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Platycodon grandiflorum (Jacq.) A. DC. is a famous medicinal plant commonly used in East Asia. Triterpene saponins isolated from P. grandiflorum are the main biologically active compounds, among which polygalacin D (PGD) has been reported to be an anti-tumor agent. However, its anti-tumor mechanism against hepatocellular carcinoma is unknown. This study aimed to explore the inhibitory effect of PGD in hepatocellular carcinoma cells and related mechanisms of action. We found that PGD exerted significant inhibitory effect on hepatocellular carcinoma cells through apoptosis and autophagy. Analysis of the expression of apoptosis-related proteins and autophagy-related proteins revealed that this phenomenon was attributed to the mitochondrial apoptosis and mitophagy pathways. Subsequently, using specific inhibitors, we found that apoptosis and autophagy had mutually reinforcing effects. In addition, further analysis of autophagy showed that PGD induced mitophagy by increasing BCL2 interacting protein 3 like (BNIP3L) levels.In vivo experiments demonstrated that PGD significantly inhibited tumor growth and increased the levels of apoptosis and autophagy in tumors. Overall, our findings showed that PGD induced cell death of hepatocellular carcinoma cells primarily through mitochondrial apoptosis and mitophagy pathways. Therefore, PGD can be used as an apoptosis and autophagy agonist in the research and development of antitumor agents.
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Humans , Mitophagy , Carcinoma, Hepatocellular/pathology , Liver Neoplasms/pathology , Cell Line , Autophagy , Apoptosis , Membrane Proteins , Proto-Oncogene Proteins/genetics , Tumor Suppressor Proteins/pharmacologyABSTRACT
Objective To investigate the association of five noninvasive diagnostic methods for liver cirrhosis, i.e., liver stiffness measurement (LSM) on FibroScan, aspartate aminotransferase-to-platelet ratio index (APRI), fibrosis-4 (FIB-4), gamma-glutamyl transpeptidase-to-platelet ratio (GPR), and red blood cell distribution width-to-platelet ratio (RPR), with traditional Chinese medicine (TCM) syndrome types in patients with compensated hepatitis B cirrhosis. Methods A retrospective analysis was performed for the clinical data of 327 patients who were diagnosed with compensated hepatitis B cirrhosis in The First Affiliated Hospital of Henan University of Chinese Medicine from January 2017 to January 2020, and based on their TCM syndrome type, they were divided into liver depression and spleen deficiency group with 160 patients, liver-gallbladder damp-heat syndrome group with 84 patients, liver-kidney Yin deficiency group with 13 patients, spleen-kidney Yang deficiency group with 5 patients, and blood stasis obstructing the collaterals group with 65 patients. Related data were collected, including clinical data, routine blood test results, liver function, LSM, and color Doppler ultrasound findings of liver, gallbladder, spleen, and pancreas. TCM syndrome differentiation was performed, and the models of APRI, FIB-4, GPR, and RPR were established. A one-way analysis of variance was used for comparison of normally distributed continuous data between multiple groups, and the least significant difference t -test was used for further comparison between two groups; the multiple independent samples Kruskal-Wallis H rank sum test was used for comparison of non-normally distributed continuous data between multiple groups, and the one- way Kruskal-Wallis ANOVA (k-sample) was used for multiple comparison; the binary logistic regression analysis was used to investigate the association between TCM syndrome types and non-invasive diagnosis of liver cirrhosis; the receiver operating characteristic (ROC) curve was used to evaluate the diagnostic capability of five noninvasive methods for predicting TCM syndrome type in compensated hepatitis B cirrhosis. Results The logistic regression analysis showed that in the liver-gallbladder damp-heat syndrome group, aspartate aminotransferase OR =1.981, 95% CI : 1.8225-2.139, P < 0.05), and LSM ( OR =2.002, 95% CI : 1.840-2.160, P < 0.05) were influencing factors for compensated hepatitis B cirrhosis; in the liver depression and spleen deficiency group, portal vein width ( OR =4.402, 95% CI : 4.050-4.754, P < 0.05), LSM ( OR =3.901, 95% CI : 3.589-4.213, P < 0.05), APRI ( OR =1.891, 95% CI : 1.740-2.042, P < 0.05), and FIB-4 ( OR =1.845, 95% CI : 1.697-1.993, P < 0.05) were influencing factors for compensated hepatitis B cirrhosis; in the blood stasis obstructing the collaterals group, LSM ( OR =2.465, 95% CI : 2.268-2.662, P < 0.05), APRI ( OR =1.298, 95% CI : 1.194-1.402, P < 0.05), and FIB-4 ( OR =1.849, 95% CI : 1.701-1.997, P < 0.05) were influencing factors for compensated hepatitis B cirrhosis. The ROC curve analysis showed that LSM and RPR had a significantly better diagnostic value than the other methods in evaluating liver-gallbladder damp-heat syndrome, and LSM and FIB-4 had a significantly better diagnostic value than the other methods in evaluating liver depression and spleen deficiency; all five noninvasive diagnostic methods had a good value in evaluating the syndrome of blood stasis obstructing the collaterals. Conclusion The five noninvasive diagnostic methods have their own advantages in evaluating different syndrome types, which provide a reference for the diagnosis of TCM syndrome types in patients with compensated hepatitis B cirrhosis.
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Objective To investigate the application value of controlled attenuation parameter (CAP) of hepatocyte steatosis measured by FibroScan in the diagnosis and traditional Chinese medicine (TCM) syndrome differentiation of nonalcoholic fatty liver disease (NAFLD). Methods A retrospective analysis was performed for related data of 364 patients with NAFLD who attended The First Affiliated Hospital of Henan University of Traditional Chinese Medicine from January 2017 to December 2019, including basic information (age, sex, and body mass index [BMI]), CAP measured by FibroScan, ultrasound findings of the liver, gallbladder, spleen, and pancreas, liver function parameters, and blood lipid parameters. TCM syndrome differentiation was performed based on the information obtained by four diagnostic methods, and then the patients were divided into liver depression and spleen deficiency group, damp turbidity and stagnation group, damp-heat accumulation group, intermingled phlegm and blood stasis group, and spleen-kidney deficiency group. The association of CAP, color Doppler ultrasound findings, liver function parameters, blood lipid parameters, and BMI with TCM syndrome was analyzed. A one-way analysis of variance was used for comparison of normally distributed continuous data between multiple groups, and the least significant difference t -test was used for further comparison between two groups; the Kruskal-Wallis H rank sum test with multiple sets of independent samples was used for comparison of non-normally distributed continuous data between multiple groups and further comparison between two groups. The chi-square test or Kruskal-Wallis H rank sum test was used for comparison of categorical data between multiple groups and further comparison between two groups. A Spearman's rank correlation analysis was used to investigate the correlation between CAP and ultrasound grading. Results Among the 364 patients with NAFLD, 169 had the syndrome of liver depression and spleen deficiency, 71 had the syndrome of damp turbidity and stagnation, 60 had the syndrome of damp-heat accumulation, 41 had the syndrome of intermingled phlegm and blood stasis, and 23 had the syndrome of spleen-kidney deficiency. There was a significant difference in CAP value between the different syndrome types ( F =14.839, P < 0.001), and further comparison between two groups showed that the spleen-kidney deficiency group and the intermingled phlegm and blood stasis group had a significantly higher CAP value than the liver depression and spleen deficiency group, the damp turbidity and stagnation group, and the damp-heat accumulation group (all P < 0.05). There was a significant difference in ultrasound grading between the different syndrome types ( χ 2 =22.947, P < 0.001); the liver depression and spleen deficiency group mainly had a mild grade (40.2%), the damp turbidity and stagnation group and the damp-heat accumulation group mainly had a moderate grade (53.5% and 53.3%, respectively), and the intermingled phlegm and blood stasis group and the spleen-kidney deficiency group mainly had a severe grade (68.3% and 43.5%, respectively). CAP was positively correlated with the severity of fatty liver ( r =0.431, P < 0.001). The spleen-kidney deficiency group and the intermingled phlegm and blood stasis group had significantly higher levels of alanine aminotransferase, aspartate aminotransferase, gamma-glutamyl transpeptidase, and BMI than the other three groups (all P < 0.001). Conclusion Association is observed between CAP and the TCM syndrome types of NAFLD, and patients with the syndrome of spleen-kidney deficiency and the syndrome of intermingled phlegm and blood stasis have a higher CAP value than those with the other syndrome types. CAP has similar efficiency to color Doppler ultrasound in the diagnosis of NAFLD.
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Nonalcoholic fatty liver disease (NAFLD) is one of the most important liver diseases worldwide. Traditional Chinese medicine has a significant effect in the treatment of NAFLD, possibly by improving lipid metabolism, reducing liver inflammation, regulating intestinal flora, improving innate immunity, and reducing liver fibrosis. This article summarizes the current data on the mechanism of action of traditional Chinese medicine in the treatment of NALFD, so as to provide a reference for clinical application.
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Objective To observe the clinical outcome of modified posterolateral approaches for the treatment of posterolateral tibial plateau fractures. Methods From January 2012 to January 2015,13 patients with posterolateral tibial plateau fractures were identified in the Second Hospital of Changzhou Affiliated to Nan?jing Medical University. All the posterolateral fractures were fixated with a plate. The knee function was evaluated at the last follow?up by the Hospital for Special Surgery( HSS) Score,and the occurrence of postoperative compli?cations were observed. Results Thirteen patients were followed up for an average of 14. 4 months,all patients obtained bony union. There were no significant differences regarding the mean HSS score among 3 months, 6 months and 1 year post?operation((71. 6±1. 5) points, (76. 4±1. 6) points, (83. 2±1. 1) points;P=0. 154) . There were no significant differences regarding the tibial plateau angle and posterior slope angle on radiograph?ies of inside and outsideamong immediate,6 and 12 months postoperation((83. 7±1. 7)°,(84. 3±1. 5)°,(85. 1 ±1. 4)°,(85. 4±1. 5)°;(7. 7±1. 5)°,(7. 7±1. 4)°,(7. 7±1. 3)°,(7. 6±1. 8)°;P=0. 223,0. 191). No com?plications associated with the approach were observed and there was no infection,no malunion or fixation failure either. Conclusion In the treatment of posterolateral tibial plateau fractures,the modified posterolateral approa?ches can result in excellent fracture reduction under direct visualization and allow for posterior buttress plating.
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Objective To compare the clinic effect of the locking compression plate (LCP) fixation and the anatomical plate in treatment of high-energy distal tibial fractures. Methods The study involved 42 patients with high-energy distal tibial fractures treated between May 2003 and May 2009. The anatomical plate group included 24 patients ( 16 males and 8 females, at average age of 39 years), of whom there were 13 patients with type A fractures, five with type B and six with type C according to the AO/ASIF classification. The LCP group included 18 patients ( 15 males and 3 females, at average age of 40 years), of whom there were 11 patients with type A fractures, three with type B and four with type C according to the AO/ASIF classification. All the patients were followed up for 8-17 months. Their functional and radiographic outcomes were collected. The operation time, intra-operative blood loss, X-ray exposure, bone healing time, post-operative complications and therapeutic effects were compared between both groups. Mazur's criteria was used to evaluate the function of the ankle. Results The LCP group was followed up for average 11.6 months and the anatomical plate group for average 14.2 months, which showed fracture healing in all the patients. The bone graft in the anatomical plate group was used more frequently than the LCP group, while the X-ray exposure in the LCP group was much more than that in the anatomical plate group. The operation time, incision size, blood loss, postoperative complications and radiographic bone healing time in the LCP group were significantly less than those in the anatomical plate group. Conclusions Both the LCP and anatomical plate are effective methods for the high energy distal tibial fractures. LCP has advantages of less trauma, quick fracture healing and less complications, is consistent with the biomechanics of internal fixation and hence is an ideal method for the treatment of the high-energy tibial fractures.
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Objective To study methods and effect of granule bone grafting into the vertebral pedicle pyramid under endoscope for treatment of thoracolumbar fractures. Methods There were 26 cases (7 males and 19 females; age range of 32 79 years, average 51.2 years) with thoracolumbar fractures. The fractures included 8 cases (30.8%) of thoracolumbar compression burst fractures with no compression of the spinal cord by broken bone fragments and 18 (69.2%) compression fractures due to senile osteoporosis. Posterior to a preliminary reduction of the lumbar region on the operating table, all cases underwent vaginal vertebral pedicle reduction under endoscope and autogenous or hererogeneous granule bone graft in order to restore the height of the fractured vertebra pyramid. The patients kept in bed for two months postoperatively; meanwhile, the excise for the back muscle was performed. Results The mean follow up period was 3 18 months. Twenty one cases (80.8%) got excellent therapeutic result, four (15.4%) moderate and one (3.8%) poor. (1) The vertebral height recovered average 29%, with mean height loss of 5% through six month follow up. (2) The posterior convex cobb angle of the spine recovered for 10? 20? (mean 13.8?). (3) No lumbago or nerve compression symptoms were found in 21 cases. Conclusions Granule bone graft into vertebra pyramid under endoscope in the treatment of thoracolumbar fractures is a minimally invasive procedure that can enhance the bone capacity of the vertebra, alleviate pain, restore the height of the fractured vertebra pyramid and accelerate bone healing.