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 electroencephalogram features of visual working memory in the delay stage based on microstate analysis.Methods:In this cross-sectional study, ten healthy male subjects aged 19-29 years old from Tianjin Medical University were selected from January to July 2015. The 32-channel electroencephalogram experimental data were recorded from these subjects during the visual working memory eye-open state for 10 min (resting-state) and the delayed matching-to-sample (DMS) task (task-state) conditions, respectively. After data pre-processing, a short-time Fourier transform was applied for time-frequency analysis to extract the characteristic time periods and frequency bands, and electroencephalogram microstates of the resting and task states of visual working memory were computed separately, using an improved k-means clustering algorithm. The Mann-Whitney U test was used to analyze the statistical differences between resting-state and task-state microstate parameters, including global field power (GFP), global explained variance (GEV), time proportion, mean spatial correlation, frequency of occurrence and duration. Results:The time-frequency distribution of the Fz channel in the responsible brain region in DMS task visual working memory showed that the energy was mainly concentrated in the theta band (4-8 Hz) during the delay stage (4.039-7.039 s). The bipolar locations of microstates A, B, C, and D were prefrontal and occipital, central frontal and occipital, right occipital and left frontal, and left occipital and right frontal, respectively. In microstates A and C, the mean spatial correlation of the task-state was both higher than that of the resting state. The comparison results for microstate A were (0.632 5±0.105 8 vs 0.624 5±0.461 4, P<0.05), and the results for microstate C were (0.589 4±0.233 4 vs 0.561 3±0.066 8, P<0.01). The parameters of the task-state microstate D were lower than those of the resting-state, including GFP (1.125±0.061 vs 1.277±0.741, P<0.05), GEV (0.077±0.061 vs 0.101±0.057, P<0.05), and time proportion (0.191±0.165 vs 0.224±0.094, P<0.05) and mean spatial correlation (0.561 2±0.211 6 vs 0.612 1±0.315 2, P<0.01). Conclusions:The critical period of visual working memory is the delay stage and the critical frequency band is the theta band. Microstate D is the characteristic feature of visual working memory in the delay stage of the theta band, and microstates A and C can also serve as its potential features.

Objective: To investigate the effects of “Three Methods and Three Acupoints” (TMTP) Tuina therapy on spinal microcirculation in sciatic nerve injury (SNI). Methods: Thirty-six Sprague–Dawley rats were randomly assigned to four groups: normal, sham operation, model, and TMTP Tuina. Successful model induction was confirmed by observable hind limb lameness. After 20 sessions, hind limb grip strength and motor nerve conduction velocity (MNCV) were measured at baseline and following the 10th and 20th intervention. CD31 and α-SMA in the ventral horn of SNI model rats were detected using immunofluorescence. Motor neurons in the ventral horn were detected by Nissl staining. PTEN levels in the ventral horn were measured by ELISA, and PI3K, Akt, BDNF, VEGF, and HIF-1α expression was determined by RT-PCR. Spinal cord microcirculation was evaluated by western blotting analysis of the levels of Akt, p-Akt, BDNF, and VEGF. Results: Hind limb grip strength and MNCV significantly improved in the TMTP Tuina group compared to the model group (both P < .001). Morphology of ventral horn motor neurons in the TMTP Tuina group improved compared to the model group, with increased expressions of α-SMA (P = .002) and CD31 (P = .006). Western blot analysis indicated increased expression of VEGF (P = .005), p-Akt (P < .001), and BDNF (P = .008) in the ventral horn following Tuina treatment. RT-PCR analysis revealed increased expression of PI3K, Akt, BDNF, VEGF and HIF-1α (all P < .05). In contrast, expression of PTEN decreased compared to the model group (P < .001). Conclusion TMTP Tuina therapy may restore motor function in rats, enhance ventral horn motor neuron morphology, and promote angiogenesis and vascular smooth muscle proliferation. The mechanism may involve the activation of the PI3K/Akt signaling pathway.

Objective:To investigate factors influencing frequent episodes (≥ 4 episodes within 1 year) in children with moderate-to-severe atopic dermatitis (AD) in China.Methods:A national multicenter cross-sectional study was conducted. Patients under the age of 18 years diagnosed with moderate-to-severe AD were enrolled at dermatology clinics in 18 medical institutions across 12 provinces and municipalities in China between June 12 and August 8, 2023. At the time of the visit, their guardians completed a structured questionnaire covering demographic characteristics, clinical features of AD, personal and family history, factors associated with frequent episodes of moderate-to-severe AD, compliance with treatment, and disease awareness. Statistical analyses included t tests, one-way analysis of variance, rank-sum tests, and chi-square tests, with multiple-response analysis applied for multiple-choice questions. Results:A total of 965 valid questionnaires were collected, and 965 children with moderate-to-severe AD were included. Among them, there were 531 males and 434 females, 678 (70.3%) were aged 2 - < 12 years, 837 (86.7%) were from urban areas, the age at onset was 2.47 ± 3.03 years, and the median frequency of AD episodes in the past year was 4 times. These children were divided into 2 groups based on the median episode frequency: < 4-episode group (439 cases, 45.5%) and ≥ 4-episode group (526 cases, 54.5%). Compared with the < 4-episode group, children in the ≥ 4-episode group showed younger ages at onset (2.22 ± 2.98 years vs. 2.76 ± 3.06 years, P = 0.006) and higher proportions of patients with comorbid allergic diseases in both the children themselves (82.9% [436/526] vs. 69.7% [306/439], χ2 = 23.42, P < 0.001) and their relatives (66.0% [347/526] vs. 57.4% [252/439], χ2 = 7.46, P = 0.006). Children in the ≥ 4- episode group also had higher monthly usage of moisturizers (150 [30, 300] g vs. 60 [6, 200] g) and daily frequency of moisturizer use, greater disease awareness, but more severe fear of medication use (all P < 0.05). The region and the human development index level were both significantly associated with the episode frequency (both P < 0.001), with the highest proportion of children from South China in the ≥ 4- episode group (36.3%, 191/526). Children in the ≥ 4-episode group also had a longer duration of topical glucocorticoid use than those in the < 4-episode group ( Z = -2.21, P = 0.027). External triggers associated with AD episodes mainly included heat exposure (50.36%, 486/965), hot water bathing (40.73%, 393/965), seafood (23.52%, 227/965), and dust mites (33.37%, 322/965) . Conclusion:In children with moderate-to-severe AD in China, factors influencing frequent episodes may include residence in southern or economically developed regions, earlier age at onset, having a personal or family history of allergic diseases, and fear of medication use.

Objective:To assess the application value of one-hour post-load glucose (1hPG) for detecting prediabetes among individuals with high risk of type 2 diabetes mellitus (T2DM).Methods:The study was conducted between August 2023 and January 2024, and individuals with a high risk of T2DM were invited to receive an oral glucose tolerance test (OGTT), structural questionnaires, physical measurements, and other biochemical examinations. The fasting, one-, and two-hour glucose and insulin were tested. According to the 1hPG cut point on hyperglycemia suggested by International Diabetes Federation (IDF), normal glucose tolerance (NGT) and prediabetes were further divided into two subgroups, respectively, i.e., NGT with 1hPG<8.6 mmol/L (NGT-1hPG-normal), NGT with 1hPG≥8.6 mmol/L (NGT-1hPG-high), prediabetes with 1hPG<8.6 mmol/L (PDM-1hPG-normal), and prediabetes with 1hPG≥8.6 mmol/L (PDM-1hPG-high). The insulin release curve was drawn by the groups as above. Insulin resistance was evaluated by homeostasis model assessment for insulin resistance (HOMA-IR), and β-cell secretory function was evaluated by homeostasis model assessment for β cell function (HOMA-β)/HOMA-IR. Spearman rank correlation analysis was used to calculate the correlation coefficients among 1hPG, 2hPG and HOMA indices, and Steiger′s Z test was used to compare the difference between two correlation coefficients. Receiver operating characteristics (ROC) curves and area under the curve (AUC) were used to assess the accuracy of 1hPG for detecting prediabetes. Results:A total of 2 469 subjects consisting of 1 485 men (60.1%) and 984 (39.9%) women, with a mean age of (45.76±6.20) years, of which 1 844 (74.7%) had 1hPG≥8.6 mmol/L. The prevalence of 1hPG≥8.6 mmol/L was 46.8%, 93.0% and 99.8% in individuals with NGT, prediabetes and newly diagnosed T2DM, respectively ( χ 2=763.78, P<0.001). The insulin release curve showed that insulin secretion increased rapidly in subjects with NGT-1hPG-high, and peaked at one hour, then decreased rapidly, with a significantly higher level of one- and two-hour insulin than those with NGT-1hPG-normal ( P<0.001). Compared to individuals with NGT-1hPG-normal, the counterparts with NGT-1hPG-high exhibited higher HOMA-IR and lower adjusted HOMA-β ( P<0.001). Spearman rank correlation analysis showed that the correlation coefficient of 1hPG with HOMA-IR was similar to the correlation coefficient of 2hPG with HOMA-IR (0.493 vs. 0.480, P=0.550), while the correlation of 1hPG with adjusted HOMA-β was significantly stronger than that of 2hPG (-0.692 vs. -0.587, P<0.001). Excluding patients with T2DM, according to the cut point recommended by IDF, the AUC of 1hPG≥8.6 mmol/L for detecting prediabetes was 0.731 (95% CI: 0.714-0.748), and the sensitivity and specificity were 0.930 and 0.532, respectively, with the kappa value of 0.45. Conclusion:1hPG is closely related to insulin resistance and islet function, and there′s substantial value for individuals with a high risk of T2DM to detect prediabetes by using the 1hPG cut points recommended by IDF.

Objective:To investigate the value of quantitative parameters of dual-layer detector spectral CT (DLCT) in preoperative prediction of lymphovascular invasion (LVI) in invasive lung adenocarcinoma.Methods:This study employed a cross-sectional design. The data of 91 patients with primary lung adenocarcinoma confirmed by postoperative pathology who underwent DLCT enhanced scanning in the First Affiliated Hospital of Zhengzhou University from March 2022 to July 2024 were retrospectively collected. The patients were divided into LVI positive group and LVI negative group according to the postoperative pathology. Gender, age, smoking status, and lesion location were recorded,the clinical T-stage and N-stage were evaluated. Spectral base data images were generated based on the spectral reconstruction algorithm. Conventional CT features such as the size and density of the lesions were analyzed. The DLCT quantitative parameters such as 40 keV single-energy CT value (CT 40 keV), iodine density (ID), standardized iodine density (NID), and effective atomic number (Z eff) were measured. The differences of parameters between the two groups were compared using t-test, Mann-Whitney U test, or χ2 test. Multivariate logistic regression analysis was used to identify independent factors for predicting invasive lung adenocarcinoma LVI. The predictive performance of individual parameters and their combinations for LVI in invasive lung adenocarcinoma was evaluated using receiver operating characteristic curve analysis and area under the curve (AUC) measurements. Results:There were significant differences in age, T stage, N stage, maximum diameter, focal density, and arteriovenous stage NID and Z eff between the LVI positive group and the LVI negative group ( P<0.05). Multiple logistic regression analysis showed that age ( OR=0.890, 95% CI 0.821-0.966), N stage( OR=12.721, 95% CI 2.676-60.473) and venous stage Z eff( OR=0.012,95% CI 0-0.668) were independent factors for predicting invasive lung adenocarcinoma LVI ( P<0.05). The combination of age, N stage, and venous-phase Z eff values demonstrated the highest predictive efficacy for LVI in invasive lung adenocarcinoma, with an AUC of 0.916. Conclusions:The quantitative parameters of DLCT are helpful for preoperative prediction of LVI status of invasive lung adenocarcinoma. The Z eff in the venous stage is an independent predictor, the combination of multiple parameters can further improve the diagnostic efficiency.

Objective To predict the potential distribution area of Halenia elliptica under current and future climate conditions;To provide a foundation for the sustainable utilization and cultivation of H.elliptica resources.Methods Based on 116 occurrence records and 36 environmental variables,this study employed correlation analysis and contribution rates to identify 10 key environmental factors of H.elliptica.The MaxEnt model,combined with Geographic Information Systems(GIS),was used to predict the potential suitable areas for H.elliptica under current and different future climate scenarios,and centroid shift analysis was performed using SDM_toolbox.Results The MaxEnt model predicted accurately,with an area under the receiver operating characteristic(ROC)curve of 0.968.Altitude,annual precipitation and mean temperature of the coldest season were identified as the primary influencing factors.The current suitable area for H.elliptica was approximately 176.04×104 km2.In the future climate conditions,the suitable habitat of H.elliptica will be moderately adjusted,especially in Sichuan and Xizang.Conclusion In the future,the suitable potential distribution areas for H.elliptica in China will increase,and there will be slight differences in the increment of different suitable potential distribution areas.This study can provide a basis for resource conservation and sustainable utilization,and highlight the importance of dynamic ecological monitoring in the context of global warming.

Objective:To observe the characteristics of multi-muscle surface electromyography (sEMG) network indices during static standing among hemiplegic stroke survivors, and to evaluate the value of the indices in assessing neuromuscular dysfunction.Methods:Ten male stroke survivors with hemiplegia were recruited into the hemiplegia group, and 10 age-matched healthy males were chosen as the control group. Both groups were required to perform 30s static standing tasks with their eyes open and closed. The sEMG signals from the bilateral gluteus maximus (GM), rectus femoris (RF) and biceps femoris (BF) muscles were synchronously collected. Linear time-frequency domain indices were then calculated from the sEMG signals, including the root mean square (RMS) and median frequency (MF). Network indices were extracted from the multiplex recurrence network and weighted networks were constructed from the sEMG signals, including the average interlayer mutual information (I), average edge overlap (ω), clustering coefficient (C), average shortest path length (L) and degree of centrality (DC).Results:With the eyes closed, the RMS values of the bilateral GMs of the hemiplegia group, as well as the values for the RF and BF on the unaffected side were significantly higher than the control group′s values. In the hemiplegia group, the RMS values of the RF and BF muscles on the unaffected side were significantly higher than on the affected side during standing with the eyes closed. For the RF muscles the RMS values on the unaffected side were, on average, significantly higher than with the eyes open. The MF of the GM muscles on the unaffected side in the hemiplegia group was significantly lower than the average MF values of the bilateral GM muscles in the control group with the eyes open or closed. With the eyes closed, the MF of the unaffected-side GM was significantly lower than that of the affected-side GM in the hemiplegia group. Compared with the control group, the hemiplegia group showed a significant increase in I and ω values, but a significant decrease in L values with the eyes open or closed. The DC values of the bilateral GM, RF and BF muscles in the hemiplegia group were significantly higher than among the control group with the eyes open, which was also true of the bilateral GM and RF muscles with the eyes closed. With the BF muscles it was true only of the unaffected side. In the hemiplegia group, the DC values of the unaffected-side GM with the eyes open or closed, and of the unaffected-side BF with the eyes closed.Conclusions:When standing still, hemiplegic stroke survivors exhibit increased overall synchronous muscle adjustment with involvement of unaffected-side muscles, especially the GM. sEMG network indices such as I, ω, L and DC can assess multi-muscle synchronous adaptability and the involvement of single muscles. sEMG network algorithms thus have potential as a new method for localizing and quantitatively assessing neuromuscular dysfunction among such patients.

Objective:To compare the efficacy and safety of crisaborole ointment 2% versus pimecrolimus cream 1% in the treatment of mild to moderate atopic dermatitis in children aged 2 years or older.Methods:A multicenter, randomized, open-label, controlled clinical trial was conducted. A total of 120 pediatric patients aged 2 - 17 years with mild to moderate atopic dermatitis were enrolled from departments of dermatology of 8 hospitals in China between March 2022 and February 2023. The participants were randomly assigned in a 1∶1 ratio to the crisaborole group and the pimecrolimus group, and received the treatment with crisaborole ointment 2% and pimecrolimus cream 1% respectively, twice a day for 4 weeks. Visits were scheduled at baseline/on day 1, as well as on days 8, 15, and 29. The primary efficacy outcome was the percentage of patients achieving the Investigator's Static Global Assessment (ISGA) success (defined as clear [0] or almost clear [1] on the ISGA scale, combined with ≥ 2‐grade improvement from baseline) on day 29. The secondary efficacy outcomes included changes in the Eczema Area and Severity Index (EASI) total scores from baseline to day 29, percentages of patients achieving ISGA improvement (defined as clear [0] or almost clear [1] on the ISGA scale), as well as changes in the Peak Pruritus Numerical Rating Scale (NRS) scores, Dermatology Life Quality Index (DLQI) /Infants' Dermatology Life Quality Index (IDLQI) /Children's Dermatology Life Quality Index (CDLQI) scores, and in the Dermatitis Family Impact (DFI) scores. Drug safety was evaluated according to the incidence of adverse events. Categorical data were compared using the chi-square test. Since measurement data did not follow a normal distribution, the rank sum test was used for comparisons of measurement data between groups.Results:A total of 106 children with mild to moderate atopic dermatitis were included in the per-protocol analysis set, with 52 in the crisaborole group (26 males and 26 females) and 54 in the pimecrolimus group (27 males and 27 females). There were no significant differences in age, disease duration, ISGA and EASI scores at baseline between the two groups (all P > 0.05). On day 29, 22 patients (42.31%) in the crisaborole group and 25 (46.30%) in the pimecrolimus group achieved ISGA success, with no significant difference between the two groups ( χ2 = 0.17, P = 0.68) ; 35 patients (67.31%) in the crisaborole group and 45 (83.33%) in the pimecrolimus group achieved ISGA improvement, also with no significant difference between the two groups ( χ2 = 3.68, P = 0.06) ; additionally, there were no significant differences in the EASI, pruritus NRS, DLQI/IDLQI/CDLQI, or DFI scores between the two groups (all P > 0.05). Adverse reactions to the two topical agents were mainly local reactions such as mild to moderate pain, itching, or worsening of itching, and no obvious systemic adverse reactions occurred. The incidence of drug-related adverse reactions was 46.15% (24 cases) in the crisaborole group and 37.04% (20 cases) in the pimecrolimus group, with no significant difference between the two groups ( χ2 = 0.91, P = 0.34) . Conclusion:The efficacy of crisaborole ointment 2% was comparable to that of pimecrolimus cream 1% in the treatment of mild to moderate atopic dermatitis in children aged ≥ 2 years, and it yielded early and rapid improvement in the quality of life of patients and their families, with good safety and tolerability profiles.

Rheumatoid arthritis （RA） is an autoimmune disease characterized primarily by erosive arthritis， with a high prevalence and disability rate. Although significant progress has been made in the treatment of RA in recent years， challenges such as suboptimal efficacy， drug resistance， severe side effects， and high costs of long-term treatment remain， especially for patients in the early stages of RA， as well as those with RA complications， comorbidities， and severe conditions. Hosted by the China-Japan Friendship Hospital and organized by the Youth Committee of the China Association of Chinese Medicine， the 27^th session of the Clinical Dominant Disease Series （Rheumatoid Arthritis） Youth Salon invited nearly 20 experts and scholars from traditional Chinese medicine （TCM）， western medicine， and interdisciplinary fields to actively discuss the clinical needs of modern medicine and the advantageous stages and aspects of TCM in RA. Experts at the salon agreed that TCM has unique advantages in the treatment of RA， especially during the early stage， periods of low to moderate disease activity， remission phase， and in addressing complications and comorbidities. TCM can achieve both prevention and treatment by regulating the immune system and restoring immune homeostasis. The integrated approach of traditional Chinese and western medicine demonstrates significant advantages in active RA， refractory cases， and stages with severe complications， by rapidly controlling disease progression， alleviating symptoms， enhancing the quality of life， and facilitating recovery. Given the frequent occurrence of multiple comorbidities in RA， TCM shows potential in regulating immunity， alleviating symptoms， and improving physical constitution， which provides new insights into the comprehensive treatment of RA with comorbidities. However， high-quality clinical studies on integrated traditional Chinese and western medicine in RA are still lacking. It is necessary to establish large-scale clinical cohorts and biological databases to provide a scientific basis for the development of precision-targeted therapies and clinical treatment protocols. In the future， individualized treatment strategies integrating traditional Chinese and western medicine are expected to become an important direction for improving the quality of life in RA patients.