1.Improvment of high fat diet induced metabolic dysfunction-associated fatty liver disease of mice by leucine
Yizhi DING ; Huiwen ZHAO ; Shan SHAN ; Liwen ZHANG ; Xiulan ZHAO
Chinese Journal of Pharmacology and Toxicology 2025;39(5):343-351
OBJECTIVE To explore the effect and underlying mechanism of leucine(Leu)on meta-bolic dysfunction-associated fatty liver disease induced by high fat diet(HFD)in mice.METHODS C57BL/6J male mice were randomly divided into chow diet(normal),chow diet+Leu(normal+Leu),HFD and HFD+Leu groups,with 10 mice in each group.The mice in the normal and normal+Leu groups received chow diet while those in the HFD and HFD+Leu groups received HFD.Drinking water for mice in the normal+Leu and HFD+Leu groups was supplemented with 1.5%Leu.The experiment lasted 24 weeks,total food and water intake of mice were recorded weekly to calculate energy and Leu intake respectively.Energy metabolism of mice was detected at week 20 by the Oxymas/CLAMS Animal Metabolic System heat production,CO2 exhalation,O2 consumption and respiratory exchange rate(RER).At the end of week 24,the mice were sacrificed and the livers were harvested,followed by the oil red O staining to reveal the fat content.Western blotting was performed to analyze the changes in the activity of the liver branched-chain α-keto acid dehydrogenase E1α(BCKDE1A),the activation of AMP-activated protein kinase alpha subunit(AMPKα),and the protein expressions of downstream effector molecules including silent information regulator 1(SIRT1)and peroxisome proliferator-activated receptor coactivator-1α(PGC-1α),fatty acid synthetase(FAS)and fatty acid binding protein 4(FABP4)in the liver of mice.RESULTS Total Leu intake of mice was significantly reduced in the HFD+Leu group,compared with the normal+Leu group.The mice fed with HFD significantly increased the energy intake body mass gain and liver mass,accompanied by fat accumulation in the liver,compared to the mice in the normal group.Simultaneously,the mice in the HFD group showed a decrease in CO2 exha-lation both by day and by night,and in the respiratory exchange ratio by day compared to the normal group.Compared with the HFD group,the body mass gain and liver mass obviously decreased in mice of the HFD+Leu group,and the liver fat accumulation was reduced.The mice in the HFD+Leu group exhib-ited higher heat production and O2 consumption,along with an increase in CO2 exhalation by day and by night.In addition,heat production,CO2 exhalation,and O2 consumption were significantly higher by night than by day(P<0.01).As for the respiratory exchange ratio,a night increase was seen in the mice from the normal group,normal+Leu group,and HFD group,but not in the HFD+Leu group.The results of Western blotting showed that compared with the normal group,the BCKDE1A phosphorylation inacti-vation was enhanced,AMPKα phosphorylation activation alleviated,the protein expressions of SIRT1 and PGC-1α downregulated(P<0.05),and the protein expressions of FAS and FABP4 increased in the livers of mice in the HFD group.Compared with the HFD group,the BCKDE1A phosphorylation inacti-vation was alleviated,AMPKα phosphorylation activation enhanced,the protein expressions of SIRT1 and PGC-1α increased,and the protein expressions of FAS and FABP4 downregulated in the livers of mice in the HFD+Leu group.CONCLUSION Leu can alleviate HFD-induced metabolic dysfunction-associated fatty liver disease in mice,which may be closely related to the promotion of energy metabo-lism and inhibition of fat synthesis.
2.Validation of a predictive model for platelet transfusion refractoriness in patients with hematological diseases
Xiulan HUANG ; Shuhan YUE ; Qun CAI ; Liqi LU ; Mengzhen HE ; Qiao LEI ; Caoyi LIU ; Jingwei ZHANG
Chinese Journal of Blood Transfusion 2025;38(4):537-545
[Objective] To validate and optimize the platelet transfusion refractoriness (PTR) prediction model for patients with hematological disorders established by our center. [Methods] The data of patients with hematological diseases who received platelet transfusions from December 2021 to December 2022 were used as the training set, and data from January 2023 to December 2023 as the validation set. The validation set data was used to validate the predictive model constructed on the training set. Relevant risk factors for PTR were collected through literature review and preliminary studies。 The patients were divided into effective and ineffective groups according to the corrected count increment (CCI) of platelet counts. Predictive factors were screened using univariate and multivariate logistic regression. The calibration of the model were assessed via calibration curves, while discrimination, accuracy, sensitivity, and specificity were evaluated using receiver operating characteristic (ROC) curves Clinical utility was further analyzed with decision curve analysis (DCA). [Results] The Hosmer-Lemeshow (H-L) goodness-of-fit test for the validation set yielded S: P=0.000, indicating that the original model needs optimization. Baseline comparisons and logistic regression identified the number of red blood cell units (RBCU) and platelet units (PLT-U) transfused as key predictors for the optimized model. The H-L goodness-of-fit test S: P values for the training and validation sets were 0.930 and 0.056, respectively; the ROC areas were 0.793 5 and 0.809 4, specificities 90.95% and 84.21%, sensitivities 59.26% and 70.04%, and accuracies 78.14% and 74.10%, respectively. DCA demonstrated clinical net benefit within a prediction probability threshold range of 0.2-0.8. [Conclusion] Transfusion volumes of RBC-U and PLT-U were inversely associated with PTR in hematological patients. The resulting PTR prediction model exhibits moderate predictive efficacy and clinical benefit.
3.The dynamic plantar pressure distribution of persons with chronic plantar fasciitis
Xiulan HAN ; Shanshan ZHANG ; Guifang ZHANG ; Zhiwei LIAN ; Shanshan BAO ; Zhenfa ZHANG ; Chuhuai WANG
Chinese Journal of Physical Medicine and Rehabilitation 2025;47(8):721-726
Objective:To analyze the dynamic plantar pressure distribution of persons with chronic plantar fasciitis (PF).Methods:Twenty persons with unilateral, chronic PF were recruited as the PF group, while twenty-three healthy counterparts were recruited as the control group. A foot-pressure measurement system was used to collect data describing the plantar pressure for each subject with or without PF while walking. The pressure data included the load of peak plantar pressure (PP), the mean plantar pressure (MP), the total foot ground contact area (TCA), and the load percentage and the foot ground contact area beneath the medial heel (MH), the lateral heel (LH), the medial longitudinal arch (MLA), the lateral longitudinal arch (LLA), the first metatarsal head (M1), the second to third metatarsal heads (M2-3), the fourth to fifth metatarsal heads (M4-5), the hallux (T1), and toes two to five (T2-5).Results:In the PF group, significant differences were observed during walking between the affected and unaffected feet in terms of PP [(2.41±0.44)kg/cm 2 versus (3.02±0.63)kg/cm 2]. Both were significantly greater than among the control group. Asymmetry in the load distribution was identified beneath the MH, M2-3, M1, MLA, M4-5 and T2-5 among the chronic PF group. There were also significant differences between the affected foot of the chronic PF group and the non-dominant foot of the control group with regard to the load percentage beneath the LH, M4-5, T2-5, M2-3 and T1. The load percentage under the LH was significantly higher under the unaffected foot of the PF group than under the dominant foot of the control group. In terms of ground contact area, the T2-5 area of the affected foot of the PF group was significantly smaller than that of the unaffected foot, as well as compared to the non-dominant foot of the control group. The TCA of both feet among the PF group was significantly smaller than under the corresponding feet of the control group. Conclusions:Patients with chronic plantar fasciitis apply plantar pressure asymmetrically during walking. They tend to shift their weight laterally onto the asymptomatic foot. During walking, those with PF apply higher plantar pressure over a smaller ground contact area.
4.The dynamic plantar pressure distribution of persons with chronic plantar fasciitis
Xiulan HAN ; Shanshan ZHANG ; Guifang ZHANG ; Zhiwei LIAN ; Shanshan BAO ; Zhenfa ZHANG ; Chuhuai WANG
Chinese Journal of Physical Medicine and Rehabilitation 2025;47(8):721-726
Objective:To analyze the dynamic plantar pressure distribution of persons with chronic plantar fasciitis (PF).Methods:Twenty persons with unilateral, chronic PF were recruited as the PF group, while twenty-three healthy counterparts were recruited as the control group. A foot-pressure measurement system was used to collect data describing the plantar pressure for each subject with or without PF while walking. The pressure data included the load of peak plantar pressure (PP), the mean plantar pressure (MP), the total foot ground contact area (TCA), and the load percentage and the foot ground contact area beneath the medial heel (MH), the lateral heel (LH), the medial longitudinal arch (MLA), the lateral longitudinal arch (LLA), the first metatarsal head (M1), the second to third metatarsal heads (M2-3), the fourth to fifth metatarsal heads (M4-5), the hallux (T1), and toes two to five (T2-5).Results:In the PF group, significant differences were observed during walking between the affected and unaffected feet in terms of PP [(2.41±0.44)kg/cm 2 versus (3.02±0.63)kg/cm 2]. Both were significantly greater than among the control group. Asymmetry in the load distribution was identified beneath the MH, M2-3, M1, MLA, M4-5 and T2-5 among the chronic PF group. There were also significant differences between the affected foot of the chronic PF group and the non-dominant foot of the control group with regard to the load percentage beneath the LH, M4-5, T2-5, M2-3 and T1. The load percentage under the LH was significantly higher under the unaffected foot of the PF group than under the dominant foot of the control group. In terms of ground contact area, the T2-5 area of the affected foot of the PF group was significantly smaller than that of the unaffected foot, as well as compared to the non-dominant foot of the control group. The TCA of both feet among the PF group was significantly smaller than under the corresponding feet of the control group. Conclusions:Patients with chronic plantar fasciitis apply plantar pressure asymmetrically during walking. They tend to shift their weight laterally onto the asymptomatic foot. During walking, those with PF apply higher plantar pressure over a smaller ground contact area.
5.Analysis of liver histological characteristics and clinically related factors in patients with inactive HBsAg carriers
Xinyang ZHANG ; Shan REN ; Sujun ZHENG ; Rongshan FAN ; Qingfa RUAN ; Wenqi HUANG ; Haibing GAO ; Yao XIE ; Minghui LI ; Xiulan XUE ; Fang YANG ; Junliang FU ; Xinyue CHEN
Chinese Journal of Hepatology 2025;33(7):660-666
Objective:To analyze the liver histological characteristics and clinically related factors in inactive hepatitis B surface antigen (HBsAg) carriers (IHC), and also explore whether antiviral treatment is necessary for IHC, as defined in the 2022 version of the hepatitis B prevention and treatment guidelines.Methods:A multicenter, retrospective cohort study was conducted. Two hundred and thirty-one IHC cases who underwent liver biopsy histopathological examination in nine medical institutions, including Beijing Youan Hospital affiliated with Capital Medical University, from January 2018 to December 2023 were included. General informative data, clinical serological markers, and transient elastography (TE) examination results were collected. Patients were divided into a positive (148 cases) and a negative group (83 cases) according to the results of hepatitis B virus (HBV) DNA detection. The differences in liver pathological inflammatory activity (G) and liver fibrosis stage (S) were analyzed between the two groups to explore the correlation between liver tissue conditions and clinically related factors. Comparsions of normally distributed continwous data, skeukd continuous data, and categorical data between groups are performed using t tests, Mann-Whitney U tests and χ2 tests, respectively. Results:The age of 231 IHC cases was 43 (38, 51) years old, with 95.2% (220/231) aged ≥30 years, and males accounted for 64.9% (150/231). HBsAg and HBV DNA levels were 131.9 (20.8, 400.9) IU/mL and 94.0 (0, 448.5) IU/mL, respectively, of which 35.9% (83/231) were HBV DNA negative (<20 IU/mL). The remarkable proportions of G≥2, S≥2, and liver injury (G≥2 and/or S≥2) in liver tissue were 16.5% (38/231), 29% (67/231), and 35.9% (83/231), respectively. The S≥2 proportion was significantly higher in the HBV DNA-negative group than the positive group (42.2% vs. 21.6%, P<0.001), and it mainly occurred in the population cohort over 30 years old (44.9% vs. 31.0%, P=0.04). The liver stiffness measurement (LSM), aspartate transaminase to platelet ratio index (APRI), and platelet (PLT) were significantly higher in the S≥2 group than the S<2 group ( P<0.05). Conclusion:Clinicians can comprehensively evaluate the degree of liver fibrosis in IHC based on clinical factors such as age, PLT, APRI, and LSM, even if the liver histological results are lacking. The China 2022 version guidelines define that nearly half of IHC has histological indications for antiviral therapy, and liver biopsy and prompt treatment can be recommended.
6.Additional benefits of pelvic floor proprioceptive training combined with conventional therapy in the treatment of female stress urinary incontinence.
Xiulan ZHANG ; Liping ZHU ; Xiaoling ZENG ; Zhaoxue LIU ; Shuo YANG ; Hong ZHANG ; Wenguang YAN ; Xuhong LI
Journal of Central South University(Medical Sciences) 2025;50(8):1385-1397
OBJECTIVES:
Stress urinary incontinence (SUI) is a common condition among women that severely impairs quality of life. Pelvic floor proprioceptive training (PFPT) has attracted increasing attention for its potential to enhance pelvic floor muscle function and alleviate SUI symptoms. This study aims to observe and compare the clinical efficacy of PFPT combined with electroacupuncture, electrical stimulation, and biofeedback therapy versus conventional therapy consisting of electroacupuncture, electrical stimulation, and biofeedback alone in women with SUI, and to explore the role of PFPT in improving symptom and functional outcomes.
METHODS:
In this randomized controlled trial, 72 women with mild to moderate SUI were recruited from the Department of Rehabilitation Medicine at Third Xiangya Hospital, Central South University, between December 2021 and October 2023. Participants were randomly assigned to an experimental group (n=36) or a control group (n=36). Both groups received health education. The control group underwent electroacupuncture combined with electrical stimulation and biofeedback therapy, while the experimental group additionally received PFPT 3 times per week for 4 weeks. The primary outcome was assessed using the International Consultation on Incontinence Questionnaire-Short Form (ICIQ-SF). Secondary outcomes included pelvic floor muscle strength, bladder neck mobility, and balance ability. The ICIQ-SF was reassessed at 1, 3, 6, and 12 months post-treatment.
RESULTS:
Both groups showed statistically significant improvements in all parameters after treatment (all P<0.05). However, there were no statistically significant differences between groups in most measures (all P>0.05). The experimental group demonstrated longer single-leg stance duration with eyes closed than the control group (left leg: P=0.026; right leg: P=0.006), with a significant increase from baseline (P<0.001). At 6 months post-treatment, the cure rate in the experimental group was significantly higher than that in the control group (P=0.037).
CONCLUSIONS
Conventional therapy effectively improves SUI symptoms, but adding PFPT provides notable additional benefits, including enhanced balance ability and sustained mid-term cure rates. These findings suggest that PFPT is a valuable adjunct to standard SUI management strategies.
Humans
;
Female
;
Urinary Incontinence, Stress/physiopathology*
;
Pelvic Floor/physiopathology*
;
Middle Aged
;
Biofeedback, Psychology
;
Adult
;
Exercise Therapy/methods*
;
Proprioception
;
Electroacupuncture/methods*
;
Quality of Life
;
Electric Stimulation Therapy/methods*
;
Treatment Outcome
;
Combined Modality Therapy
7.Improvment of high fat diet induced metabolic dysfunction-associated fatty liver disease of mice by leucine
Yizhi DING ; Huiwen ZHAO ; Shan SHAN ; Liwen ZHANG ; Xiulan ZHAO
Chinese Journal of Pharmacology and Toxicology 2025;39(5):343-351
OBJECTIVE To explore the effect and underlying mechanism of leucine(Leu)on meta-bolic dysfunction-associated fatty liver disease induced by high fat diet(HFD)in mice.METHODS C57BL/6J male mice were randomly divided into chow diet(normal),chow diet+Leu(normal+Leu),HFD and HFD+Leu groups,with 10 mice in each group.The mice in the normal and normal+Leu groups received chow diet while those in the HFD and HFD+Leu groups received HFD.Drinking water for mice in the normal+Leu and HFD+Leu groups was supplemented with 1.5%Leu.The experiment lasted 24 weeks,total food and water intake of mice were recorded weekly to calculate energy and Leu intake respectively.Energy metabolism of mice was detected at week 20 by the Oxymas/CLAMS Animal Metabolic System heat production,CO2 exhalation,O2 consumption and respiratory exchange rate(RER).At the end of week 24,the mice were sacrificed and the livers were harvested,followed by the oil red O staining to reveal the fat content.Western blotting was performed to analyze the changes in the activity of the liver branched-chain α-keto acid dehydrogenase E1α(BCKDE1A),the activation of AMP-activated protein kinase alpha subunit(AMPKα),and the protein expressions of downstream effector molecules including silent information regulator 1(SIRT1)and peroxisome proliferator-activated receptor coactivator-1α(PGC-1α),fatty acid synthetase(FAS)and fatty acid binding protein 4(FABP4)in the liver of mice.RESULTS Total Leu intake of mice was significantly reduced in the HFD+Leu group,compared with the normal+Leu group.The mice fed with HFD significantly increased the energy intake body mass gain and liver mass,accompanied by fat accumulation in the liver,compared to the mice in the normal group.Simultaneously,the mice in the HFD group showed a decrease in CO2 exha-lation both by day and by night,and in the respiratory exchange ratio by day compared to the normal group.Compared with the HFD group,the body mass gain and liver mass obviously decreased in mice of the HFD+Leu group,and the liver fat accumulation was reduced.The mice in the HFD+Leu group exhib-ited higher heat production and O2 consumption,along with an increase in CO2 exhalation by day and by night.In addition,heat production,CO2 exhalation,and O2 consumption were significantly higher by night than by day(P<0.01).As for the respiratory exchange ratio,a night increase was seen in the mice from the normal group,normal+Leu group,and HFD group,but not in the HFD+Leu group.The results of Western blotting showed that compared with the normal group,the BCKDE1A phosphorylation inacti-vation was enhanced,AMPKα phosphorylation activation alleviated,the protein expressions of SIRT1 and PGC-1α downregulated(P<0.05),and the protein expressions of FAS and FABP4 increased in the livers of mice in the HFD group.Compared with the HFD group,the BCKDE1A phosphorylation inacti-vation was alleviated,AMPKα phosphorylation activation enhanced,the protein expressions of SIRT1 and PGC-1α increased,and the protein expressions of FAS and FABP4 downregulated in the livers of mice in the HFD+Leu group.CONCLUSION Leu can alleviate HFD-induced metabolic dysfunction-associated fatty liver disease in mice,which may be closely related to the promotion of energy metabo-lism and inhibition of fat synthesis.
8.Analysis of liver histological characteristics and clinically related factors in patients with inactive HBsAg carriers
Xinyang ZHANG ; Shan REN ; Sujun ZHENG ; Rongshan FAN ; Qingfa RUAN ; Wenqi HUANG ; Haibing GAO ; Yao XIE ; Minghui LI ; Xiulan XUE ; Fang YANG ; Junliang FU ; Xinyue CHEN
Chinese Journal of Hepatology 2025;33(7):660-666
Objective:To analyze the liver histological characteristics and clinically related factors in inactive hepatitis B surface antigen (HBsAg) carriers (IHC), and also explore whether antiviral treatment is necessary for IHC, as defined in the 2022 version of the hepatitis B prevention and treatment guidelines.Methods:A multicenter, retrospective cohort study was conducted. Two hundred and thirty-one IHC cases who underwent liver biopsy histopathological examination in nine medical institutions, including Beijing Youan Hospital affiliated with Capital Medical University, from January 2018 to December 2023 were included. General informative data, clinical serological markers, and transient elastography (TE) examination results were collected. Patients were divided into a positive (148 cases) and a negative group (83 cases) according to the results of hepatitis B virus (HBV) DNA detection. The differences in liver pathological inflammatory activity (G) and liver fibrosis stage (S) were analyzed between the two groups to explore the correlation between liver tissue conditions and clinically related factors. Comparsions of normally distributed continwous data, skeukd continuous data, and categorical data between groups are performed using t tests, Mann-Whitney U tests and χ2 tests, respectively. Results:The age of 231 IHC cases was 43 (38, 51) years old, with 95.2% (220/231) aged ≥30 years, and males accounted for 64.9% (150/231). HBsAg and HBV DNA levels were 131.9 (20.8, 400.9) IU/mL and 94.0 (0, 448.5) IU/mL, respectively, of which 35.9% (83/231) were HBV DNA negative (<20 IU/mL). The remarkable proportions of G≥2, S≥2, and liver injury (G≥2 and/or S≥2) in liver tissue were 16.5% (38/231), 29% (67/231), and 35.9% (83/231), respectively. The S≥2 proportion was significantly higher in the HBV DNA-negative group than the positive group (42.2% vs. 21.6%, P<0.001), and it mainly occurred in the population cohort over 30 years old (44.9% vs. 31.0%, P=0.04). The liver stiffness measurement (LSM), aspartate transaminase to platelet ratio index (APRI), and platelet (PLT) were significantly higher in the S≥2 group than the S<2 group ( P<0.05). Conclusion:Clinicians can comprehensively evaluate the degree of liver fibrosis in IHC based on clinical factors such as age, PLT, APRI, and LSM, even if the liver histological results are lacking. The China 2022 version guidelines define that nearly half of IHC has histological indications for antiviral therapy, and liver biopsy and prompt treatment can be recommended.
9.Combined ankle joint mobilization and hip strengthening in treatment for chronic plantar fasciitis/
Xiulan HAN ; Shanshan ZHANG ; Guifang ZHANG
Chinese Journal of Rehabilitation Medicine 2024;39(12):1804-1809
Objective:To evaluate the effectiveness of ankle joint mobilization combined hip strengthening on pain and function of patients with chronic plantar fasciitis(PF).Method:Fifty patients with PF,aged 23 to 62 years,were randomly assigned to the intervention group(n=25)and the control group(n=25).Both groups of patients were received routinely stretching exercises.Addition-ally,the control group received ankle joint mobilization and the intervention group received ankle joint mobili-zation plus hip strengthening.Both groups received total 8 treatments,twice a week.The Visual Analogue pain Score(VAS)and the American Orthopedic Foot and Ankle Society(AOFAS)ankle-hindfoot scale were evaluated before and after treatment and after 3 months of follow-up,along with assessments of hip extension and abduction muscle strength,and ankle dorsiflexion range of motion.Result:After 4 weeks of treatment,both groups showed a significant difference in the VAS and AOFAS com-pared to before treatment(P<0.001),but no significant difference was found between groups.After 3 months follow-up,the VAS in the intervention group was significantly lower than that in the control group(P=0.003),and the values of AOFAS in the intervention group was significantly higher than that in the control group(P<0.001).Conclusion:Ankle joint mobilization combined with hip strengthening can effectively alleviate foot pain and improve function to the patients of chronic plantar fasciitis.
10.Effect of laparoscopic fundoplication for proton pump inhibitor dependent gastroesophageal reflux disease: a 10-year follow-up report of 160 cases in a single center
Zhiwei HU ; Jimin WU ; Meng LI ; Jiannan LIU ; Changrong DENG ; Xiulan ZHAN ; Tao JI ; Feng WANG ; Shurui TIAN ; Yu ZHANG ; Dong CHEN
Chinese Journal of General Surgery 2024;39(6):423-429
Objective:To explore the long-term efficacy of laparoscopic fundoplication for proton pump inhibitor dependent gastroesophageal reflux disease (GERD).Method:Clinical data of proton pump inhibitor dependent GERD patients who underwent fundoplication at the Rocket Force Characteristic Medical Center from Jan to Jun 2012 were analyzed, including GERD symptom score, subjective symptom relief rate, PPI discontinuation rate and surgical satisfaction, as well as recurrence and complications.Result:A total of 160 GERD patients were included in this study, with 64% of patients having respiratory symptoms. Nissen and Toupet fundoplication were performed in 43 and 117 cases, respectively, with a follow-up time of (127±3) months. The postoperative GERD symptom scores of the patients were significantly lower than before treatment (all P<0.001); The subjective relief of overall symptoms in the digestive tract and airway problem was 90% (80%, 100%) and 100%, respectively. The PPI discontinuation rate was 86%, and the overall satisfaction rate of the treatment was 92%, and the satisfaction rate of patients with respiratory symptoms was 89%. 7% of patients experienced varying degrees of symptomatic recurrence, 4% of patients re-underwent endoscopic treatment and/or laparoscopic fundoplication due to symptom recurrence. The incidence of long-term postoperative dysphagia, bloating, belching, increased exhaust, abdominal pain, diarrhea, and constipation were 11.3%, 16.9%, 0, 1.3%, 0, 2.5%, and 5.6%, respectively. Conclusions:Laparoscopic fundoplication has good long-term efficacy in the treatment of GERD. A small number of patients may experience postoperative recurrence, as well as complications such as dysphagia and gas-bloat syndrome. Most recurrent patients can achieve good therapeutic effect by redoing endoscopic treatment or redoing surgery.

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