1.Antidepressant effects and mechanisms of Wuhua herbal tea in a rat model of chronic unpredictable mild stress
Zhiwei Qi ; Lingling Qin ; Ming Gao ; Ruifeng Yang ; Congyi Liu ; Ning Wang ; Wenjing Li ; Yongxin Huang ; Lili Wu ; Tonghua Liu
Journal of Traditional Chinese Medical Sciences 2025;2025(3):364-374
ObjectiveTo evaluate the effects of Wuhua herbal tea on chronic unpredictable mild stress (CUMS)-induced depression and explore its mechanism of action in combating depression.MethodsWe tested the antidepressant effects of Wuhua herbal tea in a rat model of CUMS-induced depression using fluoxetine as a positive control. The rats were divided into four groups: control group, model group, fluoxetine group, and Wuhua herbal tea group. The rats underwent body weight measurements, sucrose preference test, and open-field test. Enzyme-linked immunosorbent assay kits were used to detect the serum levels of serotonin, dopamine, adrenocorticotropic hormone (ACTH), corticosterone, norepinephrine, and interleukin-6. Intergroup comparisons and detection of brain-derived neurotrophic factor (BDNF), cAMP-response element binding protein (CREB), Janus kinase 2 (JAK2), and signal transducer and activator of transcription 3 (STAT3) mRNA expression in the hippocampus were performed using RT-PCR. Immunohistochemistry was used to identify the expression of phosphorylated JAK2 (p-JAK2) and phosphorylated STAT3 (p-STAT3) proteins in hippocampal paraffin sections of CUMS rats.ResultsCompared with the control group, the model group rats had depressive tendencies, exhibiting low vitality and interest in various behavioral indicators which were signs of despair. The Wuhua herbal tea group statistically increased the levels of serotonin and dopamine in the serum of CUMS rats to varying degrees (P = .015 and P = .002); reduced serum levels of ACTH, corticosterone, norepinephrine, and interleukin-6 (all P .05); and decreased mRNA expression of BDNF, CREB, JAK2, and STAT3 in the hippocampus (all P .05); and decreased p-STAT3 protein levels (P = .006).ConclusionWuhua herbal tea shows antidepressant potential in CUMS rats by modulating the HPA axis and inhibiting JAK2-STAT3 overactivation, alleviating neuroinflammation. It also restores BDNF-CREB pathway function, reducing depressive symptoms.
2.Effect and Mechanism of Angelicae Sinensis Radix-Polygonati Rhizoma Herb Pair in Treatment of Simple Obesity
Wenjing LI ; Zhongyu WANG ; Yongxin HUANG ; Jingjing XU ; Ying DING ; You WU ; Zhiwei QI ; Ruifeng YANG ; Xiaotong YANG ; Lili WU ; Lingling QIN ; Tonghua LIU
Chinese Journal of Experimental Traditional Medical Formulae 2025;31(11):70-79
ObjectiveTo preliminarily explore the active components and target pathways of Angelicae Sinensis Radix-Polygonati Rhizoma (ASR-PR) herb pair in the treatment of simple obesity through network pharmacology and molecular docking, and to verify and investigate its mechanism of action via animal experiments. MethodsThe chemical constituents and targets of ASR and PR were predicted using the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform (TCMSP). Targets related to simple obesity were identified by retrieving the GeneCards, Online Mendelian Inheritance in Man (OMIM), Pharmacogenomics Knowledgebase (PharmGKB), and DisGeNET databases. The intersection of drug and disease targets was used to construct an active component-target network using Cytoscape software. This network was imported into the STRING database to construct a protein-protein interaction (PPI) network, and topological analysis was conducted to identify core genes. Gene Ontology (GO) analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis and mapping were performed using the DAVID database and the Microbioinformatics platform. AutoDock 1.5.7 software was used to perform molecular docking between the top five active components and core targets. An animal model of simple obesity was established by feeding C57BL/6J mice a high-fat diet. The mice were administered ASR (2.06 g·kg-1), PR (2.06 g·kg-1), or ASR-PR (4.11 g·kg-1) for 10 weeks, while the model group received an equal volume of purified water by gavage. After the administration period, the mice were sacrificed to measure body fat weight and serum levels of total cholesterol (TC), triglycerides (TG), high-density lipoprotein (HDL), and low-density lipoprotein (LDL). Hematoxylin-eosin (HE) staining was used to observe histopathological sections of liver and adipose tissue. Serum levels of leptin, interleukin-6 (IL-6), and tumor necrosis factor-α (TNF-α) were determined by enzyme-linked immunosorbent assay (ELISA), and the mRNA expression levels of epidermal growth factor receptor (EGFR) and signal transducer and activator of transcription 3 (STAT3) in liver tissue were detected by real-time quantitative polymerase chain reaction (Real-time PCR). ResultsNetwork pharmacology and molecular docking results indicated that the treatment of simple obesity by ASR-PR may involve the regulation of protein expression of core targets EGFR and STAT3 by its main components MOL009760 (Siberian glycoside A_qt), MOL003889 (methyl protodioscin_qt), MOL009766 (resveratrol), MOL006331 (4′,5-dihydroxyflavone), and MOL004941 (baicalin), thereby modulating the PI3K/Akt and JAK/STAT signaling pathways. The animal experiment results showed that compared with the normal group, the model group had significantly increased body weight, body fat weight, and serum levels of TG, TC, TNF-α, IL-6, and leptin (P<0.01). EGFR mRNA expression was significantly elevated (P<0.05), while STAT3 mRNA expression was significantly decreased (P<0.01). Histological analysis revealed disordered hepatic architecture in the model group, with pronounced lipid vacuoles, cytoplasmic loosening, lipid accumulation, and steatosis. Adipocytes in white adipose tissue (WAT) and brown adipose tissue (BAT) of the model group exhibited markedly increased diameters, reduced cell counts per unit area, and irregular morphology. Compared with the model group, the ASR-PR group significantly reduced body weight, body fat weight, serum TC, IL-6, TNF-α, leptin levels, and EGFR mRNA expression (P<0.01). TG levels were also significantly decreased (P<0.05), while STAT3 mRNA expression was significantly increased (P<0.01). Histopathological improvements included reduced size and number of hepatic lipid vacuoles and restoration of liver cell morphology toward that of the normal group. The diameter of adipocytes significantly decreased, and the number of adipocytes per unit area increased. ConclusionASR-PR may regulate the expression of key target proteins such as EGFR and STAT3 via its core active components, modulate the PI3K/Akt and JAK/STAT signaling pathways, repair damaged liver and adipose tissues, and thereby alleviate the progression of obesity in mice.
3.Effect and Mechanism of Angelicae Sinensis Radix-Polygonati Rhizoma Herb Pair in Treatment of Simple Obesity
Wenjing LI ; Zhongyu WANG ; Yongxin HUANG ; Jingjing XU ; Ying DING ; You WU ; Zhiwei QI ; Ruifeng YANG ; Xiaotong YANG ; Lili WU ; Lingling QIN ; Tonghua LIU
Chinese Journal of Experimental Traditional Medical Formulae 2025;31(11):70-79
ObjectiveTo preliminarily explore the active components and target pathways of Angelicae Sinensis Radix-Polygonati Rhizoma (ASR-PR) herb pair in the treatment of simple obesity through network pharmacology and molecular docking, and to verify and investigate its mechanism of action via animal experiments. MethodsThe chemical constituents and targets of ASR and PR were predicted using the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform (TCMSP). Targets related to simple obesity were identified by retrieving the GeneCards, Online Mendelian Inheritance in Man (OMIM), Pharmacogenomics Knowledgebase (PharmGKB), and DisGeNET databases. The intersection of drug and disease targets was used to construct an active component-target network using Cytoscape software. This network was imported into the STRING database to construct a protein-protein interaction (PPI) network, and topological analysis was conducted to identify core genes. Gene Ontology (GO) analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis and mapping were performed using the DAVID database and the Microbioinformatics platform. AutoDock 1.5.7 software was used to perform molecular docking between the top five active components and core targets. An animal model of simple obesity was established by feeding C57BL/6J mice a high-fat diet. The mice were administered ASR (2.06 g·kg-1), PR (2.06 g·kg-1), or ASR-PR (4.11 g·kg-1) for 10 weeks, while the model group received an equal volume of purified water by gavage. After the administration period, the mice were sacrificed to measure body fat weight and serum levels of total cholesterol (TC), triglycerides (TG), high-density lipoprotein (HDL), and low-density lipoprotein (LDL). Hematoxylin-eosin (HE) staining was used to observe histopathological sections of liver and adipose tissue. Serum levels of leptin, interleukin-6 (IL-6), and tumor necrosis factor-α (TNF-α) were determined by enzyme-linked immunosorbent assay (ELISA), and the mRNA expression levels of epidermal growth factor receptor (EGFR) and signal transducer and activator of transcription 3 (STAT3) in liver tissue were detected by real-time quantitative polymerase chain reaction (Real-time PCR). ResultsNetwork pharmacology and molecular docking results indicated that the treatment of simple obesity by ASR-PR may involve the regulation of protein expression of core targets EGFR and STAT3 by its main components MOL009760 (Siberian glycoside A_qt), MOL003889 (methyl protodioscin_qt), MOL009766 (resveratrol), MOL006331 (4′,5-dihydroxyflavone), and MOL004941 (baicalin), thereby modulating the PI3K/Akt and JAK/STAT signaling pathways. The animal experiment results showed that compared with the normal group, the model group had significantly increased body weight, body fat weight, and serum levels of TG, TC, TNF-α, IL-6, and leptin (P<0.01). EGFR mRNA expression was significantly elevated (P<0.05), while STAT3 mRNA expression was significantly decreased (P<0.01). Histological analysis revealed disordered hepatic architecture in the model group, with pronounced lipid vacuoles, cytoplasmic loosening, lipid accumulation, and steatosis. Adipocytes in white adipose tissue (WAT) and brown adipose tissue (BAT) of the model group exhibited markedly increased diameters, reduced cell counts per unit area, and irregular morphology. Compared with the model group, the ASR-PR group significantly reduced body weight, body fat weight, serum TC, IL-6, TNF-α, leptin levels, and EGFR mRNA expression (P<0.01). TG levels were also significantly decreased (P<0.05), while STAT3 mRNA expression was significantly increased (P<0.01). Histopathological improvements included reduced size and number of hepatic lipid vacuoles and restoration of liver cell morphology toward that of the normal group. The diameter of adipocytes significantly decreased, and the number of adipocytes per unit area increased. ConclusionASR-PR may regulate the expression of key target proteins such as EGFR and STAT3 via its core active components, modulate the PI3K/Akt and JAK/STAT signaling pathways, repair damaged liver and adipose tissues, and thereby alleviate the progression of obesity in mice.
4.Action mechanism of intrathecal transplantation of human umbilical cord mesenchymal stem cell-derived exosomes for repair of spinal cord injury under neuroendoscopy
Yitong ZHENG ; Yongxin WANG ; Wen LIU ; AMUJITE ; Hu QIN
Chinese Journal of Tissue Engineering Research 2025;29(36):7743-7751
BACKGROUND:Human umbilical cord mesenchymal stem cell-derived exosomes were found to be effective in promoting neural repair in spinal cord injury.OBJECTIVE:To investigate whether exosomes derived from human umbilical cord mesenchymal stem cells are able to attenuate neuroinflammation and promote recovery of motor function by promoting polarization of microglia toward the M2 type.METHODS:Totally 48 SD rats were randomly divided into a sham operation group,a model group,and an exosome group(n=16 per group).A rat spinal cord injury model was established using the modified Allen method.The exosome group was injected with 20 μL of human umbilical cord mesenchymal stem cell-derived exosomes intrathecally via neuroendoscopy 24 hours after injury.At 3,7,14,and 21 days after modeling,the recovery of the motor function of the hind limbs of the rats was assessed by BBB scoring method combined with Rivlin's slant plate test.The damage of spinal cord tissues was detected by using hematoxylin-eosin staining and Nissl staining.The expression levels of brain-derived neurotrophic factor and vascular endothelial growth factor A proteins were detected by western blot assay.The expression proportion of M1-type markers(inducible nitric oxide synthase)and M2 markers(arginase-1)in the spinal cord tissues was detected by immunofluorescence method.qRT-PCR and western blot assay were used to detect the expression levels of inducible nitric oxide synthase and arginase-1 in spinal cord tissues.ELISA was utilized to detect the levels of pro-inflammatory factors(tumor necrosis factor α,interleukin 1β,and interleukin 6)and anti-inflammatory factors(interleukin 10)levels in spinal cord tissues.RESULTS AND CONCLUSION:(1)At 3,7,and 14 days postoperatively,the BBB scores of the exosome group were better than those of the model group(P<0.05).The angles of the Rivlin slanting plate experiments of the exosome group were significantly higher than those of the model group at 7 and 14 days postoperatively(P<0.05).The results of hematoxylin-eosin staining and Nissl staining indicated that the spinal cord tissues and nerve injuries of the exosome group were reduced in comparison with those of the model group,and the levels of brain-derived neurotrophic factor and vascular endothelial growth factor A in spinal cord tissues of the exosome group were higher than those in the model group at 7 days postoperatively(P<0.05).(2)Immunofluorescence experiments showed that the number of inducible nitric oxide synthase-positive microglial cells in the lesion area of the exosome group was significantly reduced and the level of Arg1-positive microglial cells increased in the lesion area of the exosome group compared with the model group at 7 days postoperatively(P<0.05).qRT-PCR and western blot assay also confirmed the results of immunofluorescence experiments.(3)The secretion of pro-inflammatory factors tumor necrosis factor α,interleukin 1β,and interleukin 6 in spinal cord tissues of the exosome group was reduced compared with the model group(P<0.05),whereas the secretion of the inflammation-suppressing factor interleukin 10 was increased compared with the model group(P<0.05).These findings conclude that human umbilical cord mesenchymal stem cell-derived exosomes could promote the polarization of microglial cells from the M1 to the M2 type and decrease the release of pro-inflammatory factors,thereby reducing the secondary damage of neuroinflammation in spinal cord injury.
5.Action mechanism of intrathecal transplantation of human umbilical cord mesenchymal stem cell-derived exosomes for repair of spinal cord injury under neuroendoscopy
Yitong ZHENG ; Yongxin WANG ; Wen LIU ; AMUJITE ; Hu QIN
Chinese Journal of Tissue Engineering Research 2025;29(36):7743-7751
BACKGROUND:Human umbilical cord mesenchymal stem cell-derived exosomes were found to be effective in promoting neural repair in spinal cord injury.OBJECTIVE:To investigate whether exosomes derived from human umbilical cord mesenchymal stem cells are able to attenuate neuroinflammation and promote recovery of motor function by promoting polarization of microglia toward the M2 type.METHODS:Totally 48 SD rats were randomly divided into a sham operation group,a model group,and an exosome group(n=16 per group).A rat spinal cord injury model was established using the modified Allen method.The exosome group was injected with 20 μL of human umbilical cord mesenchymal stem cell-derived exosomes intrathecally via neuroendoscopy 24 hours after injury.At 3,7,14,and 21 days after modeling,the recovery of the motor function of the hind limbs of the rats was assessed by BBB scoring method combined with Rivlin's slant plate test.The damage of spinal cord tissues was detected by using hematoxylin-eosin staining and Nissl staining.The expression levels of brain-derived neurotrophic factor and vascular endothelial growth factor A proteins were detected by western blot assay.The expression proportion of M1-type markers(inducible nitric oxide synthase)and M2 markers(arginase-1)in the spinal cord tissues was detected by immunofluorescence method.qRT-PCR and western blot assay were used to detect the expression levels of inducible nitric oxide synthase and arginase-1 in spinal cord tissues.ELISA was utilized to detect the levels of pro-inflammatory factors(tumor necrosis factor α,interleukin 1β,and interleukin 6)and anti-inflammatory factors(interleukin 10)levels in spinal cord tissues.RESULTS AND CONCLUSION:(1)At 3,7,and 14 days postoperatively,the BBB scores of the exosome group were better than those of the model group(P<0.05).The angles of the Rivlin slanting plate experiments of the exosome group were significantly higher than those of the model group at 7 and 14 days postoperatively(P<0.05).The results of hematoxylin-eosin staining and Nissl staining indicated that the spinal cord tissues and nerve injuries of the exosome group were reduced in comparison with those of the model group,and the levels of brain-derived neurotrophic factor and vascular endothelial growth factor A in spinal cord tissues of the exosome group were higher than those in the model group at 7 days postoperatively(P<0.05).(2)Immunofluorescence experiments showed that the number of inducible nitric oxide synthase-positive microglial cells in the lesion area of the exosome group was significantly reduced and the level of Arg1-positive microglial cells increased in the lesion area of the exosome group compared with the model group at 7 days postoperatively(P<0.05).qRT-PCR and western blot assay also confirmed the results of immunofluorescence experiments.(3)The secretion of pro-inflammatory factors tumor necrosis factor α,interleukin 1β,and interleukin 6 in spinal cord tissues of the exosome group was reduced compared with the model group(P<0.05),whereas the secretion of the inflammation-suppressing factor interleukin 10 was increased compared with the model group(P<0.05).These findings conclude that human umbilical cord mesenchymal stem cell-derived exosomes could promote the polarization of microglial cells from the M1 to the M2 type and decrease the release of pro-inflammatory factors,thereby reducing the secondary damage of neuroinflammation in spinal cord injury.
6.Multimodal imaging for diagnosis of cardiac space-occupying lesions
Yan LI ; Qingguo WANG ; Liyuan WANG ; Wenxiu LI ; Wenxu LIU ; Yongchao NIU ; Zhen JIA ; Huiping ZHAI ; Min LIU ; Jiali XU ; Yongxin TIE ; Dandan LI ; Jinxia QIN
Chinese Journal of Interventional Imaging and Therapy 2023;20(12):745-748
Objective To observe the value of multimodal imaging for diagnosis of cardiac space-occupying lesions.Methods Data of 70 patients with cardiac space-occupying lesions who underwent echocardiography and cardiac CT(CCT)were retrospectively analyzed,among them 35 also underwent cardiac MRI(CMRI).The value of multimodal imaging for diagnosis of cardiac space-occupying lesions were explored according to the results of surgical pathology or clinical diagnosis.Results Among 70 cases,benign tumors were confirmed by surgical pathology in 43 cases,while malignant tumors were confirmed by surgical pathology in 3 cases and clinically diagnosed in 1 case.Meanwhile,non-tumor-occupying lesions were clinically diagnosed in 23 cases,all obviously shrunken after treatments.Among 70 cases,echocardiography correctly diagnosed 57 cases,misdiagnosed 8 cases and unclearly diagnosed 5 cases,with diagnostic accuracy rate of 81.43%(57/70).CCT correctly diagnosed 63 cases,misdiagnosed 4 cases but missed 3 cases,with diagnostic accuracy rate of 90.00%(63/70).CMRI outcomes in all 35 cases were consistent with surgical pathologic results,with diagnostic accuracy rate of 100%(35/35).Conclusion Multimodal imaging might provide objective evidences for diagnosis and treatment of cardiac space-occupying lesions.
7.Advances in the application of non-contrast CT radiomics and machine learning in the diagnosis and treat-ment process of hypertensive Intracerebral hemorrhage
Yanwen JIANG ; Hu QIN ; Zhaofu LENG ; Aikel-Amu PAZILIYA ; Yongxin WANG
Chinese Journal of Nervous and Mental Diseases 2023;49(10):609-614
Hypertensive intracerebral hemorrhage(HICH)is a disease with a rapid onset,rapid progression,high mortality rate,and long-term impact on the ability to function.Non-contrast agent-based CT(NCCT)is a common method for evaluating and identifying HICH.Recent radiomics in image processing and machine learning(ML)have enabled the extraction of high-dimensional feature information from medical images,which can be used to rapidly and accurately diagnose HICH and predict its course of disease.The paper describes the application of radiomics and ML techniques in HICH diagnosis and treatment,and identifies possible directions for future research.
8.Research progress on prostate-specific membrane antigen ligand positron emission tomography imaging of prostate cancer.
Yuqin LI ; Bin LIU ; Yongxin YUAN ; Wei QIN
Journal of Biomedical Engineering 2022;39(6):1263-1268
Prostate cancer is the most common malignant tumor in male urinary system, and the morbidity and mortality rate are increasing year by year. Traditional imaging examinations have some limitations in the diagnosis of prostate cancer, and the advent of molecular imaging probes and imaging technology have provided new ideas for the integration of diagnosis and treatment of prostate cancer. In recent years, prostate-specific membrane antigen (PSMA) has attracted much attention as a target for imaging and treatment of prostate cancer. PSMA ligand positron emission tomography (PET) has important reference value in the diagnosis, initial staging, detection of biochemical recurrence and metastasis, clinical decision-making guidance and efficacy evaluation of prostate cancer. This article briefly reviews the clinical research and application progress on PSMA ligand PET imaging in prostate cancer in recent years, so as to raise the efficiency of clinical applications.
Male
;
Humans
;
Prostate/pathology*
;
Ligands
;
Positron Emission Tomography Computed Tomography/methods*
;
Prostatic Neoplasms/diagnostic imaging*
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Positron-Emission Tomography
9.Neuroimaging findings, pathological features and surgical efficacy of adult gangliogliomas
Muertizha MAMUTIJIANG ; Yongxin WANG ; Yandong FAN ; Hu QIN ; Qian MA
Chinese Journal of Neuromedicine 2022;21(9):929-933
Objective:To investigate the clinical characteristics, pathological features and surgical efficacy of adult gangliogliomas.Methods:Seven patients with gangliogliomas underwent surgical treatment in our hospital from August 2010 to December 2021, were chosen; their clinical data were retrospectively analyzed, and the CT and MRI manifestations and histopathological features of gangliogliomas and surgical efficacy of these patients were concluded.Results:In these 7 patients, solid-mass type was identified in 1 patient, cystic-solid mixed type in 4 patients, and diffuse infiltrating type in 2 patients. The solid part showed slightly low or equal density on CT, and mostly showed slightly low signal on T1, slightly high signal on T2, high or slightly high signal on T2 FLAIR, and equisignal or slightly low signal on DWI of MRI. Immunohistochemical staining showed that in the tumor specimens, glial cell components were positive for glial fibrillary acidic protein, oligodendrocyte transcription factor and S-100 protein, and ganglion cell components were positive for neuronal nuclear antigen and synaptophysin. Gross total resection was achieved in 5 patients, subtotal resection in 1 patient, and partial resection in 1 patient; gangliogliomas without total resection were diffuse infiltrative type. The median Karnofsky performance status scores were 80. There was no death during the follow-up period of 7 months-11 years.Conclusions:Adult gangliogliomas are mostly cystic and solid lesions with clear boundary on imaging, and the histopathological characteristics of mixed neoplastic ganglion cells and glial cells are the main basis for their diagnosis. The surgical efficacy is usually good, but the diffuse infiltrating type is difficult to achieve total resection.
10.Neuroimaging findings, pathological features and surgical efficacy of adult gangliogliomas
Muertizha MAMUTIJIANG ; Yongxin WANG ; Yandong FAN ; Hu QIN ; Qian MA
Chinese Journal of Neuromedicine 2022;21(9):929-933
Objective:To investigate the clinical characteristics, pathological features and surgical efficacy of adult gangliogliomas.Methods:Seven patients with gangliogliomas underwent surgical treatment in our hospital from August 2010 to December 2021, were chosen; their clinical data were retrospectively analyzed, and the CT and MRI manifestations and histopathological features of gangliogliomas and surgical efficacy of these patients were concluded.Results:In these 7 patients, solid-mass type was identified in 1 patient, cystic-solid mixed type in 4 patients, and diffuse infiltrating type in 2 patients. The solid part showed slightly low or equal density on CT, and mostly showed slightly low signal on T1, slightly high signal on T2, high or slightly high signal on T2 FLAIR, and equisignal or slightly low signal on DWI of MRI. Immunohistochemical staining showed that in the tumor specimens, glial cell components were positive for glial fibrillary acidic protein, oligodendrocyte transcription factor and S-100 protein, and ganglion cell components were positive for neuronal nuclear antigen and synaptophysin. Gross total resection was achieved in 5 patients, subtotal resection in 1 patient, and partial resection in 1 patient; gangliogliomas without total resection were diffuse infiltrative type. The median Karnofsky performance status scores were 80. There was no death during the follow-up period of 7 months-11 years.Conclusions:Adult gangliogliomas are mostly cystic and solid lesions with clear boundary on imaging, and the histopathological characteristics of mixed neoplastic ganglion cells and glial cells are the main basis for their diagnosis. The surgical efficacy is usually good, but the diffuse infiltrating type is difficult to achieve total resection.


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