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 incidence rate,clinical characteristics,and prognosis of neonatal stroke in Shenzhen,China.Methods Led by Shenzhen Children's Hospital,the Shenzhen Neonatal Data Collaboration Network organized 21 institutions to collect 36 cases of neonatal stroke from January 2020 to December 2022.The incidence,clinical characteristics,treatment,and prognosis of neonatal stroke in Shenzhen were analyzed.Results The incidence rate of neonatal stroke in 21 hospitals from 2020 to 2022 was 1/15 137,1/6 060,and 1/7 704,respectively.Ischemic stroke accounted for 75％(27/36);boys accounted for 64％(23/36).Among the 36 neonates,31(86％)had disease onset within 3 days after birth,and 19(53％)had convulsion as the initial presentation.Cerebral MRI showed that 22 neonates(61％)had left cerebral infarction and 13(36％)had basal ganglia infarction.Magnetic resonance angiography was performed for 12 neonates,among whom 9(75％)had involvement of the middle cerebral artery.Electroencephalography was performed for 29 neonates,with sharp waves in 21 neonates(72％)and seizures in 10 neonates(34％).Symptomatic/supportive treatment varied across different hospitals.Neonatal Behavioral Neurological Assessment was performed for 12 neonates(33％,12/36),with a mean score of(32±4)points.The prognosis of 27 neonates was followed up to around 12 months of age,with 44％(12/27)of the neonates having a good prognosis.Conclusions Ischemic stroke is the main type of neonatal stroke,often with convulsions as the initial presentation,involvement of the middle cerebral artery,sharp waves on electroencephalography,and a relatively low neurodevelopment score.Symptomatic/supportive treatment is the main treatment method,and some neonates tend to have a poor prognosis.

Objective:To evaluate the residual risk (RR) of transfusion transmitted HIV (TT-HIV) after the implementation of nucleic acid amplification test (NAT) in blood screening test among blood centers in China.Methods:The data of blood donors and HIV infection markers from 2017 to 2020 were collected from 28 blood centers via the Platform of Comparison of blood establishments Practice in Chinese Mainland. The new infection rate/window period mathematical model was used for two types of blood screening strategies, namely, two rounds ELISA plus individual NAT take turn with pooling NAT (2ELISA+ ID-NAT/MP-NAT) and two ELISA plus one round pooling NAT (2ELISA+ MP-NAT), and the RR of HIV infection was estimated also based on first donors (FDs) and repeated donors (RDs) in different blood donation years. T-test analyses were conducted for comparing TT HIV RR among FDs and RDs in different blood donation years with two blood screening strategies, and the variation trend of RR in HIV test was observed.Results:From 2017 to 2020, the RR of FDs in 2ELISA+ ID-NAT/MP-NAT blood screening strategy was 2.869/10 6 person-year, 3.795/10 6 persons-year, 3.879/10 6 person-year, and 2.890/10 6 person-year respectively. The RR of RDs was 1.797/10 6 person-year, 1.502/10 6 person-year, 1.857/10 6 person-year, and 1.483/10 6 person-year respectively. Significant difference exists between RR of FDs and RDs, with F=9.898 and p<0.05. In 2ELISA+ MP-NAT strategy, the RR of FDs was 3.508/10 6 person-year, 1.868/10 6 person-year, 2.204/10 6 person-year, and 1.765/10 6 person-year respectively. The RR of RDs was 0.948/10 6 person-year, 0.926/10 6 person-year, 0.748/10 6 person-year, and 0.682/10 6 person-year respectively. Statistical difference existed between RR of FDs and RDs, with F=17.126 and P<0.05. There was no significant difference between the RR of FDs in these two strategies with F=3.493 and P>0.05, while there was a difference between the RR of RDs in these two strategies with F=24.516 and P<0.05, and a difference between the RR of total donors (TDs) in these two strategies F=20.216 and P<0.05. Conclusions:The RR of TT HIV significantly decreased after the introduction of NAT into blood test among blood centers in China. There were some differences in the RR of HIV testing among different blood screening strategies. There could be significant differences in the RR of HIV testing among different groups of blood donors. Compared with FDs, RDs is the low risk group for HIV.

ObjectiveUsing multi-omics technology， we conducted the present study to determine whether dexamethasone has therapeutic effect on pneumonia rats through the regulation of intestinal flora and metabolites. MethodsTotally 18 Sprague-Dawley rats were randomly divided into 3 groups （n = 6 each）： Control group， Model group and Dexamethasone （Dex） group. Lipopolysaccharide （LPS） was continuously injected intraperitoneally into rats at a dose of 4 mg/kg for 7 days to induce pneumonia except the Control group. Then the Dex group was given Dex at a dose of 2 mg/kg via oral gavage for 12 days， and both the other two groups received continuously equal volume of sterile PBS buffer for 12 days. On the 19th day， lung， plasma， feces and intestinal contents of rat were collected. Hematoxylin-eosin （H&E） staining and Bio-plex suspension chip system were applied to evaluate the effect of Dex on pneumonia. Furthermore， metagenomic sequencing and UPLC-Q-TOF-MS/MS technology were employed to determine the intestinal flora and metabolites of rats， respectively. ResultsH&E staining results showed that the lung tissue of the Model group was infiltrated with inflammatory cells， the alveolar septum was increased， alveolar hemorrhage， and histological lesions were less severe in Dex group than in the model group. The levels of 3 inflammatory cytokines including TNF-α （P < 0.000 1）， IL-1α （P = 0.009 6） and IL-6 （P < 0.000 1） in the Model group were increased compared with the Control group， while Dex treatment reduced the levels of the three inflammatory factors. Taken together， Dex treatment effectively reversed the features of pneumonia in rats. Metagenomic analysis revealed that the intestinal flora structure of the three groups of rats was changed. In contrast with the Model group， an increasing level of the Firmicutes and an elevated proportion of Firmicutes/Bacteroidetes were observed after Dex treatment. Dex-treated rats possessed notably enrichment of Bifidobacterium， Lachnospiraceae and Lactobacillus. Multivariate statistical analysis showed a great separation between Model group and Dex group， indicating metabolic profile changes. In addition， 69 metabolites （P < 0.05） were screened， including 38 up-regulated in the Model group and 31 elevated in the Dex group， all of which were mainly involved in 3 metabolic pathways： linoleic acid metabolism， tryptophan metabolism and primary bile acid biosynthesis. ConclusionsIn summary， we demonstrate the beneficial effects of Dex on the symptoms of pneumonia. Meanwhile， integrated microbiome-metabolome analysis reveals that Dex improves LPS-induced pneumonia in rats through regulating intestinal flora and host metabolites. This study may provide new insights into the mechanism of Dex treatment of pneumonia in rats.

BACKGROUND: Controversy exists as to the optimal treatment approach for ostial left anterior descending (LAD) or ostial left circumflex artery (LCx) lesions. Drug-coated balloons (DCB) may overcome some of the limitations of drug-eluting stents (DES). Therefore, we investigated the security and feasibility of the DCB policy in patients with ostial LAD or ostial LCx lesions, and compared it with the conventional DES-only strategy. METHODS: We retrospectively enrolled patients with de novo ostial lesions in the LAD or LCx who underwent interventional treatment. They were categorized into two groups based on their treatment approach: the DCB group and the DES group. The treatment strategies in the DCB group involved the use of either DCB-only or hybrid strategies, whereas the DES group utilized crossover or precise stenting techniques. Two-year target lesion revascularization was the primary endpoint, while the rates of major adverse cardiovascular events, cardiac death, target vessel myocardial infarction, and vessel thrombosis were the secondary endpoints. Using propensity score matching, we assembled a cohort with comparable baseline characteristics. To ensure result analysis reliability, we conducted sensitivity analyses, including interaction, and stratified analyses. RESULTS: Among the 397 eligible patients, 6.25% of patients who were planned to undergo DCB underwent DES. A total of 108 patients in each group had comparable propensity scores and were included in the analysis. Two-year target lesion revascularization occurred in 5 patients (4.90%) and 16 patients (16.33%) in the DCB group and the DES group, respectively (odds ratio = 0.264, 95% CI: 0.093-0.752, P = 0.008). Compared with the DES group, the DCB group demonstrated a lower major adverse cardiovascular events rate (7.84% vs. 19.39%, P = 0.017). However, differences with regard to cardiac death, non-periprocedural target vessel myocardial infarction, and definite or probable vessel thrombosis between the groups were non-significant. CONCLUSIONS The utilization of the DCB approach signifies an innovative and discretionary strategy for managing isolated ostial lesions in the LAD or LCx. Nevertheless, a future randomized trial investigating the feasibility and safety of DCB compared to the DES-only strategy specifically for de novo ostial lesions in the LAD or LCx is highly warranted.

Isolated pontine infarction (IPI) is the main type of acute brainstem infarction. Due to the application of high-resolution MRI, the research on the etiology of IPI has gradually increased in recent years. This article reviews the latest research progress on the characteristics of basilar artery plaques and disease progression mechanisms of IPI, aiming to provide reference for the etiology research of IPI.

Age-related ovarian hypofunction includes a decrease in follicle quantity and quality as well as alterations in the ovarian microenvironment，the mechanisms of which are mainly related to mitochondrial dysfunction，free radical and antioxidant systems，telomere and telomerase alterations，and apoptosis，and is one of the major factors contributing to infertility in advanced maternal age （AMA）. Despite the tremendous progress in assisted reproductive technology in recent decades，few breakthroughs have been made in alleviating age-related ovarian hypofunction and improving reproductive outcomes for AMA. In recent years，there has been an increasing number of studies on the multi-level and multi-targeted mechanisms of traditional Chinese medicine （TCM） to improve age-related ovarian hypofunction by modulating mitochondrial homeostasis，alleviating oxidative stress，and inhibiting apoptosis，while more high-quality randomized controlled trials have demonstrated the clinical efficacy of TCM in assisted reproductive technology. Given this，this article presented a systematic review of recent research and randomized controlled trials on the mechanism of Chinese medicine active ingredients，single Chinese medicine， and Chinese medicine compounds in delaying age-related ovarian hypofunction，to clarify the current status and shortcomings of the research. This paper provides medication management of TCM for effectively alleviating age-related ovarian hypofunction and improving reproductive outcomes for AMA.

Objective:To compare the effect of temporal external fixator and digital guide plate in the immediate reconstruction of mandibular defect after segmental mandibulectomy.Methods:The clinical data of all patients who received segmental mandibulectomy and immediate mandibular reconstruction with free vascularized bone graft by a single surgical team in the Department of Oral & Maxillofacial-Head & Neck Oncology, Shanghai Ninth People’s Hospital, Shanghai Jiao Tong University School of Medicine from August 2016 to December 2017 were retrospectively analyzed. According to different auxiliary methods, the patients were divided into temporal external fixator (TEF) group and computer aided design-manufacture (CAD-CAM) group. The width of mandible, length of mandibular body and vertical dimension of inferior 1/3 face were measured by CT before and one month after surgery, and the difference before and after surgery was calculated to evaluate the surgical effect. SPSS 19.0 was used for statistical analysis, and the data were expressed as Mean ± SD. Independent sample t-test was used for comparison of indexes of surgical time and surgical effect evaluation between the two groups, and P<0.05 indicated statistically significant differences. Results:A total of 29 patients were enrolled, including 13 patients in TEF group, 4 males and 9 females, aged (47.7±14.5) years, including 7 ameloblastomas, 2 squamous cell carcinomas, 2 abnormal proliferation of bone fibers, 1 rhabdomyosarcoma and 1 osteosarcoma. In the CAD-CAM group, there were 16 cases, including 11 males and 5 females, aged (42.4±19.7) years, including 10 ameloblastomas, 3 squamous cell carcinomas, 1 osteoblastoma, 1 otogenic fibromyxoma and 1 osteosarcoma. The bone grafts in 29 patients were all alive, the wounds healed primarily, and the occlusal relationship and facial contour of the patients were fine. After 3 years follow-up, there were no postoperative complications and tumor recurrence. The function of the supply area was not affected. The operative time was (7.12±1.40) h in the TEF group and (4.72±1.10) h in the CAD-CAM group, and the difference between the two groups was statistically significant ( P<0.01). In the TEF group, the difference of the width of mandible, length of mandibular body and vertical dimension of inferior 1/3 face were (1.08±1.12) mm, (2.08±1.61) mm, (1.77±3.15) mm, respectively; CAD-CAM group were (0.88±1.15) mm, (0.94±1.34) mm, (0.87±1.47) mm, respectively, and there was no statistical significance between the two groups ( P>0.05). Conclusions:It took significantly longer to perform immediate mandibular reconstruction assisted by TEF than that assisted by CAD-CAM in surgery, but both groups achieved better surgical results. It is simpler and more effective to use TEF when time is urgent or technology is too limited to carry out preoperative digital design.

Objective:To compare the effect of temporal external fixator and digital guide plate in the immediate reconstruction of mandibular defect after segmental mandibulectomy.Methods:The clinical data of all patients who received segmental mandibulectomy and immediate mandibular reconstruction with free vascularized bone graft by a single surgical team in the Department of Oral & Maxillofacial-Head & Neck Oncology, Shanghai Ninth People’s Hospital, Shanghai Jiao Tong University School of Medicine from August 2016 to December 2017 were retrospectively analyzed. According to different auxiliary methods, the patients were divided into temporal external fixator (TEF) group and computer aided design-manufacture (CAD-CAM) group. The width of mandible, length of mandibular body and vertical dimension of inferior 1/3 face were measured by CT before and one month after surgery, and the difference before and after surgery was calculated to evaluate the surgical effect. SPSS 19.0 was used for statistical analysis, and the data were expressed as Mean ± SD. Independent sample t-test was used for comparison of indexes of surgical time and surgical effect evaluation between the two groups, and P<0.05 indicated statistically significant differences. Results:A total of 29 patients were enrolled, including 13 patients in TEF group, 4 males and 9 females, aged (47.7±14.5) years, including 7 ameloblastomas, 2 squamous cell carcinomas, 2 abnormal proliferation of bone fibers, 1 rhabdomyosarcoma and 1 osteosarcoma. In the CAD-CAM group, there were 16 cases, including 11 males and 5 females, aged (42.4±19.7) years, including 10 ameloblastomas, 3 squamous cell carcinomas, 1 osteoblastoma, 1 otogenic fibromyxoma and 1 osteosarcoma. The bone grafts in 29 patients were all alive, the wounds healed primarily, and the occlusal relationship and facial contour of the patients were fine. After 3 years follow-up, there were no postoperative complications and tumor recurrence. The function of the supply area was not affected. The operative time was (7.12±1.40) h in the TEF group and (4.72±1.10) h in the CAD-CAM group, and the difference between the two groups was statistically significant ( P<0.01). In the TEF group, the difference of the width of mandible, length of mandibular body and vertical dimension of inferior 1/3 face were (1.08±1.12) mm, (2.08±1.61) mm, (1.77±3.15) mm, respectively; CAD-CAM group were (0.88±1.15) mm, (0.94±1.34) mm, (0.87±1.47) mm, respectively, and there was no statistical significance between the two groups ( P>0.05). Conclusions:It took significantly longer to perform immediate mandibular reconstruction assisted by TEF than that assisted by CAD-CAM in surgery, but both groups achieved better surgical results. It is simpler and more effective to use TEF when time is urgent or technology is too limited to carry out preoperative digital design.

Objective: To analyze the migration of the HIV/AIDS cases and related factors in Liangshan Yi autonomous prefecture (Liangshan). Methods: According to HIV/AIDS Comprehensive Response Information Management System of China Information System for Disease Control and Prevention, a total of 28 772 HIV/AIDS cases who had follow-up records in Liangshan in 2020 were included in the survey. The migration of the HIV/AIDS cases was described and the related factors were analyzed using multiple logistic regression models, and the migration destinations of the HIV/AIDS cases were mapped. Results: Among the 28 772 HIV/AIDS cases, 20.89% (6 010/28 772) had migration in 2020. Multivariate logistic regression analysis showed that among the HIV/AIDS cases, the migration related factors included being aged 15-24 years (compared with being aged 0-14 years, OR=2.74, 95%CI:2.04-3.69) and ethnic group (compared with Han ethnic group, OR=2.44, 95%CI:2.19-2.72), having education level of junior high school (compared with having education level of primary school or below, OR=1.25, 95%CI:1.14-1.38), being unmarried (compared with being married, OR=1.29, 95%CI:1.20-1.39), being engaged in business services (compared with being engaged in farming, OR=1.96, 95%CI:1.31-2.92), receiving antiviral treatment <1 year (compared with receiving antiviral treatment >3 years, OR=1.42, 95%CI:1.26-1.61), having recent CD4⁺T lymphocytes (CD4) counts >500 cells/μl (compared with having recent CD4 counts <200 cells/μl, OR=1.15, 95%CI:1.03-1.29). The geographical distribution maps showed that among all cities in Sichuan, Xichang (13.26%, 797/6 010) and Chengdu (10.12%,608/6 010) were the main migration destinations of the HIV/AIDS cases, and the provinces outside Sichuan where the HIV/AIDS cases would like to migrate to were mainly Guangdong (18.19%, 1 093/6 010) and Zhejiang provinces (7.67%, 461/6 010) in 2020. The HIV/AIDS cases who migrated where Liangshan, within Sichuan province, and to other provinces accounted for 27.67% (1 663/6 010), 15.34% (922/6 010) and 56.99% (3 425/6 010), respectively. Conclusions: More attention should be paid to the mobility characteristics and the classification management of HIV/AIDS cases according to their characteristics in Liangshan. Timely access to information on changes in the place of work and residence of HIV/AIDS cases should be warranted when they have migration. Good referrals and management for mobility of HIV/AIDS cases in different places should be made to reduce loss to follow-up and improving interventions.
Acquired Immunodeficiency Syndrome/epidemiology* ; Adolescent ; Adult ; Child ; Child, Preschool ; China/epidemiology* ; Ethnicity ; HIV Infections/epidemiology* ; Humans ; Infant ; Infant, Newborn ; Logistic Models ; Marriage ; Young Adult