1.Textual Research on Key Information and Modern Clinical Application of Classical Famous Formula Liumotang
Xinyu ZHANG ; Chong LI ; Yixuan HU ; Luming LIANG ; Ye ZHAO ; Xiaoting LU ; Yu WANG
Chinese Journal of Experimental Traditional Medical Formulae 2025;31(3):201-212
Liumotang comes from the Yuan dynasty's Effective Prescription Handed Down for Generations of Physicians. It is composed of six medicinal materials: Arecae Semen, Aquilariae Lignum Resinatum, Aucklandiae Radix, Linderae Radix, Rhei Radix et Rhizoma, and Aurantii Fructus. It is a classical formula for treating abdominal pain due to Qi stagnation and constipation accompanied by heat. This study systematically collated the records of Liumotang in ancient medical books and modern clinical literature and conducted in-depth analysis and textual research on its formula source, main diseases, composition, dosage, medical books, container capacity, processing, preparation method, usage, drug basis, formula meaning, and other key information, so as to provide a powerful reference for the development and clinical application of compound preparations of the classical formula Liumotang. The results show that Liumotang was first seen in Effective Prescription Handed Down for Generations of Physicians, and many medical books of the past dynasties have imitated this. In terms of drug basis, the dried and mature seeds of the palm plant Areca catechu, resin-containing wood of the Daphneaceae plant Aquilaria sinensis, the dried roots of the Asteraceae plant woody Aucklandia lappa, the dried tuber root of the Lauraceae plant Lindera aggregata, the dried roots and rhizomes of the knotweed plant, R. palmatum, R.tangutikum, and R. officinale, and the dried and unripe fruits of the citrus genus C. aurantium and its cultivated varieties from the family Rutaceae were selected. In terms of dosage, through the textual research on bowls in the Ming and Qing dynasties, combined with the conversion of medicines and bowl capacity in the Qing dynasty, it was estimated that the dosage of each drug in the Yuan dynasty was 10.86 g. In the Ming and Qing dynasties, the dosage of drugs was mostly equal, but the dosage of drugs was somewhat different. In terms of processing, preparation method, and usage, in the medical books of the past dynasties, the processing of drugs has slightly changed, but raw drugs are used in all preparations. The preparation method and usage did not change much during the Yuan, Ming, and Qing dynasties, except for certain differences in dosage. In terms of syndrome, Liumotang was first used to treat abdominal pain due to Qi stagnation and constipation accompanied by heat. Medical books of the past dynasties often omit the symptoms of heat. In modern clinical practice, Liumotang is mainly used in the digestive system and urinary system diseases and is mostly used to treat constipation-predominant irritable bowel syndrome, biliary reflux gastritis, functional constipation, slow transit constipation, and other diseases, with no adverse reactions found yet. The above results provide a reliable scientific basis for the development and clinical treatment of Liumotang compound preparations.
2.Different Effects of Fresh and Dried Dendrobium Huoshanense on Chronic Atrophic Gastritis
Mengqing HU ; Xinyu YANG ; Weihan GONG ; Huiqun XIE ; Lan HAN ; Daiyin PENG
Chinese Journal of Experimental Traditional Medical Formulae 2025;31(22):29-39
ObjectiveTo compare the protective effects of water extracts from fresh and dried Dendrobium huoshanense on gastric mucosa in chronic atrophic gastritis (CAG). MethodsMale SD rats (n=72) were randomly divided into 9 groups, with 8 rats in each group, which were normal group, model group, Yangwei Shu (4 g·kg-1) group, low-, medium-, and high-dose fresh D. huoshanense (3.5, 7, and 14 g·kg-1) groups, and low-, medium-, and high-dose dried D. huoshanense (0.7, 1.4, 2.8 g·kg-1) groups. The CAG rat model was successfully established by inducing with N-methyl-N'-nitro-N-nitrosoguanidine (MNNG) and other factors for a total of 11 weeks. Then, the rats were intervened with fresh and dried D. huoshanense for 4 weeks. The serum and gastric tissues of the rats were collected. The changes in gastric juice secretion volume and gastric acid pH value in each group were observed. The gastric mucosal injury was observed by naked eyes and hematoxylin-eosin(HE) staining. The gastric mucus secretion level was determined by Alcian blue and periodic acid-Schiff staining(AB-PAS) staining. The expression levels of tight junction proteins Occludin and ZO-1 in gastric tissues were determined by immunofluorescence. The expression levels of serum pepsinogen Ⅰ (PG Ⅰ), pepsinogen Ⅱ (PG Ⅱ), gastrin 17 (G-17), interleukin-1β (IL-1β), interleukin-6 (IL-6), and tumor necrosis factor-α (TNF-α) were determined by enzyme-linked immunosorbent assay (ELISA). The expression levels of aquaporin 1 (AQP1), aquaporin 3 (AQP3), and aquaporin 4 (AQP4) in gastric tissues were determined by Western blot. ResultsCompared with the normal group, the model group showed an obviously reduced gastric juice secretion volume (P0.05), significantly increased gastric acid pH value (P0.01), gastric mucosa with obvious atrophy, and a significantly reduced gastric mucus secretion volume (P0.01). The expression of Occludin and ZO-1 in the gastric mucosal barrier was significantly decreased (P0.01). The levels of PG Ⅰ and PG Ⅱ in the serum were obviously decreased (P0.05, P0.01), and the levels of G-17, IL-1β, IL-6, and TNF-α were significantly increased (P0.01). The expression level of AQP1 in the gastric tissue was significantly upregulated (P0.01), and the expression levels of AQP3 and AQP4 were significantly downregulated (P0.01). Compared with the model group, each drug administration group could improve the gastric mucosal atrophy of CAG model rats to varying degrees, obviously increase the gastric juice secretion volume of the model rats (P0.05, P0.01), significantly decrease the gastric acid pH value (P0.01), obviously increase the gastric mucus secretion volume (P0.05, P0.01), obviously decrease the expression levels of G-17, IL-6, IL-1β, and TNF-α (P0.05, P0.01), obviously increase the expression levels of Occludin, ZO-1, PG Ⅰ, and PG Ⅱ (P0.05, P0.01), obviously upregulate the expression levels of AQP3 and AQP4 (P0.05, P0.01), and obviously downregulate the expression level of AQP1 (P0.05, P0.01). ConclusionThe water extracts of fresh and dried D. huoshanense can exert therapeutic effects on CAG by improving gastric mucosal injury, reducing inflammation, and regulating water metabolism. Moreover, the dried D. huoshanense has a better effect.
3.Relationship between changes in classroom lighting environment and refractive progression among primary and secondary school students
HAN Di, LING Ruizhe, ZHANG Liye, WANG Yuehong, BAO Xinyu, SHEN Hui, HU Jia
Chinese Journal of School Health 2025;46(11):1549-1553
Objective:
To analyze the changes in classroom lighting environment of schools in Suzhou and their impact on refractive progression among primary and secondary school students, so as to provide the basis for accurate provention and control of myopia.
Methods:
A baseline investigation was conducted in October 2022 by using a stratified cluster random sampling method to recruit primary and secondary school students from Suzhou. A follow up visit was performed in October 2023. A total of 12 302 students and 360 classrooms that participated in both surveys were included analysis. The visual acuity progression over one year and classroom lighting conditions were assessed. Group comparisons were performed by using the Wilcoxon or Kruskal-Wallis rank-sum, and Chi-square tests. Multivariate Logistic regression was employed to identify the major factors influencing refractive changes.
Results:
The compliance rate of average illuminance on classroom blackboard surface increased from 72.22% to 75.28%, while the compliance rate of average illuminance on desks decreased from 89.44% to 87.22%, the overall myopia rate among students rose from 59.63% to 66.99% from 2022 to 2023. The average annual progression of equivalent spherical power(SE) in the right eye of students was -0.25(-0.75,0.06)D. Significant statistical differences were observed in the annual mean changes across different school levels, regions, baseline refractive statuses, and classroom lighting environment change groups ( Z/H =316.59, -8.27, 38.80 , 51.01, all P <0.05). Multivariate Logistic regression analysis showed that pre myopia, low myopia, junior high school, senior high school, vocational high school, and improved classroom lighting environment were protective factors of reducing the risk of rapid progression in refractive error ( OR =0.58, 0.69, 0.81, 0.50, 0.28, 0.82, all P <0.05). Conversely, female students and rural students had higher risks of rapid myopia progression ( OR =1.09, 1.42, both P <0.05).
Conclusions
Over one year follow up, the complance rate of classroom lighting indicators in Suzhou remaines stable, while students refractive status shows a trend toward myopia. Improving classroom lighting environment can reduce the risk of rapid myopia progression.
4.Clinical application of "talus home technique" in pronation open ankle fractures.
Zhenhui SUN ; Jinxi HU ; Yanci ZHANG ; Dehang LIU ; Jianyi LEI ; Jianbo GUO
Chinese Journal of Reparative and Reconstructive Surgery 2025;39(5):542-549
OBJECTIVE:
To explore the safety and effectiveness of the "talus home technique (THT) " in the surgery of pronation open ankle fractures (POAF).
METHODS:
A retrospective analysis was conducted on 14 patients with POAF admitted between January 2023 and December 2023 who met the selection criteria. There were 7 males and 7 females; age ranged from 26 to 58 years, with a median age of 53 years. Injury causes included 9 cases of traffic accident injury, 3 cases of fall from hight injury, and 2 cases of crush injury. There were 5 cases of type Ⅱ, 6 cases of type ⅢA, and 3 cases of type ⅢB according to Gustilo classification; and 6 cases of pronation-abduction grade Ⅲ and 8 cases of pronation-external rotation grade Ⅳ according to Lauge-Hansen classification. Emergency first-stage debridement of the ankle joint was performed, followed by second-stage open reduction and internal fixation surgery. The THT was used through a limited incision on the lateral malleolus to restore the height of the lateral malleolus, rotational alignment, and anatomical relationship of the distal tibiofibular syndesmosis (DTFS). Wound healing was observed postoperatively. At 4 months postoperatively, weight-bearing anteroposterior, lateral, and mortise view X-ray films and CT scans of both ankles were reviewed to measure the medial clear space (MCS), tibiofibular clear space (TFCS), distal fibular tip to lateral process of talus (DFTL), and anterior/posterior syndesmosis distances of DTFS, and the quality of reduction of ankle fractures was evaluated. Ankle joint function was assessed using the American Orthopedic Foot and Ankle Society (AOFAS) ankle-hindfoot score, and active dorsiflexion/plantar flexion range of motion were recorded at last follow-up.
RESULTS:
After second-stage internal fixation, 8 patients achieved wound healing by first intention, 1 case had skin edge necrosis, 2 cases had local skin necrosis, 1 case had extensive medial soft tissue defect, and 2 cases developed medial wound infection with sinus formation. All 14 patients were followed up 13-24 months (mean, 16.8 months). Postoperative X-ray films showed 1 case of delayed union of the lateral malleolus, which healed after bone grafting at 12 months; the remaining 13 cases achieved clinical union at 12-32 weeks (mean, 21.5 weeks). At 4 months postoperatively, X-ray films and CT examination showed no significant differences in MCS, TFCS, DFTL, and anterior/posterior syndesmosis distances of DTFS between the healthy and affected sides ( P>0.05), with no poor DTFS reduction. AOFAS ankle-hindfoot score ranged from 80 to 95, with an average of 87.7; ankle range of motion ranged from 10° to 25° (mean, 19.6°) in dorsiflexion and from 32° to 50° (mean, 41.2°) in plantar flexion.
CONCLUSION
THT is safe and effective in POAF surgery. It can restore lateral malleolar height and rotational alignment, enhance DTFS reduction quality, and obtain satisfactory short-term functional recovery of the ankle.
Humans
;
Male
;
Female
;
Middle Aged
;
Ankle Fractures/surgery*
;
Adult
;
Retrospective Studies
;
Fracture Fixation, Internal/methods*
;
Pronation
;
Fractures, Open/surgery*
;
Talus/surgery*
;
Treatment Outcome
;
Debridement/methods*
;
Ankle Joint/surgery*
;
Open Fracture Reduction/methods*
5.Clinical study on reduction of posterior malleolar fractures via modified Rammelt transfibular approach.
Shaozhen JI ; Jianyi LEI ; Jianbo GUO ; Dehang LIU ; Xiangliang GE ; Jinxi HU ; Shixin LIU ; Zhenhui SUN
Chinese Journal of Reparative and Reconstructive Surgery 2025;39(11):1441-1446
OBJECTIVE:
To evaluate the safety and effectiveness of reducing posterior malleolar fractures via the modified Rammelt transfibular approach.
METHODS:
A retrospective analysis was conducted on 26 patients with ankle fractures who met the selection criteria and were admitted between September 2023 and May 2024. There were 13 males and 13 females, aged from 14 to 59 years (median, 43.5 years). Causes of injury included traffic accident (1 case), falls (7 cases), and sprains (18 cases). Time from injury to operation ranged from 1 to 13 days (mean, 3.9 days). According to the Lauge-Hansen classification, there were 5 supination-external rotation type Ⅲ fractures and 21 supination-external rotation type Ⅳ fractures. According to the Bartoníček classification for posterior malleolar fractures, there were 12 type Ⅱ fractures, 10 type Ⅲ fractures, and 4 type Ⅳ fractures. During operation, the fracture was exposed via the modified Rammelt transfibular approach; then, the fracture reduction was achieved under direct vision using techniques such as towel clip traction, posterolateral compression, and lifting with a posterior transverse periosteal elevator; finally, the fracture was fixed using anteroposterior cannulated screws or Kirschner wires. The incision healing was observed after operation. At 4 months after operation, X-ray film and CT were reviewed to evaluate the quality of fracture reduction. The medial clear space, tibiofibular clear space, and the anterior/posterior tibiofibular syndesmotic distances were measured. At last follow-up, the ankle function was assessed using the American Orthopaedic Foot & Ankle Society (AOFAS) score and the range of motion.
RESULTS:
The marginal necrosis occurred in 2 lateral malleolar incisions, and superficial infection occurred in 1 lateral malleolar incision; the remaining incisions healed by first intention. All 26 patients were followed up 13-21 months (mean, 15.6 months). X-ray films showed that fractures in 25 patients achieved clinical union within 3-8 months (mean, 5.4 months); 1 case had delayed union of the lateral malleolus. At 4 months after operation, no significant difference was found between the injured and healthy sides in the medial clear space, tibiofibular clear space, or the anterior/posterior tibiofibular syndesmotic distances ( P>0.05). No malreduction of the posterior malleolus or the tibiofibular syndesmosis occurred. At last follow-up, the AOFAS score ranged from 80 to 100 (mean, 91.9). The range of motion ranged from 17° to 22° (mean, 21.0°) in active ankle dorsiflexion and from 40° to 49° (mean, 44.6°) in plantar flexion. Internal fixator was removed in 12 patients at 1 year after operation, with no ankle instability occurring. Ankle joint degeneration was observed in 1 patient at last follow-up.
CONCLUSION
The modified Rammelt transfibular approach is a safe and reliable technique. It enables precise reduction under direct vision, improves the quality of reduction for the distal tibial articular surface and the tibiofibular syndesmosis, and provides satisfactory ankle functional recovery in short-term follow-up.
Humans
;
Male
;
Female
;
Adult
;
Ankle Fractures/diagnostic imaging*
;
Middle Aged
;
Retrospective Studies
;
Fracture Fixation, Internal/instrumentation*
;
Adolescent
;
Treatment Outcome
;
Young Adult
;
Bone Screws
;
Ankle Joint/surgery*
;
Fibula/surgery*
;
Range of Motion, Articular
6.Impact of future-oriented coping on depression among medical staff: A chain mediation model involving psychological resilience and perceived stress.
Minghui LIU ; Xinyu CHEN ; Qing LU ; Daifeng DONG ; Yi ZHANG ; Muli HU ; Na YAO
Journal of Central South University(Medical Sciences) 2025;50(2):281-289
OBJECTIVES:
Depression is a common negative emotion that can significantly impact physical and mental health. Due to their occupational characteristics, medical staff are more susceptible to depression compared to the general population. This study aims to explore the influence of future-oriented coping on depression among medical staff and the mediating roles of psychological resilience and perceived stress, providing theoretical guidance for depression intervention strategies in this group.
METHODS:
A cross-sectional survey was conducted among medical staff at a tertiary hospital using convenience sampling. Data were collected via the "Wenjuanxing" platform. A total of 754 questionnaires were distributed; after excluding invalid responses (e.g., duplicate IPs or insufficient completion time), 655 valid questionnaires were retained (valid response rate: 86.87%). Instruments included a demographic questionnaire, the Future-Oriented Coping Scale, the Connor-Davidson Resilience Scale, the Perceived Stress Scale, and the Self-Rating Depression Scale. All scales demonstrated high internal consistency (Cronbach's α>0.88) and validity. SPSS 27.0 was used for descriptive analysis, and PROCESS macro (Model 6) was used to test the chain mediation model. Harman's one-factor test was applied to control for common method bias.
RESULTS:
Descriptive analyses showed that future-oriented coping was positively correlated with psychological resilience and negatively correlated with perceived stress and depression. Mediation analysis revealed that future-oriented coping significantly predicted lower depression levels among medical staff (β=-0.283, P<0.001). Psychological resilience partially mediated the relationship (effect size=-0.329, accounting for 34.13% of the total effect), as did perceived stress (effect size=-0.099, 10.27%). A significant chain mediation path was identified: "future-oriented coping → psychological resilience → perceived stress → depression" (effect size=-0.253, 26.24%). The total indirect effect accounted for 70.64% of the overall effect, highlighting the substantial role of the mediating pathways.
CONCLUSIONS
Future-oriented coping can reduce depressive symptoms in medical staff, with psychological resilience and perceived stress serving as key mediators in a chain structure. These findings suggest that enhancing future-oriented coping strategies and psychological resilience may improve stress adaptation and reduce depression levels in this population.
Humans
;
Adaptation, Psychological
;
Resilience, Psychological
;
Cross-Sectional Studies
;
Depression/psychology*
;
Surveys and Questionnaires
;
Stress, Psychological/psychology*
;
Male
;
Female
;
Adult
;
Middle Aged
;
Medical Staff/psychology*
;
Occupational Stress/psychology*
7.Effect of job insecurity on anxiety among university young teachers: Chain mediating roles of perceived stress and insomnia.
Xinyu CHEN ; Qing LU ; Fang ZHOU ; Muli HU ; Na YAO ; Yi ZHANG ; Fei QIU
Journal of Central South University(Medical Sciences) 2025;50(4):706-713
OBJECTIVES:
Anxiety is a common negative emotion. Under current social circumstances, university young teachers face multiple stressors and are more prone to anxiety, seriously threatening their physical and mental health. This study aims to investigate the impact of job insecurity on anxiety of university young teachers, while exploring the mediating roles of perceived stress and insomnia on this relationship.
METHODS:
Using convenience sampling, young teachers from a general university in a Chinese province were surveyed online. Scores of the Job Insecurity Scale, Perceived Stress Scale, Athens Insomnia Scale-Short Form, and Generalized Anxiety Disorder Scale were collected. A chain mediation analysis was conducted using the PROCESS macro.
RESULTS:
A total of 798 subjects were finally included. The detection rate of anxiety among university young teachers was 36.47%. Mediation analysis showed that job insecurity not only had a direct effect on anxiety, but also indirectly affected anxiety via perceived stress (46.42% of the total effect) and insomnia (7.45%), as well as through the chain-mediating path of perceived stress→ insomnia (13.18%; all P<0.05).
CONCLUSIONS
Job insecurity is a significant predictor of anxiety in young university faculty. Perceived stress and insomnia serve as sequential mediators in this relationship. Targeted interventions addressing job insecurity, stress perception, and sleep disturbances, alongside efforts to improve mental health literacy and the working environment, may help promote the overall well-being of university young teachers.
Humans
;
Sleep Initiation and Maintenance Disorders/epidemiology*
;
Universities
;
Female
;
Anxiety/psychology*
;
Male
;
Stress, Psychological/psychology*
;
Adult
;
Faculty/psychology*
;
Surveys and Questionnaires
;
China/epidemiology*
;
Occupational Stress
;
Job Security
8.Efficacy analysis of Epley procedure and Semont procedure with different lateral lying angles of the head in posterior semicircular canal BPPV.
Hui ZHANG ; Jiajia HU ; Meng WANG ; Lihong ZHAI ; Xinyu LYU ; Zhanguo JIN
Journal of Clinical Otorhinolaryngology Head and Neck Surgery 2025;39(4):357-361
Objective:To investigate the effects of the Epley and Semont procedures with varying lateral angles of the head on posterior semicircular canal benign paroxysmal positional vertigo (PC-BPPV). Methods:A total of 115 patients with unilateral PC-BPPV were randomly divided into five groups: Epley group, Semont group, Semont+10° group, Semont+20° group, and Semont+30° group, with 23 patients in each group. Corresponding reduction treatments were performed. Results:The total effective rates for the Epley group, Semont group, Semont+10° group, Semont+20° group, and Semont+30° group were 95.7% (22/23), 4.3% (1/23), 30.4% (7/23), 52.2% (12/23), and 87.0% (20/23) respectively. The inefficiencies were 4.3% (1/23), 95.7% (22/23), 69.6% (16/23), 47.8% (11/23), and 13.0% (3/23). Statistically significant differences were observed in the total effective rates among the five groups (χ²=54.11, P<0.01). The total effective rates in the Semont group, Semont+10° group, and Semont+20° group were significantly different from that of the Epley group (P<0.01), while no statistically significant difference was found between the Semont+30° group and the Epley group (P= 0.608>0.012 5). Conclusion:Among the four Semont methods with different lateral lying angles, the total effective rate of reduction treatment increased with the elevation of the lateral lying angle on the affected side. The efficacy of the Semont+30° group in treating PC-BPPV was not significantly different from the Epley group's reduction effect, which was markedly superior to that of the other four Semont methods at different angles. Therefore, the Semont+30° reduction technique is recommended for the treatment of PC-BPPV.
Adult
;
Aged
;
Female
;
Humans
;
Male
;
Middle Aged
;
Benign Paroxysmal Positional Vertigo/therapy*
;
Head
;
Posture
;
Semicircular Canals/physiopathology*
;
Treatment Outcome
9.Astrocytic dopamine D1 receptor modulates glutamatergic transmission and synaptic plasticity in the prefrontal cortex through d-serine.
Yanan YIN ; Jian HU ; Haipeng WU ; Xinyu YANG ; Jingwen QI ; Lang HUANG ; Zhengyi LUO ; Shiyang JIN ; Nengyuan HU ; Zhoucai LUO ; Tong LUO ; Hao CHEN ; Xiaowen LI ; Chunhua YUAN ; Shuji LI ; Jianming YANG ; Yihua CHEN ; Tianming GAO
Acta Pharmaceutica Sinica B 2025;15(9):4692-4710
The prefrontal cortex (PFC) plays a pivotal role in orchestrating higher-order emotional and cognitive processes, a function that depends on the precise modulation of synaptic activity. Although pharmacological studies have demonstrated that dopamine signaling through dopamine D1 receptor (DRD1) in the PFC is essential for these functions, the cell-type-specific and molecular mechanisms underlying the neuromodulatory effects remain elusive. Using cell-type-specific knockout mice and patch-clamp recordings, we investigated the regulatory role of DRD1 on neurons and astrocytes in synaptic transmission and plasticity. Furthermore, we explored the mechanisms by which DRD1 on astrocytes regulate synaptic transmission and plasticity at the cellular level, as well as emotional and cognitive functions at the behavioral level, through two-photon imaging, microdialysis, high-performance liquid chromatography, transcriptome sequencing, and behavioral testing. We found that conditional knockout of the Drd1 in astrocytes (CKOAST) increased glutamatergic synaptic transmission and long-term potentiation (LTP) in the medial prefrontal cortex (mPFC), whereas Drd1 deletion in pyramidal neurons did not affect synaptic transmission. The elevated level of d-serine in the mPFC of CKOAST mice increased glutamatergic transmission and LTP through NMDA receptors. In addition, CKOAST mice exhibited abnormal emotional and cognitive function. Notably, these behavioral changes in CKOAST mice could be reversed through the administration of d-serine degrease to the mPFC. These results highlight the critical role of the astrocytic DRD1 in modulating mPFC synaptic transmission and plasticity, as well as higher brain functions through d-serine, and may shed light on the treatment of mental disorders.
10.PARylation promotes acute kidney injury via RACK1 dimerization-mediated HIF-1α degradation.
Xiangyu LI ; Xiaoyu SHEN ; Xinfei MAO ; Yuqing WANG ; Yuhang DONG ; Shuai SUN ; Mengmeng ZHANG ; Jie WEI ; Jianan WANG ; Chao LI ; Minglu JI ; Xiaowei HU ; Xinyu CHEN ; Juan JIN ; Jiagen WEN ; Yujie LIU ; Mingfei WU ; Jutao YU ; Xiaoming MENG
Acta Pharmaceutica Sinica B 2025;15(9):4673-4691
Poly(ADP-ribosyl)ation (PARylation) is a specific form of post-translational modification (PTM) predominantly triggered by the activation of poly-ADP-ribose polymerase 1 (PARP1). However, the role and mechanism of PARylation in the advancement of acute kidney injury (AKI) remain undetermined. Here, we demonstrated the significant upregulation of PARP1 and its associated PARylation in murine models of AKI, consistent with renal biopsy findings in patients with AKI. This elevation in PARP1 expression might be attributed to trimethylation of histone H3 lysine 4 (H3K4me3). Furthermore, a reduction in PARylation levels mitigated renal dysfunction in the AKI mouse models. Mechanistically, liquid chromatography-mass spectrometry indicated that PARylation mainly occurred in receptor for activated C kinase 1 (RACK1), thereby facilitating its subsequent phosphorylation. Moreover, the phosphorylation of RACK1 enhanced its dimerization and accelerated the ubiquitination-mediated hypoxia inducible factor-1α (HIF-1α) degradation, thereby exacerbating kidney injury. Additionally, we identified a PARP1 proteolysis-targeting chimera (PROTAC), A19, as a PARP1 degrader that demonstrated superior protective effects against renal injury compared with PJ34, a previously identified PARP1 inhibitor. Collectively, both genetic and drug-based inhibition of PARylation mitigated kidney injury, indicating that the PARylated RACK1/HIF-1α axis could be a promising therapeutic target for AKI treatment.


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