BACKGROUND:Psoralen has a strong anti-osteoporotic activity and may have a restorative effect on chemotherapy-induced osteoporosis. OBJECTIVE:To explore the restorative effect of psoralen on the osteogenic differentiation of bone marrow mesenchymal stem cells in mice inhibited by cyclophosphamide and its mechanism. METHODS:C57BL/6 mouse bone marrow mesenchymal stem cells were isolated and cultured.Effect of psoralen on viability of bone marrow mesenchymal stem cells was detected by MTT assay.Osteogenic induction combined with alkaline phosphatase staining was used to determine the optimal dose of psoralen to restore the osteogenic differentiation of bone marrow mesenchymal stem cells inhibited by cyclophosphamide.The mRNA expression levels of Runx2,alkaline phosphatase,Osteocalcin,osteoprotegerin,and Wnt/β-catenin signaling pathway-related genes Wnt1,Wnt4,Wnt10b,β-catenin,and c-MYC were measured by RT-qPCR at different time points under the intervention with psoralen.The protein expression of osteogenic specific transcription factor Runx2 and Wnt/β-catenin signaling pathway related genes Active β-catenin,DKK1,c-MYC,and Cyclin D1 was determined by western blot assay at different time points under the intervention with psoralen. RESULTS AND CONCLUSION:(1)There was no significant effect of different concentrations of psoralen on the viability of bone marrow mesenchymal stem cells.The best recovery of the inhibition of osteogenic differentiation of bone marrow mesenchymal stem cells caused by cyclophosphamide was under the intervention of psoralen at a concentration of 200 μmol/L.(2)Psoralen reversed the reduction in osteogenic differentiation marker genes Runx2,alkaline phosphatase,Osteocalcin and osteoprotegerin mRNA expression and Runx2 protein expression in bone marrow mesenchymal stem cells caused by cyclophosphamide conditioned medium.(3)Psoralen reversed the decrease in Wnt/β-catenin pathway-related genes Wnt4,β-catenin,c-MYC mRNA and Active β-catenin,c-MYC,and Cyclin D1 protein expression and the increase in DKK1 protein expression in bone marrow mesenchymal stem cells caused by cyclophosphamide conditioned medium.(4)The results showed that cyclophosphamide inhibited osteogenic differentiation of bone marrow mesenchymal stem cells in mice,and psoralen had a restorative effect on it.The best intervention effect was achieved at a concentration of 200 μmol/L psoralen,and this protective effect might be related to the activation of Wnt4/β-catenin signaling pathway by psoralen.

AIM To investigate the effects of total Astragalus saponins on the improvement of sarcopenia in a rat model of type 2 diabetes mellitus(T2DM).METHODS The rats were divided into the normal group for a normal feeding and the model group for the feeding of high-sugar and high-fat diet combined with intraperitoneal injection of STZ to establish a T2DM model.The successful model rats were randomly divided into the model group,the metformin group(0.2 g/kg)and the total Astragalus saponins group(80 mg/kg),and given corresponding doses of drugs by gavage.After 12 weeks administration,the rats had their FBG,postprandial blood glucose(PG2h)and wet weight of skeletal muscle measured;their serum levels of INS,C-peptide(C-P),IGF-1,TNF-α and IL-1β detected by ELISA;their morphological changes of skeletal muscle observed by HE staining;their protein expressions of PI3K,p-Akt,mTOR,S6K1,FoxO1 and Murf1 in skeletal muscle detected by Western blot;and their mRNA expressions of Pi3k,Akt and mtor in skeletal muscle detected by RT-qPCR method.RESULTS Compared with the model group,the total Astragalus saponins group displayed decreased levels of FBG,PG2h,OGTT-AUC,HOMA-IR,TNF-α and IL-1β(P＜0.01);increased levels of INS,C-P,IGF-1 and wet weight of skeletal muscle(P＜0.05,P＜0.01);improved skeletal muscle atrophy and increased protein expressions of PI3K,p-Akt,mTOR and S6K1 in skeletal muscle(P＜0.05,P＜0.01);decreased protein expressions of FoxO1 and Murf1(P＜0.05,P＜0.01);and increased mRNA expressions of Pi3k,Akt and mtor(P＜0.01).CONCLUSION The improvement effects of total Astragalus saponins on sarcopenia in T2DM rats may be associated with the regulation of PI3K/Akt/mTOR and PI3K/Akt/FoxO1 pathways.

Objective:To investigate the influence of curative-intent resection with textbook outcomes of liver surgery (TOLS) on long-term prognosis of gallbladder carcinoma (GBC).Methods:The retrospective cohort study was conducted. The clinicopathological data of 824 patients with GBC in the national multicenter database of Biliary Surgery Group of Elite Group of Chinese Journal of Digestive Surgery, who were admitted to 15 medical centers from January 2014 to January 2021, were collected. There were 285 males and 539 females, aged (62±11)years. According to the evalua-tion criteria of TOLS, patients were divided into those who achieved TOLS and those who did not achieve TOLS. Measurement data with normal distribution were represented as Mean± SD, and com-parison between groups was conducted using the independent sample t test. Measurement data with skewed distribution were represented as M( Q1, Q3), and comparison between groups was conducted using the Mann-Whitney U test. Count data were described as absolute numbers, and comparison between groups was conducted using the chi-square test. Comparison of ordinal data were conduc-ted using the Mann-Whitney U test. The Kaplan-Meier method was used to calculate survival rate and draw survival curve, and the Log-rank test was used for survival analysis. The COX stepwise regression model with backward Wald method was used for univariate and multivariate analyses. Results:(1) Achievement of TOLS. Of the 824 patients undergoing curative-intent resection for GBC, there were 510 cases achieving TOLS and 314 cases not achieving TOLS. (2) Follow-up. Of the 824 patients undergoing curative-intent resection for GBC, after excluding 112 deaths within 90 days after discharge, 712 cases were included for the survival analysis. The median follow-up time, median overall survival time and 5-year overall survival rate of the 510 patients achieving TOLS were 22.1(11.4,30.1)months, 47.6(30.6,64.6)months and 47.5%. The median follow-up time, median overall survival time and 5-year overall survival rate of the 202 patients not achieving TOLS were 14.0(6.8,25.5)months, 24.3(20.0,28.6)months and 21.0%. There was a significant difference in overall survival between patients achieving TOLS and patients not achieving TOLS ( χ2=58.491, P<0.05). (3) Analysis of factors influencing prognosis of patients. Results of multivariate analysis showed that TOLS, carcinoembryonic antigen (CEA), CA19-9, poorly differentiation of tumor, T2 stage of eighth edition of American Joint Committee on Cancer (AJCC) staging, T3 and T4 stage of eighth edition of AJCC staging, N1 stage of the eighth edition of AJCC staging, N2 stage of the eighth edition of AJCC staging, adjuvant therapy were independent factors influencing overall survival time of patients undergoing curative-intent resection for GBC ( hazard ratio=0.452, 1.479, 1.373, 1.612, 1.455, 1.481, 1.835, 1.978, 0.538, 95% c onfidence interval as 0.352-0.581, 1.141-1.964, 1.052-1.791, 1.259-2.063, 1.102-1.920, 1.022-2.147, 1.380-2.441, 1.342-2.915, 0.382-0.758, P<0.05). Conclusion:Patients under-going curative-intent resection for GBC with TOLS can achieve better long-term prognosis.

Patients with severe trauma require an extremely timely treatment and transfusion plays an irreplaceable role in the emergency treatment of such patients. An increasing number of evidence-based medicinal evidences and clinical practices suggest that patients with severe traumatic bleeding benefit from early transfusion of low-titer group O whole blood or hemostatic resuscitation with red blood cells, plasma and platelet of a balanced ratio. However, the current domestic mode of blood supply cannot fully meet the requirements of timely and effective blood transfusion for emergency treatment of patients with severe trauma in clinical practice. In order to solve the key problems in blood supply and blood transfusion strategies for emergency treatment of severe trauma, Branch of Clinical Transfusion Medicine of Chinese Medical Association, Group for Trauma Emergency Care and Multiple Injuries of Trauma Branch of Chinese Medical Association, Young Scholar Group of Disaster Medicine Branch of Chinese Medical Association organized domestic experts of blood transfusion medicine and trauma treatment to jointly formulate Chinese expert consensus on blood support mode and blood transfusion strategies for emergency treatment of severe trauma patients ( version 2024). Based on the evidence-based medical evidence and Delphi method of expert consultation and voting, 10 recommendations were put forward from two aspects of blood support mode and transfusion strategies, aiming to provide a reference for transfusion resuscitation in the emergency treatment of severe trauma and further improve the success rate of treatment of patients with severe trauma.

OBJECTIVE Optimizing the water extraction technology of Xiangqin jiere granules. METHODS The orthogonal test of 3 factors and 3 levels was designed， and comprehensive scoring was conducted for the above indexes by using G1-entropy weight to obtain the optimized water extraction technology of Xiangqin jiere granules with water addition ratio， extraction time and extraction times as factors， using the contents of forsythoside A， baicalin， phillyrin， oroxylin A-7-O-β-D-glycoside， wogonoside， baicalein and wogonin， and extraction rate as evaluation indexes. BP neural network modeling was used to optimize the network model and water extraction process using the results of 9 groups of orthogonal tests as test and training data， the water addition multiple， decocting time and extraction times as input nodes， and the comprehensive score as output nodes. Then the two analysis methods were compared by verification test to find the best water extraction process parameters. RESULTS The water extraction technology optimized by the orthogonal test was 8-fold water， extracting 3 times， extracting for 1 h each time. Comprehensive score was 96.84 （RSD＝0.90%）. The optimal water extraction technology obtained by BP neural network modeling included 12-fold water， extracting 4 times， extracting for 0.5 h each time. The comprehensive score was 92.72 （RSD＝0.77%）， which was slightly lower than that of the orthogonal test. CONCLUSIONS The water extraction technology of Xiangqin jiere granules is optimized successfully in the study， which includes adding 8-fold water， extracting 3 times， and extracting for 1 hour each time.

AIM To evaluate the quality of Beidougen Formula Granules.METHODS Fifteen batches of standard decoctions and three batches of formula granules were prepared,after which paste rate and contents,transfer rates of magnoflorine,daurisoline,dauricine were determined.HPLC specific chromatograms were established,and cluster analysis was adopted in chemical pattern recognition.RESULTS For three batches of formula granules,the paste rates were 15.1%-16.6%,the contents of magnoflorine,daurisoline,dauricine were 18.93-19.39,9.42-9.60,6.79-6.85 mg/g with the transfer rates of 34.42%-35.25%,43.81%-44.65%,27.27%-27.51%from decoction pieces to formula granules,respectively,and there were seven characteristic peaks in the specific chromatograms with the similarities of more than 0.95,which demonstrated good consistence with those of standard decoctions and accorded with related limit requirements.Fifteen batches of standard decoctions were clustered into two types,and the medicinal materials produced from Jilin,Hebei,Shangdong could be used for the preparation of formula granules.CONCLUSION This reasonable and reliable method can provide references for the quality control and clinical application of Beidougen Formula Granules.

Renal fibrosis is a common pathological manifestation of all chronic kidney diseases.Ferroptosis is closely related to the pathogenesis of renal fibrosis and can influence the onset of renal fibrosis,and it is the most critical step in the development of renal fibrosis.The paper describes the relationship between ferroptosis and renal fibrosis,discusses the research progress of ferroptosis on renal fibrosis,and further summarizes,analyzes,and describes the effective and highly targeted natural active ingredients of traditional Chinese medicines against ferroptosis,and concludes that the reversal of renal fibrosis is achieved through the regulation of the key targets of ferroptosis,with a view to providing a broad new direction for its prospects in the field of renal fibrotic disease prevention and treatment;and to provide a scientific guide for clinical treatment and basis for clinical treatment.

Objective:To discuss the effect of oridonin on the proliferation,migration,epithelial-mesenchymal transition(EMT),and apoptosis of the human nasopharyngeal carcinoma HONE-1 cells,and to clarify its related antitumor mechanism.Methods:The HONE-1 cells were treated with different concentrations(0,5,10,20,40,80,and 160 mg·L-1)of oridonin for 48 h.CCK-8 method was used to detect the inhibitory rates of proliferation of the cells in various groups and the drug concentration for subsequent experiment was confirmed.The HONE-1 cells were divided into control group,3 mg·L-1 oridonin group,and 6 mg·L-1 oridonin group.After 24 and 48 h of culture,CCK-8 method was used to detect the proliferation activities of the cells in various groups;5-ethynyl-2'-deoxyuridine(EdU)method was used to detect the rates of EdU-positive cells in various groups;colony formation assay was used to detect the numbers of clone formation in the cells in various groups;Transwell chamber experiment and cell wound assay were used to detect the numbers of migration cells and the scratch healing rates of the cells in various groups;real-time fluorescence quantitative PCR(RT-qPCR)method was used to detect the expression levels of cyclin-dependent kinase 1(CDK1)and cyclin-dependent kinase 4(CDK4)mRNA in the cells in various groups;Western blotting method was used to detect the expression levels of E-cadherin,Vimentin,Caspase-3,and poly ADP-ribose polymerase 1(PARP1)proteins in the cells in various groups.Results:The CCK-8 method results showed that the half-maximal inhibitory concentration(IC50)of oridonin at 48 h was 12.18 mg·L-1,and 1/4 IC50 and 1/2 IC50 values were used as the concentrations for subsequent experiments.Compared with control group,after treated for 24 and 48 h,the proliferation activities of the cells in 3 and 6 mg·L-1 oridonin groups were decreased(P＜0.05 or P＜0.01),the rate of EdU-positive cells were decreased(P＜0.05 or P＜0.01),the numbers of clone formation and migraton cells were decreased(P＜0.05 or P＜0.01),the scratch healing rates were decreased(P＜0.05 or P＜0.01),the expression levels of CDK1 and CDK4 mRNA in the cells were decreased(P＜0.05 or P＜0.01),the expression levels of E-cadherin,Caspase-3,and PARP1 proteins were increased(P＜0.05 or P＜0.01),and the expression levels of Vimentin protein were decreased(P＜0.05).Conclusion:Oridonin can inhibit the proliferation,clone formation,and migration of the human nasopharyngeal carcinoma HONE-1 cells by downregulating the expression of cell cycle-related proteins and EMT,and promote the apoptosis to exert an antitumor effect.

Objective To analyze the expression levels of serum miR-21-5p and miR-100-5p in patients with esophageal squamous cell carcinoma(ESCC)and healthy controls,and to explore their impact on the differential diagnosis,clinical characteristics correlation,and patient prognosis of ESCC.Methods A total of 158 patients with advanced ESCC who underwent radiotherapy in our hospital's radiotherapy department from January 2018 to January 2022 were collected as the experimental group.Additionally,150 healthy individuals who underwent physical examinations were selected as the control group.Peripheral blood(5 ml)was collected from each subject,and serum was prepared.The expression levels of miR-21-5p and miR-100-5p were detected using real-time quantitative PCR(RT-qPCR).The expression differences of miR-21-5p and miR-100-5p between the experimental and control groups were compared using the t-test,and the clinical prognosis survival analysis was performed using the Kaplan-Meier method with Log-Rank test.Results Compared with the healthy control group,the expression levels of serum miR-21-5p and miR-100-5p in ESCC patients were significantly increased(both P＜0.001).The elevated expression levels of serum miR-21-5p and miR-100-5p can accurately distinguish ESCC from healthy controls,with an area under the curve(A UC)of 0.918 for combined diagnosis,a sensitivity of 93.2％,and a specificity of 87.1％.The increased expression of serum miR-21-5p and miR-100-5p in ESCC patients was correlated with later TNM stages and poorer disease-free survival and overall survival(both P＜0.05).Multivariate Cox analysis showed that TNM stage Ⅲ,high expression of serum miR-21-5p,and low expression of miR-100-5p are independent risk factors for the disease-free survival and overall survival of ESCC patients(all P＜0.05).Conclusion The expression levels of serum miR-21-5p and miR-100-5p are significantly increased in ESCC patients and indicate a poorer prognosis.Serum miR-21-5p and miR-100-5p hold promise as biomarkers for the diagnosis and prognostic prediction of ESCC.

Objective:To explore the predictive value of ultrasound-based radiomics for liver metastasis in pancreatic neuroendocrine tumors (pNEN).Methods:A retrospective analysis was conducted on clinical, pathological, and ultrasound data of 269 pNEN patients confirmed by pathology at Tianjin Medical University Cancer Institute and Hospital from January 2012 to June 2022, including 94 patients with liver metastasis and 175 without liver metastasis. The regions of interest (ROI) were delineated on the maximum diameter section of the tumor using ITKSNAP software, and radiomics features were extracted using Pyradiomics. Radiomics features with an intra-group correlation coefficient greater than 0.90 were retained, and the optimal features were selected using the maximum relevance minimum redundancy (MRMR) algorithm. The dataset was randomly divided into a training set and a validation set in a ratio of 7∶3, and the random forest algorithm (Rfs) was used to predict pNEN liver metastasis. Three models were constructed, including the clinical ultrasound model, the radiomics model, and the comprehensive model that combined clinical ultrasound and radiomics features. The predictive performance of different models for pNEN liver metastasis was analyzed using the ROC curve, and the predictive performance of different models was compared using the Delong test.Results:A total of 874 features were extracted from the ROI, and 12 highly robust radiomics features were retained for model construction based on inter- and intra-observer correlation grading and feature selection. The area under curve(AUC), sensitivity, specificity, and accuracy of the radiomics model, the clinical ultrasound model, and the comprehensive model for predicting liver metastasis in pNEN patients were 0.800, 0.574, 0.789, 0.714; 0.780, 0.596, 0.874, 0.777; and 0.890, 0.694, 0.874, 0.810, respectively. The Delong test showed that the comprehensive model had the best predictive performance, with an AUC superior to that of radiomics model ( Z=3.845, P=0.000 12) and clinical ultrasound model ( Z=3.506, P=0.000 45). Conclusions:The radiomics model based on ultrasound has good performance in predicting liver metastasis in pNEN, and the comprehensive model that combines clinical ultrasound and radiomics features can further improve the predictive performance of the model.