1.Mechanisms of Dihuang Yinzi in Treating Advanced Parkinson's Disease Based on Gut Microbiota-SCFAs-inflammation Axis
Renzhi MA ; Yasi LIN ; Tingyue JIANG ; Hongmei ZHU ; Jiayuan LI ; Yu WANG ; Ge ZHANG ; Wenxin FAN ; Jinli SHI
Chinese Journal of Experimental Traditional Medical Formulae 2026;32(7):11-21
ObjectiveTo observe the effects of Dihuang Yinzi (DY) on motor dysfunction in rats with advanced Parkinson's disease (PD) and to investigate the mechanisms by which DY improves advanced PD symptoms through the "gut microbiota-short-chain fatty acids (SCFAs)-inflammation-neuroprotection pathway". MethodsAn advanced PD rat model was induced by rotenone. Rats were divided into a normal group, model group, positive drug group (levodopa, 50 mg·kg-1), and DY low-, medium-, and high-dose groups (5.2, 10.4, 20.8 g·kg-1). After 7 days of administration, motor function was evaluated using the open-field, pole-climbing, and inclined plate tests. Hematoxylin-eosin (HE) staining was used to observe pathological changes in the substantia nigra and colon, and immunohistochemistry was performed to detect α-Synuclein (α-Syn) and tyrosine hydroxylase (TH) expression in the substantia nigra. Enzyme-linked immunosorbent assay (ELISA) was used to measure levels of dopamine (DA), 5-hydroxytryptamine (5-HT), 3,4-dihydroxyphenylacetic acid (DOPAC), Levodopa, homovanillic acid (HVA), tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), and interleukin-1β (IL-1β). Western blot analysis was used to detect the expression of zonula occludens-1 (ZO-1) and occludin. Gut microbiota diversity was analyzed by 16S rRNA sequencing, and gas chromatography (GC) was used to determine the content of SCFAs in colonic contents. ResultsCompared with the normal group, the model group showed significantly decreased movement speed and distance in the open-field test, prolonged pole-climbing time, and reduced retention angle on the inclined plate (P<0.01), accompanied by increased α-Syn expression (P<0.01) and decreased TH expression (P<0.01) in the brain. Compared with the model group, all DY dose groups improved motor dysfunction in advanced PD rats to varying degrees (P<0.05, P<0.01) and alleviated pathological damage in the brain and colon. High-dose DY significantly reduced α-Syn aggregation in the substantia nigra (P<0.01) and increased TH expression (P<0.01). ELISA and Western blot results showed that, compared with the normal group, the model group exhibited decreased levels of DA, 5-HT, DOPAC, Levodopa, and HVA in the striatum (P<0.01), increased levels of TNF-α, IL-6, and IL-1β in the colon and striatum (P<0.01), and significantly reduced expression of ZO-1 (P<0.05) and occludin in the colon (P<0.01). Compared with the model group, all DY dose groups increased the levels of DA, 5-HT, DOPAC, Levodopa, and HVA in the striatum to varying degrees (P<0.05, P<0.01). In the high-dose DY group, the levels of TNF-α, IL-6, and IL-1β in the colon and striatum were reduced (P<0.01), while the expression of ZO-1 (P<0.05) and occludin in the intestine was increased. The 16S rRNA sequencing results indicated that the relative abundances of Actinobacteriota, Enterobacteriaceae, and Erysipelotrichaceae were increased in the model group, whereas the relative abundances of Bacteroidota, class Clostridia, Lachnospiraceae, and Akkermansia muciniphila were decreased. These changes were effectively reversed after high-dose DY intervention. GC analysis showed that the content of SCFAs in the colonic contents of rats in the model group was decreased (P<0.05, P<0.01), while after high-dose DY intervention, the levels of acetate, propionate, isobutyrate, and butyrate were significantly increased (P<0.05, P<0.01). ConclusionDY may exert therapeutic effects in advanced PD by regulating the gut microbiota-SCFAs-inflammation pathway.
2.Insights on Peripheral Blood Biomarkers for Parkinson’s Disease
Yu-Meng LI ; Jing-Kai LIU ; Zi-Xuan CHEN ; Yu-Lin DENG
Progress in Biochemistry and Biophysics 2025;52(1):72-87
Parkinson’s disease (PD) is a common neurodegenerative disorder with profound impact on patients’ quality of life and long-term health, and early detection and intervention are particularly critical. In recent years, the search for precise and reliable biomarkers has become one of the key strategies to effectively address the clinical challenges of PD. In this paper, we systematically evaluated potential biomarkers, including proteins, metabolites, epigenetic markers, and exosomes, in the peripheral blood of PD patients. Protein markers are one of the main directions of biomarker research in PD. In particular, α‑synuclein and its phosphorylated form play a key role in the pathological process of PD. It has been shown that aggregation of α-synuclein may be associated with pathologic protein deposition in PD and may be a potential marker for early diagnosis of PD. In terms of metabolites, uric acid, as a metabolite, plays an important role in oxidative stress and neuroprotection in PD. It has been found that changes in uric acid levels may be associated with the onset and progression of PD, showing its potential as an early diagnostic marker. Epigenetic markers, such as DNA methylation modifications and miRNAs, have also attracted much attention in Parkinson’s disease research. Changes in these markers may affect the expression of PD-related genes and have an important impact on the onset and progression of the disease, providing new research perspectives for the early diagnosis of PD. In addition, exosomes, as a potential biomarker carrier for PD, are able to carry a variety of biomolecules involved in intercellular communication and pathological regulation. Studies have shown that exosomes may play an important role in the pathogenesis of PD, and their detection in blood may provide a new breakthrough for early diagnosis. It has been shown that exosomes may play an important role in the pathogenesis of PD, and their detection in blood may provide new breakthroughs in early diagnosis. In summary, through in-depth evaluation of biomarkers in the peripheral blood of PD patients, this paper demonstrates the important potential of these markers in the early diagnosis of PD and in the study of pathological mechanisms. Future studies will continue to explore the clinical application value of these biomarkers to promote the early detection of PD and individualized treatment strategies.
3.Severity Assessment Parameters and Diagnostic Technologies of Obstructive Sleep Apnea
Zhuo-Zhi FU ; Ya-Cen WU ; Mei-Xi LI ; Ping-Ping YIN ; Hai-Jun LIN ; Fu ZHANG ; Yu-Xiang YANG
Progress in Biochemistry and Biophysics 2025;52(1):147-161
Obstructive sleep apnea (OSA) is an increasingly widespread sleep-breathing disordered disease, and is an independent risk factor for many high-risk chronic diseases such as hypertension, coronary heart disease, stroke, arrhythmias and diabetes, which is potentially fatal. The key to the prevention and treatment of OSA is early diagnosis and treatment, so the assessment and diagnostic technologies of OSA have become a research hotspot. This paper reviews the research progresses of severity assessment parameters and diagnostic technologies of OSA, and discusses their future development trends. In terms of severity assessment parameters of OSA, apnea hypopnea index (AHI), as the gold standard, together with the percentage of duration of apnea hypopnea (AH%), lowest oxygen saturation (LSpO2), heart rate variability (HRV), oxygen desaturation index (ODI) and the emerging biomarkers, constitute a multi-dimensional evaluation system. Specifically, the AHI, which measures the frequency of sleep respiratory events per hour, does not fully reflect the patients’ overall sleep quality or the extent of their daytime functional impairments. To address this limitation, the AH%, which measures the proportion of the entire sleep cycle affected by apneas and hypopneas, deepens our understanding of the impact on sleep quality. The LSpO2 plays a critical role in highlighting the potential severe hypoxic episodes during sleep, while the HRV offers a different perspective by analyzing the fluctuations in heart rate thereby revealing the activity of the autonomic nervous system. The ODI provides a direct and objective measure of patients’ nocturnal oxygenation stability by calculating the number of desaturation events per hour, and the biomarkers offers novel insights into the diagnosis and management of OSA, and fosters the development of more precise and tailored OSA therapeutic strategies. In terms of diagnostic techniques of OSA, the standardized questionnaire and Epworth sleepiness scale (ESS) is a simple and effective method for preliminary screening of OSA, and the polysomnography (PSG) which is based on recording multiple physiological signals stands for gold standard, but it has limitations of complex operations, high costs and inconvenience. As a convenient alternative, the home sleep apnea testing (HSAT) allows patients to monitor their sleep with simplified equipment in the comfort of their own homes, and the cardiopulmonary coupling (CPC) offers a minimal version that simply analyzes the electrocardiogram (ECG) signals. As an emerging diagnostic technology of OSA, machine learning (ML) and artificial intelligence (AI) adeptly pinpoint respiratory incidents and expose delicate physiological changes, thus casting new light on the diagnostic approach to OSA. In addition, imaging examination utilizes detailed visual representations of the airway’s structure and assists in recognizing structural abnormalities that may result in obstructed airways, while sound monitoring technology records and analyzes snoring and breathing sounds to detect the condition subtly, and thus further expands our medical diagnostic toolkit. As for the future development directions, it can be predicted that interdisciplinary integrated researches, the construction of personalized diagnosis and treatment models, and the popularization of high-tech in clinical applications will become the development trends in the field of OSA evaluation and diagnosis.
4.Analysis on Acupuncture in the Treatment of Post-stroke Dysphagia Based on the Theory of "Latent Pathogen in Cerebral Collaterals"
Hongtao LI ; Yaqi HUANG ; Lulu YAO ; Bing GAO ; Yu YE ; Nenggui XU ; Lin WANG
Journal of Traditional Chinese Medicine 2025;66(9):901-905
Dysphagia is a common complication of stroke. Combining the principles of traditional Chinese medicine with modern research findings, it is proposed that "latent pathogen in the cerebral collaterals" constitutes the core pathogenesis of post-stroke dysphagia (PSD). In clinical practice, treatment is tailored according to the location of PSD. During the oral stage, when the pathogen invades the face and mouth, resulting in excessive salivation, acupoints are primarily selected from the foot shaoyin (少阴) kidney channel, in combination with ren mai (任脉) , du mai (督脉), chong mai (冲脉) and the spleen channel, to replenish essence and fill the marrow, dispel dampness and unblock the channels. In the pharyngeal stage, as the pathogen obstructs the throat, disrupting normal swallowing, the therapy emphasizes dredging the shaoyang (少阳) channel and warming and tonifying the jueyin (厥阴) channel, by taking acupoints mainly from the hand and foot shaoyang channels, along with the jueyin channels, so as to soothe the liver and promote bile secretion, regulate and harmonize qi and blood. During the esophageal stage, where the pathogen damages the esophagus, impeding food passage, the treatment emphasizes activating the yangming (阳明) channels and regulating taiyin (太阴) channels; acupoints are mainly selected from the foot yangming stomach channel, along with the taiyin channels, aiming to warm yang, unblock the channels and dispel stasis.
5.Study on the safety and pharmacological effect on improving dyspepsia of Shuangshu decoction in rats
Xinyuan CHEN ; Changzhou XIONG ; Jiongfen LI ; Kangyi YU ; Huan XU ; Yingxia WANG ; Dan LIAO ; Junyu TAO ; Ziyi YANG ; Caizhi LIN
China Pharmacy 2025;36(9):1059-1064
OBJECTIVE To study the safety of Shuangshu decoction in rats and its efficacy in improving functional dyspepsia (FD) in rats. METHODS In safety test, 40 rats were divided into blank control group, Shuangshu decoction low-dose, medium- dose and high-dose groups [108, 216, 324 g/(kg·d), calculated by raw medicine, the same applies below]; they were given relevant medicine intragastrically, for continuous 14 days. The mortality and toxic reactions of rats were recorded, and the organ indexes of the liver, kidney, spleen, lung and heart of rats were calculated; the pathological morphological changes in the liver, kidney, spleen, lung, heart, stomach, duodenum, and colon were observed to evaluate the acute toxicity of Shuangshu decoction. Another 40 rats were grouped and administered in the same way for 30 consecutive days. The mortality and toxic reactions of the rats were recorded, and the corresponding organ indexes were calculated. The pathological morphological changes in the corresponding organs were observed, and blood routine and serum biochemical indicators were measured, in order to assess the subacute toxicity of Shuangshu decoction. In pharmacodynamic experiments: 50 rats were divided into blank control group, model group, and Shuangshu decoction low-, medium-, and high-dose groups (9.45, 18.9, 37.8 g/kg), with 10 rats in each group. Except for blank control group, rats in all other groups were used to establish the FD rat model by subcutaneous injection of loperamide (3.5 mg/kg). Rats in each group were administered the corresponding drug solution/normal saline intragastrically, once a day, for 14 consecutive days. After the last medication, fecal moisture content, intestinal propulsion rate, gastric emptying rate and serum level of motilin were all detected, and interstitial cell of Cajal (ICC) ultrastructure of rats was observed in colon tissue. RESULTS The safety experiments showed that no death occurred in each dose group, and no significant difference was found in organ coefficient, routine blood and serum biological index, compared to blank control group (P>0.05); no abnormality was found in organ appearance and pathological sections. The results of the pharmacodynamic experiments showed that, compared with the blank control group, the fecal moisture content, gastric emptying rate, intestinal propulsion rate, and serum motilin levels in the model group were significantly decreased (P<0.05); in the colonic tissue, the mitochondria in the ICC exhibited severe swelling with the disappearance of cristae, and the endoplasmic reticulum was dilated. Compared with model group, the rats in Shuangshu decoction high-dose group showed significant increases in the above quantitative indicators (P< 0.05); additionally, there was a large number of mitochondria in the ICC of the colonic tissue, with clear cristae and regular arrangement. CONCLUSIONS Shuangshu decoction is safe and has a beneficial improving effect on FD rats; its mechanism of action may be related to the regulation of gastrointestinal hormone expression to promote gastric emptying and intestinal propulsion, as well as the repair of mitochondrial structure in ICCs to restore gastrointestinal function.
6.Predictive Modeling of Symptomatic Intracranial Hemorrhage Following Endovascular Thrombectomy: Insights From the Nationwide TREAT-AIS Registry
Jia-Hung CHEN ; I-Chang SU ; Yueh-Hsun LU ; Yi-Chen HSIEH ; Chih-Hao CHEN ; Chun-Jen LIN ; Yu-Wei CHEN ; Kuan-Hung LIN ; Pi-Shan SUNG ; Chih-Wei TANG ; Hai-Jui CHU ; Chuan-Hsiu FU ; Chao-Liang CHOU ; Cheng-Yu WEI ; Shang-Yih YAN ; Po-Lin CHEN ; Hsu-Ling YEH ; Sheng-Feng SUNG ; Hon-Man LIU ; Ching-Huang LIN ; Meng LEE ; Sung-Chun TANG ; I-Hui LEE ; Lung CHAN ; Li-Ming LIEN ; Hung-Yi CHIOU ; Jiunn-Tay LEE ; Jiann-Shing JENG ;
Journal of Stroke 2025;27(1):85-94
Background:
and Purpose Symptomatic intracranial hemorrhage (sICH) following endovascular thrombectomy (EVT) is a severe complication associated with adverse functional outcomes and increased mortality rates. Currently, a reliable predictive model for sICH risk after EVT is lacking.
Methods:
This study used data from patients aged ≥20 years who underwent EVT for anterior circulation stroke from the nationwide Taiwan Registry of Endovascular Thrombectomy for Acute Ischemic Stroke (TREAT-AIS). A predictive model including factors associated with an increased risk of sICH after EVT was developed to differentiate between patients with and without sICH. This model was compared existing predictive models using nationwide registry data to evaluate its relative performance.
Results:
Of the 2,507 identified patients, 158 developed sICH after EVT. Factors such as diastolic blood pressure, Alberta Stroke Program Early CT Score, platelet count, glucose level, collateral score, and successful reperfusion were associated with the risk of sICH after EVT. The TREAT-AIS score demonstrated acceptable predictive accuracy (area under the curve [AUC]=0.694), with higher scores being associated with an increased risk of sICH (odds ratio=2.01 per score increase, 95% confidence interval=1.64–2.45, P<0.001). The discriminatory capacity of the score was similar in patients with symptom onset beyond 6 hours (AUC=0.705). Compared to existing models, the TREAT-AIS score consistently exhibited superior predictive accuracy, although this difference was marginal.
Conclusions
The TREAT-AIS score outperformed existing models, and demonstrated an acceptable discriminatory capacity for distinguishing patients according to sICH risk levels. However, the differences between models were only marginal. Further research incorporating periprocedural and postprocedural factors is required to improve the predictive accuracy.
7.Longitudinal Association of Changes in Metabolic Syndrome with Cognitive Function: 12-Year Follow-up of the Guangzhou Biobank Cohort Study
Yu Meng TIAN ; Wei Sen ZHANG ; Chao Qiang JIANG ; Feng ZHU ; Ya Li JIN ; Shiu Lun Au YEUNG ; Jiao WANG ; Kar Keung CHENG ; Tai Hing LAM ; Lin XU
Diabetes & Metabolism Journal 2025;49(1):60-79
Background:
The association of changes in metabolic syndrome (MetS) with cognitive function remains unclear. We explored this association using prospective and Mendelian randomization (MR) studies.
Methods:
MetS components including high-density lipoprotein cholesterol (HDL-C), systolic blood pressure (SBP), waist circumference (WC), fasting plasma glucose (FPG), and triglycerides were measured at baseline and two follow-ups, constructing a MetS index. Immediate, delayed memory recall, and cognitive function along with its dimensions were assessed by immediate 10- word recall test (IWRT) and delayed 10-word recall test (DWRT), and mini-mental state examination (MMSE), respectively, at baseline and follow-ups. Linear mixed-effect model was used. Additionally, the genome-wide association study (GWAS) of MetS was conducted and one-sample MR was performed to assess the causality between MetS and cognitive function.
Results:
Elevated MetS index was associated with decreasing annual change rates (decrease) in DWRT and MMSE scores, and with decreases in attention, calculation and recall dimensions. HDL-C was positively associated with an increase in DWRT scores, while SBP and FPG were negatively associated. HDL-C showed a positive association, whereas WC was negatively associated with increases in MMSE scores, including attention, calculation and recall dimensions. Interaction analysis indicated that the association of MetS index on cognitive decline was predominantly observed in low family income group. The GWAS of MetS identified some genetic variants. MR results showed a non-significant causality between MetS and decrease in DWRT, IWRT, nor MMSE scores.
Conclusion
Our study indicated a significant association of MetS and its components with declines in memory and cognitive function, especially in delayed memory recall.
8.Impact of iron-deficiency anemia on short-term outcomes after resection of colorectal cancer liver metastasis: a US National (Nationwide) Inpatient Sample (NIS) analysis
Ko-Chao LEE ; Yu-Li SU ; Kuen-Lin WU ; Kung-Chuan CHENG ; Ling-Chiao SONG ; Chien-En TANG ; Hong-Hwa CHEN ; Kuan-Chih CHUNG
Annals of Coloproctology 2025;41(2):119-126
Purpose:
Colorectal cancer (CRC) often spreads to the liver, necessitating surgical treatment for CRC liver metastasis (CRLM). Iron-deficiency anemia is common in CRC patients and is associated with fatigue and weakness. This study investigated the effects of iron-deficiency anemia on the outcomes of surgical resection of CRLM.
Methods:
This population-based, retrospective study evaluated data from adults ≥20 years old with CRLM who underwent hepatic resection. All patient data were extracted from the 2005–2018 US National (Nationwide) Inpatient Sample (NIS) database. The outcome measures were in-hospital outcomes including 30-day mortality, unfavorable discharge, and prolonged length of hospital stay (LOS), and short-term complications such as bleeding and infection. Associations between iron-deficiency anemia and outcomes were determined using logistic regression analysis.
Results:
Data from 7,749 patients (representing 37,923 persons in the United States after weighting) were analyzed. Multivariable analysis revealed that iron-deficiency anemia was significantly associated with an increased risk of prolonged LOS (adjusted odds ratio [aOR], 2.76; 95% confidence interval [CI], 2.30–3.30), unfavorable discharge (aOR, 2.42; 95% CI, 1.83–3.19), bleeding (aOR, 5.05; 95% CI, 2.92–8.74), sepsis (aOR, 1.60; 95% CI, 1.04–2.46), pneumonia (aOR, 2.54; 95% CI, 1.72–3.74), and acute kidney injury (aOR, 1.71; 95% CI, 1.24–2.35). Subgroup analyses revealed consistent associations between iron-deficiency anemia and prolonged LOS across age, sex, and obesity status categories.
Conclusion
In patients undergoing hepatic resection for CRLM, iron-deficiency anemia is an independent risk factor for prolonged LOS, unfavorable discharge, and several critical postoperative complications. These findings underscore the need for proactive anemia management to optimize surgical outcomes.
9.Impact of iron-deficiency anemia on short-term outcomes after resection of colorectal cancer liver metastasis: a US National (Nationwide) Inpatient Sample (NIS) analysis
Ko-Chao LEE ; Yu-Li SU ; Kuen-Lin WU ; Kung-Chuan CHENG ; Ling-Chiao SONG ; Chien-En TANG ; Hong-Hwa CHEN ; Kuan-Chih CHUNG
Annals of Coloproctology 2025;41(2):119-126
Purpose:
Colorectal cancer (CRC) often spreads to the liver, necessitating surgical treatment for CRC liver metastasis (CRLM). Iron-deficiency anemia is common in CRC patients and is associated with fatigue and weakness. This study investigated the effects of iron-deficiency anemia on the outcomes of surgical resection of CRLM.
Methods:
This population-based, retrospective study evaluated data from adults ≥20 years old with CRLM who underwent hepatic resection. All patient data were extracted from the 2005–2018 US National (Nationwide) Inpatient Sample (NIS) database. The outcome measures were in-hospital outcomes including 30-day mortality, unfavorable discharge, and prolonged length of hospital stay (LOS), and short-term complications such as bleeding and infection. Associations between iron-deficiency anemia and outcomes were determined using logistic regression analysis.
Results:
Data from 7,749 patients (representing 37,923 persons in the United States after weighting) were analyzed. Multivariable analysis revealed that iron-deficiency anemia was significantly associated with an increased risk of prolonged LOS (adjusted odds ratio [aOR], 2.76; 95% confidence interval [CI], 2.30–3.30), unfavorable discharge (aOR, 2.42; 95% CI, 1.83–3.19), bleeding (aOR, 5.05; 95% CI, 2.92–8.74), sepsis (aOR, 1.60; 95% CI, 1.04–2.46), pneumonia (aOR, 2.54; 95% CI, 1.72–3.74), and acute kidney injury (aOR, 1.71; 95% CI, 1.24–2.35). Subgroup analyses revealed consistent associations between iron-deficiency anemia and prolonged LOS across age, sex, and obesity status categories.
Conclusion
In patients undergoing hepatic resection for CRLM, iron-deficiency anemia is an independent risk factor for prolonged LOS, unfavorable discharge, and several critical postoperative complications. These findings underscore the need for proactive anemia management to optimize surgical outcomes.
10.Longitudinal Association of Changes in Metabolic Syndrome with Cognitive Function: 12-Year Follow-up of the Guangzhou Biobank Cohort Study
Yu Meng TIAN ; Wei Sen ZHANG ; Chao Qiang JIANG ; Feng ZHU ; Ya Li JIN ; Shiu Lun Au YEUNG ; Jiao WANG ; Kar Keung CHENG ; Tai Hing LAM ; Lin XU
Diabetes & Metabolism Journal 2025;49(1):60-79
Background:
The association of changes in metabolic syndrome (MetS) with cognitive function remains unclear. We explored this association using prospective and Mendelian randomization (MR) studies.
Methods:
MetS components including high-density lipoprotein cholesterol (HDL-C), systolic blood pressure (SBP), waist circumference (WC), fasting plasma glucose (FPG), and triglycerides were measured at baseline and two follow-ups, constructing a MetS index. Immediate, delayed memory recall, and cognitive function along with its dimensions were assessed by immediate 10- word recall test (IWRT) and delayed 10-word recall test (DWRT), and mini-mental state examination (MMSE), respectively, at baseline and follow-ups. Linear mixed-effect model was used. Additionally, the genome-wide association study (GWAS) of MetS was conducted and one-sample MR was performed to assess the causality between MetS and cognitive function.
Results:
Elevated MetS index was associated with decreasing annual change rates (decrease) in DWRT and MMSE scores, and with decreases in attention, calculation and recall dimensions. HDL-C was positively associated with an increase in DWRT scores, while SBP and FPG were negatively associated. HDL-C showed a positive association, whereas WC was negatively associated with increases in MMSE scores, including attention, calculation and recall dimensions. Interaction analysis indicated that the association of MetS index on cognitive decline was predominantly observed in low family income group. The GWAS of MetS identified some genetic variants. MR results showed a non-significant causality between MetS and decrease in DWRT, IWRT, nor MMSE scores.
Conclusion
Our study indicated a significant association of MetS and its components with declines in memory and cognitive function, especially in delayed memory recall.

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