1.Risk factors for sarcopenia in patients with Wilson’s disease-related liver cirrhosis and their impact on clinical outcomes
Weiqi WANG ; Taohua WEI ; Nannan QIAN ; Wenming YANG ; Yulong YANG ; Yuqi SONG ; Wenjie HAO ; Yue YANG ; Hu XI ; Wei HE
Journal of Clinical Hepatology 2025;41(10):2075-2081
ObjectiveTo investigate the incidence rate of sarcopenia in patients with Wilson’s disease (WD)-related liver cirrhosis, as well as the risk factors for sarcopenia and their impact on clinical outcomes. MethodsA total of 140 patients with WD-related liver cirrhosis who were treated in The First Affiliated Hospital of Anhui University of Chinese Medicine from January 2019 to June 2020, and according to the third lumbar skeletal muscle mass index (L3 SMI), the patients were divided into sarcopenia group and non-sarcopenia group. Nutritional risk screening, anthropometric measurements, and blood biochemical tests were performed for the patients to identify the influencing factors for sarcopenia. The patients were followed up for 36 — 48 months, and survival status and complications were compared between the two groups. The independent-samples t test was used for comparison of normally distributed continuous data between two groups, and the chi-square test and the Mann-Whitney U rank sum test were used for comparison of categorical data between two groups. A binary Logistic regression analysis was used to investigate the influencing factors for sarcopenia, and univariate and multivariate Cox regression analyses were used to investigate the risk factors for the prognosis of patients with WD-related liver cirrhosis. The Kaplan-Meier survival curve was plotted, and the Log-rank test was used for comparison between groups. ResultsAmong the 140 patients with WD-related liver cirrhosis, 53 (37.9%) developed sarcopenia, with significantly lower body mass index (BMI) and L3 SMI than the patients without sarcopenia (t=10.550 and 3.982, both P<0.001). The multivariate Logistic regression analysis showed that age (odds ratio [OR]=2.243, 95% confidence interval [CI]: 1.196 — 4.208, P=0.012), sex (OR=0.450, 95%CI: 0.232 — 0.872, P=0.018), BMI (OR=0.126, 95%CI: 0.089 — 0.294, P<0.001), and hepatic encephalopathy (OR=8.367, 95%CI: 2.423 — 28.897, P<0.001) were the main influencing factors for sarcopenia in patients with WD-related liver cirrhosis. Compared with the non-sarcopenia group, the sarcopenia group had significantly higher mortality rate (χ2=6.158, P=0.019) and significantly higher incidence rates of infection (χ2=8.008, P=0.040), recurrent abdominal/pleural efflux (χ2=17.742, P<0.001), and hepatic encephalopathy (χ2=4.338, P=0.039). The multivariate Cox regression analysis showed that sarcopenia (hazard ratio [HR]=4.685, P=0.002) and hepatic encephalopathy (HR=19.156, P<0.001) were independent risk factors for death in patients with WD-related liver cirrhosis. The Kaplan-Meier survival curve analysis showed a significant reduction in survival rate in the patients with sarcopenia (P=0.003). ConclusionSarcopenia is one of the manifestations of malnutrition in patients with WD-related liver cirrhosis, which increases the risk of mortality and other complications and has an adverse effect on prognosis. There is an increased risk of sarcopenia in male patients or patients with hepatic encephalopathy, a lower level of BMI or an older age.
2.The Impact of the Number of Pelvic Lymph Nodes Removed during Radical Re-section of Cervical Cancer on Prognosis of Patients
Ying NAN ; Xiaomeng WANG ; Weiqi SONG ; Wenfang ZHONG ; Zhiqiang LI ; Chunlin CHEN ; Chen MAO
Journal of Practical Obstetrics and Gynecology 2024;40(10):816-822
Objective:To investigate the relationship between the number of removed lymph nodes(RLN)and patient prognosis during radical surgery for extensive cervical cancer(CC).Methods:Clinical data of 21416 pa-tients with CC who underwent radical hysterectomy between January 1,2004 to August 31,2018 in the Chinese Cervical Cancer Clinical Study was retrospectively reviewed.Restricted cubic spline(RCS)was used to analyze the dose-response relationship between the number of RLN and prognosis.The patients were divided into three groups according to the RCS and RLN number:1-17 group(8733 cases),18-26 group(8189 cases),and≥ 27 group(4494 cases).Kaplan-Meier survival analysis and Log-Rank tests were used to compare the OS rates and DFS rates between groups at 3 and 5 years.Multivariate Cox proportional hazards model was used to analyze the prognostic mortality risk.Results:① RCS results showed a U-shaped nonlinear dose-response relationship be-tween the number of RLN and prognosis(P<0.01).When the number of RLN was less than 26,the risk of death decreased as the number of RLN increased,and the risk was lowest when the number of RLN was 26.②There were statistically significant differences(P<0.05)in age,histological type,tumor diameter,nerve invasion,uterine invasion,vaso-lymph node space invasion,cervical invasion,number of lymph node metastasis,whether preopera-tive adjuvant therapy was received,postoperative adjuvant therapy,and whether postoperative adjuvant therapy was standardized among the 3 groups(P<0.05).③Kaplan-Meier survival curve analysis showed that the 5-year OS of the 1-17 group,18-26 group,and ≥ 27 group were 90.23%,92.28%,and 91.61%,respectively,and the 5-year DFS were 85.32%,87.90%,and 87.18%,respectively.The differences between the three groups were sta-tistically significant(P<0.01).④The results of multivariate Cox regression analysis showed that RLN number in the range of 1-17 was a significant risk factor for the 3-and 5-year OS and DFS,when compared to the 18-26 RLN group(HR>1,P<0.05).Conclusions:RLN number may be one of the prognostic indicators of CC.When the number of RLNs is between 18-26,the prognosis of the patient may be better.The number of RLN in the range of 1-17 may increase the risk of recurrence or death in CC patients.
3.The Impact of the Number of Pelvic Lymph Nodes Removed during Radical Re-section of Cervical Cancer on Prognosis of Patients
Ying NAN ; Xiaomeng WANG ; Weiqi SONG ; Wenfang ZHONG ; Zhiqiang LI ; Chunlin CHEN ; Chen MAO
Journal of Practical Obstetrics and Gynecology 2024;40(10):816-822
Objective:To investigate the relationship between the number of removed lymph nodes(RLN)and patient prognosis during radical surgery for extensive cervical cancer(CC).Methods:Clinical data of 21416 pa-tients with CC who underwent radical hysterectomy between January 1,2004 to August 31,2018 in the Chinese Cervical Cancer Clinical Study was retrospectively reviewed.Restricted cubic spline(RCS)was used to analyze the dose-response relationship between the number of RLN and prognosis.The patients were divided into three groups according to the RCS and RLN number:1-17 group(8733 cases),18-26 group(8189 cases),and≥ 27 group(4494 cases).Kaplan-Meier survival analysis and Log-Rank tests were used to compare the OS rates and DFS rates between groups at 3 and 5 years.Multivariate Cox proportional hazards model was used to analyze the prognostic mortality risk.Results:① RCS results showed a U-shaped nonlinear dose-response relationship be-tween the number of RLN and prognosis(P<0.01).When the number of RLN was less than 26,the risk of death decreased as the number of RLN increased,and the risk was lowest when the number of RLN was 26.②There were statistically significant differences(P<0.05)in age,histological type,tumor diameter,nerve invasion,uterine invasion,vaso-lymph node space invasion,cervical invasion,number of lymph node metastasis,whether preopera-tive adjuvant therapy was received,postoperative adjuvant therapy,and whether postoperative adjuvant therapy was standardized among the 3 groups(P<0.05).③Kaplan-Meier survival curve analysis showed that the 5-year OS of the 1-17 group,18-26 group,and ≥ 27 group were 90.23%,92.28%,and 91.61%,respectively,and the 5-year DFS were 85.32%,87.90%,and 87.18%,respectively.The differences between the three groups were sta-tistically significant(P<0.01).④The results of multivariate Cox regression analysis showed that RLN number in the range of 1-17 was a significant risk factor for the 3-and 5-year OS and DFS,when compared to the 18-26 RLN group(HR>1,P<0.05).Conclusions:RLN number may be one of the prognostic indicators of CC.When the number of RLNs is between 18-26,the prognosis of the patient may be better.The number of RLN in the range of 1-17 may increase the risk of recurrence or death in CC patients.
4.The Impact of the Number of Pelvic Lymph Nodes Removed during Radical Re-section of Cervical Cancer on Prognosis of Patients
Ying NAN ; Xiaomeng WANG ; Weiqi SONG ; Wenfang ZHONG ; Zhiqiang LI ; Chunlin CHEN ; Chen MAO
Journal of Practical Obstetrics and Gynecology 2024;40(10):816-822
Objective:To investigate the relationship between the number of removed lymph nodes(RLN)and patient prognosis during radical surgery for extensive cervical cancer(CC).Methods:Clinical data of 21416 pa-tients with CC who underwent radical hysterectomy between January 1,2004 to August 31,2018 in the Chinese Cervical Cancer Clinical Study was retrospectively reviewed.Restricted cubic spline(RCS)was used to analyze the dose-response relationship between the number of RLN and prognosis.The patients were divided into three groups according to the RCS and RLN number:1-17 group(8733 cases),18-26 group(8189 cases),and≥ 27 group(4494 cases).Kaplan-Meier survival analysis and Log-Rank tests were used to compare the OS rates and DFS rates between groups at 3 and 5 years.Multivariate Cox proportional hazards model was used to analyze the prognostic mortality risk.Results:① RCS results showed a U-shaped nonlinear dose-response relationship be-tween the number of RLN and prognosis(P<0.01).When the number of RLN was less than 26,the risk of death decreased as the number of RLN increased,and the risk was lowest when the number of RLN was 26.②There were statistically significant differences(P<0.05)in age,histological type,tumor diameter,nerve invasion,uterine invasion,vaso-lymph node space invasion,cervical invasion,number of lymph node metastasis,whether preopera-tive adjuvant therapy was received,postoperative adjuvant therapy,and whether postoperative adjuvant therapy was standardized among the 3 groups(P<0.05).③Kaplan-Meier survival curve analysis showed that the 5-year OS of the 1-17 group,18-26 group,and ≥ 27 group were 90.23%,92.28%,and 91.61%,respectively,and the 5-year DFS were 85.32%,87.90%,and 87.18%,respectively.The differences between the three groups were sta-tistically significant(P<0.01).④The results of multivariate Cox regression analysis showed that RLN number in the range of 1-17 was a significant risk factor for the 3-and 5-year OS and DFS,when compared to the 18-26 RLN group(HR>1,P<0.05).Conclusions:RLN number may be one of the prognostic indicators of CC.When the number of RLNs is between 18-26,the prognosis of the patient may be better.The number of RLN in the range of 1-17 may increase the risk of recurrence or death in CC patients.
5.Celastrol inhibits glutamate excitotoxicity after subarachnoid hemor-rhage by directly targeting EAAT2
Xiaoying LI ; Pida HAO ; Xiaotong FENG ; Qile SONG ; Weiqi WANG ; Guoqing ZHOU ; Yajun HOU
Chinese Journal of Pathophysiology 2024;40(11):2014-2021
AIM:To investigate the impact of celastrol intervention on excitatory amino acid transporter 2(EAAT2)and its neuroprotective role in subarachnoid hemorrhage(SAH).METHODS:Western blot analysis was uti-lized to assess the EAAT2 expression level within 72 h after SAH,while glutamate concentration in cortical brain tissues was measured.Computational simulation was employed to explore the binding of celastrol with EAAT2.Seventy SD rats were randomly assigned to sham,model,model+GT949(an EAAT2 agonist),model+dihydrokainic acid(DHK;an EAAT2 inhibitor),and model+celastrol groups.Glutamate concentration in cortical brain tissues was quantified,and brain edema was assessed by dry-wet weight method.Western blot analysis was conducted to evaluate the expression of EAAT2,aquaporin 4 and apoptosis-related proteins(Bax,Bcl-2,caspase-3 and caspase-9),and TUNEL staining was employed to assess the apoptotic cell count in each group.RESULTS:(1)EAAT2 level decreased while glutamate con-centration increased.(2)Celastrol was found to directly bind to EAAT2,enhancing EAAT2 expression and reducing glu-tamate concentration after SAH.(3)Celastrol demonstrated the ability to inhibit brain edema after SAH.(4)Celastrol was effective in reducing neuronal apoptosis after SAH.CONCLUSION:Celastrol has the potential to up-regulate EAAT2 expression,lower glutamate level,mitigate brain edema,and decrease neuronal apoptosis after SAH.
6.The Impact of the Number of Pelvic Lymph Nodes Removed during Radical Re-section of Cervical Cancer on Prognosis of Patients
Ying NAN ; Xiaomeng WANG ; Weiqi SONG ; Wenfang ZHONG ; Zhiqiang LI ; Chunlin CHEN ; Chen MAO
Journal of Practical Obstetrics and Gynecology 2024;40(10):816-822
Objective:To investigate the relationship between the number of removed lymph nodes(RLN)and patient prognosis during radical surgery for extensive cervical cancer(CC).Methods:Clinical data of 21416 pa-tients with CC who underwent radical hysterectomy between January 1,2004 to August 31,2018 in the Chinese Cervical Cancer Clinical Study was retrospectively reviewed.Restricted cubic spline(RCS)was used to analyze the dose-response relationship between the number of RLN and prognosis.The patients were divided into three groups according to the RCS and RLN number:1-17 group(8733 cases),18-26 group(8189 cases),and≥ 27 group(4494 cases).Kaplan-Meier survival analysis and Log-Rank tests were used to compare the OS rates and DFS rates between groups at 3 and 5 years.Multivariate Cox proportional hazards model was used to analyze the prognostic mortality risk.Results:① RCS results showed a U-shaped nonlinear dose-response relationship be-tween the number of RLN and prognosis(P<0.01).When the number of RLN was less than 26,the risk of death decreased as the number of RLN increased,and the risk was lowest when the number of RLN was 26.②There were statistically significant differences(P<0.05)in age,histological type,tumor diameter,nerve invasion,uterine invasion,vaso-lymph node space invasion,cervical invasion,number of lymph node metastasis,whether preopera-tive adjuvant therapy was received,postoperative adjuvant therapy,and whether postoperative adjuvant therapy was standardized among the 3 groups(P<0.05).③Kaplan-Meier survival curve analysis showed that the 5-year OS of the 1-17 group,18-26 group,and ≥ 27 group were 90.23%,92.28%,and 91.61%,respectively,and the 5-year DFS were 85.32%,87.90%,and 87.18%,respectively.The differences between the three groups were sta-tistically significant(P<0.01).④The results of multivariate Cox regression analysis showed that RLN number in the range of 1-17 was a significant risk factor for the 3-and 5-year OS and DFS,when compared to the 18-26 RLN group(HR>1,P<0.05).Conclusions:RLN number may be one of the prognostic indicators of CC.When the number of RLNs is between 18-26,the prognosis of the patient may be better.The number of RLN in the range of 1-17 may increase the risk of recurrence or death in CC patients.
7.The Impact of the Number of Pelvic Lymph Nodes Removed during Radical Re-section of Cervical Cancer on Prognosis of Patients
Ying NAN ; Xiaomeng WANG ; Weiqi SONG ; Wenfang ZHONG ; Zhiqiang LI ; Chunlin CHEN ; Chen MAO
Journal of Practical Obstetrics and Gynecology 2024;40(10):816-822
Objective:To investigate the relationship between the number of removed lymph nodes(RLN)and patient prognosis during radical surgery for extensive cervical cancer(CC).Methods:Clinical data of 21416 pa-tients with CC who underwent radical hysterectomy between January 1,2004 to August 31,2018 in the Chinese Cervical Cancer Clinical Study was retrospectively reviewed.Restricted cubic spline(RCS)was used to analyze the dose-response relationship between the number of RLN and prognosis.The patients were divided into three groups according to the RCS and RLN number:1-17 group(8733 cases),18-26 group(8189 cases),and≥ 27 group(4494 cases).Kaplan-Meier survival analysis and Log-Rank tests were used to compare the OS rates and DFS rates between groups at 3 and 5 years.Multivariate Cox proportional hazards model was used to analyze the prognostic mortality risk.Results:① RCS results showed a U-shaped nonlinear dose-response relationship be-tween the number of RLN and prognosis(P<0.01).When the number of RLN was less than 26,the risk of death decreased as the number of RLN increased,and the risk was lowest when the number of RLN was 26.②There were statistically significant differences(P<0.05)in age,histological type,tumor diameter,nerve invasion,uterine invasion,vaso-lymph node space invasion,cervical invasion,number of lymph node metastasis,whether preopera-tive adjuvant therapy was received,postoperative adjuvant therapy,and whether postoperative adjuvant therapy was standardized among the 3 groups(P<0.05).③Kaplan-Meier survival curve analysis showed that the 5-year OS of the 1-17 group,18-26 group,and ≥ 27 group were 90.23%,92.28%,and 91.61%,respectively,and the 5-year DFS were 85.32%,87.90%,and 87.18%,respectively.The differences between the three groups were sta-tistically significant(P<0.01).④The results of multivariate Cox regression analysis showed that RLN number in the range of 1-17 was a significant risk factor for the 3-and 5-year OS and DFS,when compared to the 18-26 RLN group(HR>1,P<0.05).Conclusions:RLN number may be one of the prognostic indicators of CC.When the number of RLNs is between 18-26,the prognosis of the patient may be better.The number of RLN in the range of 1-17 may increase the risk of recurrence or death in CC patients.
8.The Impact of the Number of Pelvic Lymph Nodes Removed during Radical Re-section of Cervical Cancer on Prognosis of Patients
Ying NAN ; Xiaomeng WANG ; Weiqi SONG ; Wenfang ZHONG ; Zhiqiang LI ; Chunlin CHEN ; Chen MAO
Journal of Practical Obstetrics and Gynecology 2024;40(10):816-822
Objective:To investigate the relationship between the number of removed lymph nodes(RLN)and patient prognosis during radical surgery for extensive cervical cancer(CC).Methods:Clinical data of 21416 pa-tients with CC who underwent radical hysterectomy between January 1,2004 to August 31,2018 in the Chinese Cervical Cancer Clinical Study was retrospectively reviewed.Restricted cubic spline(RCS)was used to analyze the dose-response relationship between the number of RLN and prognosis.The patients were divided into three groups according to the RCS and RLN number:1-17 group(8733 cases),18-26 group(8189 cases),and≥ 27 group(4494 cases).Kaplan-Meier survival analysis and Log-Rank tests were used to compare the OS rates and DFS rates between groups at 3 and 5 years.Multivariate Cox proportional hazards model was used to analyze the prognostic mortality risk.Results:① RCS results showed a U-shaped nonlinear dose-response relationship be-tween the number of RLN and prognosis(P<0.01).When the number of RLN was less than 26,the risk of death decreased as the number of RLN increased,and the risk was lowest when the number of RLN was 26.②There were statistically significant differences(P<0.05)in age,histological type,tumor diameter,nerve invasion,uterine invasion,vaso-lymph node space invasion,cervical invasion,number of lymph node metastasis,whether preopera-tive adjuvant therapy was received,postoperative adjuvant therapy,and whether postoperative adjuvant therapy was standardized among the 3 groups(P<0.05).③Kaplan-Meier survival curve analysis showed that the 5-year OS of the 1-17 group,18-26 group,and ≥ 27 group were 90.23%,92.28%,and 91.61%,respectively,and the 5-year DFS were 85.32%,87.90%,and 87.18%,respectively.The differences between the three groups were sta-tistically significant(P<0.01).④The results of multivariate Cox regression analysis showed that RLN number in the range of 1-17 was a significant risk factor for the 3-and 5-year OS and DFS,when compared to the 18-26 RLN group(HR>1,P<0.05).Conclusions:RLN number may be one of the prognostic indicators of CC.When the number of RLNs is between 18-26,the prognosis of the patient may be better.The number of RLN in the range of 1-17 may increase the risk of recurrence or death in CC patients.
9.The Impact of the Number of Pelvic Lymph Nodes Removed during Radical Re-section of Cervical Cancer on Prognosis of Patients
Ying NAN ; Xiaomeng WANG ; Weiqi SONG ; Wenfang ZHONG ; Zhiqiang LI ; Chunlin CHEN ; Chen MAO
Journal of Practical Obstetrics and Gynecology 2024;40(10):816-822
Objective:To investigate the relationship between the number of removed lymph nodes(RLN)and patient prognosis during radical surgery for extensive cervical cancer(CC).Methods:Clinical data of 21416 pa-tients with CC who underwent radical hysterectomy between January 1,2004 to August 31,2018 in the Chinese Cervical Cancer Clinical Study was retrospectively reviewed.Restricted cubic spline(RCS)was used to analyze the dose-response relationship between the number of RLN and prognosis.The patients were divided into three groups according to the RCS and RLN number:1-17 group(8733 cases),18-26 group(8189 cases),and≥ 27 group(4494 cases).Kaplan-Meier survival analysis and Log-Rank tests were used to compare the OS rates and DFS rates between groups at 3 and 5 years.Multivariate Cox proportional hazards model was used to analyze the prognostic mortality risk.Results:① RCS results showed a U-shaped nonlinear dose-response relationship be-tween the number of RLN and prognosis(P<0.01).When the number of RLN was less than 26,the risk of death decreased as the number of RLN increased,and the risk was lowest when the number of RLN was 26.②There were statistically significant differences(P<0.05)in age,histological type,tumor diameter,nerve invasion,uterine invasion,vaso-lymph node space invasion,cervical invasion,number of lymph node metastasis,whether preopera-tive adjuvant therapy was received,postoperative adjuvant therapy,and whether postoperative adjuvant therapy was standardized among the 3 groups(P<0.05).③Kaplan-Meier survival curve analysis showed that the 5-year OS of the 1-17 group,18-26 group,and ≥ 27 group were 90.23%,92.28%,and 91.61%,respectively,and the 5-year DFS were 85.32%,87.90%,and 87.18%,respectively.The differences between the three groups were sta-tistically significant(P<0.01).④The results of multivariate Cox regression analysis showed that RLN number in the range of 1-17 was a significant risk factor for the 3-and 5-year OS and DFS,when compared to the 18-26 RLN group(HR>1,P<0.05).Conclusions:RLN number may be one of the prognostic indicators of CC.When the number of RLNs is between 18-26,the prognosis of the patient may be better.The number of RLN in the range of 1-17 may increase the risk of recurrence or death in CC patients.
10.The Impact of the Number of Pelvic Lymph Nodes Removed during Radical Re-section of Cervical Cancer on Prognosis of Patients
Ying NAN ; Xiaomeng WANG ; Weiqi SONG ; Wenfang ZHONG ; Zhiqiang LI ; Chunlin CHEN ; Chen MAO
Journal of Practical Obstetrics and Gynecology 2024;40(10):816-822
Objective:To investigate the relationship between the number of removed lymph nodes(RLN)and patient prognosis during radical surgery for extensive cervical cancer(CC).Methods:Clinical data of 21416 pa-tients with CC who underwent radical hysterectomy between January 1,2004 to August 31,2018 in the Chinese Cervical Cancer Clinical Study was retrospectively reviewed.Restricted cubic spline(RCS)was used to analyze the dose-response relationship between the number of RLN and prognosis.The patients were divided into three groups according to the RCS and RLN number:1-17 group(8733 cases),18-26 group(8189 cases),and≥ 27 group(4494 cases).Kaplan-Meier survival analysis and Log-Rank tests were used to compare the OS rates and DFS rates between groups at 3 and 5 years.Multivariate Cox proportional hazards model was used to analyze the prognostic mortality risk.Results:① RCS results showed a U-shaped nonlinear dose-response relationship be-tween the number of RLN and prognosis(P<0.01).When the number of RLN was less than 26,the risk of death decreased as the number of RLN increased,and the risk was lowest when the number of RLN was 26.②There were statistically significant differences(P<0.05)in age,histological type,tumor diameter,nerve invasion,uterine invasion,vaso-lymph node space invasion,cervical invasion,number of lymph node metastasis,whether preopera-tive adjuvant therapy was received,postoperative adjuvant therapy,and whether postoperative adjuvant therapy was standardized among the 3 groups(P<0.05).③Kaplan-Meier survival curve analysis showed that the 5-year OS of the 1-17 group,18-26 group,and ≥ 27 group were 90.23%,92.28%,and 91.61%,respectively,and the 5-year DFS were 85.32%,87.90%,and 87.18%,respectively.The differences between the three groups were sta-tistically significant(P<0.01).④The results of multivariate Cox regression analysis showed that RLN number in the range of 1-17 was a significant risk factor for the 3-and 5-year OS and DFS,when compared to the 18-26 RLN group(HR>1,P<0.05).Conclusions:RLN number may be one of the prognostic indicators of CC.When the number of RLNs is between 18-26,the prognosis of the patient may be better.The number of RLN in the range of 1-17 may increase the risk of recurrence or death in CC patients.

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