BACKGROUND:Mesoporous bioactive glass has great application potential in bone repair due to its excellent biocompatibility and osteoinductive activity.Incorporating therapeutic ions into mesoporous bioactive glass particles can give the material more ideal biological properties.OBJECTIVE:To synthesize copper-doped mesoporous bioactive glass and investigate its in vitro angiogenesis and osteogenic differentiation properties.METHODS:Mesoporous bioactive glass and copper-doped mesoporous bioactive glass were synthesized by microemulsion-assisted sol-gel method.The morphology,structure,composition,and ion release performance of the materials were characterized by scanning electron microscopy,transmission electron microscopy,energy dispersive spectroscopy,and X-ray diffraction.The extracts of mesoporous bioactive glass and copper-doped mesoporous bioactive glass were co-cultured with mouse fibroblasts L929.Biocompatibility of the materials was evaluated by live/dead staining and CCK-8 assay.The extracts of the two materials were co-cultured with human umbilical vein endothelial cells.The angiogenesis-promoting properties of the materials were evaluated by Transwell assay,scratch assay,and CD31 immunofluorescence staining.The extracts of the two materials were co-cultured with mouse bone marrow mesenchymal stem cells.The osteogenic properties of the materials were evaluated by alkaline phosphatase staining(without osteogenic induction solution)and Alizarin red staining(with osteogenic induction solution).RESULTS AND CONCLUSION:(1)The characterization results exhibited that both mesoporous bioactive glass and copper-doped mesoporous bioactive glass presented a tightly packed granular morphology with similar internal mesoporous structures,and copper-doped mesoporous bioactive glass could continuously release copper ions.(2)The live/dead staining and CCK-8 assay results showed that compared with mesoporous bioactive glass,copper-doped mesoporous bioactive glass could promote the proliferation of L929 cells and had good biocompatibility.(3)The results of Transwell assay,scratch assay,and CD31 immunofluorescence staining exhibited that compared with mesoporous bioactive glass,copper-doped mesoporous bioactive glass could promote the migration of human umbilical vein endothelial cells and the expression of CD31 protein,and promote angiogenesis.(4)The results of alkaline phosphatase staining and alizarin red staining demonstrated that the osteogenic performance of copper-doped mesoporous bioactive glass was stronger than that of mesoporous bioactive glass.The results indicate that copper-doped mesoporous bioactive glass has excellent biocompatibility and the potential to promote angiogenesis and bone regeneration.

Purpose To analyze the value of a deep learning(DL)radiomics model based on dynamic contrast-enhanced MRI images in predicting the expression of Ki-67 status in breast cancer.Materials and Methods A retrospective analysis of 152 breast cancer patients confirmed by pathological results at Guangdong Women and Children Hospital,MRI images and clinical pathological data were reviewed,and based on postoperative immunohistochemistry results,the images of the high and low expression groups of Ki-67 were randomly sampled in a ratio of 8∶2 to form a training set of 122 cases and a validation set of 30 cases.Single-factor and multi-factor Logistic regression analyses of clinical data were performed to select independent predictors of breast cancer expressing Ki-67 status.The ResNet-18 model was used as the basic model for DL feature extraction.Hand-crafted radiomic features and DL features were extracted.Eight machine learning models were constructed based on clinical features,hand-crafted radiomic features,DL features,and their combinations.The area under the receiver operating characteristic curve was used to evaluate the predictive performance of the models,and the best model was determined as the output model.Results The progesterone receptor status(OR=0.764,P=0.040)and human epidermal growth factor receptor-2 status(OR=1.187,P=0.046)were independent clinical predictors of breast cancer expressing Ki-67 status.The combined feature models demonstrated superior performance over the individual feature models,and the support vector machine algorithm had the highest prediction performance in the validation set,with an area under the curve of 0.847.Conclusion The DL radiomics model based on dynamic contrast-enhanced MRI images can effectively predict the expression of Ki-67 status in breast cancer.The support vector machine algorithm combined with feature model is the best,which can help the clinical diagnosis and treatment of breast cancer and prognosis evaluation.

Purpose To analyze the value of a deep learning(DL)radiomics model based on dynamic contrast-enhanced MRI images in predicting the expression of Ki-67 status in breast cancer.Materials and Methods A retrospective analysis of 152 breast cancer patients confirmed by pathological results at Guangdong Women and Children Hospital,MRI images and clinical pathological data were reviewed,and based on postoperative immunohistochemistry results,the images of the high and low expression groups of Ki-67 were randomly sampled in a ratio of 8∶2 to form a training set of 122 cases and a validation set of 30 cases.Single-factor and multi-factor Logistic regression analyses of clinical data were performed to select independent predictors of breast cancer expressing Ki-67 status.The ResNet-18 model was used as the basic model for DL feature extraction.Hand-crafted radiomic features and DL features were extracted.Eight machine learning models were constructed based on clinical features,hand-crafted radiomic features,DL features,and their combinations.The area under the receiver operating characteristic curve was used to evaluate the predictive performance of the models,and the best model was determined as the output model.Results The progesterone receptor status(OR=0.764,P=0.040)and human epidermal growth factor receptor-2 status(OR=1.187,P=0.046)were independent clinical predictors of breast cancer expressing Ki-67 status.The combined feature models demonstrated superior performance over the individual feature models,and the support vector machine algorithm had the highest prediction performance in the validation set,with an area under the curve of 0.847.Conclusion The DL radiomics model based on dynamic contrast-enhanced MRI images can effectively predict the expression of Ki-67 status in breast cancer.The support vector machine algorithm combined with feature model is the best,which can help the clinical diagnosis and treatment of breast cancer and prognosis evaluation.

Objective:To evaluate the efficacy of lamb′s tripe extract and vitamin B 12 capsule (LTEVB 12C) on chronic atrophic gastritis (CAG) at different locations (antrum lesser curvature, antrum greater curvature, gastric angle, corpus lesser curvature, and corpus greater curvature). Methods:From August 2011 to January 2013, 715 patients with CAG in a multicenter, randomized, double-blind, placebo-controlled trial were enrolled from 16 tertiary first-class hospitals across the country, including the First Affiliated Hospital of Air Force Medical University, Nanfang Hospital of Southern Medical University, the First Hospital of Jilin University, West China Hospital of Sichuan University, etc., there were 476 cases in the LTEVB 12C group and 239 cases in the placebo group. The patients of the LTEVB 12C group received LTEVB 12C, and the patients of placebo group received LTEVB 12C mimetic, all the medications were taken 3 capsules each time and 3 times a day after meals, and the treatment course of 2 groups were both 6 months. The efficacy evaluation criteria included the effective rate (a decrease of ≥1 in histopathological score compared with baseline after 6 months of treatment) and the reversal rate (a decrease of ≥ 2 in histopathological score compared with baseline after 6 months of treatment in the patients with moderate to severe CAG). The impact of lesion sites on the therapeutic effects of LTEVB 12C was analyzed by logistic regression analysis. The two-way unordered Cochran-Mantel-Haenszel chi-square test considering the center effect and Pearson chi-square test were used for statistical analysis. Results:The effective rates of chronic inflammation at the antrum greater curvature and corpus greater curvature (23.3%, 110/473 vs. 13.0%, 31/239; 20.3%, 96/472 vs. 12.6%, 30/239), the effective rates of atrophy at the antrum lesser curvature, antrum greater curvature, gastric angle, corpus lesser curvature, and the corpus greater curvature (27.0%, 118/437 vs. 15.7%, 34/216; 29.2%, 126/432 vs. 18.5%, 38/205; 27.8%, 121/435 vs. 16.7%, 36/216; 32.5%, 127/391 vs. 19.8%, 37/187; 33.0%, 119/361 vs. 21.8%, 39/179), and the effective rates of intestinal metaplasia at the antrum lesser curvature, antrum greater curvature, gastric angle, and the corpus lesser curvature (45.0%, 112/249 vs. 29.8%, 31/104; 53.8%, 86/160 vs. 33.9%, 21/62; 45.8%, 103/225 vs. 24.0%, 25/104; 51.9%, 83/160 vs. 28.3%, 17/60) of the LTEVB 12C group were all higher than those of the placebo group, and the differences were statistically significant ( χ2=10.76, 6.39, 9.69, 7.91, 11.05, 9.62, 8.57, 5.20, 7.11, 12.45, and 6.73; all P<0.05). The reversal rates of chronic inflammation at the corpus lesser curvature and corpus greater curvature (5.2%, 12/231 vs. 0, 0/123; 4.7%, 8/170 vs. 0, 0/88), the reversal rates of atrophy at the antrum lesser curvature, antrum greater curvature, corpus lesser curvature, and the corpus greater curvature (6.8%, 22/323 vs. 1.3%, 2/151; 9.2%, 29/315 vs. 1.4%, 2/144; 14.2%, 38/267 vs. 2.5%, 3/121; 20.8%, 35/168 vs. 5.8%, 4/69), and the reversal rates of intestinal metaplasia at the antrum lesser curvature, antrum greater curvature, gastric angle, and the corpus lesser curvature (29.8%, 39/131 vs. 9.1%, 4/44; 41.0%, 32/78 vs. 12.5%, 3/24; 33.3%, 44/132 vs. 4.8%, 3/63; 50.0%, 37/74 vs. 8.7%, 2/23) of the LTEVB 12C group were all higher than those of the placebo group, and the differences were statistically significant ( χ2=6.58, 5.12, 5.60, 8.61, 11.43, 6.59, 7.30, 4.95, 15.92, 7.62; all P<0.05). There were no statistically significant differences in the effective rates and reversal rates of active inflammation at different locations between the LTEVB 12C group and the placebo group (all P>0.05). The results of logistic regression analysis (taking the antrum lesser curvature as the reference) further confirmed that the reversal rates of chronic inflammation ( OR=0.22, 95% confidence interval (95% CI): 0.07 to 0.67; OR=0.24, 95% CI: 0.07 to 0.80), atrophy ( OR=0.28, 95% CI: 0.16 to 0.49; OR=0.28, 95% CI: 0.16 to 0.49), and intestinal metaplasia ( OR=0.42, 95% CI: 0.24 to 0.77; OR=0.20, 95% CI: 0.08 to 0.52) at the corpus lesser curvature and corpus greater curvature were all higher than those at the antrum lesser curvature, and the differences were statistically significant (all P<0.05). There were no statistically siginificant differences in the reversal rates of the aforementioned pathological features between the antrum greater curvature, gastric angle, and the antrum lesser curvature (all P>0.05). Conclusion:LTEVB 12C can achieve good efficacy in the treatment of CAG, and the chronic inflammation, atrophy, and intestinal metaplasia at multiple locations are improved, especially at the corpus lesser curvature and the corpus greater curvature.

Metabolic dysfunction-associated steatotic liver disease (MASLD) comprises a spectrum of liver injuries, including steatosis to steatohepatitis (MASH), liver fibrosis, cirrhosis, and relevant complications. The liver mainly comprises hepatocytes, liver sinusoidal endothelial cells (LSECs), Kupffer cells (KCs), immune cells (T cells, B cells), and hepatic stellate cells (HSCs). Crosstalk among these different liver cells, endogenous aberrant glycolipid metabolism, and altered gut dysbiosis are involved in the pathophysiology of MASLD. This review systematically examines advances in understanding the molecular pathogenesis of MASLD, with a focus on emerging therapeutic targets and translational clinical trials. We first delineate the crucial regulatory mechanisms involving diverse liver cells and the gut-liver axis in MASLD development. These cell-specific pathogenic insights offer valuable perspectives for advancing precision medicine approaches in MASLD treatment. Furthermore, we evaluate potential therapeutic targets and summarize clinical trials currently underway. By comprehensively updating the MASLD pathophysiology and identifying promising strategies, this review aims to facilitate the development of novel pharmacotherapies for this increasingly prevalent condition.
Humans ; Fatty Liver/therapy* ; Animals ; Liver/pathology* ; Kupffer Cells/metabolism* ; Hepatocytes/metabolism* ; Hepatic Stellate Cells/metabolism*

BACKGROUND:Mesoporous bioactive glass has great application potential in bone repair due to its excellent biocompatibility and osteoinductive activity.Incorporating therapeutic ions into mesoporous bioactive glass particles can give the material more ideal biological properties.OBJECTIVE:To synthesize copper-doped mesoporous bioactive glass and investigate its in vitro angiogenesis and osteogenic differentiation properties.METHODS:Mesoporous bioactive glass and copper-doped mesoporous bioactive glass were synthesized by microemulsion-assisted sol-gel method.The morphology,structure,composition,and ion release performance of the materials were characterized by scanning electron microscopy,transmission electron microscopy,energy dispersive spectroscopy,and X-ray diffraction.The extracts of mesoporous bioactive glass and copper-doped mesoporous bioactive glass were co-cultured with mouse fibroblasts L929.Biocompatibility of the materials was evaluated by live/dead staining and CCK-8 assay.The extracts of the two materials were co-cultured with human umbilical vein endothelial cells.The angiogenesis-promoting properties of the materials were evaluated by Transwell assay,scratch assay,and CD31 immunofluorescence staining.The extracts of the two materials were co-cultured with mouse bone marrow mesenchymal stem cells.The osteogenic properties of the materials were evaluated by alkaline phosphatase staining(without osteogenic induction solution)and Alizarin red staining(with osteogenic induction solution).RESULTS AND CONCLUSION:(1)The characterization results exhibited that both mesoporous bioactive glass and copper-doped mesoporous bioactive glass presented a tightly packed granular morphology with similar internal mesoporous structures,and copper-doped mesoporous bioactive glass could continuously release copper ions.(2)The live/dead staining and CCK-8 assay results showed that compared with mesoporous bioactive glass,copper-doped mesoporous bioactive glass could promote the proliferation of L929 cells and had good biocompatibility.(3)The results of Transwell assay,scratch assay,and CD31 immunofluorescence staining exhibited that compared with mesoporous bioactive glass,copper-doped mesoporous bioactive glass could promote the migration of human umbilical vein endothelial cells and the expression of CD31 protein,and promote angiogenesis.(4)The results of alkaline phosphatase staining and alizarin red staining demonstrated that the osteogenic performance of copper-doped mesoporous bioactive glass was stronger than that of mesoporous bioactive glass.The results indicate that copper-doped mesoporous bioactive glass has excellent biocompatibility and the potential to promote angiogenesis and bone regeneration.

Objective:To evaluate the efficacy of lamb′s tripe extract and vitamin B 12 capsule (LTEVB 12C) on chronic atrophic gastritis (CAG) at different locations (antrum lesser curvature, antrum greater curvature, gastric angle, corpus lesser curvature, and corpus greater curvature). Methods:From August 2011 to January 2013, 715 patients with CAG in a multicenter, randomized, double-blind, placebo-controlled trial were enrolled from 16 tertiary first-class hospitals across the country, including the First Affiliated Hospital of Air Force Medical University, Nanfang Hospital of Southern Medical University, the First Hospital of Jilin University, West China Hospital of Sichuan University, etc., there were 476 cases in the LTEVB 12C group and 239 cases in the placebo group. The patients of the LTEVB 12C group received LTEVB 12C, and the patients of placebo group received LTEVB 12C mimetic, all the medications were taken 3 capsules each time and 3 times a day after meals, and the treatment course of 2 groups were both 6 months. The efficacy evaluation criteria included the effective rate (a decrease of ≥1 in histopathological score compared with baseline after 6 months of treatment) and the reversal rate (a decrease of ≥ 2 in histopathological score compared with baseline after 6 months of treatment in the patients with moderate to severe CAG). The impact of lesion sites on the therapeutic effects of LTEVB 12C was analyzed by logistic regression analysis. The two-way unordered Cochran-Mantel-Haenszel chi-square test considering the center effect and Pearson chi-square test were used for statistical analysis. Results:The effective rates of chronic inflammation at the antrum greater curvature and corpus greater curvature (23.3%, 110/473 vs. 13.0%, 31/239; 20.3%, 96/472 vs. 12.6%, 30/239), the effective rates of atrophy at the antrum lesser curvature, antrum greater curvature, gastric angle, corpus lesser curvature, and the corpus greater curvature (27.0%, 118/437 vs. 15.7%, 34/216; 29.2%, 126/432 vs. 18.5%, 38/205; 27.8%, 121/435 vs. 16.7%, 36/216; 32.5%, 127/391 vs. 19.8%, 37/187; 33.0%, 119/361 vs. 21.8%, 39/179), and the effective rates of intestinal metaplasia at the antrum lesser curvature, antrum greater curvature, gastric angle, and the corpus lesser curvature (45.0%, 112/249 vs. 29.8%, 31/104; 53.8%, 86/160 vs. 33.9%, 21/62; 45.8%, 103/225 vs. 24.0%, 25/104; 51.9%, 83/160 vs. 28.3%, 17/60) of the LTEVB 12C group were all higher than those of the placebo group, and the differences were statistically significant ( χ2=10.76, 6.39, 9.69, 7.91, 11.05, 9.62, 8.57, 5.20, 7.11, 12.45, and 6.73; all P<0.05). The reversal rates of chronic inflammation at the corpus lesser curvature and corpus greater curvature (5.2%, 12/231 vs. 0, 0/123; 4.7%, 8/170 vs. 0, 0/88), the reversal rates of atrophy at the antrum lesser curvature, antrum greater curvature, corpus lesser curvature, and the corpus greater curvature (6.8%, 22/323 vs. 1.3%, 2/151; 9.2%, 29/315 vs. 1.4%, 2/144; 14.2%, 38/267 vs. 2.5%, 3/121; 20.8%, 35/168 vs. 5.8%, 4/69), and the reversal rates of intestinal metaplasia at the antrum lesser curvature, antrum greater curvature, gastric angle, and the corpus lesser curvature (29.8%, 39/131 vs. 9.1%, 4/44; 41.0%, 32/78 vs. 12.5%, 3/24; 33.3%, 44/132 vs. 4.8%, 3/63; 50.0%, 37/74 vs. 8.7%, 2/23) of the LTEVB 12C group were all higher than those of the placebo group, and the differences were statistically significant ( χ2=6.58, 5.12, 5.60, 8.61, 11.43, 6.59, 7.30, 4.95, 15.92, 7.62; all P<0.05). There were no statistically significant differences in the effective rates and reversal rates of active inflammation at different locations between the LTEVB 12C group and the placebo group (all P>0.05). The results of logistic regression analysis (taking the antrum lesser curvature as the reference) further confirmed that the reversal rates of chronic inflammation ( OR=0.22, 95% confidence interval (95% CI): 0.07 to 0.67; OR=0.24, 95% CI: 0.07 to 0.80), atrophy ( OR=0.28, 95% CI: 0.16 to 0.49; OR=0.28, 95% CI: 0.16 to 0.49), and intestinal metaplasia ( OR=0.42, 95% CI: 0.24 to 0.77; OR=0.20, 95% CI: 0.08 to 0.52) at the corpus lesser curvature and corpus greater curvature were all higher than those at the antrum lesser curvature, and the differences were statistically significant (all P<0.05). There were no statistically siginificant differences in the reversal rates of the aforementioned pathological features between the antrum greater curvature, gastric angle, and the antrum lesser curvature (all P>0.05). Conclusion:LTEVB 12C can achieve good efficacy in the treatment of CAG, and the chronic inflammation, atrophy, and intestinal metaplasia at multiple locations are improved, especially at the corpus lesser curvature and the corpus greater curvature.

This article is based on the core pathogenesis of yin-yang poisoning recorded in the Synopsis of the Golden Chamber and clarifies the characteristics of"yin poisoning"and"yang poisoning"as considered during the Han and Tang dynasties.It is found that the classification criteria for the two are based on the manifestation of syndromes rather than the cold and heat of the pathogenesis.By analyzing the syndrome of yin-yang poisoning in the Synopsis of the Golden Chamber and combining the records with people's understanding of the efficacy of various medicinals in Shengma Biejia Decoction during the Han and Tang dynasties,it is demonstrated that the core pathogenesis is stagnation,mainly reflected in three aspects:accumulation of toxins,stagnation of qi and blood,and stagnation of yang qi.Among these,the degree and location of stagnation of yang qi are the reasons for the difference between yin poisoning and yang poisoning.The disease of yang poisoning is characterized by sufficient yang qi in the body,obstruction of pathogenic factors on the surface,and intense competition between vital qi and evil qi.Therefore,yang stagnation on the surface is more severe and leads to heat symptoms.The disease of yin poisoning is characterized by deficient yang qi in the body,an inability to resist pathogen,and the deepening of evil qi.The yang qi is suppressed by depression and is relatively mild,making it unable to circulate and warm the body,resulting in cold symptoms.Therefore,when treating yang poisoning,ZHANG Zhongjing used medicinals that were pungent,warm and dispersed to relieve the yang depression on the surface.If the yang depression was dispersed,the heat would naturally dissipate.When treating yin poisoning,only internal medicine is used to relieve internal yang qi stagnation,and when yang qi is extended,cold will naturally disappear.In summary,we aimed to enhance our understanding of the efficacy of Shengma Biejia Decoction from the perspectives of promoting the dispersion of toxins,promoting blood circulation,and promoting yang stagnation,in order to provide new ideas for the clinical use of this formula and expand its application scope.

Objective To investigate the application value of rice bag in 1.5T MR imaging of maxillofacial frequency selective saturated fat suppression(FS)sequence.Methods Forty-one patients with maxillofacial MR examination were collected.Rapid fast spin echo(FSE)FS T2 routine scan and rice bag FSE FS T2 special scan were used to evaluate and analyze the sequence images of the two kinds by two experienced associate chief physicians in the department according to the Likert 7-point scoring system.The evaluation included FS,magnetic sensitive artifact,motion artifact,and overall image quality.Wilcoxon sign rank sum test was used to analyze the difference of image quality scores,and Kappa consistency test was used to analyze the correlation between two viewers.Results All the 41 patients completed the examination,and the FSE FS T2 plus rice bag group had significantly higher FS,magnetic sensitive artifact,motion artifact and overall image quality than the conventional FSE FS T2 group,with statistical significance(P<0.01).Kappa consistency was good in correlation analysis between the two viewers(Kappa value=0.737-0.877,P<0.01).Conclusion The application of rice bag in the 1.5T MR maxillofacial FS sequence scan has the advantages of good image quality,good FS effect and few artifacts,which can better display the maxillofacial anatomical structure and lesions,and has important clinical application value for the diagnosis of maxillofacial diseases.

Objective:To investigate the prevalence, clinical characteristics, risk factors, and prognosis of chronic drug-induced liver injury (DILI).Methods:A multicenter, open, retrospective, non-interventional epidemiological survey was conducted. According to the inclusion criteria, patients with DILI and hospitalized in 308 hospitals in China from January 1, 2012 to December 31, 2014 were enrolled, and medical records of the patients were collected. The patients with DILI were divided into chronic and acute DILI groups. The clinical characteristics, laboratory tests, and prognosis in patients of the 2 groups were compared, and the suspected drugs that induced the liver injury were analyzed. Univariate and multivariate logistic regression analyses were used to analyze the influencing factors of chronic DILI.Results:A total of 25 927 patients were enrolled in the study, including 22 556 (87%) with acute DILI (acute DILI group) and 3 371 (13%) with chronic DILI (chronic DILI group). In the chronic DILI group, there were high proportion of women and the patients were older in age; more patients were with a history of liver disease and the time from medication to DILI was longer; more patients had digestive system symptoms (including loss of appetite, abdominal distension, nausea, vomiting, etc.), fatigue, jaundice, pruritus, liver pain/discomfort, bleeding tendency; the alanine aminotransferase, aspartate aminotransferase, alkaline phosphatase, total bilirubin, and international normalized ratio were higher, while the serum albumin and platelet counts were lower; the proportion of patients with model for end-stage liver disease score ≥ 15 was higher; the all-cause mortality rate and liver disease-related mortality rate were higher, compared with the acute DILI group. The differences above-mentioned were statistically significant (all P<0.05). Multivariate logistic regression analysis showed that male was protective factor [odds ratio ( OR)=0.76, 95% confidence interval ( CI): 0.69-0.83], while previous liver disease history ( OR=2.00, 95% CI: 1.82-2.19) and hypoalbuminemia ( OR=0.96, 95% CI: 0.95-0.96) were independent risk factors for chronic DILI. Conclusions:In the study period, the proportion of chronic DILI among DILI inpatients is 13.0% in the 308 hospitals. Compared with those with acute DILI, more chronic DILI patients were female, and patients with chronic DILI have higher ages, severer conditions, and poorer prognoses; female, previous liver disease history, and hypoalbuminemia are independent risk factors for chronic DILI.