1.Exploring Mechanism of Anti-atherosclerosis Effect of Huangqi Chifengtang Based on AMPK/PPARα Signaling Pathway and NLRP3 Inflammasome
Yuqin LIANG ; Jie LIU ; Chi ZHANG ; Pingping CHEN ; Fang LU ; Shumin LIU
Chinese Journal of Experimental Traditional Medical Formulae 2026;32(1):131-139
ObjectiveTo explore the improving effect of Huangqi Chifengtang(HCT) on atherosclerosis(AS), and elucidate its mechanism in relation to adenosine monophosphate-activated protein kinase(AMPK)/peroxisome proliferator-activated receptor α(PPARα) signaling pathway and nucleotide-binding oligomerization domain(NOD)-like receptor thermal protein domain associated protein 3(NLRP3) inflammasome. MethodsEight C57BL/6J mice were set as the normal group, and 32 ApoE-/- mice were randomly divided into the model group, the positive drug group(atorvastatin, 5 mg·kg-1·d-1), HCT low- and high-dose groups(1.95, 3.90 g·kg-1·d-1). ApoE-/- mice were fed with high-fat and high-cholesterol feed to establish an AS mouse model. After modeling, they were orally administered corresponding dose of drugs for 28 days, while the normal and model groups received an equal volume of physiological saline via oral gavage. Hematoxylin-eosin(HE) staining was used to observe the pathological status of the aorta and liver in mice, Biochemical testing and enzyme-linked immunosorbent assay(ELISA) were used to detect the levels of total cholesterol(TC), triglycerides(TG), low-density lipoprotein cholesterol(LDL-C), alanine aminotransferase(ALT), aspartate aminotransferase(AST), C-reactive protein(CRP), interleukin(IL)-1β, IL-18 in the serum, as well as superoxide dismutase(SOD), malondialdehyde(MDA), and reduced glutathione(GSH) in the liver. Real-time fluorescence quantitative polymerase chain reaction(Real-time PCR) was used to measure the mRNA expression levels of NLRP3, apoptosis-associated speck-like protein(ASC), cysteinyl aspartate specific proteinase-1(Caspase-1), Toll-like receptor 4(TLR4) in the aorta, and fatty acid synthase(FAS), stearoyl-CoA desaturase 1(SCD1), PPARα, and carnitine palmitoyltransferase 1A(CPT1A) in the liver. Immunohistochemistry was used to determine the protein expressions of NLRP3, Caspase-1, and ASC in the aorta, and Western blot was used to measure the protein expressions of AMPK, p-AMPK, sterol regulatory element binding protein-1c(SREBP-1c), CPT1A, and FAS in the liver. ResultsCompared with the normal group, the model group showed a significant increase in lipid plaque deposition in the aorta and lipid accumulation in the liver, the levels of TC, TG, LDL-C, AST, ALT, IL-1β, IL-18 and CRP in the serum were significantly increased(P<0.01), and the mRNA and protein expressions of aortic TLR4, NLRP3, Caspase-1 and ASC were significantly upregulated(P<0.01). The levels of SOD and GSH in the liver were significantly reduced, while the level of MDA was significantly increased(P<0.01). The mRNA expressions of FAS and SCD1 in the liver were significantly downregulated, while the mRNA expressions of PPARα and CPT1A were significantly upregulated. The protein expressions of p-AMPK/AMPK and CPT1A in the liver were significantly reduced, while the expressions of SREBP-1c and FAS proteins were significantly increased(P<0.01). Compared with the model group, the low- and high-dose HCT groups showed significant improvements in aortic plaques and hepatic lipid deposition. The levels of TC, LDL-C, AST, IL-1β and IL-18 in the serum of the low-dose HCT group, as well as TC, TG, LDL-C, AST, ALT, IL-1β, IL-18 and CRP in the serum of the high-dose HCT group, were significantly reduced(P<0.01). The mRNA expressions of TLR4, NLRP3 and Caspase-1 in the aorta of the low-dose HCT group, as well as TLR4, NLRP3, Caspase-1 and ASC in the aorta of the high-dose HCT group, were significantly downregulated(P<0.01). The protein expressions of Caspase-1 and ASC in the aorta of the low-dose HCT group, as well as NLRP3, Caspase-1 and ASC in the high-dose HCT group, were significantly downregulated(P<0.01). The levels of SOD and GSH in the liver of the low- and high-dose HCT groups were significantly increased, while the level of MDA in the high-dose HCT group was significantly decreased(P<0.05, P<0.01). In the HCT-treated group, the mRNA expressions of FAS and SCD1 in the liver were significantly upregulated, while the mRNA expressions of PPARα and CPT1A were significantly downregulated, the protein expressions of p-AMPK/AMPK and CPT1A in the liver were significantly increased, while the protein expressions of SREBP-1c and FAS were significantly decreased(P<0.05, P<0.01). ConclusionHCT can improve lipid metabolism by activating the AMPK/PPARα pathway and inhibit NLRP3 inflammasome-mediated inflammatory responses, thereby reducing hepatic lipid deposition and AS plaque formation.
2.Transcriptomic characteristics of keloid-adjacent dermal fibroblasts: a preliminary study
Daoning ZHANG ; Pingping LIN ; Jie TIAN ; Guohong ZHANG ; Hang LI
Chinese Journal of Dermatology 2025;58(2):145-153
Objective:To explore the potential lesional range of keloids by analyzing the transcriptomic characteristics, and to provide a molecular basis for understanding the recurrence of keloids following surgical excision.Methods:From July to December in 2022, 3 patients clinically diagnosed with keloids and treated with surgical excision at the Department of Dermatology and Venereology, Peking University First Hospital were included in the study. Samples of keloids and keloid-adjacent dermis were collected from these 3 patients, and normal dermal tissues adjacent to benign skin tumors were collected from 4 patients and served as controls. Dermal fibroblasts were obtained by primary cell culture and purification, which were then subsequently passaged to the second generation for transcriptome sequencing. Differential gene expression analysis, gene ontology (GO) -based functional analysis, and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis were performed. While analyzing differential expression genes, those with a fold change (FC) > 2 and a P value < 0.05 were defined as upregulated genes, whereas those with a FC < 0.5 and a P value < 0.05 were considered downregulated genes. The accuracy of the results was further validated by comparing them with published single-cell sequencing data on keloid and keloid-adjacent tissues (HRA000425 in GSA database) and single-cell sequencing data on the normal dermis (GSE130973 in GEO database). Key genes in keloid-adjacent dermal fibroblasts were validated in tissue samples from this study and the literature. Results:Compared with keloid-derived fibroblasts, keloid-adjacent and control dermal fibroblasts shared 63 upregulated genes enriched in biological processes including lipid transport ( P = 0.038) and ion transport ( P = 0.040) ; compared with control dermal fibroblasts, keloid-adjacent and keloid-derived fibroblasts shared 56 upregulated genes enriched in the transforming growth factor β signaling pathway ( P < 0.001), etc. When comparing keloid-derived fibroblasts and keloid-adjacent fibroblasts with control dermal fibroblasts, 79 genes were uniquely upregulated only in keloid-adjacent fibroblasts; after filtering based on gene expression thresholds and consistency, 13 candidate genes (average expression level > 1 000 and variance of expression level within groups < 30 000) closely related to the transcriptomic characteristics of keloid-derived fibroblasts were identified, including genes inhibiting keloid formation such as SMAD6 and SMAD7, as well as those promoting keloid formation such as MSX1, SNAI1, and EDN1, which were enriched in the biological processes such as cell growth, ossification and cartilage development (all P < 0.01). The enrichment analysis of the above-mentioned 13 genes on the ChEA3 website identified some enriched transcription factors, such as myogenic differentiation protein 1 (MYOD1) and myogenin (MYOG) (both P < 0.05) . Conclusions:Compared with keloid-derived fibroblasts and control dermal fibroblasts, the transcriptomics of keloid-adjacent fibroblasts were characterized by high-level coexpression of genes involved in both the inhibition and promotion of keloid formation, which may provide a molecular explanation for the similarity in morphology between keloid-adjacent tissues and normal skin tissues as well as for the potential mechanisms underlying the high recurrence rate of keloids.
3.Predictive value of clinical combined MRI scoring scale in placenta previa with placenta implantation
Qi YAO ; Oucheng WANG ; Pingping JIE ; Liulu ZHANG ; Yao XIAO
Journal of Practical Radiology 2025;41(1):72-76
Objective To explore the clinical value of clinical combined MRI scoring scale in predicting placenta previa with pla-centa accreta spectrum disorders(PAS).Methods The clinical and MRI data of 96 pregnant women with placenta previa were ana-lyzed retrospectively,including 37 cases in the non-PAS group and 59 cases in the PAS group.In the PAS group,there were 14 cases in the placenta accreta(PA)group,33 cases in the placenta increta(PI)group and 12 cases in the placenta percreta(PP)group.The differences in clinical and imaging features of the variables between non-PAS,PA,PI,and PP groups were analyzed to establish a sco-ring scale,and the receiver operating characteristic(ROC)curves were used to calculate the critical values of the different groups.Results Ten clinical and 15 imaging features were included for evaluation,there were statistically significant differences in 14 indicators,including the number of caesarean sections,placental thickness,abnormal subplacental vessels,and short T2 signal bands within the placenta(P<0.05).Incorporate the above indicators into the MRI scoring scale.The ROC curves showed that the area under the curve(AUC)of the MRI scoring scale analyzed diagnostic non-PAS group versus PA group was 0.874,with a significance of 0.000 and a critical value of 5.5,the AUC of the PA group versus PI group was 0.784,with a significance of 0.002 and a critical value of 9.5,and the AUC of the PI group versus PP group was 0.986,with a significance of 0.000 and a critical value of 14.5.Conclusion Clini-cal combined MRI scoring scale can evaluate whether placenta previa is accompanied by PAS and evaluate the depth of PAS,which has important clinical value.
4.Effect of remote ischemic conditioning combined with binaural beat music training in patients with cognitive dys-function after cerebral infarction
Xing XUE ; Haiyan ZHAO ; Shuling YUE ; Jie CHENG ; Qiqun TANG ; Xiaohua CHENG ; Zonghai GUO ; Pingping LIU
Chinese Journal of Rehabilitation Theory and Practice 2025;31(9):1057-1065
Objective To explore the effect of remote ischemic conditioning(RIC)combined with binaural beat music(BBM)train-ing in patients with cognitive dysfunction after cerebral infarction.Methods From June,2024 to January,2025,200 patients with cognitive dysfunction after cerebral infarction in the Affil-iated Hospital of North China University of Science and Technology were randomly divided into control group(n=50),RIC group(n=50),BBM group(n=50)and combined group(n=50).All the groups received stan-dardized routine training,RIC group received RIC,BBM group received BBM,and the combined group received RIC+BBM,for 14 days.They were assessed with Montreal Cognitive Assessment(MoCA)and Stroke-Specific Quality of Life Scale(SS-QOL)at baseline,day 14,and day 90.Results Two cases in the control group,four in RIC group,three in BBM group and three in the combined group dropped out.For MoCA scores,the inter-group effect,intra-group effect and interaction effect were all significant(F>13.463,P<0.001).After intervention,on both day 14 and day 90,the score of MoCA was higher in each in-tervention group than in the control group(P<0.05),and was higher in the combined group than in both BBM and RIC groups(P<0.05);and on day 90,it was higher in RIC group than in BBM group(P<0.05).For SS-QOL,the score increased with time in all the groups(χ2>75.182,P<0.001).After intervention,there was signif-icant difference at each time point among four groups(H>18.260,P<0.001).On day 14 and day 90,the score of SS-QOL was higher in the combined group than in the control and BBM groups(|Z|>3.149,P<0.05);on day 90,the score was higher in RIC group than in the control group(|Z|=3.590,P<0.05),and it was higher in the combined group than in RIC group(|Z|=3.186,P<0.05).Conclusion RIC,BBM and their combination all improved cognitive function after cerebral infarction.RIC was superior to BBM,and the combined intervention yielded the greatest benefit.Both RIC and the combined intervention im-proved quality of life,with the combined approach being the most effective.
5.Transcriptomic characteristics of keloid-adjacent dermal fibroblasts: a preliminary study
Daoning ZHANG ; Pingping LIN ; Jie TIAN ; Guohong ZHANG ; Hang LI
Chinese Journal of Dermatology 2025;58(2):145-153
Objective:To explore the potential lesional range of keloids by analyzing the transcriptomic characteristics, and to provide a molecular basis for understanding the recurrence of keloids following surgical excision.Methods:From July to December in 2022, 3 patients clinically diagnosed with keloids and treated with surgical excision at the Department of Dermatology and Venereology, Peking University First Hospital were included in the study. Samples of keloids and keloid-adjacent dermis were collected from these 3 patients, and normal dermal tissues adjacent to benign skin tumors were collected from 4 patients and served as controls. Dermal fibroblasts were obtained by primary cell culture and purification, which were then subsequently passaged to the second generation for transcriptome sequencing. Differential gene expression analysis, gene ontology (GO) -based functional analysis, and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis were performed. While analyzing differential expression genes, those with a fold change (FC) > 2 and a P value < 0.05 were defined as upregulated genes, whereas those with a FC < 0.5 and a P value < 0.05 were considered downregulated genes. The accuracy of the results was further validated by comparing them with published single-cell sequencing data on keloid and keloid-adjacent tissues (HRA000425 in GSA database) and single-cell sequencing data on the normal dermis (GSE130973 in GEO database). Key genes in keloid-adjacent dermal fibroblasts were validated in tissue samples from this study and the literature. Results:Compared with keloid-derived fibroblasts, keloid-adjacent and control dermal fibroblasts shared 63 upregulated genes enriched in biological processes including lipid transport ( P = 0.038) and ion transport ( P = 0.040) ; compared with control dermal fibroblasts, keloid-adjacent and keloid-derived fibroblasts shared 56 upregulated genes enriched in the transforming growth factor β signaling pathway ( P < 0.001), etc. When comparing keloid-derived fibroblasts and keloid-adjacent fibroblasts with control dermal fibroblasts, 79 genes were uniquely upregulated only in keloid-adjacent fibroblasts; after filtering based on gene expression thresholds and consistency, 13 candidate genes (average expression level > 1 000 and variance of expression level within groups < 30 000) closely related to the transcriptomic characteristics of keloid-derived fibroblasts were identified, including genes inhibiting keloid formation such as SMAD6 and SMAD7, as well as those promoting keloid formation such as MSX1, SNAI1, and EDN1, which were enriched in the biological processes such as cell growth, ossification and cartilage development (all P < 0.01). The enrichment analysis of the above-mentioned 13 genes on the ChEA3 website identified some enriched transcription factors, such as myogenic differentiation protein 1 (MYOD1) and myogenin (MYOG) (both P < 0.05) . Conclusions:Compared with keloid-derived fibroblasts and control dermal fibroblasts, the transcriptomics of keloid-adjacent fibroblasts were characterized by high-level coexpression of genes involved in both the inhibition and promotion of keloid formation, which may provide a molecular explanation for the similarity in morphology between keloid-adjacent tissues and normal skin tissues as well as for the potential mechanisms underlying the high recurrence rate of keloids.
6.Predictive value of clinical combined MRI scoring scale in placenta previa with placenta implantation
Qi YAO ; Oucheng WANG ; Pingping JIE ; Liulu ZHANG ; Yao XIAO
Journal of Practical Radiology 2025;41(1):72-76
Objective To explore the clinical value of clinical combined MRI scoring scale in predicting placenta previa with pla-centa accreta spectrum disorders(PAS).Methods The clinical and MRI data of 96 pregnant women with placenta previa were ana-lyzed retrospectively,including 37 cases in the non-PAS group and 59 cases in the PAS group.In the PAS group,there were 14 cases in the placenta accreta(PA)group,33 cases in the placenta increta(PI)group and 12 cases in the placenta percreta(PP)group.The differences in clinical and imaging features of the variables between non-PAS,PA,PI,and PP groups were analyzed to establish a sco-ring scale,and the receiver operating characteristic(ROC)curves were used to calculate the critical values of the different groups.Results Ten clinical and 15 imaging features were included for evaluation,there were statistically significant differences in 14 indicators,including the number of caesarean sections,placental thickness,abnormal subplacental vessels,and short T2 signal bands within the placenta(P<0.05).Incorporate the above indicators into the MRI scoring scale.The ROC curves showed that the area under the curve(AUC)of the MRI scoring scale analyzed diagnostic non-PAS group versus PA group was 0.874,with a significance of 0.000 and a critical value of 5.5,the AUC of the PA group versus PI group was 0.784,with a significance of 0.002 and a critical value of 9.5,and the AUC of the PI group versus PP group was 0.986,with a significance of 0.000 and a critical value of 14.5.Conclusion Clini-cal combined MRI scoring scale can evaluate whether placenta previa is accompanied by PAS and evaluate the depth of PAS,which has important clinical value.
7.Effect of remote ischemic conditioning combined with binaural beat music training in patients with cognitive dys-function after cerebral infarction
Xing XUE ; Haiyan ZHAO ; Shuling YUE ; Jie CHENG ; Qiqun TANG ; Xiaohua CHENG ; Zonghai GUO ; Pingping LIU
Chinese Journal of Rehabilitation Theory and Practice 2025;31(9):1057-1065
Objective To explore the effect of remote ischemic conditioning(RIC)combined with binaural beat music(BBM)train-ing in patients with cognitive dysfunction after cerebral infarction.Methods From June,2024 to January,2025,200 patients with cognitive dysfunction after cerebral infarction in the Affil-iated Hospital of North China University of Science and Technology were randomly divided into control group(n=50),RIC group(n=50),BBM group(n=50)and combined group(n=50).All the groups received stan-dardized routine training,RIC group received RIC,BBM group received BBM,and the combined group received RIC+BBM,for 14 days.They were assessed with Montreal Cognitive Assessment(MoCA)and Stroke-Specific Quality of Life Scale(SS-QOL)at baseline,day 14,and day 90.Results Two cases in the control group,four in RIC group,three in BBM group and three in the combined group dropped out.For MoCA scores,the inter-group effect,intra-group effect and interaction effect were all significant(F>13.463,P<0.001).After intervention,on both day 14 and day 90,the score of MoCA was higher in each in-tervention group than in the control group(P<0.05),and was higher in the combined group than in both BBM and RIC groups(P<0.05);and on day 90,it was higher in RIC group than in BBM group(P<0.05).For SS-QOL,the score increased with time in all the groups(χ2>75.182,P<0.001).After intervention,there was signif-icant difference at each time point among four groups(H>18.260,P<0.001).On day 14 and day 90,the score of SS-QOL was higher in the combined group than in the control and BBM groups(|Z|>3.149,P<0.05);on day 90,the score was higher in RIC group than in the control group(|Z|=3.590,P<0.05),and it was higher in the combined group than in RIC group(|Z|=3.186,P<0.05).Conclusion RIC,BBM and their combination all improved cognitive function after cerebral infarction.RIC was superior to BBM,and the combined intervention yielded the greatest benefit.Both RIC and the combined intervention im-proved quality of life,with the combined approach being the most effective.
8.Treatment of Neurological Diseases with Tianma Goutengyin: A Review
Jianping DUAN ; Jie ZHANG ; Xu WANG ; Xiaoyu SONG ; Simin LI ; Pingping DUAN
Chinese Journal of Experimental Traditional Medical Formulae 2024;30(11):255-264
Neurological diseases are common and frequent in clinical practices, which are the main reasons that affect the quality of life and physical and mental health of patients seriously. Tianma Goutengyin (TGY) is from the New Significance of Patterns and Treatment in Miscellaneous Diseases, which was compiled by a famous doctor, HU Guangci. TGY is widely used in clinical practice and has the effects of calming the liver and calming the wind, clearing heat and activating the blood, tranquilization, and nourishing the liver and kidneys. Clinical studies have confirmed that modified TGY can be used either alone or in combination with acupuncture or western medicine to treat dementia, headache, vertigo, hypertension, insomnia, Parkinson's disease, stroke, epilepsy, and other common neurological diseases, with significant curative effect, few side effects, and high safety. The main active constituents of single flavor drugs in the composition of TGY mainly include gastrodin, gastrodia elata blume polysaccharides, p-hydroxybenzyl alcohol, rhynchophylline, baicalein, leonurine, stachydrine, geniposide, 2,3,5,4,-tetrahydroxystilbene-2-Ο-β-D-glucoside, pinoresinol diglucoside, pachymic acid, β-ecdysteroid, avicularin, etc. It has been found that TGY and these constituents have the effects of ferroptosis inhibition, anti-apoptosis, anti-inflammation, and oxidation resistance, and they can regulate neurotransmitters and autophagy, reduce cerebral edema reduction, lower blood lipid and blood pressure, and improve blood circulation through multiple targets and pathways. This paper reviewed the clinical application of and the mechanism of the whole prescription and single flavor drugs of TGY in the treatment of neurological diseases, so as to provide a theoretical basis for the clinical application of TGY and offer ideas for the follow-up mechanism research of this prescription.
9.Clinical characteristics and genetic analysis of children and adolescents with monogenic diabetes
Jie FANG ; Pingping ZHANG ; Yueying FENG ; Shuxia DING ; Lulu YAN ; Haibo LI
Chinese Journal of Medical Genetics 2024;41(7):783-789
Objective:To explore the clinical characteristics and molecular basis for children and adolescents with monogenic diabetes.Methods:A retrospective analysis was carried out for the clinical manifestations and laboratory data of 116 children and adolescents diagnosed with diabetes at Ningbo Women and Children′s Hospital from January 2020 to March 2023. Whole exome sequencing and mitochondrial gene sequencing were carried out on 21 children with suspected monogenic diabetes.Results:A total of 10 cases of monogenic diabetes were diagnosed, all of which were Maturity-onset Diabetes Of the Young (MODY). Six cases of MODY2 were due to GCK gene mutations, 1 case of MODY3 was due to HNF1A gene mutation, 2 cases of MODY12 were due to ABCC8 gene mutations, and 1 case of MODY13 was due to KCNJ11 gene mutation. Nine of the 10 patients with MODY had no typical symptoms of diabetes. A family history of diabetes was significantly more common in the MODY group compared with the T1DM and T2DM groups ( P<0.05). The BMI of the MODY group was higher than that of the T1DM group ( P<0.05). The initial blood glucose level was lower than that of the T1DM group ( P<0.05), and there was no significant difference compared with the T2DM group. The fasting C-peptide level of the MODY group was higher than that of the T1DM group ( P<0.05), and there was no significant difference compared with the T2DM group. Glycosylated hemoglobin of the MODY group was lower than both the T1DM and T2DM groups ( P<0.05). Conclusion:In this study, MODY has accounted for the majority of monogenic diabetes among children and adolescents, and the common mutations were those of the GCK gene in association with MODY2. Blood glucose and glycosylated hemoglobin of children with MODY were slightly increased, whilst the islet cell function had remained, and the clinical manifestations and laboratory tests had overlapped with those of type 2 diabetes. WES and mitochondrial gene sequencing can clarify the etiology of monogenic diabetes and facilitate precise treatment.
10.Clinical application of V-shaped folded submental flap in the repair of oral defect
Ruohuang LU ; Haobin DENG ; Xincheng GUO ; Jie DAI ; Pingping GAN
Journal of Central South University(Medical Sciences) 2024;49(2):273-278
Objective:The repair of small and medium-sized defects in the oral has always been a challenge,free skin flap and distal pedicled tissue flaps are difficult to meet clinical needs,and the traditional under-chin flap has the risk of donor-area injury.This study aims to investigate the efficacy of V-shaped folded submental flap in the repair of small-sized and medium-sized oral defects. Methods:The clinical data of 28 patients with oral defect lesions,who were hospitalized in the Department of Stomatology,Third Xiangya Hospital of Central South University from March 2019 to December 2022,were retrospectively analyzed.Patients were divided into a V-shaped folded group(17 cases)and a conventional group(11 cases)according to different surgical methods.The V-shaped folded group was treated with a V-shaped folded submental flap for postoperative soft tissue repair,while the conventional group was treated with a conventional submental flap for repair.The postoperative follow-up time was 6-48 months.The survival status,repair time,and repair effect of the 2 groups were compared. Results:There was no significant difference in flap survival rate,flap size,flap preparation time,repair surgery time,and postoperative hospital stay between the 2 groups(all P>0.05).At 6 months after the surgery,the V-shaped folded group had no difficulty in raising the head or everting the lower lip,no"cat ear"deformity in the submental skin.Scars in the V-shaped folding group were hidden at the lower edge of the mandible.The wound aesthetics and functional scores in the V-shaped folded group were significantly higher than those in the conventional group(both P<0.05). Conclusion:The V-shaped foldable submental flap has the advantages of flexible design,simple preparation,reliable blood supply,and protection of the donor area,which can effectively protect the appearance of the chin and avoid functional disorders.

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