1.Treatment Effect on Structure and Function of Submandibular Gland in Sjögren's Syndrome Model Mice by Artemisinin
Ziwei HUANG ; Qian HE ; Jiahe LIAO ; Xinbo YU ; Jing LUO ; Weijiang SONG ; Qingwen TAO
Chinese Journal of Experimental Traditional Medical Formulae 2025;31(4):158-165
ObjectiveTo investigate the effects of artemisinin (ART) on histopathological damage and salivary secretion in the submandibular gland (SMG) of mice with Sjögren's syndrome (SS) model,and on the expression of aquaporin 5 (AQP5) in SMG cells. MethodsThe NOD/Ltj mice were used as a model of SS and randomly divided into the SS model group,the ART group,and the hydroxychloroquine sulfate (HCQ) group,with six mice per group. Another 6 female BALB/c mice at the same week were selected as the control group. Mice in the ART group was fed with the ART solution daily in the dosage of 50 mg·kg-1,and mice in the HCQ group was given with the HCQ solution (1 300 mg·kg-1). Mice in the SS model and control groups were given saline daily. The treatment lasted for 8 weeks. The 24-hour average water intake,salivary flow rate,SMG pathology scores of mice in each group were measured,as well as the expression levels of AQP5 protein and gene in the SMG tissues. ResultsCompared with the control group,the 24-hour average water intake of mice in the model group was significantly increased (P<0.01),and the saliva flow rate was significantly decreased (P<0.01). Compared to the SS model group,the 24-hour average water intake of mice in the ART and HCQ groups was significantly reduced (P<0.01),and the salivary flow rate was significantly increased in the ART group(P<0.01),comparisons between groups showed that the ART was superior to the HCQ in reducing water intake and improving saliva flow rate in SS model mice (P<0.05). The HE staining results showed that,compared with the normal group,the number of lymphocyte infiltration foci in SMG tissue in the model group increased,and the pathological score increased (P<0.01). Compared to the SS model group,after the intervention of the ART and HCQ,the number of lymphocytic infiltration foci in the SMG tissue decreased,the area of the lymphocytic infiltration foci was reduced,and the pathology score of the SMG tissues was lowered in the ART group(P<0.01). However,there was no difference in pathological scores between the ART and HCQ groups . The results of IHC,Western blot,and Real-time PCR showed that,compared with the normal group,the expression levels of AQP5 protein and gene in SMG tissue in the model group significantly decreased (P<0.05). Comparing with the SS model group,the ART and HCQ groups could significantly up-regulated the expression levels of AQP5 protein and mRNA in the SMG tissue,and the treatment effect was better than that of HCQ. ConclusionART was able to ameliorate SMG structural damage and salivary secretion function in SS model mice,and its mechanism of action may be related to the up-regulation of AQP5 protein and gene expression levels in SMG cells.
2.Clinical analysis of patients with pregnancy complicating paroxysmal nocturnal hemoglobinuria and literature review
Yafei JIANG ; Zhoushan FENG ; Yafei WANG ; Qingwen NIE ; Fang HE
Chongqing Medicine 2025;54(1):142-147
Objective To investigate the clinical characteristics and research progress of the patients with pregnancy complicating paroxysmal nocturnal hemoglobinuria(PNH).Methods The clinical data of 10 case-times of pregnancy complicating PNH admitted and treated in the Third Affiliated Hospital of Guang-zhou Medical University from September 2009 to January 2023 were retrospectively analyzed."Paroxysmal nocturnal hemoglobinuria"and"pregnancy"served as the English keywords,the literatures included in PubMed were retrieved."paroxysmal nocturnal hemoglobinuria"and"pregnancy"served as the Chinese key-words,the literatures included in CNKI and Wan Fang Databases from January 1986 to December 2022 were retrieved.The clinical characteristics,pregnancy diagnosis and treatment,and pregnancy outcome of together 43 case-times pregnancies complicating with PNH in 10 case-times by retrospective analysis and 33 case-times by retrieval report were analyzed by descriptive statistic method.Results Among 43 case-times of pregnancy,the common clinical symptoms had 29 case-times of anemia(67.44%),17 case-times of thrombocytopenia(39.53%),15 case-times of soy sauce color urine(34.88%),6 case-times of fatigue(13.95%),5 case-times of abdominal pain(11.63%),8 case-times of thrombosis(18.60%)during pregnancy and childbirth and 10 cases of complicating preeclampsia(23.25%).There were 31 case-times(72.09%)of red blood cell transfusions and 11 case-times(30.23%)of platelet transfusions;19 case-times(48.83%)of glucocorticoids use and 25 case-times(46.51%)of low molecular weight heparin(LMWH)use.There were 11 case-times(25.58%)of fetal growth restriction,17 case-times of premature delivery(39.53%),in which 6 case-times(28-33+6 weeks)of early stage premature delivery,the early premature delivery rate was 13.95%,there were 11 case-times of late premature delivery(34-36+6 weeks),the rate of late premature delivery was 25.58%.There were 3 case-times(6.97%)of stillbirth.Conclusion The incidence rate of mother and infant complications and adverse outcomes in the patients with pregnancy complicating PNH is high,which should be jointly man-aged by the doctors in hematology department and obstetric doctors with the experience for treating high risk pregnancy in general hospitals.
3.Effect of hip abductor muscle exercise on three-dimensional gait and collapse rate in patients with non-traumatic femoral head necrosis
Yingjia YUAN ; Yanzi YI ; Jin LI ; Ke WANG ; Yu WANG ; Tianye LIN ; Qingwen ZHANG ; Wei HE ; Qiushi WEI
Chinese Journal of Tissue Engineering Research 2025;29(33):7211-7216
BACKGROUND:Non-traumatic necrosis of the femoral head is a difficult joint disease,and preserving one's own femoral head is of great significance for young patients.Currently,there is a lack of regular and unified functional exercise plans.OBJECTIVE:To investigate the effect of hip abductor muscle exercise on the three-dimensional gait and collapse rate of patients with non-traumatic femoral head necrosis,and to provide theoretical basis for effective rehabilitation of patients with non-traumatic femoral head necrosis.METHODS:Totally 81 non-traumatic and non-surgical patients with femoral head necrosis(81 hips)admitted to the Third Affiliated Hospital of Guangzhou University of Chinese Medicine from June 2020 to June 2022 were included.Patients were randomly divided into a control group(n=40)and a hip abductor muscle exercise group(n=41).The control group received routine physical therapy and medication treatment.The hip abductor muscle exercise group underwent hip abductor muscle exercise on the basis of the control group.The gait status(hip joint range of motion,step length difference,and ground contact time difference)of two groups of patients was evaluated using the Tecnobody balance assessment system before and 12 weeks after treatment.The BIODEX-S4 isokinetic muscle strength testing system was used to test the peak force distance of hip abduction isokinetic muscle strength.Gluteus medius width ratio was compared between two groups.The collapse rate was compared between two groups of patients 1 year after treatment.RESULTS AND CONCLUSION:(1)There was no statistically significant difference between the hip abductor muscle exercise group and the control group in terms of age,gender,side profile,body mass index,and etiology(P>0.05).(2)Before treatment,there was no significant statistical difference in the range of motion of the affected hip joint between the two groups(P>0.05).After treatment,the range of motion of the affected hip joint in both groups improved compared to before treatment(P<0.05),and the range of motion of the affected hip joint in the hip abductor muscle exercise group was significantly higher than that in the control group(P<0.05).(3)Before treatment,there was no significant statistical difference in the step length and touchdown time between the two groups(P>0.05).12 weeks after treatment,the difference in step length and touchdown time between the two groups decreased compared to before treatment(P<0.05),and the difference in step length and touchdown time between the hip abductor muscle exercise group after treatment was significantly greater than that of the control group(P<0.05).(4)Before treatment,there was no significant statistical difference in gluteus medius width ratio between the two groups(P>0.05).12 weeks after treatment,the gluteus medius width ratio of both groups increased compared to that before treatment(P<0.05),and the gluteus medius width ratio of the hip abductor muscle exercise group was significantly higher than that of the control group(P<0.05).(5)At 1 year after treatment,the comparison of femoral head collapse rates between the two groups showed significant statistical significance(P<0.05),and that in the hip abductor muscle exercise group(22%)was significantly lower than that in the control group(45%).(6)It is concluded that exercise of the hip abductor muscle effectively enhances hip joint function,improves gait,and reduces the rate of femoral head collapse in patients with non-traumatic femoral head necrosis.It is recommended to use hip abductor muscle exercise as one of the basic methods for hip preservation in non-traumatic femoral head necrosis.
4.Effect of hip abductor muscle exercise on three-dimensional gait and collapse rate in patients with non-traumatic femoral head necrosis
Yingjia YUAN ; Yanzi YI ; Jin LI ; Ke WANG ; Yu WANG ; Tianye LIN ; Qingwen ZHANG ; Wei HE ; Qiushi WEI
Chinese Journal of Tissue Engineering Research 2025;29(33):7211-7216
BACKGROUND:Non-traumatic necrosis of the femoral head is a difficult joint disease,and preserving one's own femoral head is of great significance for young patients.Currently,there is a lack of regular and unified functional exercise plans.OBJECTIVE:To investigate the effect of hip abductor muscle exercise on the three-dimensional gait and collapse rate of patients with non-traumatic femoral head necrosis,and to provide theoretical basis for effective rehabilitation of patients with non-traumatic femoral head necrosis.METHODS:Totally 81 non-traumatic and non-surgical patients with femoral head necrosis(81 hips)admitted to the Third Affiliated Hospital of Guangzhou University of Chinese Medicine from June 2020 to June 2022 were included.Patients were randomly divided into a control group(n=40)and a hip abductor muscle exercise group(n=41).The control group received routine physical therapy and medication treatment.The hip abductor muscle exercise group underwent hip abductor muscle exercise on the basis of the control group.The gait status(hip joint range of motion,step length difference,and ground contact time difference)of two groups of patients was evaluated using the Tecnobody balance assessment system before and 12 weeks after treatment.The BIODEX-S4 isokinetic muscle strength testing system was used to test the peak force distance of hip abduction isokinetic muscle strength.Gluteus medius width ratio was compared between two groups.The collapse rate was compared between two groups of patients 1 year after treatment.RESULTS AND CONCLUSION:(1)There was no statistically significant difference between the hip abductor muscle exercise group and the control group in terms of age,gender,side profile,body mass index,and etiology(P>0.05).(2)Before treatment,there was no significant statistical difference in the range of motion of the affected hip joint between the two groups(P>0.05).After treatment,the range of motion of the affected hip joint in both groups improved compared to before treatment(P<0.05),and the range of motion of the affected hip joint in the hip abductor muscle exercise group was significantly higher than that in the control group(P<0.05).(3)Before treatment,there was no significant statistical difference in the step length and touchdown time between the two groups(P>0.05).12 weeks after treatment,the difference in step length and touchdown time between the two groups decreased compared to before treatment(P<0.05),and the difference in step length and touchdown time between the hip abductor muscle exercise group after treatment was significantly greater than that of the control group(P<0.05).(4)Before treatment,there was no significant statistical difference in gluteus medius width ratio between the two groups(P>0.05).12 weeks after treatment,the gluteus medius width ratio of both groups increased compared to that before treatment(P<0.05),and the gluteus medius width ratio of the hip abductor muscle exercise group was significantly higher than that of the control group(P<0.05).(5)At 1 year after treatment,the comparison of femoral head collapse rates between the two groups showed significant statistical significance(P<0.05),and that in the hip abductor muscle exercise group(22%)was significantly lower than that in the control group(45%).(6)It is concluded that exercise of the hip abductor muscle effectively enhances hip joint function,improves gait,and reduces the rate of femoral head collapse in patients with non-traumatic femoral head necrosis.It is recommended to use hip abductor muscle exercise as one of the basic methods for hip preservation in non-traumatic femoral head necrosis.
5.Chinese thyroid imaging reporting and data system(C-TIRADS)combined with intranodular and perinodular stiffness for distinguishing benign and malignant thyroid nodules
Yaping HE ; Xiangliu OUYANG ; Lichun ZHENG ; Yongli XIA ; Zechao HAN ; Qingwen WANG
Chinese Journal of Medical Imaging Technology 2024;40(1):37-41
Objective To explore the value of Chinese thyroid imaging reporting and data system(C-TIRADS)combined with intranodular and perinodular stiffness for distinguishing benign and malignant thyroid nodules.Methods Data of routine ultrasound and ultrasonic shear wave elastography(SWE)in 117 patients with thyroid nodules confirmed by fine needle aspiration cytology(FNAC)and/or surgical pathology were retrospectively analyzed.The nodules were classified according to C-TIRADS and SWE parameters of nodules and surrounding 2 mm glands measured with SWE technique,including Young's modulus of thyroid nodules(E)and perinodular glandular(Eshell)(the maximum[Emax/Eshellmax],the mean[Emean/Eshellmean]and the minimum[Emin/Eshellmin]as well as standard deviation[ESD/EshellSD]values).Then receiver operating characteristic(ROC)curve was drawn,and area under the curve(AUC)was calculated to assess the efficacy of C-TIRADS,SWE and the combination for differentiating benign and malignant thyroid nodules.Results Totally 117 thyroid nodules of 117 patients were enrolled,including 50 benign and 67 malignant ones.SWE parameters of malignant thyroid nodules were higher than those of benign ones(all P<0.001).AUC of C-TIRADS for differentiating benign and malignant thyroid nodules was 0.736,with sensitivity of 79.10%,specificity of 68.00%and accuracy of 74.36%.AUC of Emax,Emean,Emin and ESD was 0.816,0.752,0.664 and 0.705,respectively,of Emax was the highest.AUC of Eshellmax,Eshellmean,Eshellmin and EshellSD was 0.834,0.804,0.693 and 0.697,respectively,of Eshellmax was the highest,which was not statistically difference with that of Emax(Z=1.044,P=0.297).AUC of C-TIRADS+Emax and C-TIRADS+Eshellmax was 0.835 and 0.843,respectively,being not significantly different(Z=0.574,P=0.566)but higher than that of C-TIRADS(AUC=0.736,Z=2.510,2.230,both P<0.05),with diagnostic specificity and accuracy both higher than those of C-TIRADS(all P<0.05).Conclusion C-TIRADS combined with intranodular and perinodular stiffness could be used to effectively distinguish benign and malignant thyroid nodules,which might improve diagnostic efficiency of C-TIRDAS.
6.Effects of Huashi Runzao Prescription on apoptosis and function of the submandibular gland in Sj?gren's syndrome model mice by regulating Hippo-YAP/TAZ expression
Ziwei HUANG ; Qingwen TAO ; Jiahe LIAO ; Xinbo YU ; Qian HE ; Bojie TANG ; Jing LUO
Journal of Beijing University of Traditional Chinese Medicine 2024;47(11):1527-1540
Objective To explore the effects of modulating the Hippo-YAP/TAZ pathway using Huashi Runzao Prescription(HRP)on the apoptosis and salivary secretion function of submandibular gland cells in a naive non-obese diabetic(NOD/Ltj)mouse model of Sj?gren's syndrome(SS).Methods Eight-week-old female BALB/c mice were selected as the blank group.Eight-week-old female NOD/Ltj were randomly divided into the model,HRP-L,HRP-M,HRP-H,and hydroxychloroquine sulphate(HCQ)groups.After eight weeks of drug administration,the water consumption and salivary flow rate of each group were recorded.The histopathological damage of the submandibular gland in each group was determined using hematoxylin and eosin staining,the apoptosis rate of the submandibular gland was determined using TUNEL staining,and AQP5,Bax,Bcl-2,beclin-1,YAP,p-YAP,and TAZ expressions in submandibular gland tissues were determined using immunohistochemistry and Western blotting.Results Compared with the blank group,the Hippo-YAP/TAZ pathway was inhibited in the submandibular gland tissues of the model group,lymphocyte infiltration increased,water consumption increased,salivary flow rate decreased,AQP5 expression decreased,and submandibular gland cells apoptosis rate increased(P<0.05).Compared with all other administered groups,in the HRP-M group,the Hippo-YAZ/TAZ pathway was significantly activated,lymphocyte infiltration in submandibular gland tissues was reduced,water consumption was reduced,the salivary flow rate and AQP5 expression were increased,and the apoptosis rate of submandibular gland cells was reduced(P<0.05).Conclusion HRP reduced the pathological damage and apoptosis of submandibular gland cells in SS model mice.It improved the overall secretory function of submandibular gland tissues,which may be related to Hippo pathway activation and downregulating YAP/TAZ expression.
7.Effects of Huashi Runzao Prescription on apoptosis and function of the submandibular gland in Sj?gren's syndrome model mice by regulating Hippo-YAP/TAZ expression
Ziwei HUANG ; Qingwen TAO ; Jiahe LIAO ; Xinbo YU ; Qian HE ; Bojie TANG ; Jing LUO
Journal of Beijing University of Traditional Chinese Medicine 2024;47(11):1527-1540
Objective To explore the effects of modulating the Hippo-YAP/TAZ pathway using Huashi Runzao Prescription(HRP)on the apoptosis and salivary secretion function of submandibular gland cells in a naive non-obese diabetic(NOD/Ltj)mouse model of Sj?gren's syndrome(SS).Methods Eight-week-old female BALB/c mice were selected as the blank group.Eight-week-old female NOD/Ltj were randomly divided into the model,HRP-L,HRP-M,HRP-H,and hydroxychloroquine sulphate(HCQ)groups.After eight weeks of drug administration,the water consumption and salivary flow rate of each group were recorded.The histopathological damage of the submandibular gland in each group was determined using hematoxylin and eosin staining,the apoptosis rate of the submandibular gland was determined using TUNEL staining,and AQP5,Bax,Bcl-2,beclin-1,YAP,p-YAP,and TAZ expressions in submandibular gland tissues were determined using immunohistochemistry and Western blotting.Results Compared with the blank group,the Hippo-YAP/TAZ pathway was inhibited in the submandibular gland tissues of the model group,lymphocyte infiltration increased,water consumption increased,salivary flow rate decreased,AQP5 expression decreased,and submandibular gland cells apoptosis rate increased(P<0.05).Compared with all other administered groups,in the HRP-M group,the Hippo-YAZ/TAZ pathway was significantly activated,lymphocyte infiltration in submandibular gland tissues was reduced,water consumption was reduced,the salivary flow rate and AQP5 expression were increased,and the apoptosis rate of submandibular gland cells was reduced(P<0.05).Conclusion HRP reduced the pathological damage and apoptosis of submandibular gland cells in SS model mice.It improved the overall secretory function of submandibular gland tissues,which may be related to Hippo pathway activation and downregulating YAP/TAZ expression.
8.Effects of Huashi Runzao Prescription on apoptosis and function of the submandibular gland in Sj?gren's syndrome model mice by regulating Hippo-YAP/TAZ expression
Ziwei HUANG ; Qingwen TAO ; Jiahe LIAO ; Xinbo YU ; Qian HE ; Bojie TANG ; Jing LUO
Journal of Beijing University of Traditional Chinese Medicine 2024;47(11):1527-1540
Objective To explore the effects of modulating the Hippo-YAP/TAZ pathway using Huashi Runzao Prescription(HRP)on the apoptosis and salivary secretion function of submandibular gland cells in a naive non-obese diabetic(NOD/Ltj)mouse model of Sj?gren's syndrome(SS).Methods Eight-week-old female BALB/c mice were selected as the blank group.Eight-week-old female NOD/Ltj were randomly divided into the model,HRP-L,HRP-M,HRP-H,and hydroxychloroquine sulphate(HCQ)groups.After eight weeks of drug administration,the water consumption and salivary flow rate of each group were recorded.The histopathological damage of the submandibular gland in each group was determined using hematoxylin and eosin staining,the apoptosis rate of the submandibular gland was determined using TUNEL staining,and AQP5,Bax,Bcl-2,beclin-1,YAP,p-YAP,and TAZ expressions in submandibular gland tissues were determined using immunohistochemistry and Western blotting.Results Compared with the blank group,the Hippo-YAP/TAZ pathway was inhibited in the submandibular gland tissues of the model group,lymphocyte infiltration increased,water consumption increased,salivary flow rate decreased,AQP5 expression decreased,and submandibular gland cells apoptosis rate increased(P<0.05).Compared with all other administered groups,in the HRP-M group,the Hippo-YAZ/TAZ pathway was significantly activated,lymphocyte infiltration in submandibular gland tissues was reduced,water consumption was reduced,the salivary flow rate and AQP5 expression were increased,and the apoptosis rate of submandibular gland cells was reduced(P<0.05).Conclusion HRP reduced the pathological damage and apoptosis of submandibular gland cells in SS model mice.It improved the overall secretory function of submandibular gland tissues,which may be related to Hippo pathway activation and downregulating YAP/TAZ expression.
9.Effects of Huashi Runzao Prescription on apoptosis and function of the submandibular gland in Sj?gren's syndrome model mice by regulating Hippo-YAP/TAZ expression
Ziwei HUANG ; Qingwen TAO ; Jiahe LIAO ; Xinbo YU ; Qian HE ; Bojie TANG ; Jing LUO
Journal of Beijing University of Traditional Chinese Medicine 2024;47(11):1527-1540
Objective To explore the effects of modulating the Hippo-YAP/TAZ pathway using Huashi Runzao Prescription(HRP)on the apoptosis and salivary secretion function of submandibular gland cells in a naive non-obese diabetic(NOD/Ltj)mouse model of Sj?gren's syndrome(SS).Methods Eight-week-old female BALB/c mice were selected as the blank group.Eight-week-old female NOD/Ltj were randomly divided into the model,HRP-L,HRP-M,HRP-H,and hydroxychloroquine sulphate(HCQ)groups.After eight weeks of drug administration,the water consumption and salivary flow rate of each group were recorded.The histopathological damage of the submandibular gland in each group was determined using hematoxylin and eosin staining,the apoptosis rate of the submandibular gland was determined using TUNEL staining,and AQP5,Bax,Bcl-2,beclin-1,YAP,p-YAP,and TAZ expressions in submandibular gland tissues were determined using immunohistochemistry and Western blotting.Results Compared with the blank group,the Hippo-YAP/TAZ pathway was inhibited in the submandibular gland tissues of the model group,lymphocyte infiltration increased,water consumption increased,salivary flow rate decreased,AQP5 expression decreased,and submandibular gland cells apoptosis rate increased(P<0.05).Compared with all other administered groups,in the HRP-M group,the Hippo-YAZ/TAZ pathway was significantly activated,lymphocyte infiltration in submandibular gland tissues was reduced,water consumption was reduced,the salivary flow rate and AQP5 expression were increased,and the apoptosis rate of submandibular gland cells was reduced(P<0.05).Conclusion HRP reduced the pathological damage and apoptosis of submandibular gland cells in SS model mice.It improved the overall secretory function of submandibular gland tissues,which may be related to Hippo pathway activation and downregulating YAP/TAZ expression.
10.Effects of Huashi Runzao Prescription on apoptosis and function of the submandibular gland in Sj?gren's syndrome model mice by regulating Hippo-YAP/TAZ expression
Ziwei HUANG ; Qingwen TAO ; Jiahe LIAO ; Xinbo YU ; Qian HE ; Bojie TANG ; Jing LUO
Journal of Beijing University of Traditional Chinese Medicine 2024;47(11):1527-1540
Objective To explore the effects of modulating the Hippo-YAP/TAZ pathway using Huashi Runzao Prescription(HRP)on the apoptosis and salivary secretion function of submandibular gland cells in a naive non-obese diabetic(NOD/Ltj)mouse model of Sj?gren's syndrome(SS).Methods Eight-week-old female BALB/c mice were selected as the blank group.Eight-week-old female NOD/Ltj were randomly divided into the model,HRP-L,HRP-M,HRP-H,and hydroxychloroquine sulphate(HCQ)groups.After eight weeks of drug administration,the water consumption and salivary flow rate of each group were recorded.The histopathological damage of the submandibular gland in each group was determined using hematoxylin and eosin staining,the apoptosis rate of the submandibular gland was determined using TUNEL staining,and AQP5,Bax,Bcl-2,beclin-1,YAP,p-YAP,and TAZ expressions in submandibular gland tissues were determined using immunohistochemistry and Western blotting.Results Compared with the blank group,the Hippo-YAP/TAZ pathway was inhibited in the submandibular gland tissues of the model group,lymphocyte infiltration increased,water consumption increased,salivary flow rate decreased,AQP5 expression decreased,and submandibular gland cells apoptosis rate increased(P<0.05).Compared with all other administered groups,in the HRP-M group,the Hippo-YAZ/TAZ pathway was significantly activated,lymphocyte infiltration in submandibular gland tissues was reduced,water consumption was reduced,the salivary flow rate and AQP5 expression were increased,and the apoptosis rate of submandibular gland cells was reduced(P<0.05).Conclusion HRP reduced the pathological damage and apoptosis of submandibular gland cells in SS model mice.It improved the overall secretory function of submandibular gland tissues,which may be related to Hippo pathway activation and downregulating YAP/TAZ expression.

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