The primary role of transfer RNA(tRNA)is to connect a specific amino acid to its 3' end, use its anticodon to match the codon on messenger RNA(mRNA), and deliver the corresponding amino acid to the ribosome for protein synthesis.tRNA exists in two forms: precursor tRNA and mature tRNA.When acted upon by enzymes like Dicer, elaC ribonuclease Z 2(ELAC2), angiopoietin(ANG), and other ribonucleases, tRNA is broken down into tRNA-derived stress-induced RNA(tiRNA)and tRNA-derived fragments(tRF).Recent advancements in RNA sequencing technology have led to increased interest in tiRNA and tRF, shedding light on their roles in various physiological and pathological processes.tRNA-derived small molecules(tsRNA)function similarly to microRNA(miRNA), influencing gene expression and protein synthesis.They show promise as diagnostic markers and potential therapeutic targets for age-related diseases.This review offers a comprehensive analysis of tsRNA classification, biological functions, research advancements, and clinical applications in age-related conditions.

BACKGROUND: The primary limitation to kidney transplantation is organ shortage. Recent progress in gene editing and immunosuppressive regimens has made xenotransplantation with porcine organs a possibility. However, evidence in pig-to-human xenotransplantation remains scarce, and antibody-mediated rejection (AMR) is a major obstacle to clinical applications of xenotransplantation. METHODS: We conducted a kidney xenotransplantation in a brain-dead human recipient using a porcine kidney with five gene edits (5GE) on March 25, 2024 at Xijing Hospital, China. Clinical-grade immunosuppressive regimens were employed, and the observation period lasted 22 days. We collected and analyzed the xenograft function, ultrasound findings, sequential protocol biopsies, and immune surveillance of the recipient during the observation. RESULTS: The combination of 5GE in the porcine kidney and clinical-grade immunosuppressive regimens prevented hyperacute rejection. The xenograft kidney underwent delayed graft function in the first week, but urine output increased later and the single xenograft kidney maintained electrolyte and pH homeostasis from postoperative day (POD) 12 to 19. We observed AMR at 24 h post-transplantation, due to the presence of pre-existing anti-porcine antibodies and cytotoxicity before transplantation; this AMR persisted throughout the observation period. Plasma exchange and intravenous immunoglobulin treatment mitigated the AMR. We observed activation of latent porcine cytomegalovirus toward the end of the study, which might have contributed to coagulation disorder in the recipient. CONCLUSIONS 5GE and clinical-grade immunosuppressive regimens were sufficient to prevent hyperacute rejection during pig-to-human kidney xenotransplantation. Pre-existing anti-porcine antibodies predisposed the xenograft to AMR. Plasma exchange and intravenous immunoglobulin were safe and effective in the treatment of AMR after kidney xenotransplantation.
Transplantation, Heterologous/methods* ; Kidney Transplantation/methods* ; Heterografts/pathology* ; Immunoglobulins, Intravenous/administration & dosage* ; Graft Survival/immunology* ; Humans ; Animals ; Sus scrofa ; Graft Rejection/prevention & control* ; Kidney/pathology* ; Gene Editing ; Species Specificity ; Immunosuppression Therapy/methods* ; Plasma Exchange ; Brain Death ; Biopsy ; Male ; Aged

Objective:To investigate the effect of left colonic artery (LCA) preservation on rectal cancer patients' short-term postoperative anal function and quality of life.Methods:Two-hundred ninty-two patients with rectal cancer at the Department of Gastrointestinal Surgery of Peking University First Hospital between Jan 2022 and Dec 2023 were enrolled . The patients were divided into two groups according to whether the LCA was preserved during surgery or not. The LARS scale and EORTC QLQ-CR29 quality of life questionnaire were used to assess postoperative anal function and quality of life.Results:There were no significant differences between the two groups in terms of the amount of surgical blood loss and the number of lymph node dissections in the root No. 253 group and the time to postoperative voiding (all P>0.05). However, the LARS scores at 1 and 3 months postoperatively were significantly lower in the preserved LCA group than in the LCA nonpreserved group, especially for gas incontinence, loose stool leakage, and number of bowel movements (all P<0.05). The EORTC QLQ-CR29 scores showed that the LCA preserved group recovered significantly better than the non-preserved group in terms of postoperative voiding dysfunction ( P=0.007), urinary incontinence ( P=0.006), mucus discharge ( P=0.009), and fecal incontinence symptoms ( P<0.001). Male sexual dysfunction recovery was quicker in the preserved LCA group ( P=0.043), but there was no significant difference between the two groups at 3 months postoperatively( P>0.05). Conclusion:Preservation of the left colonic artery in low anterior resection of rectal cancer helps to reduce the incidence of postoperative low anterior resection syndrome, improve genitourinary symptoms, and improve patients' quality of life.

Objective:Analyze the risk factors of gastrointestinal perforation caused by foreign body and summarize the experience of surgical treatment of foreign bodies.Method:From Jan 2008 to Dec 2023, 89 patients with foreign bodies in the digestive tract were admitted to the Department of Gastrointestinal Surgery, Peking University First Hospital. Relevant data were collected and binary logistic regression was used to analyze the independent risk factors for intestinal perforation, resection and anastomosis of intestine or enterostomy/colostomy.Results:The mean age of 89 patients was (60.1±16.2) years old, 65 patients (73%) had unintentionally ingested foreign bodies. The most common foreign bodies were jujube pits (40 cases). Thirty-nine patients diagnosed with gastrointestinal perforation. Binary Logistic regression analysis showed that the total number of leukocytes ( OR=4.085, 95% CI: 1.214-13.745, P=0.023), sharp foreign body ( OR=26.124, 95% CI: 5.194-131.392, P<0.001), and the location of foreign body ( OR=3.980, 95% CI: 1.178-13.465, P=0.026) were the independent risk factors for gastrointestinal perforation. Thirty-three patients underwent gastrointestinal repair surgery, and 36 patients underwent resection and anastomosis of intestine or enterostomy/colostomy. Binary Logistic regression analysis showed that the foreign body located in the colorectum ( OR=71.928, 95% CI: 4.646-1 113.479, P=0.002) and the length of the foreign body ≤2.5 cm ( OR=5.791, 95% CI: 1.606-20.882, P=0.007) were the independent risk factors for resection and anastomosis of intestine or enterostomy/colostomy. Conclusions:Leukocyte count ≥10×10 9/L, sharp foreign body, and location of foreign body are independent risk factors for gastrointestinal perforation. Foreign body located in the colorectum and foreign body length ≤2.5 cm are risk factors for resection and anastomosis of intestine or enterostomy/colostomy.

Objective:To investigate the incidence of visual fatigue among military pilots during flights or simulated flights and analyze the correlations among the multidimensional evaluation indicators of visual fatigue.Methods:A total of 172 pilots from an Air Force unit were selected between March 2022 and August 2023. A self-made pilot visual fatigue scale [involving the basic information, visual fatigue status scale (VFSS), and visual quality scale (VQS) was used. The visual fatigue among pilots of different types was compared. Pearson correlation analysis was used to explore the correlations between the cumulative duration of visual display terminal (VDT) and the dimensions of the VFSS, as well as between dimensions of the VFSS and the VQS. Multiple linear regression was used to identify the determinants of the score of the VQS.Results:A total of 172 questionnaires were issued, 146 of which were valid, with an effective rate of 84.88%. Among the 146 military pilots, 73 were fighter pilots and 73 were pilots of other aircraft types (20 bombers, 5 helicopters, 36 transporters, 8 trainers, and 4 fighter-bombers). There were significant differences in the scores of various dimensions and the total score of the VFSS between pilots who were different in age, aircraft types, maximum single-sortie flight durations, and in the proportion of time spent viewing cockpit displays during flight missions ( F=4.93-14.41, t=2.37-4.86, all P<0.01 or <0.05). Significant differences in visual disturbance, systemic symptoms, environmental factors, and the total visual fatigue score were observed between pilots whose total flying hours were different ( F=14.18, 4.90, 4.66, 8.12, P<0.001, =0.009,0.011, <0.001). However, there were no significant differences in the scores of any dimension or in the total score of the VFSS between pilots with a history of ocular trauma or disease and those without (all P>0.05). The cumulative duration of VDT use was positively correlated with the scores of all dimensions and the total score of the VFSS ( r=0.353, 0.303, 0.312, 0.250, 0.356, P<0.001, <0.001, <0.001, =0.002, <0.001), the dimensions of which were positively correlated with those of the VQS ( r=0.448-0.781, all P<0.01). Age ( B=1.524, 95% CI: 0.503-2.545), proportions of time spent viewing cockpit displays during flight missions ( B=3.721, 95% CI: 1.683-5.759), starburst ( B=2.346, 95% CI: 0.516-4.176), blurred vision ( B=3.517, 95% CI: 1.168-5.866), visual fluctuation ( B=2.997, 95% CI: 1.036-4.957) and halo ( B=2.415, 95% CI: 0.469-4.362) were contributors to the total visual fatigue score. Conclusions:The scores of various dimensions and the total score of visual fatigue status in military pilots can increase with age, peak in the group ages 40 to 49, and then decline. Fighter pilots experience lower levels of visual fatigue than those of other aircraft types. The visual quality scale can serve as a reference for assessing pilots′ visual fatigue status. Cumulative durations of VDT use are positively correlated with the degree of visual fatigue. Age, proportions of time spent viewing cockpit displays during flight missions, starburst, blurred vision, visual fluctuation and halo can be used to quickly assess the risk level of visual fatigue among pilots.

OBJECTIVE The emergence of evolving variants of Coronavirus disease 2019(COVID-19)has fostered the need for change of newer and adaptive treatments for these infections.During the COVID-19 pandemic and persists,traditional Chinese medicine(TCM)herbs exhibit significant bioactivity and therapeutic effect.This study is aimed to evaluate the efficacy of four TCM preparations on 28-day mortality risk of patients and changes of the laboratory indicators.METHODS The retrospective cohort study included patients with COVID-19 who were admitted to the Jiangsu Province Hospital of Chinese Medicine from December 15,2022 to January 15,2023,and those died within 48 hours of admission or cannot be tracked for outcomes were excluded.The pri-mary outcome was survival status in 28 days(death or survival)starting from the day of admission.The second outcomes were labora-tory indicators,including absolute lymphocyte count,lactate dehydrogenase,creatinine,and blood urea nitrogen.Binary logistic re-gressions were used to estimate the effect of TCM preparations on the primary and secondary outcomes in main analysis.Meanwhile,heterogeneity and robustness of results from main analysis were assessed by subgroup analyses and multiple sensitivity analyses.RESULTS 1 816 eligible patients were included in analysis dataset,including 573 patients received standard care(control group)and 1 243 patients received TCM preparations(hospital preparation group).The 28-day mortality rate of hospital preparation group was lower than that of control group(4.75%vs.14.83%),and the difference was statistically significant(χ2=54.666,P<0.001).The risk of 28-day mortality was 0.535 times lower in the hospital preparation group as compared with the control group(OR=0.46,95%CI:0.305-0.708,P<0.001)showed by multivariable binary logistic regressions.Subgroup analyses showed that taking TCM preparations reduced the 28-day mortality risk.Sensitivity analyses demonstrated that the results of the main analysis for primary outcomes were robust.For secondary outcomes,the risk of abnormal absolute lymphocyte counts at discharge in the hospital prepara-tion group decreased by 0.284 times(OR=0.703,95%CI:0.515-0.961,P=0.027).CONCLUSION Compared with standard of care,taking four hospital preparations including Kanggan Heji,Feining Heji,Qishen Gubiao Keli,and Qianghuo Qushi Qingwen Heji decreased risk of 28-day mortality among hospitalized COVID-19 patients.TCM therapy achieves adequate therapeutic effects in COVID-19.

With the extension of the global population's lifespan and the increasingly severe aging problem,cardio-vascular diseases have become the leading cause of death among the elderly population.Most cardiovascular diseases orig-inate from the formation of atherosclerotic plaques.In addition to common risk factors such as dyslipidemia,diabetes,hy-pertension,smoking,and obesity,circadian rhythm disruption is also regarded as an important but often overlooked risk factor for atherosclerosis.The circadian rhythm is involved in regulating key physiological processes such as inflammation and metabolism,which in turn affect the pathological processes of arteriosclerosis and thrombosis.In this process,the key genes that maintain the stability of the circadian rhythm,namely clock gene,play a crucial role.Clock gene have an important role in the pathological mechanism of atherosclerosis,and they may become potential new targets for the preven-tion and treatment of atherosclerosis.This paper reviews the latest research progress on the mechanism of action of clock gene in the occurrence and development of atherosclerosis.These findings may provide new ideas for the diagnosis and treatment of atherosclerosis.

OBJECTIVE The emergence of evolving variants of Coronavirus disease 2019(COVID-19)has fostered the need for change of newer and adaptive treatments for these infections.During the COVID-19 pandemic and persists,traditional Chinese medicine(TCM)herbs exhibit significant bioactivity and therapeutic effect.This study is aimed to evaluate the efficacy of four TCM preparations on 28-day mortality risk of patients and changes of the laboratory indicators.METHODS The retrospective cohort study included patients with COVID-19 who were admitted to the Jiangsu Province Hospital of Chinese Medicine from December 15,2022 to January 15,2023,and those died within 48 hours of admission or cannot be tracked for outcomes were excluded.The pri-mary outcome was survival status in 28 days(death or survival)starting from the day of admission.The second outcomes were labora-tory indicators,including absolute lymphocyte count,lactate dehydrogenase,creatinine,and blood urea nitrogen.Binary logistic re-gressions were used to estimate the effect of TCM preparations on the primary and secondary outcomes in main analysis.Meanwhile,heterogeneity and robustness of results from main analysis were assessed by subgroup analyses and multiple sensitivity analyses.RESULTS 1 816 eligible patients were included in analysis dataset,including 573 patients received standard care(control group)and 1 243 patients received TCM preparations(hospital preparation group).The 28-day mortality rate of hospital preparation group was lower than that of control group(4.75%vs.14.83%),and the difference was statistically significant(χ2=54.666,P<0.001).The risk of 28-day mortality was 0.535 times lower in the hospital preparation group as compared with the control group(OR=0.46,95%CI:0.305-0.708,P<0.001)showed by multivariable binary logistic regressions.Subgroup analyses showed that taking TCM preparations reduced the 28-day mortality risk.Sensitivity analyses demonstrated that the results of the main analysis for primary outcomes were robust.For secondary outcomes,the risk of abnormal absolute lymphocyte counts at discharge in the hospital prepara-tion group decreased by 0.284 times(OR=0.703,95%CI:0.515-0.961,P=0.027).CONCLUSION Compared with standard of care,taking four hospital preparations including Kanggan Heji,Feining Heji,Qishen Gubiao Keli,and Qianghuo Qushi Qingwen Heji decreased risk of 28-day mortality among hospitalized COVID-19 patients.TCM therapy achieves adequate therapeutic effects in COVID-19.

Objective:To investigate the effect of verbascoside(VERB)on high-fat diet-induced atherosclerosis(AS)in ApoE-/-mice and the effect on high mobility histone 1(HMGB1)/receptor for glycation end products(RAGE)/nuclear factor κB(NF-κB)pathway.Methods:A total of 90 ApoE-/-mice were randomly divided into normal group,AS group,VERB group,simvastatin group and VERB+pathway activator HMGB1 group,with 18 mice per group.After 8 weeks of group administration,blood and aorta samples were taken.Fasting serum triacylglycerol(TG),total cholesterol(TC)and low density lipoprotein(LDL)levels were deter-mined by automatic biochemical analyzer.Oil red O,HE and TUNEL staining were performed to observe apoptosis of aortic plaque and endothelial cell(EC).Flow cytometry was performed to analyze circulating EC numbers.Immunohistochemistry was performed to analyze the infiltration area of macrophages(CD68+)and T lymphocytes(CD3+)in aortic plaques.Western blot was performed to detect expressions of HMGB1/RAGE/NF-κB pathway,inflammation and adhesion molecules.Results:Compared with normal group,AS group had lipid plaques in arterial intima,thickness of the media was uneven,TG,TC,LDL levels,lession proportion,plaque area,circulating EC number,arterial EC apoptosis rate,macrophage(CD68+)and T lymphocyte(CD3+)infiltration areas,TNF-α,monocyte chemoattractant protein-1(MCP-1),vascular cell adhesion molecule-1(VCAM-1),intercellular adhesion molecule-1(ICAM-1),cytoplasm HMGB1,total HMGB1,total RAGE protein levels and nuclear/total p65 NF-κB levels were increased(P<0.05),while nuclear HMGB1 protein,nuclear/total HMGB1 and cytosolic p65 NF-κB levels were decreased(P<0.05).After VERB or simvastatin intervention,arterial lesions were alleviated,TG,TC,LDL levels,lession proportion,plaque area,circulating EC number,arterial EC apoptosis rate,macrophage(CD68+)and T lymphocyte(CD3+)infiltration areas,TNF-α,MCP-1,VCAM-1,ICAM-1,cytoplasm HMGB1,total HMGB1,RAGE protein levels and nuclear/total p65 NF-κB level were decreased(P<0.05),while nuclear HMGB1 protein,nuclear/total HMGB1 and cytosolic p65 NF-κB levels were increased(P<0.05),and HMGB1 was able to antagonize the protective effect of VERB on AS mice.Conclusion:VERB can inhibit expressions of inflammatory and adhesion fac-tors in arterial plaques in ApoE-/-mice,reduce EC shedding and apoptosis,therefore improve AS symptoms in ApoE-/-mice,and the mechanism may be related to the inhibition of HMGB1/RAGE and NF-κB pathway.