or Fisher's exact test.(2)Clinical history,radiological presenta-tions,surgical data,and histopathological features of the TFE3-VT patients were comprehensively charac-terized.(3)Survival analysis was performed for the TFE3-VT patients.Follow-up data of the TFE3-VT patients were described in detail,and their survival outcomes were compared with the TFE3-non-VT and non-TFE3-VT patients.When compared with the TFE3-non-VT counterparts,Kaplan-Meier method was used to generate PFS and OS curves among:(1)the TFE3-RCC patients across clinical stages Ⅰ-Ⅳ;(2)TFE3-VT versus TFE3-non-VT cohorts;(3)stage Ⅲ subgroups of the TFE3-VT and TFE3-non-VT patients.Intergroup survival differences were statistically evaluated using Log-rank tests.For comparisons with the non-TFE3-VT patients,a 1∶1 propensity score matching(PSM)was implemented to balance baseline characteristics between the two cohorts.Post-matching Kaplan-Meier curves were generated to compare PFS and OS between the matched groups,with Log-rank tests employed to determine statistical significance of survival disparities.All statistical analyses were conducted with R software(v 4.2.3),and two-tailed P＜0.05 was considered statistically significant.Results:The study included 45 TFE3-RCC patients:13 TFE3-VT and 32 TFE3-non-VT cases.Additionally,523 non-TFE3-VT patients were enrolled.Among the 13 TFE3-VT patients,9 were female(69.2％)and 4 male(30.8％),with a mean age of(37.9±14.4)years,mean BMI of(22.2±3.5)kg/m2,median age-adjusted Charlson comorbidity index(aCCI)of 1.0(0.0,1.0),and preoperative creatinine level of(75.3±15.9)μmol/L;tumors were located in the left kidney in 7 patients(53.8％)and right kidney in 6(46.2％);preoperative distant metastasis(M1 stage)was present in 6 patients(46.2％),while 7(53.8％)showed no metastasis;VT distribution by Mayo level comprised 7 cases(53.8％)at level 0,1 case each at levels Ⅰ and Ⅳ(7.7％respectively),and 2 cases each at levels Ⅱ and Ⅲ(15.4％respectively);surgical approaches comprised open surgery(n=2,15.4％),laparoscopic surgery(n=6,46.1％),and robot-assisted laparoscopic surgery(n=5,38.5％);mean operative time was(273±79)min,and intraoperative blood loss was(722±570)mL;mean maximum tumor diameter was(10.8±2.4)cm.All the 13 patients underwent TFE3 protein immunohistochemistry(IHC)staining,with 7 confirmed by fluorescence in situ hybridization(FISH).Tumor recurrence or metastasis occurred in 11 patients(84.6％),and 9(69.2％)patients died during follow-up.Median PFS was 4 months(1 year PFS rate:31％),and median OS was 13 months(1 year OS rate:54％).Survival analysis of 45 TFE3-RCC pa-tients revealed statistically significant differences in PFS and OS across all the clinical stages(P＜0.001).The TFE3-VT patients exhibited significantly worse PFS and OS than the TFE3-non-VT patients(P＜0.001),with persistent significance in stage Ⅲ subgroup analysis(P＜0.05).After PSM,TFE3-VT pa-tients showed significantly inferior PFS compared with non-TFE3-VT(P=0.01),though no significant difference was shown between the OS curves(P=0.11).Conclusion:TFE3-VT predominantly occurs in young females with frequent preoperative metastases.Strongly-positive staining of TFE3 protein in IHC stai-ning and red-green split signals in FISH tests are reliable diagnostic markers.TFE3-VT patients exhibit in-ferior survival compared with TFE3-non-VT patients and earlier progression than non-TFE3-VT patients.

Objective:To review the clinicopathological features of TFE3-rearranged renal cell carcino-ma(TFE3-RCC)with venous tumor thrombus(VT)(TFE3-VT),to explore treatment strategies and to prognostic characteristics,and to provide diagnostic and therapeutic references for TFE3-VT patients.Methods:Patients who underwent surgery at Department of Urology,Peking University Third Hospital from January 2013 to January 2024 were enrolled,including three cohorts:Pathologically confirmed TFE3-VT patients,TFE3-RCC patients without VT(TFE3-non-VT),and non-TFE3-rearranged renal cell carcinoma patients with VT(non-TFE3-VT).Clinical history,imaging data,pathological data,and follow-up records were collected.Primary and secondary endpoints were progression-free survival(PFS)and overall survival(OS),respectively.(1)Baseline characteristics were compared between the TFE3-VT and TFE3-non-VT patients.Normally distributed continuous variables were expressed as mean±SD and compared using Student's t-test;non-normally distributed variables were expressed as M(P25,P75)and analyzed with Mann-Whitney U test;categorical variables were described as frequency and percentage[n(％)]and compared by x2 test or Fisher's exact test.(2)Clinical history,radiological presenta-tions,surgical data,and histopathological features of the TFE3-VT patients were comprehensively charac-terized.(3)Survival analysis was performed for the TFE3-VT patients.Follow-up data of the TFE3-VT patients were described in detail,and their survival outcomes were compared with the TFE3-non-VT and non-TFE3-VT patients.When compared with the TFE3-non-VT counterparts,Kaplan-Meier method was used to generate PFS and OS curves among:(1)the TFE3-RCC patients across clinical stages Ⅰ-Ⅳ;(2)TFE3-VT versus TFE3-non-VT cohorts;(3)stage Ⅲ subgroups of the TFE3-VT and TFE3-non-VT patients.Intergroup survival differences were statistically evaluated using Log-rank tests.For comparisons with the non-TFE3-VT patients,a 1∶1 propensity score matching(PSM)was implemented to balance baseline characteristics between the two cohorts.Post-matching Kaplan-Meier curves were generated to compare PFS and OS between the matched groups,with Log-rank tests employed to determine statistical significance of survival disparities.All statistical analyses were conducted with R software(v 4.2.3),and two-tailed P＜0.05 was considered statistically significant.Results:The study included 45 TFE3-RCC patients:13 TFE3-VT and 32 TFE3-non-VT cases.Additionally,523 non-TFE3-VT patients were enrolled.Among the 13 TFE3-VT patients,9 were female(69.2％)and 4 male(30.8％),with a mean age of(37.9±14.4)years,mean BMI of(22.2±3.5)kg/m2,median age-adjusted Charlson comorbidity index(aCCI)of 1.0(0.0,1.0),and preoperative creatinine level of(75.3±15.9)μmol/L;tumors were located in the left kidney in 7 patients(53.8％)and right kidney in 6(46.2％);preoperative distant metastasis(M1 stage)was present in 6 patients(46.2％),while 7(53.8％)showed no metastasis;VT distribution by Mayo level comprised 7 cases(53.8％)at level 0,1 case each at levels Ⅰ and Ⅳ(7.7％respectively),and 2 cases each at levels Ⅱ and Ⅲ(15.4％respectively);surgical approaches comprised open surgery(n=2,15.4％),laparoscopic surgery(n=6,46.1％),and robot-assisted laparoscopic surgery(n=5,38.5％);mean operative time was(273±79)min,and intraoperative blood loss was(722±570)mL;mean maximum tumor diameter was(10.8±2.4)cm.All the 13 patients underwent TFE3 protein immunohistochemistry(IHC)staining,with 7 confirmed by fluorescence in situ hybridization(FISH).Tumor recurrence or metastasis occurred in 11 patients(84.6％),and 9(69.2％)patients died during follow-up.Median PFS was 4 months(1 year PFS rate:31％),and median OS was 13 months(1 year OS rate:54％).Survival analysis of 45 TFE3-RCC pa-tients revealed statistically significant differences in PFS and OS across all the clinical stages(P＜0.001).The TFE3-VT patients exhibited significantly worse PFS and OS than the TFE3-non-VT patients(P＜0.001),with persistent significance in stage Ⅲ subgroup analysis(P＜0.05).After PSM,TFE3-VT pa-tients showed significantly inferior PFS compared with non-TFE3-VT(P=0.01),though no significant difference was shown between the OS curves(P=0.11).Conclusion:TFE3-VT predominantly occurs in young females with frequent preoperative metastases.Strongly-positive staining of TFE3 protein in IHC stai-ning and red-green split signals in FISH tests are reliable diagnostic markers.TFE3-VT patients exhibit in-ferior survival compared with TFE3-non-VT patients and earlier progression than non-TFE3-VT patients.

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 effect of pulmonary rehabilitation therapy on the exercise capacity and dyspnea of persons with chronic obstructive pulmonary disease (COPD).Methods:One hundred COPD patients were randomly divided into a control group and an observation group, each of 50. Both groups were given routine medication, while the observation group was additionally provided with health guidance, oxygen therapy, respiratory physiological therapy and exercise for 3 months. Before and after the intervention, both groups′ forced expiratory volume in 1 second (FEV1) and the first and second forced expiratory volume as a percentage of FEV (FEV1%) were measured. The subjects′ motor functioning was evaluated using the 6-minute walk test. Enzyme-linked immunosorbent assays and immunoturbidimetry quantified their expression of inflammatory factors. And their ability in the activities of daily living (ADL) was evaluated using the Barthel index. The COPD quality of life questionnaire (CRQ) was also used to assess their life quality.Results:After the intervention, the average clinical efficacy in the observation group was 96%, significantly higher than that of the control group (80%). Moreover, the average FEV1, FEV1%, 6-minute walk test time of the former group were all significantly better than before the intervention and better than the control group′s results after the intervention. Their average CRP, IL-6 and TNF-α levels were all significantly lower as well. After the intervention, the observation group′s average total CRQ score and its average scores on the instrument′s emotion, fatigue, wheezing and disease control components were all better than the control group′s averages. The observation group′s average ADL score was also significantly higher than that of the control group.Conclusions:Supplementing conventional medication with pulmonary rehabilitation therapy can effectively improve the lung function, motor functioning and life quality of COPD patients. It can also lower their level of serum inflammatory factors.

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 evaluate comparability of two different assay system for detecting CRP.Methods Following the profile of Clinical and Laboratory Standard Institute (CLSI)document EP9-A2,50 blood samples with anti-coagulant ED-TA-2K were collected from emergency patients at Changhai Hospital.The test result of samples by the i-CHROMA Reader was compared and evaluated with those by Beckman Immage 800.Results The linear regression equation for plasma CRP was:Y=1.076 5X-3.031 5,R2=0.986.The linear regression equation for whole blood CRP was:Y=0.882 6X-1.180 8, R2=0.931 1.For whole blood samples with low HCT (<30.45%).Used correction equation:CRP (after corrected)=CRP (before corrected)/(1-HCT).The regression equation (after corrected)was:Y=1.006 8X-3.612 2,R2=0.950 9.Con-clusion CRP concentration detected by i-CHROMA showed good correlation and comparability compared to laboratory ref-erence system by using plasma samples.Results form whole blood samples with low HCT should be corrected to improve comparability.

Objective:To study the expression of CXCL 8 in the serum and CXCL8 mRNA in the peripheral blood mononuclear cells(PBMCs) of the children with Mycoplasma pneumoniae pneumonia (MPP) and its clinical significance.Methods: Forty-eight children(severe cases 12,light cases 36) with MPP were recruited from October 2013 to March 2015 in the Maternal and Child Health-Care Hospital of Huainan.The concentration of the CXCL8 in serum and the level of CXCL8 mRNA in the PBMCs were measured by enzyme linked immunosorbent assay ( ELISA) and polymerase chain reaction ( PCR).Taking GAPDH as the internal reference ,the ratio of lgcDNA/lgGAPDH was regarded as the extreme level of CXCL 8 mRNA.Results: The serum level of CXCL8 and expression of CXCL8 mRNA in PBMCs in the children with MPP were ( 298.917 ±51.860 ) pg/ml and ( 1.848 ±0.525 ) lgcDNA/lgGAPDH.Compared with the normal control ,there were significant differences between the two groups ( P<0.05 ) .Further observation showed that the levels of CXCL8 in serum were no significant difference between in light cases and severe illness (P>0.05).However, the expression of CXCL8 mRNA in peripheral blood of the children with severe illness was significantly higher than those in light cases (P<0.05).Intravenous infusion of Erythromycin was provided in the acute phase for seven to ten days ,so that the children′s condition could be significantly controlled , and the symptoms of pulmonary inflammation were also relieved .Followed by the use of sequential therapy of Azithromycin for about two to three weeks ,the children′s condition were gradually from acute stage to recovery stage .At this time,the CXCL8 and its mRNA levels in peripheral blood of the sick children were all significantly decreased comparing with those in the acute stage(P<0.05).Conclusion: The expression of CXCL8 and its mRNA were increased in the peripheral blood of the sick children with Mycoplasma pneumonia ,and also correlated with the severity of the disease .CXCL8 can participate in the pathogenesis of Mycoplasma pneumonia ,and has a certain cue effect on the severity and prognosis of the disease .Azithromycin can reduce the content of CXCL8 in serum of the sick children via the pathway of inhibiting the proliferation of Mycoplasma pneumoniae ,and down regulate the expression of mRNA ,so that the immune injury mediated by Mycoplasma pneumoniae may be gradually inhibited .