1.Mechanism of Qiju Dihuang Wan in Treatment of Diabetic Retinopathy Based on NLRP3/Caspase-1/GSDMD Signaling Pathway
Ge ZHANG ; Chunlin ZHAO ; Li PAN ; Ying ZHANG ; Zehai CHEN ; Siya ZHANG ; Yiming FANG ; Wei SHI
Chinese Journal of Experimental Traditional Medical Formulae 2026;32(20):11-21
ObjectiveTo investigate the protective effect of Qiju Dihuang Wan on diabetic retinopathy (DR) and its regulatory mechanism on the NOD-like receptor protein 3/Cysteinyl aspartate-specific proteinase-1/Gasdermin D (NLRP3/Caspase-1/GSDMD) signaling pathway. MethodsHuman retinal microvascular endothelial cells (HRMEC) were divided into the blank group, model group, and Qiju Dihuang Wan low- and high-dose groups. Except for the blank group, all groups were induced with 40 mmol·L-1 high glucose, and the treatment groups were supplemented with 6% and 12% Qiju Dihuang Wan-containing serum, respectively, based on the induction. After 24 h of culture, the levels of interleukin (IL)-1β and IL-18 were measured by enzyme-linked immunosorbent assay (ELISA), pyroptosis-related protein expression was detected by immunofluorescence and Western blot, and the mRNA levels of NLRP3/Caspase-1/GSDMD signaling pathway-related molecules were determined by real-time polymerase chain reaction (Real-time PCR). The mice were randomly divided into the blank group, model group, Qiju Dihuang Wan low-, medium-, and high-dose groups (11, 22, 44 g·kg-1·d-1), and calcium dobesilate group (0.13 g·kg-1·d-1). Except for the blank group, all groups were intraperitoneally injected with streptozotocin to establish the DR model. After successful modeling, the treatment groups received corresponding doses of Qiju Dihuang Wan crude drug or calcium dobesilate suspension by gavage once daily, while the blank group and model group received an equal volume of normal saline, for 8 consecutive weeks. Fundus changes were examined by optical coherence tomography, optical coherence tomography angiography, and fundus fluorescein angiography. Retinal pathological morphology was observed by hematoxylin-eosin staining. Real-time PCR was used to detect the mRNA levels of NLRP3, Caspase‑1, GSDMD, IL‑1β, and IL‑18 in retinal tissue, and Western blot was used to detect the protein expression of NLRP3, ASC, cleaved Caspase‑1, and GSDMD‑N. ResultsCell experiments showed that compared with the blank group, the model group showed significantly decreased HRMEC viability (P<0.01), and significantly increased levels of IL-1β, IL-18, as well as increased protein expression of NLRP3, cleaved Caspase-1, and GSDMD-N (P<0.01). Compared with the model group, the above indicators were significantly reduced in the high-dose Qiju Dihuang Wan groups (P<0.05, P<0.01). Animal experiments showed that compared with the blank group, the model group had elevated blood glucose (P<0.01), decreased retinal thickness and vascular density (P<0.01), up‑regulated mRNA expression of NLRP3, Caspase‑1, GSDMD, IL‑1β and IL‑18 in retinal tissue (P<0.01), and up‑regulated protein expression of NLRP3, ASC, cleaved Caspase‑1 and GSDMD‑N (P<0.01). Compared with the model group, the Qiju Dihuang Wan medium- and high‑dose groups showed decreased blood glucose (P<0.01), increased retinal thickness and vascular density (P<0.01), alleviated retinal pathological damage, and down‑regulated mRNA expression of NLRP3, Caspase‑1, GSDMD, IL‑1β, IL‑18, as well as protein expression of NLRP3, ASC, cleaved Caspase‑1, and GSDMD‑N (P<0.05, P<0.01). ConclusionQiju Dihuang Wan may exert protective effects against diabetic retinopathy by inhibiting the activation of the NLRP3/Caspase-1/GSDMD signaling pathway and alleviating high glucose-induced retinal pyroptosis.
2.Mechanism of Qiju Dihuang Wan in Treatment of Diabetic Retinopathy Based on NLRP3/Caspase-1/GSDMD Signaling Pathway
Ge ZHANG ; Chunlin ZHAO ; Li PAN ; Ying ZHANG ; Zehai CHEN ; Siya ZHANG ; Yiming FANG ; Wei SHI
Chinese Journal of Experimental Traditional Medical Formulae 2026;32(20):11-21
ObjectiveTo investigate the protective effect of Qiju Dihuang Wan on diabetic retinopathy (DR) and its regulatory mechanism on the NOD-like receptor protein 3/Cysteinyl aspartate-specific proteinase-1/Gasdermin D (NLRP3/Caspase-1/GSDMD) signaling pathway. MethodsHuman retinal microvascular endothelial cells (HRMEC) were divided into the blank group, model group, and Qiju Dihuang Wan low- and high-dose groups. Except for the blank group, all groups were induced with 40 mmol·L-1 high glucose, and the treatment groups were supplemented with 6% and 12% Qiju Dihuang Wan-containing serum, respectively, based on the induction. After 24 h of culture, the levels of interleukin (IL)-1β and IL-18 were measured by enzyme-linked immunosorbent assay (ELISA), pyroptosis-related protein expression was detected by immunofluorescence and Western blot, and the mRNA levels of NLRP3/Caspase-1/GSDMD signaling pathway-related molecules were determined by real-time polymerase chain reaction (Real-time PCR). The mice were randomly divided into the blank group, model group, Qiju Dihuang Wan low-, medium-, and high-dose groups (11, 22, 44 g·kg-1·d-1), and calcium dobesilate group (0.13 g·kg-1·d-1). Except for the blank group, all groups were intraperitoneally injected with streptozotocin to establish the DR model. After successful modeling, the treatment groups received corresponding doses of Qiju Dihuang Wan crude drug or calcium dobesilate suspension by gavage once daily, while the blank group and model group received an equal volume of normal saline, for 8 consecutive weeks. Fundus changes were examined by optical coherence tomography, optical coherence tomography angiography, and fundus fluorescein angiography. Retinal pathological morphology was observed by hematoxylin-eosin staining. Real-time PCR was used to detect the mRNA levels of NLRP3, Caspase‑1, GSDMD, IL‑1β, and IL‑18 in retinal tissue, and Western blot was used to detect the protein expression of NLRP3, ASC, cleaved Caspase‑1, and GSDMD‑N. ResultsCell experiments showed that compared with the blank group, the model group showed significantly decreased HRMEC viability (P<0.01), and significantly increased levels of IL-1β, IL-18, as well as increased protein expression of NLRP3, cleaved Caspase-1, and GSDMD-N (P<0.01). Compared with the model group, the above indicators were significantly reduced in the high-dose Qiju Dihuang Wan groups (P<0.05, P<0.01). Animal experiments showed that compared with the blank group, the model group had elevated blood glucose (P<0.01), decreased retinal thickness and vascular density (P<0.01), up‑regulated mRNA expression of NLRP3, Caspase‑1, GSDMD, IL‑1β and IL‑18 in retinal tissue (P<0.01), and up‑regulated protein expression of NLRP3, ASC, cleaved Caspase‑1 and GSDMD‑N (P<0.01). Compared with the model group, the Qiju Dihuang Wan medium- and high‑dose groups showed decreased blood glucose (P<0.01), increased retinal thickness and vascular density (P<0.01), alleviated retinal pathological damage, and down‑regulated mRNA expression of NLRP3, Caspase‑1, GSDMD, IL‑1β, IL‑18, as well as protein expression of NLRP3, ASC, cleaved Caspase‑1, and GSDMD‑N (P<0.05, P<0.01). ConclusionQiju Dihuang Wan may exert protective effects against diabetic retinopathy by inhibiting the activation of the NLRP3/Caspase-1/GSDMD signaling pathway and alleviating high glucose-induced retinal pyroptosis.
3.The Predictive Value of Dual-layer Spectral Detector CT Parameters on Lymph Node Metastasis of Nonfunctional Pancreatic Neuroendocrine Tumor
Mingjie CHEN ; Ke LI ; Jiadan LUO ; Jiayi YANG ; Huasong CAI ; Shiting FENG ; Yanji LUO ; Siya SHI
Journal of Sun Yat-sen University(Medical Sciences) 2026;47(5):868-879
ObjectiveTo investigate the value of preoperative dual-layer spectral detector CT (DLCT) parameters in predicting lymph node metastasis (LNM) of non-functional pancreatic neuroendocrine neoplasms (NF-pNENs). MethodsA retrospective study was conducted on patients with pathologically confirmed NF-pNENs who underwent preoperative contrast-enhanced DLCT examination between September 2019 and July 2024. Regions of interest (ROIs) were manually delineated on three representative slices of the solid component of the lesion, and the mean values were recorded. Conventional CT parameters, monochromatic energy images (40 keV, 70 keV, 100 keV), iodine concentration maps, and effective atomic number (Zeff) maps in the pancreatic parenchymal phase and portal venous phase were acquired. A total of 34 parameters, including clinical characteristics, imaging features, conventional CT and DLCT quantitative parameters, were analyzed. Intergroup differences were compared between the LNM and non-LNM groups. Independent predictive factors were screened using logistic regression and least absolute shrinkage and selection operator (LASSO) regression. Receiver operating characteristic (ROC) curves were generated for each predictive model, and the area under the curve (AUC) was calculated to evaluate the predictive efficacy. ResultsA total of 82 patients with NF-pNENs were enrolled, including 37 males and 45 females, with a mean age of 49.7±14.7 years. Thirty patients were performed with LNM and 52 were with non-LNM. After univariate logistic regression, LASSO regression and multivariate stepwise logistic regression analyses, body mass index (BMI), organ invasion, normalized CT value in the portal venous phase (nCTv) and normalized iodine concentration in the portal venous phase (nICv) were identified as independent predictive factors. The AUCs of the clinical-radiological qualitative model (BMI+organ invasion), conventional CT model (nCTv), DLCT model (nICv) and comprehensive model (organ invasion+nICv) were 0.815 (0.719, 0.910), 0.750 (0.642, 0.858), 0.829 (0.733, 0.925) and 0.865 (0.879, 0.953), respectively. The comprehensive model combining clinical-radiological and DLCT characteristics exhibited superior predictive performance. ConclusionDLCT parameters are more effective than conventional CT parameters in predicting LNM in NF-pNENs, enabling non-invasive preoperative prediction and assisting clinical decision-making.
4.The Predictive Value of Dual-layer Spectral Detector CT Parameters on Lymph Node Metastasis of Nonfunctional Pancreatic Neuroendocrine Tumor
Mingjie CHEN ; Ke LI ; Jiadan LUO ; Jiayi YANG ; Huasong CAI ; Shiting FENG ; Yanji LUO ; Siya SHI
Journal of Sun Yat-sen University(Medical Sciences) 2026;47(5):868-879
ObjectiveTo investigate the value of preoperative dual-layer spectral detector CT (DLCT) parameters in predicting lymph node metastasis (LNM) of non-functional pancreatic neuroendocrine neoplasms (NF-pNENs). MethodsA retrospective study was conducted on patients with pathologically confirmed NF-pNENs who underwent preoperative contrast-enhanced DLCT examination between September 2019 and July 2024. Regions of interest (ROIs) were manually delineated on three representative slices of the solid component of the lesion, and the mean values were recorded. Conventional CT parameters, monochromatic energy images (40 keV, 70 keV, 100 keV), iodine concentration maps, and effective atomic number (Zeff) maps in the pancreatic parenchymal phase and portal venous phase were acquired. A total of 34 parameters, including clinical characteristics, imaging features, conventional CT and DLCT quantitative parameters, were analyzed. Intergroup differences were compared between the LNM and non-LNM groups. Independent predictive factors were screened using logistic regression and least absolute shrinkage and selection operator (LASSO) regression. Receiver operating characteristic (ROC) curves were generated for each predictive model, and the area under the curve (AUC) was calculated to evaluate the predictive efficacy. ResultsA total of 82 patients with NF-pNENs were enrolled, including 37 males and 45 females, with a mean age of 49.7±14.7 years. Thirty patients were performed with LNM and 52 were with non-LNM. After univariate logistic regression, LASSO regression and multivariate stepwise logistic regression analyses, body mass index (BMI), organ invasion, normalized CT value in the portal venous phase (nCTv) and normalized iodine concentration in the portal venous phase (nICv) were identified as independent predictive factors. The AUCs of the clinical-radiological qualitative model (BMI+organ invasion), conventional CT model (nCTv), DLCT model (nICv) and comprehensive model (organ invasion+nICv) were 0.815 (0.719, 0.910), 0.750 (0.642, 0.858), 0.829 (0.733, 0.925) and 0.865 (0.879, 0.953), respectively. The comprehensive model combining clinical-radiological and DLCT characteristics exhibited superior predictive performance. ConclusionDLCT parameters are more effective than conventional CT parameters in predicting LNM in NF-pNENs, enabling non-invasive preoperative prediction and assisting clinical decision-making.
5.Pharmacological advances in pharmacological research on the treatment of dry age-related macular degeneration with traditional Chinese medicine
Siya ZHANG ; Yu PEI ; Xi CHEN ; Li PAN ; Ge ZHANG ; Yuanchen DING ; Meihui WEI ; Wei SHI
Recent Advances in Ophthalmology 2025;45(12):981-985
The incidence of age-related macular degeneration(AMD)is rising with the intensifying aging trend,be-coming a critical challenge that demands urgent solutions.Dry AMD(dAMD)accounts for approximately 80%of all AMD cases,and there is currently a lack of highly effective treatment options.In recent years,traditional Chinese medicine(TCM)has been proven to effectively treat dAMD through actions such as antioxidation,anti-apoptosis,anti-inflammation,and lipid-lowering.By reviewing domestic and international literature,this article discusses TCM monomers,extracts,and compound formulations for dAMD,analyzing their various mechanisms.Based on traditional TCM efficacy theories and in-tegrated with modern mechanisms of action,it targets the active components of TCM to elucidate the connection between effective medicinal targets of TCM and dAMD,thereby clarifying the efficacy and scientific basis of TCM monomers,com-pounds,and extracts in treating dAMD.The aim is to provide new perspectives for the prevention and clinical treatment of dAMD.
6.Pharmacological advances in pharmacological research on the treatment of dry age-related macular degeneration with traditional Chinese medicine
Siya ZHANG ; Yu PEI ; Xi CHEN ; Li PAN ; Ge ZHANG ; Yuanchen DING ; Meihui WEI ; Wei SHI
Recent Advances in Ophthalmology 2025;45(12):981-985
The incidence of age-related macular degeneration(AMD)is rising with the intensifying aging trend,be-coming a critical challenge that demands urgent solutions.Dry AMD(dAMD)accounts for approximately 80%of all AMD cases,and there is currently a lack of highly effective treatment options.In recent years,traditional Chinese medicine(TCM)has been proven to effectively treat dAMD through actions such as antioxidation,anti-apoptosis,anti-inflammation,and lipid-lowering.By reviewing domestic and international literature,this article discusses TCM monomers,extracts,and compound formulations for dAMD,analyzing their various mechanisms.Based on traditional TCM efficacy theories and in-tegrated with modern mechanisms of action,it targets the active components of TCM to elucidate the connection between effective medicinal targets of TCM and dAMD,thereby clarifying the efficacy and scientific basis of TCM monomers,com-pounds,and extracts in treating dAMD.The aim is to provide new perspectives for the prevention and clinical treatment of dAMD.
7.Application effect of divisional design in composite reduction labiaplasty
Siya ZHANG ; Fengchao CHEN ; Fengyong LI
Chinese Journal of Plastic Surgery 2022;38(8):881-886
Objective:To explore the clinical effect of the composite reduction labiaplasty by divisional design.Methods:From January 2020 to February 2022, the clinical data of patients with complex labia minora and clitoris prepuce hypertrophy who were treated in the Medical Cosmetic Center of Beijing Friendship Hospital Affiliated to Capital Medical University were collected and analysed. The inner side of their labia minora showed no chalasis in the vertical direction, but the outer side were slack with folds, accompanied by clitoris prepuce hyperplasia. We adopted the composite reduction labiaplasty by divisional design. The outer side of the labia minora and the clitoral prepuce were considered as a whole, and a wedge-shaped incision line was designed to remove the excess tissue in the vertical direction. On this basis, an arc was projected on the inner side of the labia minora to form an arcuate incision line on the inner side. The composite reduction labiaplasty was performed with the combination of wedge resection and edge resection. The postoperative follow-up observations included: postoperative complications, the symmetry of the labia minora and clitoris prepuce, the improvement of frictional discomfort, the cleanliness of the labia minora and the clitoris prepuce, and the patient's satisfaction with the shape of the labia minora and clitoris prepuce. For patients with sexual experience, follow-up content also includes changes in sexual satisfaction.Results:A total of 17 female patients aged 20 to 35 years, with an average age of 27 years, were included in this study. Follow-up was conducted 2 months after the operation. All incisions healed by first intention with no sawtooth-like deformity at the incision margin, and had natural appearance. Patients felt that the bilateral labia minora and clitoral foreskin were completely symmetrical in 3 cases, basically symmetrical in 12 cases, and partially asymmetric in 2 cases. These 2 cases of partial asymmetry did not require further surgical repair. In all 17 patients, the frictional discomfort was completely resolved, and the labia minora and clitoral foreskin were easier to clean. The patients were very satisfied with the appearance in 5 cases, satisfied in 10 cases, and dissatisfied in 2 case. There were 15 patients with previous sexual life experience, of which 10 patients had improved sexual satisfaction, and 5 patients had no change in sexual satisfaction after the operation.Conclusions:Through the divisional design, wedge resection and edge resection are performed in the composite reduction labiaplasty, which can solve the friction and discomfort caused by the hyperplasia of labia minora and clitoris prepuce in a single operation, and achieve better aesthetic results at the same time.
8.Application effect of divisional design in composite reduction labiaplasty
Siya ZHANG ; Fengchao CHEN ; Fengyong LI
Chinese Journal of Plastic Surgery 2022;38(8):881-886
Objective:To explore the clinical effect of the composite reduction labiaplasty by divisional design.Methods:From January 2020 to February 2022, the clinical data of patients with complex labia minora and clitoris prepuce hypertrophy who were treated in the Medical Cosmetic Center of Beijing Friendship Hospital Affiliated to Capital Medical University were collected and analysed. The inner side of their labia minora showed no chalasis in the vertical direction, but the outer side were slack with folds, accompanied by clitoris prepuce hyperplasia. We adopted the composite reduction labiaplasty by divisional design. The outer side of the labia minora and the clitoral prepuce were considered as a whole, and a wedge-shaped incision line was designed to remove the excess tissue in the vertical direction. On this basis, an arc was projected on the inner side of the labia minora to form an arcuate incision line on the inner side. The composite reduction labiaplasty was performed with the combination of wedge resection and edge resection. The postoperative follow-up observations included: postoperative complications, the symmetry of the labia minora and clitoris prepuce, the improvement of frictional discomfort, the cleanliness of the labia minora and the clitoris prepuce, and the patient's satisfaction with the shape of the labia minora and clitoris prepuce. For patients with sexual experience, follow-up content also includes changes in sexual satisfaction.Results:A total of 17 female patients aged 20 to 35 years, with an average age of 27 years, were included in this study. Follow-up was conducted 2 months after the operation. All incisions healed by first intention with no sawtooth-like deformity at the incision margin, and had natural appearance. Patients felt that the bilateral labia minora and clitoral foreskin were completely symmetrical in 3 cases, basically symmetrical in 12 cases, and partially asymmetric in 2 cases. These 2 cases of partial asymmetry did not require further surgical repair. In all 17 patients, the frictional discomfort was completely resolved, and the labia minora and clitoral foreskin were easier to clean. The patients were very satisfied with the appearance in 5 cases, satisfied in 10 cases, and dissatisfied in 2 case. There were 15 patients with previous sexual life experience, of which 10 patients had improved sexual satisfaction, and 5 patients had no change in sexual satisfaction after the operation.Conclusions:Through the divisional design, wedge resection and edge resection are performed in the composite reduction labiaplasty, which can solve the friction and discomfort caused by the hyperplasia of labia minora and clitoris prepuce in a single operation, and achieve better aesthetic results at the same time.
9.Application effect of divisional design in composite reduction labiaplasty
Siya ZHANG ; Fengchao CHEN ; Fengyong LI
Chinese Journal of Plastic Surgery 2022;38(8):881-886
Objective:To explore the clinical effect of the composite reduction labiaplasty by divisional design.Methods:From January 2020 to February 2022, the clinical data of patients with complex labia minora and clitoris prepuce hypertrophy who were treated in the Medical Cosmetic Center of Beijing Friendship Hospital Affiliated to Capital Medical University were collected and analysed. The inner side of their labia minora showed no chalasis in the vertical direction, but the outer side were slack with folds, accompanied by clitoris prepuce hyperplasia. We adopted the composite reduction labiaplasty by divisional design. The outer side of the labia minora and the clitoral prepuce were considered as a whole, and a wedge-shaped incision line was designed to remove the excess tissue in the vertical direction. On this basis, an arc was projected on the inner side of the labia minora to form an arcuate incision line on the inner side. The composite reduction labiaplasty was performed with the combination of wedge resection and edge resection. The postoperative follow-up observations included: postoperative complications, the symmetry of the labia minora and clitoris prepuce, the improvement of frictional discomfort, the cleanliness of the labia minora and the clitoris prepuce, and the patient's satisfaction with the shape of the labia minora and clitoris prepuce. For patients with sexual experience, follow-up content also includes changes in sexual satisfaction.Results:A total of 17 female patients aged 20 to 35 years, with an average age of 27 years, were included in this study. Follow-up was conducted 2 months after the operation. All incisions healed by first intention with no sawtooth-like deformity at the incision margin, and had natural appearance. Patients felt that the bilateral labia minora and clitoral foreskin were completely symmetrical in 3 cases, basically symmetrical in 12 cases, and partially asymmetric in 2 cases. These 2 cases of partial asymmetry did not require further surgical repair. In all 17 patients, the frictional discomfort was completely resolved, and the labia minora and clitoral foreskin were easier to clean. The patients were very satisfied with the appearance in 5 cases, satisfied in 10 cases, and dissatisfied in 2 case. There were 15 patients with previous sexual life experience, of which 10 patients had improved sexual satisfaction, and 5 patients had no change in sexual satisfaction after the operation.Conclusions:Through the divisional design, wedge resection and edge resection are performed in the composite reduction labiaplasty, which can solve the friction and discomfort caused by the hyperplasia of labia minora and clitoris prepuce in a single operation, and achieve better aesthetic results at the same time.
10.Application effect of divisional design in composite reduction labiaplasty
Siya ZHANG ; Fengchao CHEN ; Fengyong LI
Chinese Journal of Plastic Surgery 2022;38(8):881-886
Objective:To explore the clinical effect of the composite reduction labiaplasty by divisional design.Methods:From January 2020 to February 2022, the clinical data of patients with complex labia minora and clitoris prepuce hypertrophy who were treated in the Medical Cosmetic Center of Beijing Friendship Hospital Affiliated to Capital Medical University were collected and analysed. The inner side of their labia minora showed no chalasis in the vertical direction, but the outer side were slack with folds, accompanied by clitoris prepuce hyperplasia. We adopted the composite reduction labiaplasty by divisional design. The outer side of the labia minora and the clitoral prepuce were considered as a whole, and a wedge-shaped incision line was designed to remove the excess tissue in the vertical direction. On this basis, an arc was projected on the inner side of the labia minora to form an arcuate incision line on the inner side. The composite reduction labiaplasty was performed with the combination of wedge resection and edge resection. The postoperative follow-up observations included: postoperative complications, the symmetry of the labia minora and clitoris prepuce, the improvement of frictional discomfort, the cleanliness of the labia minora and the clitoris prepuce, and the patient's satisfaction with the shape of the labia minora and clitoris prepuce. For patients with sexual experience, follow-up content also includes changes in sexual satisfaction.Results:A total of 17 female patients aged 20 to 35 years, with an average age of 27 years, were included in this study. Follow-up was conducted 2 months after the operation. All incisions healed by first intention with no sawtooth-like deformity at the incision margin, and had natural appearance. Patients felt that the bilateral labia minora and clitoral foreskin were completely symmetrical in 3 cases, basically symmetrical in 12 cases, and partially asymmetric in 2 cases. These 2 cases of partial asymmetry did not require further surgical repair. In all 17 patients, the frictional discomfort was completely resolved, and the labia minora and clitoral foreskin were easier to clean. The patients were very satisfied with the appearance in 5 cases, satisfied in 10 cases, and dissatisfied in 2 case. There were 15 patients with previous sexual life experience, of which 10 patients had improved sexual satisfaction, and 5 patients had no change in sexual satisfaction after the operation.Conclusions:Through the divisional design, wedge resection and edge resection are performed in the composite reduction labiaplasty, which can solve the friction and discomfort caused by the hyperplasia of labia minora and clitoris prepuce in a single operation, and achieve better aesthetic results at the same time.

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