To compare the performance differences between the multidisciplinary team (MDT) model and the conventional diagnostic and treatment model for lung cancer, and to explore a high-quality development pathway for optimizing lung cancer diagnostic and treatment resources.

The mandibular condyle is a critical growth center in craniofacial bone development, especially during postnatal stages. Postnatal condyle osteogenesis requires precise spatiotemporal coordination of growth factor signaling cascades and hierarchical gene regulatory networks. Plagl1, which encodes a zinc finger transcription factor, is a paternally expressed gene. We demonstrate that PLAGL1 is highly expressed in cranial neural crest cell (CNCC)-derived lineage cells in mouse condyles. Using the CNCC-derived lineage-specific Plagl1 knockout mouse model, we evaluate the function of PLAGL1 during postnatal mouse condyle development. Our findings show that PLAGL1 contributes significantly to osteoblast differentiation, and its deficiency impairs osteogenic lineage differentiation, which consequently disrupts mandibular condyle development. Mechanistically, insulin-like growth factor 2 (IGF2) in complex with IGF-binding proteins (IGFBPs) has been identified as the principal PLAGL1 effector responsible for osteogenic regulation during postnatal condyle morphogenesis. Plagl1 deficiency significantly downregulates the IGF2/IGFBP pathway, leading to disordered glucose metabolism, defective extracellular matrix organization, and impaired ossification. Exogenous IGF2 treatment rescues impaired osteoblast differentiation caused by Plagl1 deficiency. In conclusion, the PLAGL1-IGF2 axis is a critical regulator of osteogenesis during mandibular condyle development.
Animals ; Osteogenesis/genetics* ; Insulin-Like Growth Factor II/metabolism* ; Mice ; Transcription Factors/metabolism* ; Mice, Knockout ; Cell Differentiation ; DNA-Binding Proteins/genetics* ; Mandibular Condyle/growth & development* ; Osteoblasts/cytology* ; Signal Transduction ; Neural Crest/cytology*

OBJECTIVE To investigate the therapeutic effect of Qingchang Huazhuo Formula(QCHZF)on mice with ulcerative colitis(UC)and the influences of fecal metabolites based on non-targeted metabolomics to investigate the mechanism of action of QCHZF in the treatment of UC.METHODS UC mice were induced by dextran sulfate sodium salt(DSS)and were administered with QCHZF.During the experiment,the body weight,stool characteristics and blood in stool were recorded daily,and the disease activity index(DAI)was calculated.At the end of the experiment,the length of colon was measured,colonic tissue damage in mice were ob-served by hematoxylin-eosin and alcian blue staining,mRNA expression levels of inflammatory factors,IL-6,IL-18 and IL-1β,and intestinal barrier factors,ZO-1 and Muc2,were detected in colon tissues via qPCR method,and protein expression level of intestinal barrier,Muc2,was detected with immunofluorescence.Fecal metabolite changes in mice were detected employing un-targeted metabo-lomics and analyzed by MetaboAnalyst 5.0 for metabolic pathway enrichment.RESULTS QCHZF significantly alleviated colitis symptoms,increased body weight,decreased DAI score,reversed colonic shortening,inhibited inflammatory factors expression,im-proved colonic tissue structure disorders,increased the number of goblet cells,and restored the intestinal barrier in UC mice,regulated 58 metabolites,mainly involving pathways of methionine and cysteine metabolism,purine metabolism,steroid hormone biosynthesis,vitamin B6 metabolism,tryptophan metabolism and primary bile acid pathways.CONCLUSION QCHZF can improve colitis symp-toms,repaire the intestinal barrier and modulate fecal metabolites and related metabolic pathways in UC mice.

Objective To promote the objectification and intelligence of clinical TCM tongue diagnosis in ulcerative colitis(UC).Methods Daosheng DS01-B tongue and face diagnosis information collection system was used to prospectively collect tongue image pictures of patients with ulcerative colitis damp-heat in the large intestine syndrome(DCSR)and spleen deficiency dampness retention syndrome(PXSY),with totaling 1096 images.After UC tongue image segmentation,preprocessing,and data augmentation,a data set of UC tongue images was formed.Based on ResNet50,a UC tongue image classification model was constructed using feature fusion methods and attention modules.Results The UC tongue image classification model constructed had better classification performance,with an average F1 value of 85.09%,an AUC value of 0.83 for PXSY,and an AUC value of 0.81 for DCSR,both of which were higher than the VGG11 and ResNet50 models.Conclusion The constructed UC tongue image classification model can effectively identify DCSR and PXSY,providing a new approach to improve the accuracy and objectivity of UC differentiation and assisting in the intelligence of TCM tongue diagnosis.

Objective To promote the objectification and intelligence of clinical TCM tongue diagnosis in ulcerative colitis(UC).Methods Daosheng DS01-B tongue and face diagnosis information collection system was used to prospectively collect tongue image pictures of patients with ulcerative colitis damp-heat in the large intestine syndrome(DCSR)and spleen deficiency dampness retention syndrome(PXSY),with totaling 1096 images.After UC tongue image segmentation,preprocessing,and data augmentation,a data set of UC tongue images was formed.Based on ResNet50,a UC tongue image classification model was constructed using feature fusion methods and attention modules.Results The UC tongue image classification model constructed had better classification performance,with an average F1 value of 85.09%,an AUC value of 0.83 for PXSY,and an AUC value of 0.81 for DCSR,both of which were higher than the VGG11 and ResNet50 models.Conclusion The constructed UC tongue image classification model can effectively identify DCSR and PXSY,providing a new approach to improve the accuracy and objectivity of UC differentiation and assisting in the intelligence of TCM tongue diagnosis.

OBJECTIVE To explore the possible mechanism of Qingchang Huashi Formula in the treatment of ulcerative colitis(UC).METHODS Fifty C57BL/6 male mice were randomly divided into a control(Ctrl)group,a model group,a low-dose Qingchang Huashi Formula group,a high-dose Qingchang Huashi Formula group,and a 5-aminosalicylic acid(5-ASA)group based on body weight.The UC model was established in mice by drinking 3%dextran sulfate sodium(DSS)for 6 d.On d7 and d8,DSS was withdrawn and ultrapure water was given daily.Ultrapure water or different drugs were administered orally throughout the experiment:Ctrl and model groups received 0.2 mL of ultrapure water,while the low-dose and high-dose Qingchang Huashi Formula groups re-ceived 6 and 12 g·kg-1,respectively,and the concentration of 5-ASA was 100 mg·kg-1.Body weight and fecal characteristics of the mice were recorded daily,and the experiment ended on d9.Serum was collected from mice for serum metabolomics and inflam-matory factor expression analysis.The colons of the mice were isolated and their lengths were measured,and the distal colon was ob-tained for pathological analysis.The livers and colons of the mice were isolated for subsequent total bile acid analysis.RESULTS Compared with the Ctrl group,the model group mice showed a significant decrease in body weight and colon length(P<0.000 1),a remarkable increase in disease activity index(P<0.000 1).The concentration of inflammatory factors IL-1β and TNF-α was signifi-cantly increased(P<0.000 1).High-dose and low-dose Qingchang Huashi Formula,as well as 5-ASA could significantly alleviate the loss of body weight,increased DAI,colon shortening,and disappearance of colon tissue morphology in mice.Through ELISA tes-ting,it was found the concentration of IL-1β and TNF-α was remarkably decreased after Qingchang Huashi Formula and 5-ASA treat-ment(P<0.01,P<0.000 1).Through LC-MS analysis of serum metabolites and KEGG enrichment analysis,we found that interven-tion with Qingchang Huashi Formula could significantly affect the primary bile acid synthesis,secondary bile acid synthesis and bile se-cretion.Using total bile acid reagent kit,we found that the total bile acid in the liver of colitis mice did not show significant changes when compared with the Ctrl group of mice,and the concentration of total bile acid in the serum was significantly reduced,the concen-tration of TBA in the colon was significantly increased(P<0.05).After intervention with the Qingchang Huashi Formula,the concen-tration of total bile acid in the serum of mice was significantly increased,while the concentration of total bile acid in the colon was re-duced(P<0.05).Compared with mice in Ctrl group,the levels of deoxycholic acid(DCA)and taurine deoxycholic acid(TDCA)in serum of colitis mice were significantly reduced(P<0.05).After intervention with Qingchang Huashi Formula,the levels of DCA,TD-CA and Ursodeoxycholic acid(UDCA)in serum of mice were restored(P<0.01).CONCLUSION Qingchang Huashi Formula can effectively relieve DSS-induced colitis in mice,reducing immune inflammatory response,reregulating the disorder of serum metabolism and enterohepatic circulation.

OBJECTIVE To explore the possible mechanism of Qingchang Huashi Formula in the treatment of ulcerative colitis(UC).METHODS Fifty C57BL/6 male mice were randomly divided into a control(Ctrl)group,a model group,a low-dose Qingchang Huashi Formula group,a high-dose Qingchang Huashi Formula group,and a 5-aminosalicylic acid(5-ASA)group based on body weight.The UC model was established in mice by drinking 3%dextran sulfate sodium(DSS)for 6 d.On d7 and d8,DSS was withdrawn and ultrapure water was given daily.Ultrapure water or different drugs were administered orally throughout the experiment:Ctrl and model groups received 0.2 mL of ultrapure water,while the low-dose and high-dose Qingchang Huashi Formula groups re-ceived 6 and 12 g·kg-1,respectively,and the concentration of 5-ASA was 100 mg·kg-1.Body weight and fecal characteristics of the mice were recorded daily,and the experiment ended on d9.Serum was collected from mice for serum metabolomics and inflam-matory factor expression analysis.The colons of the mice were isolated and their lengths were measured,and the distal colon was ob-tained for pathological analysis.The livers and colons of the mice were isolated for subsequent total bile acid analysis.RESULTS Compared with the Ctrl group,the model group mice showed a significant decrease in body weight and colon length(P<0.000 1),a remarkable increase in disease activity index(P<0.000 1).The concentration of inflammatory factors IL-1β and TNF-α was signifi-cantly increased(P<0.000 1).High-dose and low-dose Qingchang Huashi Formula,as well as 5-ASA could significantly alleviate the loss of body weight,increased DAI,colon shortening,and disappearance of colon tissue morphology in mice.Through ELISA tes-ting,it was found the concentration of IL-1β and TNF-α was remarkably decreased after Qingchang Huashi Formula and 5-ASA treat-ment(P<0.01,P<0.000 1).Through LC-MS analysis of serum metabolites and KEGG enrichment analysis,we found that interven-tion with Qingchang Huashi Formula could significantly affect the primary bile acid synthesis,secondary bile acid synthesis and bile se-cretion.Using total bile acid reagent kit,we found that the total bile acid in the liver of colitis mice did not show significant changes when compared with the Ctrl group of mice,and the concentration of total bile acid in the serum was significantly reduced,the concen-tration of TBA in the colon was significantly increased(P<0.05).After intervention with the Qingchang Huashi Formula,the concen-tration of total bile acid in the serum of mice was significantly increased,while the concentration of total bile acid in the colon was re-duced(P<0.05).Compared with mice in Ctrl group,the levels of deoxycholic acid(DCA)and taurine deoxycholic acid(TDCA)in serum of colitis mice were significantly reduced(P<0.05).After intervention with Qingchang Huashi Formula,the levels of DCA,TD-CA and Ursodeoxycholic acid(UDCA)in serum of mice were restored(P<0.01).CONCLUSION Qingchang Huashi Formula can effectively relieve DSS-induced colitis in mice,reducing immune inflammatory response,reregulating the disorder of serum metabolism and enterohepatic circulation.

OBJECTIVE To investigate the therapeutic effect of Qingchang Huazhuo Formula(QCHZF)on mice with ulcerative colitis(UC)and the influences of fecal metabolites based on non-targeted metabolomics to investigate the mechanism of action of QCHZF in the treatment of UC.METHODS UC mice were induced by dextran sulfate sodium salt(DSS)and were administered with QCHZF.During the experiment,the body weight,stool characteristics and blood in stool were recorded daily,and the disease activity index(DAI)was calculated.At the end of the experiment,the length of colon was measured,colonic tissue damage in mice were ob-served by hematoxylin-eosin and alcian blue staining,mRNA expression levels of inflammatory factors,IL-6,IL-18 and IL-1β,and intestinal barrier factors,ZO-1 and Muc2,were detected in colon tissues via qPCR method,and protein expression level of intestinal barrier,Muc2,was detected with immunofluorescence.Fecal metabolite changes in mice were detected employing un-targeted metabo-lomics and analyzed by MetaboAnalyst 5.0 for metabolic pathway enrichment.RESULTS QCHZF significantly alleviated colitis symptoms,increased body weight,decreased DAI score,reversed colonic shortening,inhibited inflammatory factors expression,im-proved colonic tissue structure disorders,increased the number of goblet cells,and restored the intestinal barrier in UC mice,regulated 58 metabolites,mainly involving pathways of methionine and cysteine metabolism,purine metabolism,steroid hormone biosynthesis,vitamin B6 metabolism,tryptophan metabolism and primary bile acid pathways.CONCLUSION QCHZF can improve colitis symp-toms,repaire the intestinal barrier and modulate fecal metabolites and related metabolic pathways in UC mice.

Objective To analyze the clinical efficacy of transcatheter tricuspid valve replacement (TTVR) in cardiac implantable electronic lead-related tricuspid regurgitation (TR). Methods The patients with severe TR who underwent LuX-Valve TTVR in 9 Chinese medical centers from June 2020 to August 2021 were retrospectively enrolled. They were divided into a cardiac implantable electronic device (CIED) group and a non-CIED group based on whether they had pre-existing CIED implantation. Success of the procedure was defined as safe implantation of the LuX-Valve and complete withdrawal of the delivery system. Prognostic improvement was defined as a decrease of TR grade to≤2+ and an improvement of cardiac function by≥2 grades. Surgical success and postoperative prognosis were compared between the two groups. Results A total of 190 patients were collected, including 50 males and 140 females with a mean age of 66.2±7.8 years. There were 29 patients in the CIED group, and 161 patients in the non-CIED group. In the CIED group, 28 patients were implanted with a permanent pacemaker and 1 patient with a cardioverter-defibrillator. Preoperative New York Heart Association (NYHA) cardiac function class, TR degree, left ventricular ejection fraction, tricuspid annular plane systolic excusion, and cardiac risk scores were comparable between the two groups (P>0.05). Postoperative TR was reduced to≤2+ in all patients, and there was no statistical difference in the incidence of perivalvular leakage between the two groups (P=0.270). Postoperative CT of CIED patients showed the valve was in place, and the lead was not extruded, twisted, or deflected. The in-hospital mortality of the two groups were 10.3% and 1.9%, respectively, and the difference was statistically significant (P=0.047). In addition, there was no statistical difference between the two groups in terms of postoperative improvement of cardiac function and mortality in the 1- and 2-year follow-up. Conclusion TTVR is feasible, safe, and effective in patients with CIED implantation, and the pre-existing lead has no significant effect on the clinical efficacy.

Liver disease is one of the most important health problems around the world， and early diagnosis and timely intervention and treatment are the key to preventing liver-related morbidity and mortality rates. The development of endoscopic techniques has provided new diagnostic and intervention methods for liver diseases. This article reviews the application and development of endoscopic techniques in liver diseases from the following aspects： the technical advances and advantages of endoscopic ultrasound-guided liver biopsy； the application and development of endoscopic techniques in the treatment of portal hypertension caused by liver abscess/hepatic cyst and liver diseases， as well as interventional techniques in the treatment of liver tumors； the efficacy and prospects of the endoscopic techniques for weight loss， which are relatively new in China， in the treatment of nonalcoholic fatty liver disease/nonalcoholic steatohepatitis. Endoscopic techniques may hold promise for wide clinical application and exploration in in liver-related diseases in China， so as to provide more options for patients and doctors.