1.Biomechanical effects of postural and cognitive loads on trunk of workers performing assembly tasks at hand functional height
Huishuan WU ; Yu JIN ; Yan LIU ; Siyi ZENG ; Cunwen QIAN ; Kezhi JIN
Journal of Environmental and Occupational Medicine 2025;42(4):392-399
Background The neck, shoulders, and lower back are the primary affected areas of work-related musculoskeletal disorders. In manual tasks, combinations of hand functional height (defined as working height below the waist), awkward postures, and cognitive load are common risk factors. However, there is limited literature documenting how these factors specifically alter biomechanical load on the neck, shoulders, and lower back when working at hand functional height. Objective To explore quantitative differences in biomechanical load on the neck, shoulders, and lower back of workers performing manual tasks at hand functional height under different postures and cognitive load combinations. Methods A 3x2 within-subject design was implemented, with three postures (squat, kneeling, and stoop) and two levels of cognitive load (with cognitive load induced by a 2back task and without cognitive load). Ten male university students were recruited to perform a predetermined assembly task (a sequence of loosening and tightening screws) at hand functional height. Surface electromyography (sEMG) and 3D motion capture system were employed to assess the participants’ trunk biomechanical load in executing the tasks. Additionally, subjective perception, including fatigue, muscle pain, and cognitive load, were evaluated using scales. Results Significant variations in biomechanical load were observed across the three postures (P<0.05). The stoop posture exhibited the lowest muscle activation in most target muscles, except for the sternocleidomastoid, and showed the fastest decline in instantaneous median frequency (IMF) of the erector spinae, with a rate of (-0.050±0.008) Hz per unit time (0.128 s), and the greatest trunk flexion angle (35.14°±4.40°). Performing the task by squatting resulted in the highest muscle activation, especially in the upper trapezius, where maximum voluntary contraction percentage reached 20.07%±1.26%. In addition, the squatting posture also resulted in larger joint angles in the sagittal plane for the neck (−7.03°±2.70°), shoulders (60.20°±7.89°), and lower back (34.42°±4.20°). The kneeling posture showed intermediate muscle activation, the slowest IMF decline for the erector spinae in the lower back (−0.005±0.008) Hz per unit time (0.128s), and the joint angles were closest to neutral. The task performance results were also superior in the kneeling posture. Regarding cognitive load, no significant differences were found for most biomechanical indicators, except for subjective cognitive load scores, neck flexion, and shoulder external rotation angles. Conclusion In assembly tasks performed at hand functional height, kneeling results in moderate biomechanical load on the neck, shoulders, and lower back while also improves task performance compared to squatting and forward bending. Additionally, no significant effects of cognitive load under the 2back condition on biomechanical load are observed.
2.Exploration of radiotherapy as a combined treatment modality with in situ vaccines in the treatment of advanced soft tissue sarcomas
TAN Siyi, ; WANG Xiaolu ; WANG Qin ; DU Shiyao ; YIN Fangtao ; YANG Yiqi ; SUN Wu ; LIU Juan ; ZHOU Xia ; LIU Baorui, ; LI Rutian
Chinese Journal of Cancer Biotherapy 2025;32(4):418-424
[摘 要] 目的:评估放疗作为原位疫苗的联合治疗模式在晚期软组织肉瘤(STS)患者中的有效性和安全性。方法:回顾性分析2020年12月至2024年9月期间在南京大学医学院附属鼓楼医院肿瘤中心接受联合治疗模式的12例晚期STS患者的临床资料。12例患者均接受了联合治疗。放疗主要以大分割为主。靶向治疗:安罗替尼10例、阿帕替尼2例。免疫治疗以PD-1抗体为主。主要研究终点为疾病控制率(DCR),次要研究终点为客观有效率(ORR)及安全性。结果:接受联合治疗的12例STS患者中有0例CR,4例PR,7例SD,1例PD。ORR为33%,DCR为91.7%,其中靶病灶的DCR为100%。12例患者中,9例出现Ⅰ~Ⅱ级不良反应。最常发生的血液学不良反应是贫血(6例)、肝功能检查结果异常(3例)。最常发生的非血液学不良反应是尿蛋白(5例)、高血压(4例)、甲状腺功能异常(3例)、厌食(3例)、恶心呕吐(2例);仅2例发生Ⅲ级血液毒性,有1例发生Ⅲ级气胸。结论:放疗作为原位疫苗的联合治疗模式在晚期STS患者中展现出较高的DCR,且未出现严重不良反应。该联合治疗模式具有良好的有效性与安全性。
3.Pharmacokinetic Differences of Seven Components in Different Phases of Banxia Xiexintang in Rats
Chao HE ; Siyi LIU ; Mingyun WANG ; Qi WANG ; Jingwen ZHOU ; Tong ZHANG ; Yiqiong PU
Chinese Journal of Experimental Traditional Medical Formulae 2025;31(13):215-222
ObjectiveTo evaluate the effects of phases on the pharmacokinetic behavior of seven components from Banxia Xiexintang(BXT) in normal rats by investigating and comparing their pharmacokinetic profiles in different phase samples. MethodsThe phase separation of BXT was carried out by centrifugation-dialysis method, and three phase samples were obtained, including the precipitated phase(PP), colloidal phase(CP) and true solution phase(TP). A total of 24 male SD rats were randomly divided into BXT, PP, CP and TP groups(n=6). The BXT group was gavaged at a dose of 24.1 g·kg-1(calculated by the dosage of raw materials). After proper treatments, PP, CP and TP groups were administrated at the same dose as that of BXT group, respectively. Blood was collected from each group at set time points after gavage of BXT and the phase samples. The contents of 7 components(baicalin, wogonoside, wogonin, berberine, palmatine, ammonium glycyrrhizinate and isoliquiritin) in rat plasma were determined by ultra-high performance liquid chromatography-triple quadrupole tandem mass spectrometry(UPLC-QqQ-MS/MS), and the pharmacokinetic parameters of each component were analyzed by DAS 2.0. ResultsThe peak concentration of baicalin was the highest among the blood-entered components in each group, followed by wogonoside. The results of the concentration-time curves and pharmacokinetic parameters of the 7 components showed that the area under the concentration-time curve(AUC) of isoliquiritin in the BXT group was the highest, followed by that in the CP group. AUC values of baicalin, wogonoside, wogonin and ammonium glycyrrhizinate in the BXT group were similar to those of the CP group, and AUC of palmatine in the BXT group was similar to that of the PP group. The elimination half-life(t1/2) values of baicalin and wogonoside in the BXT group was the longest, the t1/2 values of ammonium glycyrrhizinate and berberine were similar to those of the CP group, and the t1/2 of palmatine was similar to that of the PP group. The t1/2 of wogonin was the longest in the PP group, and the t1/2 of isoliquiritin was the longest in the TP group was the longest, which was similar to that in the PP group. Except for isoliquiritin, the other 6 components showed double peaks in the concentration-time curve of the PP group, indicating that the above components might be reabsorbed through the enterohepatic circulation in vivo, which resulted in the maintenance of high plasma concentrations for a long time, and consequently exhibited sustained-release properties. ConclusionThe pharmacokinetic characteristics of the components in different phases were different, and the CP phase may be the effective phase from the perspective of the pharmacological action of BXT. Compared with the BXT group, the in vivo action times of some components in the CP and PP groups were prolonged. The study explores the phase differences of traditional Chinese medicine(TCM) compound decoction in the aspect of pharmacokinetics, and verifies that the phase states from TCM compound decoction will affect the pharmacokinetic behaviors of the active components, which may consequently lead to the difference in in vivo effects.
4.Pharmacokinetic Differences of Seven Components in Different Phases of Banxia Xiexintang in Rats
Chao HE ; Siyi LIU ; Mingyun WANG ; Qi WANG ; Jingwen ZHOU ; Tong ZHANG ; Yiqiong PU
Chinese Journal of Experimental Traditional Medical Formulae 2025;31(13):215-222
ObjectiveTo evaluate the effects of phases on the pharmacokinetic behavior of seven components from Banxia Xiexintang(BXT) in normal rats by investigating and comparing their pharmacokinetic profiles in different phase samples. MethodsThe phase separation of BXT was carried out by centrifugation-dialysis method, and three phase samples were obtained, including the precipitated phase(PP), colloidal phase(CP) and true solution phase(TP). A total of 24 male SD rats were randomly divided into BXT, PP, CP and TP groups(n=6). The BXT group was gavaged at a dose of 24.1 g·kg-1(calculated by the dosage of raw materials). After proper treatments, PP, CP and TP groups were administrated at the same dose as that of BXT group, respectively. Blood was collected from each group at set time points after gavage of BXT and the phase samples. The contents of 7 components(baicalin, wogonoside, wogonin, berberine, palmatine, ammonium glycyrrhizinate and isoliquiritin) in rat plasma were determined by ultra-high performance liquid chromatography-triple quadrupole tandem mass spectrometry(UPLC-QqQ-MS/MS), and the pharmacokinetic parameters of each component were analyzed by DAS 2.0. ResultsThe peak concentration of baicalin was the highest among the blood-entered components in each group, followed by wogonoside. The results of the concentration-time curves and pharmacokinetic parameters of the 7 components showed that the area under the concentration-time curve(AUC) of isoliquiritin in the BXT group was the highest, followed by that in the CP group. AUC values of baicalin, wogonoside, wogonin and ammonium glycyrrhizinate in the BXT group were similar to those of the CP group, and AUC of palmatine in the BXT group was similar to that of the PP group. The elimination half-life(t1/2) values of baicalin and wogonoside in the BXT group was the longest, the t1/2 values of ammonium glycyrrhizinate and berberine were similar to those of the CP group, and the t1/2 of palmatine was similar to that of the PP group. The t1/2 of wogonin was the longest in the PP group, and the t1/2 of isoliquiritin was the longest in the TP group was the longest, which was similar to that in the PP group. Except for isoliquiritin, the other 6 components showed double peaks in the concentration-time curve of the PP group, indicating that the above components might be reabsorbed through the enterohepatic circulation in vivo, which resulted in the maintenance of high plasma concentrations for a long time, and consequently exhibited sustained-release properties. ConclusionThe pharmacokinetic characteristics of the components in different phases were different, and the CP phase may be the effective phase from the perspective of the pharmacological action of BXT. Compared with the BXT group, the in vivo action times of some components in the CP and PP groups were prolonged. The study explores the phase differences of traditional Chinese medicine(TCM) compound decoction in the aspect of pharmacokinetics, and verifies that the phase states from TCM compound decoction will affect the pharmacokinetic behaviors of the active components, which may consequently lead to the difference in in vivo effects.
5.Reflections on Research and Development of New Tibetan Medicines Based on Ancient Famous Classical Formulas
Siyi LIU ; Xiu XIANG ; Wei HAN
Chinese Journal of Experimental Traditional Medical Formulae 2025;31(18):261-267
With the increasing attention paid by the state to traditional medicine and the need for the inheritance and innovative development of Tibetan medicine in the new era, the research and development of new Tibetan medicines has attracted the attention of the industry. This article analyzes the characteristics of prescriptions, dosage forms, preparation methods, and processing of the 34 Tibetan medicine formulas included in the Catalogue of Ancient Famous Classical Formulas(Second Batch), discusses the problems and challenges in the research and development of ancient famous classical formulas of Tibetan medicine, and puts forward opinions and suggestions in order to promote the research and development of new Tibetan medicine. The main issues that may be encountered in the research and development of 34 Tibetan medicine formulas are as follows:①Some medicinal material resources are scarce, and planting/breeding technologies are not yet mature. Among the 34 formulas, there are not only ingredients derived from endangered protected animals, but also national second-class protected plants and rare high-altitude wild species. ②The quality control level of Tibetan medicinal materials urgently needs to be strengthened and improved. After review, among the 102 medicinal materials in the 34 Tibetan medicine formulas, there are 2 varieties that currently have no national or local medicinal material standards/decoction piece processing specifications. Excluding those without quality standards, the proportion of varieties without any quantitative testing items is 49%. ③There are a large number of mineral medicines in Tibetan medicine formulas, making quality control difficult. The proportion of formulas containing mineral medicines among the 34 formulas is 35%, and most of them have not yet established a targeted quality standard system. ④Some Tibetan medicinal materials in the 34 formulas have unclear origins, with issues such as different substances with the same name and the same substance with different names. ⑤The 34 formulas contain medicinal materials labeled as toxic or slightly toxic in the current quality standards. It is recommended to accelerate the verification of key information of Tibetan medicine, and on this basis, to intensify research on planting and breeding, quality control in response to the above issues. It is also suggested to encourage the rational use of new technologies and processes that are suitable for the characteristics of preparations to develop new drugs from ancient famous classical formulas of Tibetan medicine, and promote the inheritance and innovative development of Tibetan medicine.
6.Modified Lianpoyin Formula Treats Hp-associated Gastritis by Regulating Mitochondrial Autophagy and NLRP3 Inflammasome Signaling Pathway
Siyi ZHANG ; Haopeng DANG ; Wenliang LYU ; Wentao ZHOU ; Wei GUO ; Lin LIU ; Lan ZENG ; Yujie SUN ; Luming LIANG ; Yi ZHAO
Chinese Journal of Experimental Traditional Medical Formulae 2025;31(21):178-187
ObjectiveTo explore the effect of modified Lianpoyin formula (LPYJWF) in the treatment of Helicobacter pylori (Hp)-associated gastric mucosal damage based on mitochondrial autophagy and NLRP3 inflammasome signaling pathway. MethodsA total of 60 eight-week-old Balb/c male mice were assigned via the random number table method into control, model, high-dose LPYJWF (LPYJWF-H, 27.3 g·kg-1·d-1), medium-dose LPYJWF (LPYJWF-M, 13.65 g·kg-1·d-1), low-dose LPYJWF (LPYJWF-L, 6.83 g·kg-1·d-1), and quadruple therapy groups. Except the control group, other groups were modeled for Hp infection. Mice were administrated with LPYJWF at corresponding doses by gavage. Quadruple therapy group was given omeprazole (6.06 mg·kg-1·d-1) + amoxicillin (303 mg·kg-1·d-1) + clarithromycin (151.67 mg·kg-1·d-1) + colloidal pectin capsules (30.3 mg·kg-1·d-1) by gavage. The control group was given an equal volume of 0.9% NaCl for 14 days. Hematoxylin-eosin (HE) staining was used to observe the pathological changes of gastric mucosa, and Warthin-Starry (W-S) silver staining was used to detect Hp colonization. Transmission electron microscopy was employed to observe the mitochondrial ultrastructure of the gastric tissue, and immunofluorescence co-localization assay was adopted to detect the expression of mitochondrial transcription factor A (TFAM) and translocase of the outer mitochondrial membrane member 20 (TOMM20). The water-soluble tetrazolium salt method and thiobarbituric acid method were used to determine the levels of superoxide dismutase (SOD) and malondialdehyde (MDA), respectively, in the gastric tissue. Western blot was employed to measure the protein levels of PTEN-induced kinase 1 (PINK1), Parkin, p62, microtubule-associated protein 1 light chain 3 (LC3), NOD-like receptor protein 3 (NLRP3), apoptosis-associated speck-like protein containing a CARD (ASC), interleukin-1β (IL-1β), and interleukin-18 (IL-18). Real-time quantitative PCR was employed to assess the mRNA levels of PINK1, Parkin, p62, and LC3. ResultsCompared with the control group, the model group presented obvious gastric mucosal damage, colonization of a large number of Hp, severe mitochondrial damage, vacuolated structures due to excessive autophagy, reduced TOMM20 and TFAM co-expression in the gastric mucosal tissue, and reduced SOD and increased MDA (P<0.01). In addition, the gastric tissue in the model group showed up-regulated protein and mRNA levels of PINK1, Parkin, and LC3 and down-regulated protein and mRNA levels of p62 (P<0.01, as well as increased expression of inflammasome-associated proteins NLRP3, ASC, IL-1β, and IL-18 (P<0.01). Compared with the model group, the LPYJWF and quadruple therapy groups showed alleviated pathological damage of gastric mucosa, reduced Hp colonization, mitigated mitochondrial damage, and increased co-expression of TOMM20 and TFAM. The SOD level was elevated in the LPYJWF-L group (P<0.01), and the MDA levels became lowered in the LPYJWF and quadruple therapy groups (P<0.05, P<0.01). Furthermore, the LPYJWF and quadruple therapy groups showed down-regulated mRNA levels of PINK1, Parkin, and LC3 and protein levels of PINK1 and Parkin, and up-regulated mRNA level of p62 (P<0.01). The LPYJWF-M, LPYJWF-H, and quadruple therapy groups showcased down-regulated LC3 Ⅱ/LC3 Ⅰ level (P<0.05, P<0.01) and up-regulated protein level of p62 (P<0.01). The expression of inflammasome-associated proteins NLRP3, ASC, IL-1β, and IL-18 were reduced in the LPYJWF and quadruple therapy groups (P<0.05, P<0.01). ConclusionLPYJWF ameliorates gastric mucosal damage and exerts mucosa-protective effects in Hp-infected mice, which may be related to the inhibition of excessive mitochondrial autophagy, thereby inhibiting the activation of the NLRP3 inflammasome pathway.
7.Modified Lianpoyin Formula Treats Hp-associated Gastritis by Regulating Mitochondrial Autophagy and NLRP3 Inflammasome Signaling Pathway
Siyi ZHANG ; Haopeng DANG ; Wenliang LYU ; Wentao ZHOU ; Wei GUO ; Lin LIU ; Lan ZENG ; Yujie SUN ; Luming LIANG ; Yi ZHAO
Chinese Journal of Experimental Traditional Medical Formulae 2025;31(21):178-187
ObjectiveTo explore the effect of modified Lianpoyin formula (LPYJWF) in the treatment of Helicobacter pylori (Hp)-associated gastric mucosal damage based on mitochondrial autophagy and NLRP3 inflammasome signaling pathway. MethodsA total of 60 eight-week-old Balb/c male mice were assigned via the random number table method into control, model, high-dose LPYJWF (LPYJWF-H, 27.3 g·kg-1·d-1), medium-dose LPYJWF (LPYJWF-M, 13.65 g·kg-1·d-1), low-dose LPYJWF (LPYJWF-L, 6.83 g·kg-1·d-1), and quadruple therapy groups. Except the control group, other groups were modeled for Hp infection. Mice were administrated with LPYJWF at corresponding doses by gavage. Quadruple therapy group was given omeprazole (6.06 mg·kg-1·d-1) + amoxicillin (303 mg·kg-1·d-1) + clarithromycin (151.67 mg·kg-1·d-1) + colloidal pectin capsules (30.3 mg·kg-1·d-1) by gavage. The control group was given an equal volume of 0.9% NaCl for 14 days. Hematoxylin-eosin (HE) staining was used to observe the pathological changes of gastric mucosa, and Warthin-Starry (W-S) silver staining was used to detect Hp colonization. Transmission electron microscopy was employed to observe the mitochondrial ultrastructure of the gastric tissue, and immunofluorescence co-localization assay was adopted to detect the expression of mitochondrial transcription factor A (TFAM) and translocase of the outer mitochondrial membrane member 20 (TOMM20). The water-soluble tetrazolium salt method and thiobarbituric acid method were used to determine the levels of superoxide dismutase (SOD) and malondialdehyde (MDA), respectively, in the gastric tissue. Western blot was employed to measure the protein levels of PTEN-induced kinase 1 (PINK1), Parkin, p62, microtubule-associated protein 1 light chain 3 (LC3), NOD-like receptor protein 3 (NLRP3), apoptosis-associated speck-like protein containing a CARD (ASC), interleukin-1β (IL-1β), and interleukin-18 (IL-18). Real-time quantitative PCR was employed to assess the mRNA levels of PINK1, Parkin, p62, and LC3. ResultsCompared with the control group, the model group presented obvious gastric mucosal damage, colonization of a large number of Hp, severe mitochondrial damage, vacuolated structures due to excessive autophagy, reduced TOMM20 and TFAM co-expression in the gastric mucosal tissue, and reduced SOD and increased MDA (P<0.01). In addition, the gastric tissue in the model group showed up-regulated protein and mRNA levels of PINK1, Parkin, and LC3 and down-regulated protein and mRNA levels of p62 (P<0.01, as well as increased expression of inflammasome-associated proteins NLRP3, ASC, IL-1β, and IL-18 (P<0.01). Compared with the model group, the LPYJWF and quadruple therapy groups showed alleviated pathological damage of gastric mucosa, reduced Hp colonization, mitigated mitochondrial damage, and increased co-expression of TOMM20 and TFAM. The SOD level was elevated in the LPYJWF-L group (P<0.01), and the MDA levels became lowered in the LPYJWF and quadruple therapy groups (P<0.05, P<0.01). Furthermore, the LPYJWF and quadruple therapy groups showed down-regulated mRNA levels of PINK1, Parkin, and LC3 and protein levels of PINK1 and Parkin, and up-regulated mRNA level of p62 (P<0.01). The LPYJWF-M, LPYJWF-H, and quadruple therapy groups showcased down-regulated LC3 Ⅱ/LC3 Ⅰ level (P<0.05, P<0.01) and up-regulated protein level of p62 (P<0.01). The expression of inflammasome-associated proteins NLRP3, ASC, IL-1β, and IL-18 were reduced in the LPYJWF and quadruple therapy groups (P<0.05, P<0.01). ConclusionLPYJWF ameliorates gastric mucosal damage and exerts mucosa-protective effects in Hp-infected mice, which may be related to the inhibition of excessive mitochondrial autophagy, thereby inhibiting the activation of the NLRP3 inflammasome pathway.
8.The Applications and Challenges of Generative Artificial Intelligence in Theoretical and Case Analysis Assessment for Resident Physician Education
Yuankai ZHOU ; Jun SUN ; Shengjun LIU ; Yingying YANG ; Siyi YUAN ; Huaiwu HE ; Yun LONG
Medical Journal of Peking Union Medical College Hospital 2025;16(5):1352-1356
Generative artificial intelligence (GAI) represents a prominent research focus in medicine, with medical education being a key application area. GAI demonstrates potential to enhance residency training efficacy through personalized instruction, automated assessment item generation, question bank updating, and intelligent scoring systems. However, current limitations exist regarding output accuracy and content consistency. To address these constraints, strategic measures are required: continuous GAI model refinement, development of standardized usage guidelines, enhanced data quality control, and implementation of human verification protocols for generated content. Concurrently, residents should proactively acquire GAI utilization skills to strengthen the practical application of theoretical knowledge. With these advancements, GAI is anticipated to evolve into a valuable asset for improving the efficiency and quality of residency training programs.
9.LIU Xing's experience in treatment of peripheral facial paralysis with combined therapy of acupotomy, cupping and herbal medication.
Dunlin FANG ; Siyi LI ; Wanchun HU ; Tong LIU ; Changchang ZHANG ; Pengpeng PENG ; Junjie ZHANG ; Xing LIU
Chinese Acupuncture & Moxibustion 2025;45(11):1639-1644
This article introduces Professor LIU Xing's clinical experience in treatment of peripheral facial paralysis at the recovery and sequelae stages with the combination of acupotomy, cupping and herbal medication. Based on the analysis of etiology and pathogenesis of peripheral facial paralysis, Professor LIU believes that "invasion of pathogenic wind to collaterals and obstruction of qi and blood" is crucial. Therefore, the treatment focuses on "dispelling wind and harmonizing blood". The compound therapeutic mode is proposed, with acupotomy, cupping and herbal decoction involved, in which, "three-step sequential method of acupotomy" is predominated. Firstly, in the prone position, five "feng" (wind) points are stimulated in patient, Fengfu (GV16), Fengchi (GB20), Yifeng (TE17), Bingfeng (SI12) and Fengmen (BL12). Secondly, in the lateral position, three-facial points are stimulated (FaceⅠneedle: Yangbai [GB14]-Yuyao [EX-HN4]; Face Ⅱ needle: Sibai [ST2]-Quanliao [SI18]; Face Ⅲ needle: Jiache [ST6]-Dicang [ST4]) to restore the deviated facial muscles. Finally, in the supine, two Dantian points are stimulated on the forehead and chest, respectively (upper Dantian: Yintang [GV24+], middle Dantian: Danzhong [CV17]), to regulate qi and blood. As the adjunctive therapies, cupping is used to remove stasis, and herbal decoction is to harmonize the body interior. In view of holistic regulation, the treatment is administered in accordance with the affected meridians, so as to expel wind, remove obstruction in collaterals and regulate qi and blood.
Humans
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Facial Paralysis/drug therapy*
;
Drugs, Chinese Herbal/administration & dosage*
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Acupuncture Therapy
;
Male
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Female
;
Middle Aged
;
Adult
;
Combined Modality Therapy
;
Acupuncture Points
;
Cupping Therapy
;
Aged
;
Young Adult
10.Noncoding RNA Terc-53 and hyaluronan receptor Hmmr regulate aging in mice.
Sipeng WU ; Yiqi CAI ; Lixiao ZHANG ; Xiang LI ; Xu LIU ; Guangkeng ZHOU ; Hongdi LUO ; Renjian LI ; Yujia HUO ; Zhirong ZHANG ; Siyi CHEN ; Jinliang HUANG ; Jiahao SHI ; Shanwei DING ; Zhe SUN ; Zizhuo ZHOU ; Pengcheng WANG ; Geng WANG
Protein & Cell 2025;16(1):28-48
One of the basic questions in the aging field is whether there is a fundamental difference between the aging of lower invertebrates and mammals. A major difference between the lower invertebrates and mammals is the abundancy of noncoding RNAs, most of which are not conserved. We have previously identified a noncoding RNA Terc-53 that is derived from the RNA component of telomerase Terc. To study its physiological functions, we generated two transgenic mouse models overexpressing the RNA in wild-type and early-aging Terc-/- backgrounds. Terc-53 mice showed age-related cognition decline and shortened life span, even though no developmental defects or physiological abnormality at an early age was observed, indicating its involvement in normal aging of mammals. Subsequent mechanistic study identified hyaluronan-mediated motility receptor (Hmmr) as the main effector of Terc-53. Terc-53 mediates the degradation of Hmmr, leading to an increase of inflammation in the affected tissues, accelerating organismal aging. adeno-associated virus delivered supplementation of Hmmr in the hippocampus reversed the cognition decline in Terc-53 transgenic mice. Neither Terc-53 nor Hmmr has homologs in C. elegans. Neither do arthropods express hyaluronan. These findings demonstrate the complexity of aging in mammals and open new paths for exploring noncoding RNA and Hmmr as means of treating age-related physical debilities and improving healthspan.
Animals
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Mice
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RNA, Untranslated/metabolism*
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Aging/genetics*
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Mice, Transgenic
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Telomerase/metabolism*
;
RNA/genetics*
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Hippocampus/metabolism*
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Humans
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Mice, Inbred C57BL

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