1.Guizhi Fulingwan Alleviate Hepatic Fibrosis by Modulating mtDNA/NLRP3/Caspase-1/GSDMD Signaling Pathway
Yu TANG ; Xuli YANG ; Qiang YANG ; Xiaojie WANG ; Yongxiang GAO ; Xueping LI
Chinese Journal of Experimental Traditional Medical Formulae 2026;32(14):91-99
ObjectiveTo investigate the mechanism of Guizhi Fulingwan (GFW) against hepatic fibrosis, focusing on elucidating the regulatory effect of GFW on the mitochondrial DNA (mtDNA)/NOD-like receptor protein 3 (NLRP3)/cysteinyl aspartate-specific proteinase-1 (Caspase-1)/gasdermin D (GSDMD) signaling pathway. MethodsForty-two male Sprague-Dawley (SD) rats were randomly allocated into six groups (n=7): control, model, low/medium/high-dose (0.14, 0.28, 0.56 g·kg-1·d-1) GFW (GFW-L, GFW-M, GFW-H), and Dahuang Zhechong pills (DZW, 1.8 g·kg-1·d-1). The rat model of hepatic fibrosis was induced by intraperitoneal injection of carbon tetrachloride. General conditions of the rats were observed. Serum levels of alanine aminotransferase (ALT) and aspartate aminotransferase (AST) levels were measured. Liver histopathology and collagen deposition were observed through hematoxylin and eosin (HE) staining and Masson's trichrome staining. Transmission electron microscopy (TEM) was employed to observe structural alterations and damage of cellular ultrastructures including mitochondria. Mitochondrial membrane potential (MMP, ΔΨm) was detected by flow cytometry. Serum levels of interleukin-1β (IL-1β) and interleukin-18 (IL-18) were measured by enzyme-linked immunosorbent assay (ELISA). The mRNA levels of mtDNA and NLRP3 in the liver tissue were quantified by Real-time polymerase chain reaction (Real-time PCR). The protein levels of key molecules in the NLRP3/Caspase-1/GSDMD signaling pathway in the liver tissue were determined by Western blot. ResultsCompared with the control group, the model group exhibited a decrease in body weight (P<0.01), an increase in liver index (P<0.01), elevations in serum ALT and AST levels (P<0.01), and typical fibrotic features such as disorganized hepatocytes, inflammatory infiltration, and increased collagen deposition in the liver tissue. TEM revealed significant karyotheca degeneration, mitochondrial swelling, endoplasmic reticulum expansion, and organelle efflux in the model group. In addition, the model group showed decreased ΔΨm (P<0.01), up-regulated mRNA levels of mtDNA and NLRP3 (P<0.01) and protein levels of NLRP3, Caspase-1, and GSDMD (P<0.01) in the liver tissue, and increased serum levels of IL-1β and IL-18 (P<0.01). Compared with that in the model group, the body weight increased in GFW-L, GFW-M, and DZW groups (P<0.05) and markedly increased in the GFW-H group (P<0.01). The liver index decreased in the GFW groups and DZW group (P<0.01). The serum ALT level declined in the GFW-L group (P<0.05), and the serum ALT and AST levels decreased in the GFW-M, GFW-H, and DZW groups (P<0.01). Histopathological damage and fibrosis were alleviated to varying degrees, and TEM revealed mitigated ultrastructural injuries including mitophagy, mitochondrial swelling, and endoplasmic reticulum expansion in the drug intervention groups. The ΔΨm increased in GFW groups without statistical significance. The mRNA level of mtDNA in the liver tissue was down-regulated in the GFW-M (P<0.05), GFW-H (P<0.01), and DZW (P<0.01) groups. The mRNA level of NLRP3 was down-regulated in GFW-M, GFW-H, and DZW groups (P<0.01). Western blot analysis showed significantly down-regulated protein level of NLRP3 in all the GFW groups and the DZW group (P<0.01). The protein level of GSDMD-N was down-regulated in GFW-H and DZW groups (P<0.01). The protein level of cleaved Caspase-1 was down-regulated in GFW-M (P<0.05), GFW-H (P<0.01), and DZW (P<0.01) groups. In addition, the serum levels of IL-1β and IL-18 declined in GFW-H and DZW groups (P<0.01). ConclusionGFW can suppress pyroptosis to ameliorate CCl4-induced hepatic fibrosis, potentially through mitigating mitochondrial damage, inhibiting inflammasome assembly and activation, and blocking pro-inflammatory cytokine release.
2.Targeted inhibition of macrophage STING signaling alleviates inflammatory injury and ventricular remodeling in acute myocardial infarction.
Huan YAO ; Qingman HE ; Shujun WEI ; Li XIANG ; Yuanyuan LUO ; Cong HUANG ; Weiwei LIU ; Chuan ZHENG ; Xueping LI ; Yongxiang GAO
Acta Pharmaceutica Sinica B 2025;15(8):4030-4046
Mitochondrial DNA (mtDNA) acts as a damage-associated molecular pattern to activate the stimulator of interferon genes (STING) signaling in macrophages, promoting tissue inflammation. However, its role in acute myocardial infarction (AMI) remains unclear. Macrophage-specific Sting1 knockout mice were used to validate STING's pathological role in AMI. Cardiac and liver mtDNA were used to activate macrophages in co-culture systems with cardiomyocytes to assess fibrosis and hypertrophy. Panaxatriol saponin (PTS) was tested for its ability to block mtDNA-driven macrophage activation and subsequent cardiomyocyte damage. STING-PTS binding ability was analyzed. AMI rats received PTS to evaluate its effects on myocardial inflammation and ventricular remodeling. In vivo, macrophage-specific Sting1 knockout reduced myocardial inflammation and injury after AMI. In vitro, mtDNA-activated macrophages induced cardiomyocyte fibrosis and hypertrophy through STING signaling. PTS suppressed mtDNA-driven macrophage activation by directly binding STING, thereby blocking inflammatory cascades. In AMI rats, PTS treatment attenuated acute inflammation and reversed ventricular remodeling. These findings establish the mtDNA-STING axis in macrophages as a critical driver of post-AMI inflammation and identify pharmacological STING inhibition with PTS as a promising therapeutic strategy. The study bridges genetic validation with translational applications, highlighting macrophage STING as a novel target for ischemic heart disease management.
3.Analysis of distant metastasis characteristics in hormone-sensitive and castration-resistant prostate cancer based on prostate-specific membrane antigen PET-CT
Xingming WANG ; Yongxiang TANG ; Xiaomei GAO ; Minfeng CHEN ; Shuo HU ; Lin QI ; Yi CAI
Chinese Journal of Surgery 2025;63(12):1118-1124
Objective:To explore the distant metastatic characteristics of metastatic hormone-sensitive prostate cancer (mHSPC) and metastatic castration-resistant prostate cancer (mCRPC) based on prostate-specific membrane antigen (PSMA) PET-CT.Methods:This is a retrospective cohort study. Ultimately, data from 227 patients with metastatic prostate cancer who underwent PSMA PET-CT examinations at Xiangya Hospital, Central South University between March 2016 and May 2025 were retrospectively reviewed, including 117 mHSPC patients with an age of (68.8±7.6) years (range:53 to 89 years) and 110 mCRPC patients with an age of (69.4±7.5) years (range: 49 to 88 years). Clinical and pathological data, along with metastatic characteristics identified via PSMA PET-CT, were collected and compared. Intergroup comparisons were performed using χ 2 tests. Results:The incidence rates of lymph node metastasis, bone metastasis, and visceral metastasis in the mHSPC group were 71.8% (84/117), 89.7% (105/117), and 11.1% (13/117), respectively, while those in the mCRPC group were 52.7% (58/110), 91.8% (101/110), and 15.5% (17/110), respectively. The incidence of lymph node metastasis in the mHSPC group was significantly higher than that in the mCRPC group ( χ2=8.800, P=0.003). Among patients with bone metastasis, the rates of osteoblastic metastasis, osteolytic metastasis, and mixed metastasis in the mHSPC group were 76.2% (80/105), 8.6% (9/105), and 15.2% (16/105), respectively, while the corresponding rates in the mCRPC group were 74.3% (75/101), 7.3% (8/101), and 16.4% (18/101), respectively, all indicating a relatively high probability of osteolytic and mixed bone metastases ( χ2=0.260, P=0.878). Among patients with mHSPC and mCRPC who tested positive for visceral metastasis, lung metastasis (9/13 and 8/17) and liver metastasis (4/13 and 9/17) were the most common sites of metastasis, but there was no significant difference in the composition of visceral metastasis between the two groups ( χ2=0.933, P=0.564). In this study, among 20 patients who progressed from mHSPC to mCRPC, 35.0% (7/20) had persistent or progressive activity at the original metastatic site, 35.0% (7/20) developed new metastatic lesions, and 30.0% (6/20) showed inhibitory changes in the original metastatic lesions. Among patients with imaging progression, 1/14 of patients with osteoblastic metastatic lesions at the mHSPC stage exhibited osteolytic changes upon progression to mCRPC. Conclusion:Compared with the mCRPC group, the mHSPC group has a higher lymph node metastasis rate,and both groups have common rates of osteolytic and mixed bone metastases and visceral metastasis.
4.Exploration on the Role of Macrophage Polarization in Rheumatoid Arthritis Based on TCM Yin-Yang Theory
Xuemei YANG ; Jiayue YANG ; Zehua ZHU ; Yongxiang GAO
Chinese Journal of Information on Traditional Chinese Medicine 2025;32(11):13-18
Rheumatoid arthritis(RA)is a chronic autoimmune disease with a high risk of disability.Macrophages,as important immune cells,participate in the regulation of inflammatory response and bone homeostasis in RA by polarization to different phenotypes.This article reviewed the etiology and pathogenesis of RA in TCM.It was found that imbalance in macrophage polarization is a key factor contributing to inflammation and imbalance in bone homeostasis in RA.During the development of RA,M1 and M2 macrophages have different characteristics of yin and yang attributes and play different roles,which are similar to the connotation of mutual opposition,mutual restriction and mutual transformation of yin and yang theory of TCM.Based on yin-yang theory of TCM,it is proposed to regulate the balance of yin and yang and restore the homeostasis of macrophage to delay the progression of RA,hoping to provide ideas for clinical treatment of RA.
5.A comparative study of the diagnostic efficacy of 68Ga-PSMA-617 PET/CT versus mpMRI for prostate cancer with extraprostatic extension and seminal vesicle invasion
Yinzhao WANG ; Xiaomei GAO ; Yongxiang TANG ; Xiaoping YI ; Jinwei ZHANG ; Shuo HU ; Minfeng CHEN ; Lin QI ; Yi CAI
Chinese Journal of Urology 2025;46(1):23-29
Objective:To compare the diagnostic efficacy of 68Ga-prostate-specific membrane antigen (PSMA)-617 PET/CT and multiparametric magnetic resonance imaging (mpMRI) in detecting extraprostatic extension (EPE) and seminal vesicle invasion (SVI) in prostate cancer. Methods:A retrospective analysis was conducted on the clinical data of 113 patients with localized prostate cancer who underwent both 68Ga-PSMA-617 PET/CT and mpMRI at Xiangya Hospital, Central South University, from May 2018 to May 2024 prior to radical prostatectomy (RP). The median age of the patients was 66.0 (61.3, 71.0) years old, with a median body mass index of 28.86 (19.01, 24.77) kg/m 2, and a median prostate-specific antigen (PSA) level of 13.50(9.26, 21.99) ng/ml. The pathological results after RP were used as the gold standard to compare the sensitivity, specificity, positive predictive value, and negative predictive value of the two imaging modalities in diagnosing EPE and SVI. Additionally, the diagnostic value of combining both imaging modalities was explored, employing a parallel strategy where a positive result from either modality was deemed positive, and only when both tests were negative was the result considered negative. Results:Pathological results after RP indicated EPE in 46 cases (40.71%) and SVI in 11 cases (9.70%). In diagnosing EPE, the sensitivity, specificity, positive predictive value, and negative predictive value of 68Ga-PSMA-617 PET/CT were 17.39% (8/46), 97.01% (65/67), 80.00% (8/10), and 63.11% (65/103), respectively, while for mpMRI they were 34.78% (16/46), 83.58% (56/67), 59.26% (16/27), and 65.12% (56/86), respectively. The sensitivity of mpMRI was significantly higher than that of 68Ga-PSMA-617 PET/CT ( P=0.048), while the specificity was the opposite ( P=0.008). When combining both imaging modalities, the sensitivity, specificity, positive predictive value, and negative predictive value were 45.65% (21/46), 80.60% (54/67), 61.76% (21/34), and 68.35% (54/79), respectively. In diagnosing SVI, the sensitivity, specificity, positive predictive value, and negative predictive value of 68Ga-PSMA-617 PET/CT were 27.27% (3/11), 96.08% (98/102), 42.86% (3/7), and 92.45% (98/106), respectively, while for mpMRI they were 36.36% (4/11), 88.24% (90/102), 25.00% (4/16), and 92.78% (90/97), respectively. The specificity of 68Ga-PSMA-617 PET/CT was significantly higher than that of mpMRI ( P=0.033). When combining both imaging modalities, the sensitivity, specificity, positive predictive value, and negative predictive value were 45.45% (5/11), 85.29% (87/102), 25.00% (5/20), and 93.55% (87/93), respectively. Conclusions:mpMRI has higher sensitivity in diagnosing EPE and SVI in prostate cancer, while 68Ga-PSMA-617 PET/CT shows higher specificity. The combined use of both imaging modalities can increase diagnostic sensitivity but may reduce specificity. PSMA PET/MRI may be a more accurate diagnostic tool for discerning EPE and SVI.
6.Exploration on the Role of Macrophage Polarization in Rheumatoid Arthritis Based on TCM Yin-Yang Theory
Xuemei YANG ; Jiayue YANG ; Zehua ZHU ; Yongxiang GAO
Chinese Journal of Information on Traditional Chinese Medicine 2025;32(11):13-18
Rheumatoid arthritis(RA)is a chronic autoimmune disease with a high risk of disability.Macrophages,as important immune cells,participate in the regulation of inflammatory response and bone homeostasis in RA by polarization to different phenotypes.This article reviewed the etiology and pathogenesis of RA in TCM.It was found that imbalance in macrophage polarization is a key factor contributing to inflammation and imbalance in bone homeostasis in RA.During the development of RA,M1 and M2 macrophages have different characteristics of yin and yang attributes and play different roles,which are similar to the connotation of mutual opposition,mutual restriction and mutual transformation of yin and yang theory of TCM.Based on yin-yang theory of TCM,it is proposed to regulate the balance of yin and yang and restore the homeostasis of macrophage to delay the progression of RA,hoping to provide ideas for clinical treatment of RA.
7.A comparative study of the diagnostic efficacy of 68Ga-PSMA-617 PET/CT versus mpMRI for prostate cancer with extraprostatic extension and seminal vesicle invasion
Yinzhao WANG ; Xiaomei GAO ; Yongxiang TANG ; Xiaoping YI ; Jinwei ZHANG ; Shuo HU ; Minfeng CHEN ; Lin QI ; Yi CAI
Chinese Journal of Urology 2025;46(1):23-29
Objective:To compare the diagnostic efficacy of 68Ga-prostate-specific membrane antigen (PSMA)-617 PET/CT and multiparametric magnetic resonance imaging (mpMRI) in detecting extraprostatic extension (EPE) and seminal vesicle invasion (SVI) in prostate cancer. Methods:A retrospective analysis was conducted on the clinical data of 113 patients with localized prostate cancer who underwent both 68Ga-PSMA-617 PET/CT and mpMRI at Xiangya Hospital, Central South University, from May 2018 to May 2024 prior to radical prostatectomy (RP). The median age of the patients was 66.0 (61.3, 71.0) years old, with a median body mass index of 28.86 (19.01, 24.77) kg/m 2, and a median prostate-specific antigen (PSA) level of 13.50(9.26, 21.99) ng/ml. The pathological results after RP were used as the gold standard to compare the sensitivity, specificity, positive predictive value, and negative predictive value of the two imaging modalities in diagnosing EPE and SVI. Additionally, the diagnostic value of combining both imaging modalities was explored, employing a parallel strategy where a positive result from either modality was deemed positive, and only when both tests were negative was the result considered negative. Results:Pathological results after RP indicated EPE in 46 cases (40.71%) and SVI in 11 cases (9.70%). In diagnosing EPE, the sensitivity, specificity, positive predictive value, and negative predictive value of 68Ga-PSMA-617 PET/CT were 17.39% (8/46), 97.01% (65/67), 80.00% (8/10), and 63.11% (65/103), respectively, while for mpMRI they were 34.78% (16/46), 83.58% (56/67), 59.26% (16/27), and 65.12% (56/86), respectively. The sensitivity of mpMRI was significantly higher than that of 68Ga-PSMA-617 PET/CT ( P=0.048), while the specificity was the opposite ( P=0.008). When combining both imaging modalities, the sensitivity, specificity, positive predictive value, and negative predictive value were 45.65% (21/46), 80.60% (54/67), 61.76% (21/34), and 68.35% (54/79), respectively. In diagnosing SVI, the sensitivity, specificity, positive predictive value, and negative predictive value of 68Ga-PSMA-617 PET/CT were 27.27% (3/11), 96.08% (98/102), 42.86% (3/7), and 92.45% (98/106), respectively, while for mpMRI they were 36.36% (4/11), 88.24% (90/102), 25.00% (4/16), and 92.78% (90/97), respectively. The specificity of 68Ga-PSMA-617 PET/CT was significantly higher than that of mpMRI ( P=0.033). When combining both imaging modalities, the sensitivity, specificity, positive predictive value, and negative predictive value were 45.45% (5/11), 85.29% (87/102), 25.00% (5/20), and 93.55% (87/93), respectively. Conclusions:mpMRI has higher sensitivity in diagnosing EPE and SVI in prostate cancer, while 68Ga-PSMA-617 PET/CT shows higher specificity. The combined use of both imaging modalities can increase diagnostic sensitivity but may reduce specificity. PSMA PET/MRI may be a more accurate diagnostic tool for discerning EPE and SVI.
8.Analysis of distant metastasis characteristics in hormone-sensitive and castration-resistant prostate cancer based on prostate-specific membrane antigen PET-CT
Xingming WANG ; Yongxiang TANG ; Xiaomei GAO ; Minfeng CHEN ; Shuo HU ; Lin QI ; Yi CAI
Chinese Journal of Surgery 2025;63(12):1118-1124
Objective:To explore the distant metastatic characteristics of metastatic hormone-sensitive prostate cancer (mHSPC) and metastatic castration-resistant prostate cancer (mCRPC) based on prostate-specific membrane antigen (PSMA) PET-CT.Methods:This is a retrospective cohort study. Ultimately, data from 227 patients with metastatic prostate cancer who underwent PSMA PET-CT examinations at Xiangya Hospital, Central South University between March 2016 and May 2025 were retrospectively reviewed, including 117 mHSPC patients with an age of (68.8±7.6) years (range:53 to 89 years) and 110 mCRPC patients with an age of (69.4±7.5) years (range: 49 to 88 years). Clinical and pathological data, along with metastatic characteristics identified via PSMA PET-CT, were collected and compared. Intergroup comparisons were performed using χ 2 tests. Results:The incidence rates of lymph node metastasis, bone metastasis, and visceral metastasis in the mHSPC group were 71.8% (84/117), 89.7% (105/117), and 11.1% (13/117), respectively, while those in the mCRPC group were 52.7% (58/110), 91.8% (101/110), and 15.5% (17/110), respectively. The incidence of lymph node metastasis in the mHSPC group was significantly higher than that in the mCRPC group ( χ2=8.800, P=0.003). Among patients with bone metastasis, the rates of osteoblastic metastasis, osteolytic metastasis, and mixed metastasis in the mHSPC group were 76.2% (80/105), 8.6% (9/105), and 15.2% (16/105), respectively, while the corresponding rates in the mCRPC group were 74.3% (75/101), 7.3% (8/101), and 16.4% (18/101), respectively, all indicating a relatively high probability of osteolytic and mixed bone metastases ( χ2=0.260, P=0.878). Among patients with mHSPC and mCRPC who tested positive for visceral metastasis, lung metastasis (9/13 and 8/17) and liver metastasis (4/13 and 9/17) were the most common sites of metastasis, but there was no significant difference in the composition of visceral metastasis between the two groups ( χ2=0.933, P=0.564). In this study, among 20 patients who progressed from mHSPC to mCRPC, 35.0% (7/20) had persistent or progressive activity at the original metastatic site, 35.0% (7/20) developed new metastatic lesions, and 30.0% (6/20) showed inhibitory changes in the original metastatic lesions. Among patients with imaging progression, 1/14 of patients with osteoblastic metastatic lesions at the mHSPC stage exhibited osteolytic changes upon progression to mCRPC. Conclusion:Compared with the mCRPC group, the mHSPC group has a higher lymph node metastasis rate,and both groups have common rates of osteolytic and mixed bone metastases and visceral metastasis.
9.Comparison of the predictive value of multiparametric MRI and prostate-specific membrane antigen PET/CT for pelvic lymph node metastasis in prostate cancer
Wei TANG ; Yi CAI ; Yongxiang TANG ; Xiaoping YI ; Xiaomei GAO ; Lin QI
Chinese Journal of Surgery 2024;62(11):1008-1015
Objective:To compare the diagnostic performance of multiparametric magnetic resonance imaging (mpMRI) and prostate-specific membrane antigen (PSMA) PET/CT in detecting pelvic lymph node metastasis in prostate cancer.Methods:This is a retrospective case series study. A retrospective analysis was conducted on the data of 115 prostate cancer patients who underwent both mpMRI and PSMA PET/CT before undergoing radical prostatectomy and extended pelvic lymph node dissection at the Department of Urology, Xiangya Hospital, Central South University, between March 2020 and September 2023. The age ( M(IQR)) was 67(10) years (range: 45 to 84 years), and the body mass index was 24(4) kg/m 2 (range: 18 to 30 kg/m 2). Pathological and imaging data were obtained from the patients. Lymph node pathology results were used as the gold standard to evaluate the diagnostic performance of mpMRI and PSMA PET/CT for detecting pelvic lymph node metastasis in PCa through diagnostic evaluation tests. Comparisons between groups were performed using independent samples t-test, Mann-Whitney U test, or χ2 test. Results:The positive rate for detecting pelvic lymph node metastasis was 18.3% (21/115) with mpMRI and 25.2% (29/115) with PSMA PET/CT. The pathological positive rate for lymph nodes was 28.7% (33/115). In patient-based analysis, the diagnostic sensitivity of PSMA PET/CT was significantly higher than that of mpMRI (63.6% vs. 30.3%, χ2=7.36, P=0.007). In lesion-based analysis, both the sensitivity and positive predictive value of PSMA PET/CT were significantly higher than those of mpMRI (sensitivity: 68.0% vs. 21.6%, χ2=42.20, P<0.01; positive predictive value: 50.0% vs. 23.1%, χ2=7.54, P=0.006). Conclusions:PSMA PET/CT and mpMRI both demonstrates good specificity in predicting pelvic lymph node metastasis in prostate cancer. However, PSMA PET/CT is significantly superior to mpMRI in terms of sensitivity and the detection rate of pathologically positive lymph nodes.
10.A Study on the Influence of the Type of Finals on the Onset Time of the Stop Voice of Hearing Impaired Children
Yongxiang GAO ; Di WU ; Yan FENG ; Ye FENG ; Jiaru WANG ; Ying YU ; Chenghua TIAN
Journal of Audiology and Speech Pathology 2024;32(1):38-42
Objective To investigate the effect of final vowel types on the voice onset time(VOT)of differ-ent stops in children with hearing impairment,and to provide a basis for the acquisition and correction of stop sounds.Methods A total of 22 hearing-impaired children aged 3~6 and 22 children with normal hearing were ran-domly selected-18 consonant-vowel(CV)syllables composed of 6 stops and 3 single finals were recorded,using first tone.Using Praat 6.1.29 software to analyze and extract the stops VOT.Two-way ANOVA was used for each stop,the dependent variable was VOT,and the independent variables were hearing status and final type.Results Children in the hearing-impaired group had articulation errors in/t/,/g/,and/k/.Hearing status had significant effect on the main effect of plosives/g/,/p/,/t/,/k/(P<0.05),and the VOT of slurs/g/,/p/,/t/,/k/in the normal hearing group significantly greater than the hearing-impaired group(P<0.05).The main effect of finals on the VOT of the stops/b/,/p/and/t/was significant(P<0.05).Hearing status and final type had an interac-tive effect on the stop/t/,and the simple main effect showed that the difference in VOT of/ti/between the hear-ing-impaired group and the normal hearing group was greater than that of/ta/and/tu/.Conclusion The stops/g/,/p//t/,/k/VOT of hearing-impaired children are smaller than those of with normal hearing.The difference in VOT of/ti/sound between the hearing impaired group and the normal hearing group is greater than that of/ta/sound and/tu/sound.In the teaching of the initial/t/sound for hearing-impaired children,we can start with/ta/and/tu/with less difference,and the/ti/sound is consolidated later.Pay attention to breathing and oral exercise training,to lay a good foundation for clear pronunciation.

Result Analysis
Print
Save
E-mail