1.Effects of Yishen paidu formula on renal fibrosis in rats with chronic renal failure by regulating the ROS/TXNIP/NLRP3 pathway
Li FENG ; Bowen PENG ; Bin PENG ; Xue FENG ; Shuangyi ZHU ; Wei XIONG ; Xi HU ; Xiaohui SUN
China Pharmacy 2026;37(2):174-179
OBJECTIVE To investigate the effects and mechanism of the Yishen paidu formula on renal fibrosis in rats with chronic renal failure (CRF) through the reactive oxygen species (ROS)/thioredoxin-interacting protein (TXNIP)/NOD-like receptor thermal protein domain associated protein 3 (NLRP3) pathway. METHODS Rats were randomly divided into control group, model group, Yishen paidu formula low-dose (Yishen paidu formula-L) group, Yishen paidu formula high-dose (Yishen paidu formula- H) group, Yishen paidu formula-H+pcDNA-NC group, and Yishen paidu formula-H+ pcDNA-TXNIP group, with 10 rats in each group. Except for control group, all other rats were fed a diet containing 0.5% adenine to establish a CRF model; the rats were then administered corresponding drugs or normal saline intragastrically or via tail vein, once daily, for 8 consecutive weeks. After the last administration, the levels of serum creatinine (Scr), blood urea nitrogen (BUN), ROS, superoxide dismutase (SOD), malondialdehyde (MDA), tumor necrosis factor-α (TNF-α), interleukin (IL)-6, and IL-1β were measured in each group. Pathological changes in renal tissue were observed, and the protein expression levels of Collagen Ⅲ, α-smooth muscle actin (α-SMA), transforming growth factor-β1 (TGF-β1), TXNIP and NLRP3 in renal tissue were detected. RESULTS Compared with model group, the renal histopathological damage and fibrosis of rats in Yishen paidu formula-L group and Yishen paidu formula-H group were significantly alleviated. The levels of Scr, BUN, ROS, MDA, TNF- α, IL-6 and IL-1β, and the protein expressions of Collagen Ⅲ, α-SMA, TGF-β1, TXNIP and NLRP3 were significantly decreased, while SOD levels were significantly increased (P<0.05). Moreover, the changes were more pronounced in the Yishen paidu formula-H group (P<0.05). Compared with Yishen paidu formula-H+pcDNA-NC group, above indexes of rats in Yishen paidu formula-H+pcDNA-TXNIP group were reversed significantly (P<0.05). CONCLUSIONS Yishen paidu formula can inhibit renal fibrosis in CRF rats by suppressing the ROS/TXNIP/NLRP3 pathway.
2.Role of aspirin in metabolic associated fatty liver disease
Yongqi LI ; Yanqiu LI ; Lina SUN ; Chaoran WANG ; Ying FENG ; Liang WANG ; Xianbo WANG
Journal of Clinical Hepatology 2026;42(1):178-182
Metabolic associated fatty liver disease (MAFLD) is the main type of chronic liver disease in the world, with an increasingly higher incidence rate and a younger age of onset. At present, the treatment of MAFLD mainly depends on lifestyle intervention and comorbidity management, and there is still a lack of effective drugs for MAFLD itself. As a classic nonsteroidal anti-inflammatory drug of the salicylic acid family, aspirin can intervene in the pathological process of MAFLD by regulating lipid metabolism, relieving insulin resistance, reducing liver inflammation and oxidative stress response, exerting an anti-liver fibrosis effect, and inhibiting hepatocellular carcinoma, and therefore, it has the value of preventing disease onset, delaying disease progression, and reversing disease condition. This article systematically reviews the mechanism of action and safety of aspirin in the treatment of MAFLD, in order to provide more drug treatment options for MAFLD patients.
3.Exploring on Quality Evaluation Methods of Clinical Case Reports in Traditional Chinese Medicine Based on China Clinical Cases Library of Traditional Chinese Medicine
Kaige ZHANG ; Feng ZHANG ; Bo ZHOU ; Haimin CHEN ; Yong ZHU ; Changcheng HOU ; Liangzhen YOU ; Weijun HUANG ; Jie YANG ; Guoshuang ZHU ; Shukun GONG ; Jianwen HE ; Yang YE ; Yuqiu AN ; Chunquan SUN ; Qingjie YUAN ; Buman LI ; Xingzhong FENG ; Kegang CAO ; Hongcai SHANG ; Jihua GUO ; Xiaoxiao ZHANG ; Zhining TIAN
Chinese Journal of Experimental Traditional Medical Formulae 2026;32(1):271-276
As the core vehicle for preserving and transmitting traditional Chinese medicine(TCM) academic thought and clinical experience, the establishment of a robust quality evaluation system for TCM clinical case reports is a crucial component in the current standardization and modernization of TCM. Based on the practical experience of constructing the China Clinical Cases Library of Traditional Chinese Medicine by the China Association of Chinese Medicine, this study conducted a comprehensive analysis of critical challenges, including insufficient authenticity and unfocused evaluation criteria. It proposed a three-dimensional evaluation framework grounded in the structure-process-outcome logic, encompassing three dimensions of authenticity and standardization, characteristics and advantages, application and translational impact. This framework integrated 12 key evaluation indicators in a systematic manner. The model preserved the academic characteristics of TCM syndrome differentiation and treatment, while aligning with modern scientific research standards, achieving a balance between individualized TCM experience and standardized evaluation. Concurrently, this study provided theoretical foundations and methodological guidance for evaluating the quality of TCM clinical cases, contributing significantly to the inheritance of TCM knowledge, evidence-based practice, and the reform of talent evaluation mechanisms.
4.Optimization of Quality Standards for Polygalae Radix Based on Characteristic Chromatograms and QAMS for Xanthones
Humin XIE ; Xiaoqing CUI ; Weihong FENG ; Yu LU ; Xiaoqian LIU ; Xiaoli SUN ; Yanrong LI ; Zhimin WANG ; Chun LI
Chinese Journal of Experimental Traditional Medical Formulae 2026;32(9):196-204
ObjectiveTo address the limitations of the current quality standard for Polygalae Radix(PR), which relies on a single component for quality assessment and struggles to holistically control its intrinsic quality, by constructing a comprehensive quality evaluation system integrating "macro-characterization of chemical profile, synchronous quantification of multiple index components, and quantitative analysis of multi-components by single marker(QAMS) for key component groups". This study aims to facilitate the scientific revision of the quality standard for PR. MethodsHigh performance liquid chromatography(HPLC) characteristic chromatograms were established for 11 batches of PR medicinal materials(YZ), 10 batches of PR decoction pieces(YP), and 10 batches of licorice-processed PR decoction pieces(ZYZ), followed by similarity evaluation and identification of common peaks. HPLC-QAMS was developed for xanthones(sibiricaxanthone B, polygalaxanthone Ⅺ, polygalaxanthone Ⅲ) in the characteristic chromatograms. Simultaneously, the external standard method(ESM) was used to determine the contents of the corresponding xanthones and 3,6'-disinapoyl sucrose in YZ, YP, and ZYZ, followed by multivariate statistical analysis and Spearman correlation analysis. ResultsThe similarity between the characteristic chromatograms of 31 batches of PR samples and the reference chromatogram was>0.9. A total of 13 common peaks were identified, and 10 of these peaks were characterized through reference standard comparison. The successfully constructed QAMS method showed that the relative correction factors(RCFs) of sibiricaxanthone B and polygalaxanthone Ⅺ to polygalaxanthone Ⅲ were 0.76 and 0.88, and their relative retention times(RRTs) were 0.85 and 0.97, respectively. The results calculated by the QAMS method showed no significant difference from those obtained by the ESM. According to the limit standard for polygalaxanthone Ⅲ in the 2020 edition of the Pharmacopoeia of the People's Republic of China(hereinafter referred to as the Chinese Pharmacopoeia), the pass rate of 31 batches of samples was only 19.35%. Multivariate statistical analysis indicated certain compositional differences between different batches of YZ and YP, as well as between YP and ZYZ, with 3,6'-disinapoyl sucrose identified as the main differentiating component. Furthermore, correlation analysis revealed that the content of polygalaxanthone Ⅲ was positively correlated with the contents of sibiricaxanthone B and polygalaxanthone Ⅺ, but showed no association with the content of 3,6'-disinapoyl sucrose. ConclusionIt is recommended that the content limit for polygalaxanthone Ⅲ in YZ,YP and ZYZ be revised to not less than 0.07%, or the total content of polygalaxanthone Ⅲ, sibiricaxanthone B and polygalaxanthone Ⅺ be not less than 0.18%. The newly established triple quality control model of "holistic control via characteristic chromatograms, precise quantification of oligosaccharide esters, and efficient detection of xanthones by QAMS" provides a systematic and precise solution for quality evaluation of PR and similar Chinese herbal medicines.
5.Three-dimensional Electrical Impedance Tomography for Monitoring Gastric Hemorrhage
Zi-Han ZHAO ; Bo SUN ; Jing-Shi HUANG ; Zhi-Wei LI ; Yang WU ; Nan LI ; Jia-Feng YAO ; Tong ZHAO
Progress in Biochemistry and Biophysics 2026;53(4):1062-1075
ObjectiveGastric hemorrhage is one of the most common and life-threatening emergencies of the upper digestive tract. Early identification and continuous monitoring are essential for reducing rebleeding rates and mortality, particularly within the critical early hours after onset. Although endoscopy and radiological imaging can accurately localize bleeding sites, these approaches are invasive, resource-intensive, and unsuitable for continuous bedside monitoring. Electrical impedance tomography (EIT), as a noninvasive and radiation-free functional imaging technique, offers real-time visualization of conductivity distribution and has the potential for detecting intragastric bleeding based on the electrical contrast between blood and surrounding gastric tissues. In this study, a three-dimensional gastric EIT (3D-gEIT) framework is proposed to achieve noninvasive, real-time, and dynamic monitoring of gastric hemorrhage, with emphasis on spatial localization and quantitative volume assessment. MethodsA three-dimensional upper-abdominal simulation model incorporating the stomach, gastric wall, gastric contents, and surrounding tissues was established. Three electrode configurations, namely the dual layer ring, the four layer staggered ring, and the opposed dual plane array, were designed and systematically compared to evaluate their influence on depth sensitivity and spatial resolution. Based on the Tikhonov-Noser hybrid regularization scheme, a region-clustering constraint was introduced to develop the TK-Noser-RCC algorithm. This approach aggregates spatially adjacent elements with similar conductivity variations, thereby enhancing structural continuity and suppressing isolated noise artifacts. To validate the proposed framework, an upper-abdominal physical phantom was constructed using agar to simulate background tissue conductivity. Hemispherical high-conductivity inclusions with volumes ranging from 10 ml to 50 ml were attached to the inner gastric wall to mimic localized bleeding under different gastric filling states. Boundary voltages were acquired under a 120 kHz excitation current and reconstructed using the TK-Noser-RCC algorithm. Furthermore, an in vivo animal experiment was performed using a porcine model with adult-scale abdominal dimensions. A total of 100 ml of autologous blood was injected incrementally into the stomach to simulate progressive gastric hemorrhage, and time-difference EIT reconstruction was conducted at each injection stage to assess the dynamic system response under physiological conditions. ResultsSimulation results demonstrated that the opposed dual-plane electrode array achieved superior depth sensitivity distribution and spatial resolution. For a 40 ml hemorrhage model, the average ICC and SSIM improved by 55.9% and 38.8% compared with the dual-layer ring configuration, and by 64.0% and 39.5% compared with the four-layer staggered configuration. The proposed region-clustering constraint significantly enhanced reconstruction stability. Under added Gaussian noise of 40 dB and 30 dB, ICC values remained approximately 0.85, indicating effective artifact suppression and preservation of boundary integrity. In physical phantom experiments, reconstructed hemorrhage volumes increased approximately linearly with the preset hemispherical volumes, and the reconstructed high-conductivity regions closely matched the actual bleeding locations. Both empty-stomach and full-stomach conditions were evaluated, demonstrating that the opposed dual-plane configuration maintained stable imaging performance across varying gastric contents. In the animal experiment, reconstructed low-impedance regions expanded progressively with increasing injected blood volume. The spatial localization of the hemorrhage remained stable throughout the procedure, and no significant artifacts were observed. Quantitative analysis showed that reconstructed volume and average conductivity variation exhibited an approximately linear growth trend with injected blood volume, confirming the sensitivity of the system to dynamic intragastric conductivity changes. ConclusionThe proposed 3D-gEIT framework enables quantitative reconstruction of gastric hemorrhage volume and spatial distribution with improved depth sensitivity, structural continuity, and noise robustness compared with conventional EIT approaches. By integrating optimized electrode configuration and a region-clustering-constrained reconstruction algorithm, the system provides stable dynamic monitoring under both controlled phantom conditions and in vivo physiological environments. This method offers a noninvasive, real-time, and low-cost imaging strategy for early diagnosis, postoperative monitoring, and bedside surveillance of gastric bleeding.
6.Differentiation and Treatment of Small Cell Lung Cancer from the Perspective of "Internal Wind in Hidden Circulation"
Shengjuan HU ; Li HOU ; Tao SUN ; Li FENG
Journal of Traditional Chinese Medicine 2026;67(9):1003-1007
Small cell lung cancer (SCLC) is characterized by rapid onset, high invasiveness, and a strong tendency for recurrence and metastasis, which aligns with the pathogenic characteristics of wind pathogen in traditional Chinese medicine (TCM). This paper explores the pathological mechanism and dynamic pattern identification and treatment of SCLC from the perspective of "internal wind in hidden circulation". It is proposed that the core pathogenesis of SCLC is rooted in depletion of healthy qi, with binding of phlegm, stasis, and toxin. When pathogenic factors become excessive, the ascending and descending of yang qi becomes disordered, transforming into wind. This leads to internal wind in hidden circulation, which moves erratically and damages healthy qi. In the limited stage, cancer toxin accumulates and internal wind arises covertly, treatment for which should focus on regulating qi and resolving toxin, defending against wind and resisting pathogen with modified Bufei Decoction (补肺汤) and Shengjiang Powder (升降散). In the early extensive stage, phlegm and stasis generate wind, and internal wind spreads through collate-rals; treatment should resolve phlegm and dispel stasis, extinguish wind and resolve toxin, with modified Lingjiao Gouteng Decoction (羚角钩藤汤) combined with Tianma Gouteng Beverage (天麻钩藤饮). During the treatment stage, there is qi and yin depletion, and deficient wind harassing the interior, for which it is recommended to boost qi and nourish yin, soften the liver and extinguish wind, with modified Zhengan Xifeng Decoction (镇肝熄风汤) combined with Qingzao Jiufei Decoction (清燥救肺汤). In the progression stage, internal wind stirs again and cancer toxin scurries; treatment should focus on strengthening the healthy qi and replenishing essence, restraining wind and penetrating toxin, with modified Sanjia Fumai Decoction (三甲复脉汤). In the terminal stage, yin and yang are on the verge of dissociation and depleted yang floats upward; treatment should constrain and astringe to prevent collapse, rescue yang and contain yin, with modified Dihuang Drink (地黄饮子) combined with Laifu Decoction (来复汤).
7.Differentiation and Treatment of Small Cell Lung Cancer from the Perspective of "Internal Wind in Hidden Circulation"
Shengjuan HU ; Li HOU ; Tao SUN ; Li FENG
Journal of Traditional Chinese Medicine 2026;67(9):1003-1007
Small cell lung cancer (SCLC) is characterized by rapid onset, high invasiveness, and a strong tendency for recurrence and metastasis, which aligns with the pathogenic characteristics of wind pathogen in traditional Chinese medicine (TCM). This paper explores the pathological mechanism and dynamic pattern identification and treatment of SCLC from the perspective of "internal wind in hidden circulation". It is proposed that the core pathogenesis of SCLC is rooted in depletion of healthy qi, with binding of phlegm, stasis, and toxin. When pathogenic factors become excessive, the ascending and descending of yang qi becomes disordered, transforming into wind. This leads to internal wind in hidden circulation, which moves erratically and damages healthy qi. In the limited stage, cancer toxin accumulates and internal wind arises covertly, treatment for which should focus on regulating qi and resolving toxin, defending against wind and resisting pathogen with modified Bufei Decoction (补肺汤) and Shengjiang Powder (升降散). In the early extensive stage, phlegm and stasis generate wind, and internal wind spreads through collate-rals; treatment should resolve phlegm and dispel stasis, extinguish wind and resolve toxin, with modified Lingjiao Gouteng Decoction (羚角钩藤汤) combined with Tianma Gouteng Beverage (天麻钩藤饮). During the treatment stage, there is qi and yin depletion, and deficient wind harassing the interior, for which it is recommended to boost qi and nourish yin, soften the liver and extinguish wind, with modified Zhengan Xifeng Decoction (镇肝熄风汤) combined with Qingzao Jiufei Decoction (清燥救肺汤). In the progression stage, internal wind stirs again and cancer toxin scurries; treatment should focus on strengthening the healthy qi and replenishing essence, restraining wind and penetrating toxin, with modified Sanjia Fumai Decoction (三甲复脉汤). In the terminal stage, yin and yang are on the verge of dissociation and depleted yang floats upward; treatment should constrain and astringe to prevent collapse, rescue yang and contain yin, with modified Dihuang Drink (地黄饮子) combined with Laifu Decoction (来复汤).
8.Treatment Modalities and Long-Term Outcomes in Unruptured Vertebrobasilar Fusiform Aneurysms: A Nationwide Observational Cohort Study
Linggen DONG ; Dachao WEI ; Xiheng CHEN ; Mingtao LI ; Yang ZHAO ; Yong SUN ; Qingbin NIE ; Jun FENG ; Guomin XIAO ; Jinghua ZHOU ; Shengli HU ; Lifei FENG ; Lifeng QI ; Hongen LIU ; Geng GUO ; Yufang LI ; Renfu TIAN ; Jianghua YU ; Dianshi JIN ; Liang HAO ; Tian TIAN ; Shizhong ZHANG ; Yang WANG ; Liping LIU ; Ming LV
Journal of Stroke 2026;28(2):250-262
Background:
and Purpose Vertebrobasilar fusiform aneurysms (VBFAs) carry substantial morbidity and mortality, but optimal management for unruptured VBFAs remains unclear. We compared the safety and efficacy of conservative management (CM), stent-assisted coiling (SAC), and flow diverters (FDs) in patients with unruptured VBFAs, focusing on long-term prognosis.
Methods:
This study included data from a nationwide Chinese cohort of patients with vertebrobasilar dissecting aneurysms. Inverse probability of treatment weighting (IPTW) balanced confounders across groups. The primary outcome was poor prognosis (modified Rankin Scale score >2). Secondary outcomes included aneurysm rupture, ischemic stroke, compression symptoms, and VBFA-related deaths. Logistic regression estimated odds ratios (ORs) and 95% confidence intervals (CIs). Subgroup and sensitivity analyses were performed.
Results:
Among 1,115 patients with unruptured VBFAs, 838 (median age, 54 years; 655 men) were included. After IPTW, baseline characteristics were balanced. Median follow-up was 54 months. FD was associated with a lower risk of poor prognosis than CM (OR, 0.48 [95% CI, 0.30 to 0.77]; p=0.002), with no difference between CM and SAC. FD also reduced aneurysm rupture (OR, 0.20 [95% CI, 0.07 to 0.60]; p=0.004) and compression symptoms (OR, 0.30 [95% CI, 0.13 to 0.68]; p=0.004) versus CM. Time-to-event analyses further revealed significant differences in vertebral artery lesions and Type I–II VBFAs, whereas no significant differences were observed in basilar or vertebrobasilar junction lesions or in Type III–IV VBFAs.
Conclusions
Compared with CM, FD was associated with improved long-term outcomes in unruptured VBFAs, particularly in vertebral artery lesions and Type I–II VBFAs, although residual confounding cannot be excluded.
9.SIRT5 Potentiates Hepatocarcinogenesis by Modulating Protein Acylation in Mice
Yu ZHANG ; Feng-Rui REN ; Jia-Yun LI ; Xiang-Yu CHEN ; Zi-Yi WANG ; Qi SUN ; Jun-Cheng ZHAO ; Ye ZHANG ; Zhen HUANG ; Hao HU ; Tao-Tao WEI ; Min XIAO
Progress in Biochemistry and Biophysics 2026;53(6):1712-1722
ObjectiveHepatocellular carcinoma (HCC) represents 90% of all primary liver cancers. The main risk factors associated with HCC include viral hepatitis (B and/or C), alcohol abuse, and metabolic dysfunction-associated steatotic liver disease (MASLD), which progressively advance to liver fibrosis, cirrhosis, and ultimately evolve into HCC. Surgical resection represents the most effective treatment for HCC, while recent advances in immunotherapy, including immune checkpoint inhibitors and adoptive cell therapies, have provided improved treatment prospects for patients with unresectable HCC. However, the complex metabolic heterogeneity of HCC limits the therapeutic efficacy. Metabolic intermediates acyl-CoA not only provide energy and substrates for numerous biochemical reactions but also serve as donors for protein lysine acylation, a major class of post-translational modification (PTM). Therefore, a deeper understanding of the molecular mechanisms underlying protein lysine acylation and hepatocarcinogenesis is urgently needed. MethodsThe levels of protein lysine acylation and silence information regulator 5 (SIRT5) expression levels in clinical HCC samples were analyzed by Western blot. Quantitative malonylome and succinylome of HCC samples were analyzed by antibody-based affinity enrichment coupled with tandem mass spectrometry. The proliferation of HCC cells was analyzed with Cell Counting Kit-8 (CCK-8) assays, the apoptosis was quantified by Annexin V-FITC/propidium iodide (PI) staining coupled with flow cytometry, and the ability of cells to migrate was assayed by Transwell assays. The enzymatic activity of glutathione S-transferase Mu 1 (GSTM1) was quantified. Transgenic mice with hepatic overexpression of SIRT5 were constructed using CRISPR-Cas9, and primary hepatocarcinogenesis was induced by administration of diethylnitrosamine. ResultsWestern blot analysis indicated that the expression level of SIRT5 was elevated in clinical samples from HCC patients, and the levels of lysine malonylation, glutarylation, and succinylation were significantly reduced in HCC tissues. Knockout of SIRT5 in MHCC-97H and MHCC-97L hepatoma cells suppressed cell proliferation, and increased the percentage of apoptotic cells significantly. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses of the differentially malonylome and succinylome of HCC samples revealed significant enrichment in two major classes of biological processes: core energy metabolism (e.g., glycolysis/gluconeogenesis, tricarboxylic acid metabolic process, fatty acid beta oxidation) and detoxification and oxidative stress response (e.g., response to toxic substance, chemical carcinogenesis, reactive oxygen species (ROS)). SIRT5 removes malonylation from lysine residues in GSTM1 and restores its detoxification activity, which is crucial for the survival of hepatocytes under stressed conditions. More importantly, in vivo experiment indicated that hepatic-specific overexpression of SIRT5 in mice accelerated diethylnitrosamine-induced liver fibrosis and hepatocarcinogenesis, indicating the critical role of SIRT5 in HCC progression. ConclusionThis study highlights the previously unrecognized SIRT5-GSTM1 axis as a key regulator in hepatocarcinogenesis, and suggests a potential target for the treatment of patients with HCC.
10.Risk factors and altered functional connectivity of brain networks in end-stage renal disease complicated with frailty
Zhaohua SUN ; Dashan LI ; Nan FENG ; Zilian CHEN ; Pei ZHANG ; Yonggui WU
Acta Universitatis Medicinalis Anhui 2026;61(5):894-900
ObjectiveTo explore the risk factors and alterations in functional connectivity of brain networks in end-stage renal disease (ESRD) patients complicated by frailty. MethodsA total of 84 patients with ESRD were enrolled and divided into the frailty group (31 cases) and non-frailty group (53 cases) according to the Chinese version of the Tilburg Frailty Indicator (TFI). Cranial magnetic resonance imaging (MRI) data, neuropsychological test results and clinical data were collected for all subjects. Logistic regression analysis was used to explore risk factors for frailty in ESRD patients, and image preprocessing and independent component analysis were performed to compare differences in brain network functional connectivity between the two groups. ResultsLogistic regression analysis showed that high blood urea nitrogen level, depression, malnutrition, and sleep disturbance were risk factors for frailty in patients with ESRD (P<0.05), while a higher level of education served as a protective factor (P<0.05). Compared with the non-frailty group, the frailty group exhibited significantly weakened functional connectivity between the sensorimotor network and the visual network (P<0.05). ConclusionHigh levels of blood urea nitrogen, depression, malnutrition, and sleep disorders can increase the risk of frailty in patients with end-stage renal disease (ESRD), while a higher educational level may reduce this risk. Patients with ESRD complicated by frailty exhibit a significant decrease in functional connectivity between the sensorimotor network (SMN) and visual network (VN), which provides novel imaging evidence for exploring the central neural mechanisms underlying the development of frailty in ESRD patients.

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