Objective To investigate the regulatory effect of Jianpi Huayu Prescription(Ginseng Radix et Rhizoma,Poria,Atractylodis Macrocephalae Rhizoma,Salviae Miltiorrhizae Radix et Rhizoma,etc.)on epithelial-mesenchymal transition(EMT)and angiogenesis of hepatocellular carcinoma through TGF-β1/Smad7 pathway.Methods(1)Hep3B tumor-bearing mouse model was established by BALB/C-nu nude mice.The mice were randomly divided into control group and Jianpi Huayu Prescription low-,medium-and high-dose groups(3.844,7.689,15.378 g·kg-1·d-1),with five mice in each group.Intragastric administration was performed once a day for 21 days.(2)Hep3B cells were divided into blank group,model group(10 ng·mL-1 TGF-β1),low-concentration group(10 ng·mL-1 TGF-β1+4 mg·mL-1 Jianpi Huayu Prescription),and high-concentration group(10 ng·mL-1 TGF-β1+6 mg·mL-1 Jianpi Huayu Prescription).After 48 hours of TGF-β1 induction,the cells were replaced with the corresponding concentration of Jianpi Huayu Prescription complete culture medium(0,4,6 mg·mL-1)and cultured for 24 hours.(3)HUVEC cells were divided into normal group,model group,Chinese medicine group,model plus Chinese medicine group.The cells in the normal group were cultured with conditioned medium without TGF-β1;the cells in the model group were cultured with conditioned medium containing TGF-β1.The cells in the Chinese medicine group were cultured in conditioned medium containing 4 mg·mL-1 Jianpi Huayu Prescription without TGF-β 1.The cells in the model plus Chinese medicine group were cultured with conditioned medium containing 4 mg·mL-1 Jianpi Huayu Prescription and TGF-β1.After 24 hours of continuous culture,the cells were collected for subsequent experiments.(4)The tumor mass index and tumor inhibition rate of subcutaneous transplantation tumor of Hep3B tumor-bearing nude mice were calculated.The expression of CD31 in subcutaneous xenografts of tumor-bearing nude mice was detected by immunofluorescence.The microvessel density of subcutaneous transplanted tumor in nude mice was detected by immunohistochemistry.The migration ability of Hep3B cells was detected by cell scratch test.Transwell assay was used to detect the invasion ability of Hep3B/HUVEC cells.The tube formation ability of HUVEC cells was detected.The expression levels of related proteins in subcutaneous transplanted tumors,Hep3B and HUVEC cells of tumor-bearing nude mice were detected by Western Blot.Results(1)Compared with the control group,the weight and tumor mass index of subcutaneous transplanted tumor in nude mice in the medium-and high-dose groups of Jianpi Huayu Prescription were significantly decreased(P＜0.01).The expression of CD31 and microvessel density in subcutaneous transplanted tumors of nude mice in low-,medium-and high-dose groups were significantly decreased(P＜0.05,P＜0.01),the protein expressions of VE-cadherin,EphA2 and N-cadherin were significantly down-regulated(P＜0.05,P＜0.01),and the protein expressions of E-cadherin and Smad7 was significantly up-regulated(P＜0.01).(2)Compared with the blank group,the relative migration rate of Hep3B cells in the model group was significantly increased(P＜0.05),and the number of invasive cells was significantly increased(P＜0.01).The protein expressions of Vimentin and N-cadherin were significantly up-regulated(P＜0.01),and the protein expressions of E-cadherin and Smad7 was significantly down-regulated(P＜0.01).Compared with the model group,the relative migration rate of Hep3B cells in the low-and high-concentration groups of Jianpi Huayu Prescription was significantly decreased(P＜0.01),and the number of invasive cells was significantly decreased(P＜0.01).The protein expressions of Vimentin and N-cadherin was significantly down-regulated(P＜0.01),and the protein expressions of E-cadherin and Smad7 were significantly up-regulated(P＜0.01).(3)Compared with the normal group,the number of tubular branching points formed by HUVEC cells in the model group was significantly increased(P＜0.01),the length of tubular branching was significantly increased(P＜0.01),and the number of invasive cells was significantly increased(P＜0.01).The protein expressions of VE-cadherin and EphA2 were significantly up-regulated(P＜0.01),and the protein expression of Smad7 was significantly down-regulated(P＜0.01).Compared with the model group,the number of tubular branching points formed by HUVEC cells in the model plus Chinese medicine group was significantly reduced(P＜0.01),the length of tubular branching was significantly shortened(P＜0.01),and the number of invasive cells was significantly reduced(P＜0.01).The protein expressions of VE-cadherin and EphA2 were significantly down-regulated(P＜0.01),and the protein expression of Smad7 was significantly up-regulated(P＜0.01).Conclusion Jianpi Huayu Prescription can significantly inhibit the growth,invasion and migration of hepatocellular carcinoma,which may be related to the regulation of EMT and angiogenesis mediated by TGF-β1/Smad7 pathway.

The Piezo protein is a non-selective mechanosensitive cation channel that exhibits sensitivity to mechanical stimuli such as pressure and shear stress. It converts mechanical signals into bioelectric activity within cells, thus triggering specific biological responses. In the digestive system, Piezo protein plays a crucial role in maintaining normal physiological activities, including digestion, absorption, metabolic regulation, and immune modulation. However, dysregulation in Piezo protein expression may lead to the occurrence of several pathological conditions, including visceral hypersensitivity, impairment of intestinal mucosal barrier function, and immune inflammation.Therefore, conducting a comprehensive review of the physiological functions and pathological roles of Piezo protein in the digestive system is of paramount importance. In this review, we systematically summarize the structural and dynamic characteristics of Piezo protein, its expression patterns, and physiological functions in the digestive system. We particularly focus on elucidating the mechanisms of action of Piezo protein in digestive system tumor diseases, inflammatory diseases, fibrotic diseases, and functional disorders. Through the integration of the latest research findings, we have observed that Piezo protein plays a crucial role in the pathogenesis of various digestive system diseases. There exist intricate interactions between Piezo protein and multiple phenotypes of digestive system tumors such as proliferation, apoptosis, and metastasis. In inflammatory diseases, Piezo protein promotes intestinal immune responses and pancreatic trypsinogen activation, contributing to the development of ulcerative colitis, Crohn’s disease, and pancreatitis. Additionally, Piezo1, through pathways involving co-action with the TRPV4 ion channel, facilitates neutrophil recruitment and suppresses HIF-1α ubiquitination, thereby mediating organ fibrosis in organs like the liver and pancreas. Moreover, Piezo protein regulation by gut microbiota or factors like age and gender can result in increased or decreased visceral sensitivity, and alterations in intestinal mucosal barrier structure and permeability, which are closely associated with functional disorders like irritable bowel sydrome (IBS) and functional consitipaction (FC). A thorough exploration of Piezo protein as a potential therapeutic target in digestive system diseases can provide a scientific basis and theoretical support for future clinical diagnosis and treatment strategies.

Cancerous fever is a non-infectious fever that occurs during the progression of malignant tumors,which is directly related to the tumor or is caused by tumor treatment.Based on the yin-fire theory,Professor WANG Xi-Xing believes that the qi deficiency of spleen and stomach and the upward flaming of yin-fire are the key pathogenesis of cancerous fever.The cancerous fever involves the three zang-organs of liver,spleen and kidney,and its treatment should be achieved mainly by replenishing qi with warm-sweet medicinals,invigorating spleen and elevating yang,and clearing and purging yin-fire.Moreover,the correlation between earth(spleen)and wood(liver)should be taken into account,and harmonizing spleen and stomach can be achieved by nourishing blood and relieving depression,and soothing liver to disperse fire;the transmission of yin-fire should be blocked through the method of nourishing yin and clearing heat,and inducing fire to return to the source.After years of clinical experience,Professor WANG Xi-Xing establised Buzhong Tiaogan Decoction(mainly composed of Astragali Radix,Codonopsis Radix,Atractylodis Macrocephalae Rhizoma,Cimicifugae Rhizoma,Bupleuri Radix,Angelicae Sinensis Radix,Paeoniae Radix Alba,Ophiopogonis Radix,Schisandrae Chinensis Fructus,Citri Reticulatae Pericarpium,Scolopendra,Salviae Chinensis Herba,Fructus Akebiae,and Glycyrrhizae Radix et Rhizoma Praeparata cum Melle),which is derived from Buzhong Yiqi Decoction.Buzhong Tiaogan Decoction is effective on relieving the symptoms of cancerous fever in cancer patients by benefiting the middle energizer qi,nourishing liver blood,regulating liver qi,eliminating abdominal mass and dissipating mass,so as to correct the cold,heat,yin and yang of the human body.

Objective To explore the value of deep learning(DL)models semi-automatic training system for automatic optimization of clinical image quality control of transthoracic echocardiography(TTE).Methods Totally 1 250 TTE videos from 402 patients were retrospectively collected,including 490 apical four chamber(A4C),310 parasternal long axis view of left ventricle(PLAX)and 450 parasternal short axis view of great vessel(PSAXGv).The videos were divided into development set(245 A4C,155 PLAX,225 PSAXGV),semi-automated training set(98 A4C,62 PLAX,90 PSAXGV)and test set(147 A4C,93 PLAX,135 PSAXGV)at the ratio of 5:2:3.Based on development set and semi-automatic training set,DL model of quality control was semi-automatically iteratively optimized,and a semi-automatic training system was constructed,then the efficacy of DL models for recognizing TTE views and assessing imaging quality of TTE were verified in test set.Results After optimization,the overall accuracy,precision,recall,and F1 score of DL models for recognizing TTE views in test set improved from 97.33％,97.26％,97.26％and 97.26％to 99.73％,99.65％,99.77％and 99.71％,respectively,while the overall accuracy for assessing A4C,PLAX and PSAXGV TTE as standard views in test set improved from 89.12％,83.87％and 90.37％to 93.20％,90.32％and 93.33％,respectively.Conclusion The developed DL models semi-automatic training system could improve the efficiency of clinical imaging quality control of TTE and increase iteration speed.

Objective:To analyze the factors affecting overall survival(OS)of adult patients with core-binding factor acute myeloid leukemia(CBF-AML)and establish a prediction model.Methods:A total of 216 newly diagnosed patients with CBF-AML in the First Affiliated Hospital of Zhengzhou University from May 2015 to July 2021 were retrospectively analyzed.The 216 CBF-AML patients were divided into the training and the validation cohort at 7:3 ratio.The Cox regression model was used to analyze the clinical factors affecting OS.Stepwise regression was used to establish the optimal model and the nomogram.Receiver operating characteristic(ROC)curve,calibration curve and decision curve analysis(DCA)were used to evaluate the model performance.Results:Age(≥ 55 years old),peripheral blood blast(≥80％),fusion gene(AML1-ETO),KIT mutations were identified as independent adverse factors for OS.The area under the ROC curve at 3-year was 0.772 and 0.722 in the training cohort and validation cohort,respectively.The predicted value of the calibration curve is in good agreement with the measured value.DCA shows that this model performs better than a single factor.Conclusion:This prediction model is simple and feasible,and can effectively predict the OS of CBF-AML,and provide a basis for treatment decision.

Objective:To provide reference for hospital drug selection and clinical rational drug selection,through evaluating the nutritional value of six commonly used balanced compound amino acid injection (BCAA) in clinical practice,including 18AA (250 mL:12.5 g),18AA-I (250 mL:17.5 g),18AA-Ⅱ(250 mL:21.25 g),18AA-IV (250 mL:8.7 g),18AA-V (250 mL:8.06 g),and 18AA-V-SF (250 mL:8.06 g). Methods:Based on the whole egg protein model,the nutritional value of six varieties of BCAA from two aspects were evaluated,including the first limiting amino acid chemical score (CS),value of essential amino acid (EAA) and the comprehensive quality of total EAA (both essential amino acid index and closeness to standard protein). Results:The first limiting amino acid CS value from high to low was 18AA-Ⅱ>18AA>18AA-V=18AA-V-SF>18AA-I=18AA-Ⅳ. Total EAA comprehensive quality:the essential amino acid index from high to low was 18AA-Ⅱ>18AA>18AA-I>18AA-Ⅳ>18AA-V=18AA-V-SF. The closeness to whole egg protein from high to low was 18AA-Ⅱ=18AA=18AA-I>18AA-Ⅳ>18AA-V=18AA-V-SF. Ultimately,the nutritional value of the 6 varieties of BCAA decreased from high to low:18AA-Ⅱ>18AA>18AA-I>18AA-Ⅳ>18AA-V=18AA-V-SF. Conclusions:Among the six varieties of BCAA,18AA-Ⅱ has the highest nutritional value and the highest amino acid content in the same liquid volume,making it the preferred drug for patients with normal liver and kidney function.

Purpose: Molecular residual disease (MRD) is a promising biomarker in colorectal cancer (CRC) for prognosis and guiding treatment, while the whole-exome sequencing (WES) based tumor-informed assay is standard for evaluating MRD based on circulating tumor DNA (ctDNA). In this study, we assessed the feasibility of a fixed-panel for evaluating MRD in CRC. Materials and Methods: Seventy-five patients with resectable stage I-III CRC were enrolled. Tumor tissues obtained by surgery, and preoperative and postoperative day 7 blood samples were collected. The ctDNA was evaluated using the tumor-agnostic and tumor-informed fixed assays, as well as the WES-based and panel-based personalized assays in randomly selected patients. Results: The tumor-informed fixed assay had a higher preoperative positive rate than the tumor-agnostic assay (73.3% vs. 57.3%). The preoperative ctDNA status failed to predict disease-free survival (DFS) in either of the fixed assays, while the tumor-informed fixed assay-determined postoperative ctDNA positivity was significantly associated with worse DFS (hazard ratio [HR], 20.74; 95% confidence interval [CI], 7.19 to 59.83; p < 0.001), which was an independent predictor by multivariable analysis (HR, 28.57; 95% CI, 7.10 to 114.9; p < 0.001). Sub-cohort analysis indicated the WES-based personalized assay had the highest preoperative positive rate (95.1%). The two personalized assays and the tumor-informed fixed assay demonstrated same results in postoperative landmark (HR, 26.34; 95% CI, 6.01 to 115.57; p < 0.001), outperforming the tumor-agnostic fixed panel (HR, 3.04; 95% CI, 0.94 to 9.89; p=0.052). Conclusion Our study confirmed the prognostic value of the ctDNA positivity at postoperative day 7 by the tumor-informed fixed panel. The tumor-informed fixed panel may be a cost-effective method to evaluate MRD, which warrants further studies in future.

Cell Differentiation ; Myeloid Differentiation Factor 88/metabolism* ; NF-kappa B/metabolism* ; Particulate Matter/toxicity* ; Signal Transduction ; Toll-Like Receptor 4/metabolism* ; RAW 264.7 Cells

Objective: To compare the predictive efficacy of the two thrombosis risk assessment scores (Padua and IMPEDE scores) in venous thromboembolism (VTE) within 6 months in patients with newly diagnosed multiple myeloma (NDMM) in China. Methods: This study reviewed the clinical data of 421 patients with NDMM hospitalized in Beijing Jishuitan Hospital from April 2014 to February 2022. The sensitivity, specificity, accuracy, and Youden index of the two scores were calculated to quantify the thrombus risk assessment of VTE by the Padua and IMPEDE scores. The receiver operating characteristics curves of the two evaluation scores were drawn. Results: The incidence of VTE was 14.73%. The sensitivity, specificity, accuracy, and Youden index of the Padua score were 100%, 0%, 14.7%, and 0% and that of the IMPEDE score was 79%, 44%, 49.2%, and 23%, respectively. The areas under the curve of Padua and IMPEDE risk assessment scores were 0.591 and 0.722, respectively. Conclusion: IMPEDE score is suitable for predicting VTE within 6 months in patients with NDMM.
Humans ; Venous Thromboembolism/etiology* ; Multiple Myeloma/diagnosis* ; Risk Assessment ; Risk Factors ; ROC Curve ; Retrospective Studies

OBJECTIVE: This study was aimed at investigating the carrier rate of, and molecular variation in, α- and β-globin gene mutations in Hunan Province. METHODS: We recruited 25,946 individuals attending premarital screening from 42 districts and counties in all 14 cities of Hunan Province. Hematological screening was performed, and molecular parameters were assessed. RESULTS: The overall carrier rate of thalassemia was 7.1%, including 4.83% for α-thalassemia, 2.15% for β-thalassemia, and 0.12% for both α- and β-thalassemia. The highest carrier rate of thalassemia was in Yongzhou (14.57%). The most abundant genotype of α-thalassemia and β-thalassemia was -α ^3.7/αα (50.23%) and β ^IVS-II-654/β ^N (28.23%), respectively. Four α-globin mutations [CD108 (ACC>AAC), CAP +29 (G>C), Hb Agrinio and Hb Cervantes] and six β-globin mutations [CAP +8 (C>T), IVS-II-848 (C>T), -56 (G>C), beta nt-77 (G>C), codon 20/21 (-TGGA) and Hb Knossos] had not previously been identified in China. Furthermore, this study provides the first report of the carrier rates of abnormal hemoglobin variants and α-globin triplication in Hunan Province, which were 0.49% and 1.99%, respectively. CONCLUSION Our study demonstrates the high complexity and diversity of thalassemia gene mutations in the Hunan population. The results should facilitate genetic counselling and the prevention of severe thalassemia in this region.
Humans ; beta-Thalassemia/genetics* ; alpha-Thalassemia/genetics* ; Hemoglobinopathies/genetics* ; China/epidemiology* ; High-Throughput Nucleotide Sequencing