1.Relationship between retinol binding protein, lipoprotein (a), and obesity and the risk of cardiovascular disease in prehypertensive population
Jingjing LI ; Cheng DUAN ; Yuanyuan YAO
Journal of Public Health and Preventive Medicine 2026;37(2):112-115
Objective To explore the relationship between levels of retinol binding protein (RBP) and lipoprotein (a) [Lp(a)], and obesity and the occurrence risk of cardiovascular disease in population with prehypertension (PH). Methods A total of 301 patients with PH who were admitted to the First Affiliated Hospital of Anhui University of Science and Technology for physical examination from July 2021 to July 2024 were selected as the study subjects. The levels of serum RBP and Lp(a) were determined, and the waist circumference (WC) and body mass index (BMI) were measured to evaluate the obesity of patients. All patients were followed up. According to whether cardiovascular disease occurred during the follow-up period, they were classified into a study group (with cardiovascular disease) and a control group (without cardiovascular disease). The effects of serum RBP and Lp(a) levels, WC and BMI on the risk of cardiovascular disease were analyzed. Results The follow-up results showed that 53 out of 301 cases developed cardiovascular disease. The levels of RBP, Lp(a), WC, and BMI in the study group were higher than those in the control group (P<0.05). Receiver operating characteristic curve revealed that the areas under the curves of RBP, Lp(a), WC, and BMI for predicting the cardiovascular disease were 0.823, 0.741, 0.768, and 0.841, respectively. Serum RBP, Lp(a), WC, and BMI were influencing factors of the occurrence of cardiovascular disease (P<0.05). Conclusion RBP, Lp(a), WC, and BMI are the influencing factors for the occurrence of cardiovascular disease in patients with prehypertension. These four indicators have certain predictive value on the occurrence of cardiovascular disease.
2.Real-world efficacy and safety of azvudine in hospitalized older patients with COVID-19 during the omicron wave in China: A retrospective cohort study.
Yuanchao ZHU ; Fei ZHAO ; Yubing ZHU ; Xingang LI ; Deshi DONG ; Bolin ZHU ; Jianchun LI ; Xin HU ; Zinan ZHAO ; Wenfeng XU ; Yang JV ; Dandan WANG ; Yingming ZHENG ; Yiwen DONG ; Lu LI ; Shilei YANG ; Zhiyuan TENG ; Ling LU ; Jingwei ZHU ; Linzhe DU ; Yunxin LIU ; Lechuan JIA ; Qiujv ZHANG ; Hui MA ; Ana ZHAO ; Hongliu JIANG ; Xin XU ; Jinli WANG ; Xuping QIAN ; Wei ZHANG ; Tingting ZHENG ; Chunxia YANG ; Xuguang CHEN ; Kun LIU ; Huanhuan JIANG ; Dongxiang QU ; Jia SONG ; Hua CHENG ; Wenfang SUN ; Hanqiu ZHAN ; Xiao LI ; Yafeng WANG ; Aixia WANG ; Li LIU ; Lihua YANG ; Nan ZHANG ; Shumin CHEN ; Jingjing MA ; Wei LIU ; Xiaoxiang DU ; Meiqin ZHENG ; Liyan WAN ; Guangqing DU ; Hangmei LIU ; Pengfei JIN
Acta Pharmaceutica Sinica B 2025;15(1):123-132
Debates persist regarding the efficacy and safety of azvudine, particularly its real-world outcomes. This study involved patients aged ≥60 years who were admitted to 25 hospitals in mainland China with confirmed SARS-CoV-2 infection between December 1, 2022, and February 28, 2023. Efficacy outcomes were all-cause mortality during hospitalization, the proportion of patients discharged with recovery, time to nucleic acid-negative conversion (T NANC), time to symptom improvement (T SI), and time of hospital stay (T HS). Safety was also assessed. Among the 5884 participants identified, 1999 received azvudine, and 1999 matched controls were included after exclusion and propensity score matching. Azvudine recipients exhibited lower all-cause mortality compared with controls in the overall population (13.3% vs. 17.1%, RR, 0.78; 95% CI, 0.67-0.90; P = 0.001) and in the severe subgroup (25.7% vs. 33.7%; RR, 0.76; 95% CI, 0.66-0.88; P < 0.001). A higher proportion of patients discharged with recovery, and a shorter T NANC were associated with azvudine recipients, especially in the severe subgroup. The incidence of adverse events in azvudine recipients was comparable to that in the control group (2.3% vs. 1.7%, P = 0.170). In conclusion, azvudine showed efficacy and safety in older patients hospitalized with COVID-19 during the SARS-CoV-2 omicron wave in China.
3.The impact of prenatal exposure to organophosphorus flame retardants on attention deficit and hyperactive disorder-like symptoms in 4-year-old children: a nested case-control study
Jingjing LI ; Xiaomeng CHENG ; Yan ZHANG ; Luanluan LI ; Xiaodan YU ; Tao YUAN ; Yu GAO ; Ying TIAN
Shanghai Journal of Preventive Medicine 2025;37(10):858-864
ObjectiveThis nested case-control study, based on the Shanghai Birth Cohort (SBC), aimed to explore the impact of early pregnancy exposure to organophosphorus flame retardants (OPFRs) on attention deficit hyperactive disorder (ADHD)-like symptoms in 4-year-old children, so as to provide epidemiological evidence regarding the health effects of emerging contaminant OPFRs in children. MethodsStrengths and Difficulties Questionnaire (SDQ) was used to assess ADHD like symptoms in 4-year-old children. Children with an SDQ hyperactivity subscale score ≥6 points were defined as cases, while those with a score <5 points were considered as controls. The case and control groups were matched at 1∶1 based on the child’s age (±6 months), sex, and parental or primary caregiver’s education level. A total of 105 cases and 112 controls were included eventually. Concentrations of eight OPFRs metabolites in early pregnancy urine samples were measured using ultra-high performance liquid chromatography tandem mass spectrometry (UPLC-MS/MS), including di-phenyl phosphate (DPHP), di-m-cresylphosphate (DmCP), di-o-cresylphosphate (DoCP), di-p-cresylphosphate (DpCP), di-n-butyl phosphate (DnBP), di-iso-butyl phosphate (DiBP), bis(2-butoxyethyl) phosphate (BBOEP), and bis(2-ethylhexyl) phosphate (BEHP). Basic demographic information of mothers and children were collected through questionnaire surveys and medical records extraction. Binary logistic regression models were used to analyze the effect of individual OPFRs exposure during early pregnancy on ADHD-like symptoms, while a quantile g-computation (Qgcomp) regression model was employed to assess the effects of mixed OPFRs exposure (with detection rates >75%) on ADHD-like symptoms in 4-year-old children. ResultsIn this study, the detection rates of DPHP, DoCP, and the DmCP&DpCP in the urine of early pregnancy women were higher than 75%, with DPHP having the highest detection rate (86.18%). The median concentrations of DPHP were highest in both the case and control groups (0.396 μg·L-1 and 0.305 μg·L-1, respectively). Binary logistic regression analyses revealed that exposure to DPHP during early pregnancy increased the risk of ADHD-like symptoms in 4-year-old children (OR=1.262, 95%CI: 1.017‒1.565). The mixed exposure model analyses showed that early pregnancy co-exposure to OPFRs increased the risk of ADHD-like symptoms (OR=1.508, 95%CI: 1.012‒2.258), with DPHP being the primary contributor to the association. ConclusionEarly pregnancy exposure to DPHP is positively associated with an increased risk of ADHD-like symptoms in 4-year-old children. Additionally, DPHP contributed the most to the adverse effects of mixed OPFRs exposure on ADHD-like symptoms. However, these findings require further validation through other large-scale prospective cohort studies.
4.Risk factors and outcomes of postoperative cognitive impairment in elderly patients with heart disease
Liang HAN ; Qinghui CHENG ; Jingjing CHEN ; Na LU ; Yunzhong LIU ; Ruiling HE ; Qunying ZHU ; Yibin OU
Chinese Journal of Geriatric Heart Brain and Vessel Diseases 2025;27(10):1349-1353
Objective To analyze the risk factors and clinical outcomes of cognitive impairment in elderly patients with heart disease after surgery.Methods A total of 156 patients with heart valve diseases undergoing coronary artery bypass surgery admitted to the First Affiliated Hospital of H ainan Medical University from October 2021 to December 2023 were prospectively recruited.At 7 d postoperatively,Montreal cognitive assessment(MoCA)scale was used to assess their cogni-tive function,and based on MoCA score<26 or not,they patients were divided into a cognitive impairment group(n=61)and a control group(n=95).The clinical features were compared be-tween the two groups,and the risk factors for cognitive impairment were analyzed.All patients were followed up for 1 year to compare the outcomes of the two groups.Results The cognitive impairment group had significantly advanced age,larger proportions of concomitant chronic respiratory diseases and sarcopenia,increased ratio of undergoing open heart surgery,and elevated incidence of intraoperative hypotension than the control group(P<0.05,P<0.01).Multivariate logistic regression analysis indicated that age,chronic respiratory diseases,sarcopenia,open heart surgery,and intraoperative hypotension were independent risk factors for postoperative cognitive impairment in elderly patients with heart diseases(OR=1.081,95%CI:1.007-1.161,P=0.030;OR=2.538,95%CI:1.062-6.066,P=0.036;OR=2.650,95%CI:1.174-5.985,P=0.019;OR=3.104,95%CI:1.391-6.929,P=0.006;OR=3.478,95%CI:1.298-9.322,P=0.0013).There was no statistical difference in preoperative MoCA scores between the two groups(27.90±1.40 vs 28.20±1.40,P=0.195).The MoCA score at 7 d and 6 and 12 months after surgery were obviously lower in the cognitive impairment group than the control group(22.90±1.27 vs 27.73±1.08,P=0.000;24.72±1.66 vs 27.73±1.23,P=0.000;25.48±1.73 vs 27.62±1.22,P=0.000).Age was identified as an independent factor affecting the outcome of cognitive function in the patients(OR=1.168,95%CI:1.035-1.318).Conclusion The incidence of postoperative cog-nitive impairment is relatively high in elderly patients with heart disease.So,relevant risk factors should be addressed to strengthen the prevention and management.
5.Role of hippocampal activating transcription factor 5 in cognitive impairment induced by neuropathic pain in mice: relationship with mitochondrial unfolded protein response
Fei XING ; Xiaoshan SHI ; Yaowei XU ; Xin WEI ; Mingcui QU ; Dan CHENG ; Jingjing YUAN ; Zhongyu WANG ; Na XING ; Yanna LI
Chinese Journal of Anesthesiology 2025;45(3):329-334
Objective:To evaluate the role of hippocampal activating transcription factor 5 (ATF5) in cognitive impairment induced by neuropathic pain and the relationship with mitochondrial unfolded protein response(mtUPR) in mice.Methods:This study was conducted in 2 parts. Experiment Ⅰ Twenty-four SPF healthy male C57BL/6 mice, aged 6-8 weeks, weighing 20-25 g, were divided into 2 groups ( n=12 each) using a random number table method: sham operation group (S1 group) and neuropathic pain group (NP group). Neuropathic pain was induced by chronic constriction injury to the sciatic nerve. The mechanical paw withdrawal threshold (MWT) and thermal paw withdrawal latency (TWL) were measured before developing the model and at 7, 14, 21 and 28 days after developing the model. Mouse cognitive function was assessed using the novel object recognition test from 30-31 days after developing the model. After the end of the novel object recognition test, mice were sacrificed and the hippocampal CA1 region was harvested for determination of the expression of ATF5 (by Western blot) and the expression of ATF5 in neurons, microglia and astrocytes (by immunofluorescence double staining). Experiment Ⅱ Thirty-six SPF healthy male C57BL/6 mice, aged 6-8 weeks, weighing 20-25 g, were divided into 3 groups ( n=12 each) using a random number table method: sham operation group (S2 group), neuropathic pain + ATF5 up-regulation group (NA group), and neuropathic pain + empty virus group (NE group). On day 14 after developing the model, a virus that specifically up-regulated ATF5 expression in neurons and empty virus were injected into the hippocampal CA1 region. The MWT and TWL were measured at days 28 and 35 after developing the model. The novel object recognition test was performed on day 36 after developing the model to evaluate the cognitive function. After the end of the behavioral test, mice were sacrificed and the hippocampal CA1 region was harvested for detection of the expression of ATF5 and mtUPR marker proteins (Lon protease [LONP1] and heat shock protein 60 [HSP60]) by Western blot. Results:Experiment Ⅰ Compared with S1 group, no statistically significant change was found in the MWT and TWL before developing the model ( P>0.05), the MWT and TWL were significantly decreased on days 7, 14, 21 and 28 after developing the model, the discrimination index (DI) was decreased at day 31 after developing the model, the expression of ATF5 was down-regulated, the expression of ATF5 in neurons was down-regulated ( P<0.05), and no statistically significant change was found in the expression of ATF5 in mircrolia and astrocytes in NP group ( P>0.05). Experiment Ⅱ Compared with S2 group, the MWT and TWL were significantly decreased on days 28 and 35 after developing the model in NE group and NA group, DI was decreased, and the expression of ATF5, LONP1 and HSP60 was down-regulated in NE group ( P<0.05), and no significant change was found in NA group ( P>0.05). Compared with NE group, no significant change was found in the MWT and TWL in NA group ( P>0.05), DI was significantly increased, and the expression of ATF5, LONP1 and HSP60 was up-regulated in NA group ( P<0.05). Conclusions:Down-regulated ATF5 in the hippocampus is involved in the process of cognitive impairment caused by neuropathic pain, and the mechanism may be related to the inhibition of mtUPR.
6.Identification of associated factors and construction of a predictive model for membranous nephropathy patients with IgM deposition
Lei HE ; Yunhui ZHANG ; Jingjing JIN ; Meijuan CHENG ; Shenglei ZHANG ; Yaling BAI ; Jinsheng XU
Chinese Journal of Nephrology 2025;41(7):489-497
Objective:To explore the associated factors for membranous nephropathy (MN) patients with IgM deposition, and to construct a prediction model.Methods:This study was a retrospective cohort study. Patients diagnosed with MN with IgM deposition by renal biopsy in the Fourth Hospital of Hebei Medical University from February 2017 to December 2023 were retrospectively included. Clinical and pathological data were collected. The study population was randomized into a training set and a validation set at a 7:3 ratio. The endpoint event was defined as the remission of MN, and the patients were divided into remission group and non-remission group to compare the clinical and pathological examination results. Least absolute shrinkage and selection operator regression analysis and Cox regression analysis were used to explore the associated factors of poor prognosis of MN patients with IgM deposition. Internal validation was conducted using the validation set data. The clinical efficacy of the predictive model was evaluated by calculating the area under the receiver operating characteristic (ROC) curve and generating calibration curves. The total nomogram score for each patient was calculated based on the training set data, and the predictive performance was assessed by plotting the ROC curve. Patients were then stratified into low-risk and high-risk groups according to the optimal cut-off value derived from the ROC analysis of the total nomogram score. Kaplan-Meier survival analysis was performed to compare the remission rate between the two groups. Model performance was evaluated using the validation set.Results:A total of 200 MN patients with IgM deposition were included, and 49.0% of them achieved clinical remission. In the training set, statistically significant differences were observed in 24-hour urine protein quantification ( Z=-2.638, P=0.008), renal arteriolar wall thickening ( χ2=6.891, P=0.009), the proportion of patients receiving immunosuppressive therapy ( χ2=21.381, P<0.001), and the proportion of patients treated with corticosteroids combined with cyclophosphamide ( χ2=10.107, P=0.001). Through least absolute shrinkage and selection operator regression and Cox regression, 2 factors associated with clinical remission in MN patients with IgM deposition were simultaneously identified from 16 potential associated factors, including the use of immunosuppressants ( HR=3.823, 95% CI 2.055-7.113, P<0.001), and renal arteriolar wall thickening ( HR=0.428, 95% CI 0.221-0.831, P=0.012). Incorporating the clinical measurement of phospholipase A2 receptor (PLA2R) antibodies, a predictive model was established. The performance of the model was evaluated using the training dataset, yielding an area under the ROC curve of 0.731 (95% CI 0.648-0.814), with a sensitivity of 88.7% and a specificity of 55.1%. The optimal cut-off value was a total nomogram score of 41.7 points. The Kaplan-Meier survival analysis showed that the remission rate was significantly higher in the low-risk group than that of the high-risk group (Log-rank test, χ2=33.525, P<0.001). Model validation was performed using the validation dataset, which showed an AUC of 0.715 (95% CI 0.591-0.839), sensitivity of 70.4%, and specificity of 63.6%. Similarly, the Kaplan-Meier survival analysis demonstrated a significantly higher remission rate in the low-risk group than in the high-risk group (Log-rank test, χ2=8.467, P=0.004). Conclusion:A nomogram predictive model for remission of MN patients with IgM deposition, based on serum PLA2R antibody levels, the use of immunosuppressive therapy, and renal arteriolar wall thickening is developed. The model demonstrates a moderate clinical applicability.
7.TAFRO syndrome caused by Castleman disease: a case report and literature review
Wenyuan LOU ; Jingjing WANG ; Duqun CHEN ; Yuanmao TU ; Dandan QIU ; Zhen CHENG ; Haitao ZHANG
Chinese Journal of Nephrology 2025;41(7):544-548
TAFRO syndrome is an idiopathic systemic inflammatory disease that overlaps with idiopathic multicentric Castleman disease (iMCD). The clinical features of TAFRO syndrome include thrombocytopenia (T), anasarca (A), fever (F), reticulin fibrosis/renal insufficiency (R) and organomegaly (O). The paper reports a special clinical subtype of iMCD—TAFRO syndrome in a patient, manifested as multiple-system involvement including serous effusion (ascites), fever, thrombocytopenia, anemia, multiple lymphadenopathies, pancreatitis and renal insufficiency. Bone marrow biopsy pathology showed active bone marrow hyperplasia. Renal biopsy revealed renal thrombotic microangiopathy, acute renal tubular interstitial injury combined with chronic lesions. Lymph node biopsy demonstrated lymphoproliferative lesions consistent with Castleman disease (hyaline vascular type). Following diagnosis, glucocorticoids, tacrolimus, rituximab and lenalidomide were administered, resulting in significant symptomatic improvement: ascites disappeared, and urinary findings, erythrocyte counts, renal function and hematological indexes normalized. The paper describes the patient's clinical manifestations, diagnosis and treatment process, and prognosis, and reviews relevant literature, to improve clinicians' understanding of this rare disease.
8.Study on AlignRT guided set-up of breast-conserving radiotherapy and the impact of patients′ thoracic characteristic parameters
Ailin WU ; Lin YAN ; Xinglei WU ; Peng ZHANG ; Jingjing CHENG ; Chunbao ZANG ; Hongbo ZHANG ; Aidong WU
Chinese Journal of Radiological Medicine and Protection 2025;45(1):24-30
Objective:To compare the impact of the AlignRT-based optical guidance method with the traditional marker line method on the accuracy of positioning, and explore the effect of patient′s different thoracic characteristic parameters on the precision of optical guidance positioning.Methods:A total of sixty breast cancer patients who received post breast-conserving radiotherapy at Anhui Cancer Hospital from July 2022 to September 2023 were retrospectively selected. Then these patients were equally divided into traditional cross hairs set-up (marker line group) and surface-guided set-up (SGRT group). The cone-beam CT scanning results were used as the gold standard, the three-dimensional set-up errors and the CTV-PTV target area external radiotherapy boundaries of two groups were studied comparatively. Multiple patient′s thoracic characteristic parameters were defined and the correction between each parameter and set-up error of SGRT was analyzed.Results:The mean value of three-dimensional set-up errors in the SGRT group and the marker line group was within 0.2 cm and 0.5 cm, respectively. The differences in three-dimensional set-up errors and total displacements between two groups were statistically significant ( z=-2.93, -3.21, -2.59, -4.76, P<0.05). The SGRT group reduced the CTV-PTV boundary from 0.5 cm of conventional marker line group to 0.3 cm. The thoracic aspect ratio H/W, the affected side pinch angle α1, and the healthy side pinch angle α2 were positively correlated with the x-direction posing error ( r=0.49, 0.59, 0.71, P<0.05); whereas, the affected side and the healthy side mammary gland heights D1 and D2 were negatively correlated with the z-direction posing error ( r=-0.46, -0.49, P<0.05). Conclusions:For breast-conserving postoperative radiotherapy patients, SGRT can obtain a more accurate radiotherapy set-up than the traditional marker line method, and can effectively reduce the target area externally expanded range. Meanwhile, the monitoring accuracy of SGRT is affected by the patient′s thoracic characteristic parameters, and clinical attention should be paid to breast-conserving radiotherapy patients with thick body shape, narrow body width, and small breast glands.
9.Association analysis of factors influencing high hospitalization costs for cancer patients based on FP-Growth and Apriori algorithm
Jingjing YE ; Dian ZHOU ; Di TIAN ; Yuan ZHOU ; Yu ZHANG ; Manchen LYU ; Tongbin XUE ; Huan BAI ; Cheng GUO ; Ye WU
Chinese Journal of Hospital Administration 2025;41(3):216-222
Objective:Exploring the association rules of factors influencing high hospitalization costs for cancer patients, providing references for hospitals to optimize medical cost management measures.Methods:In the inpatient case information system of a tertiary general hospital, the medical record homepages of inpatients in the DRG groups of the oncology department in 2022 were obtained. The upper four scores of hospitalization costs was used as the threshold for patient grouping. Patients with hospitalization costs≥this threshold were the high-cost group, while other patients were control group; 12 factors, including age, gender, and admission condition, etc, were considered as potential influencing factors of high hospitalization costs. FP-Growth and Apriori algorithms were used to excavate the potential association rules between the influencing factors of high hospitalization costs. Logistic regression was used to analyze the independent influencing factors of high hospitalization costs.Results:A total of 5 512 hospitalized patients were included, including 1 378 patients in the high-cost group. Thirteen validated strong association rules for factors influencing high hospitalization costs were obtained, of which the rule antecedents included age (≥70 years), number of days in hospital (≥7 days), other diagnoses (≥5), surgery, planned readmission, use of antibiotics, admission (general/critical), living admission score (61~99), level of care (level 1/level 2), non-day ward, criticality during hospitalisation. Logistic regression results showed that all nine influencing factors except gender, use of antibiotics, and readmission plans were independent influences on high hospitalization costs ( P<0.05). Conclusions:The joint application of FP-Growth and Apriori algorithm could effectively explore the association rules of high hospitalization costs for oncology patients. The early warning information mainly included the number of hospitalization days, the number of other diagnoses, surgeries, and so on. It was suggested that medical institutions can reasonably control the high hospitalization costs through clinical pathway management, diagnosis and treatment process reengineering, admission risk assessment, and multidisciplinary collaborative diagnosis and treatment strategies.
10.Association between cardiometabolic multimorbidity and mild cognitive impairment among older adults in urban communities
Bingyu ZHANG ; Jingjing ZHANG ; Cheng CAI ; Juan ZHOU ; Jing LIU ; Xiaoyu LOU ; Yan ZENG ; Guirong CHENG ; Dan LIU
Chinese Journal of Geriatrics 2025;44(12):1757-1765
Objective:To explore the association between cardiometabolic multimorbidity(CMM), the number of cardiometabolic diseases(CMD)and mild cognitive impairment(MCI)among the older adults in urban communities.Methods:Based on the baseline data of the Hubei Memory and Aging Cohort Study(HMACS)from 2018 to 2023, CMM was defined as the coexistence of two or more CMDs(Type 2 diabetes, stroke and ischemic heart disease). Multivariate logistic regression was employed to examine the association between CMM, the number of CMDs and the prevalence of MCI, as well as subgroup heterogeneity.Results:This study included 6 113 urban participants aged ≥65 years(55.6% were female; mean age 71.9±5.7 years). The prevalence of MCI was 19.3%, with an increasing trend observed as the number of CMD increased(17.7%, 20.5%, 24.6%, 28.3%). After adjusting for all variables, a significant association was observed between CMM group and the prevalence of MCI( OR: 1.24, 95% CI: 1.01-1.52)compared with the non-CMM group.As the number of CMD increased, the prevalence of MCI increased( Ptrend=0.011), but the association was only significant in the group with two CMDs.Subgroup analyses revealed that in males( OR: 1.48, 95% CI: 1.10-2.00), those with more than 9 years of education( OR: 1.52, 95% CI: 1.15-2.02), and those with hypertension( OR: 1.33, 95% CI: 1.05-1.67), CMM was significantly associated with MCI, and the association with MCI increased significantly with the increase in the number of CMDs(all Pfor trend <0.05). Conclusions:Among urban community-dwelling older adults aged ≥65 years in China, CMM and the cumulative number of CMDs are significantly associated with an increase of MCI, particularly in males, those with higher education levels, and those with hypertension.In the future, the need for enhanced MCI screening for CMM patients should be strengthened, and targeted prevention and control of cognitive impairment should be implemented for high-risk populations.


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