OBJECTIVE To investigate the effect and mechanism of picroside Ⅱ on the malignant progression of non-small cell lung cancer （NSCLC）. METHODS A549 cells were divided into the control group， picroside Ⅱ low-， medium- and high- concentration groups， K6PC-5 [sphingosine kinase 1 （SPHK1） activator] group， and picroside Ⅱ high-dose+K6PC-5 group. Cell proliferation， migration and invasion were detected. Besides， the expression of proliferating cell nuclear antigen （PCNA）， matrix metalloproteinase-2 （MMP-2）， MMP-9， SPHK1， sphingosine-1-phosphate receptor 3 （S1PR3） and extracellular signal-regulated kinase 1/2 （ERK1/2） protein in the cells were also observed. BALB/c nude mice were subcutaneously inoculated with A549 cell suspension to establish NSCLC xenograft models. Then they were assigned to the nude mouse-control group， nude mouse-picroside Ⅱ low-， medium- and high-dose groups， nude mouse-K6PC-5 group， and nude mouse-picroside Ⅱ high-dose+K6PC-5 group （with 5 mice in each group） to investigate the effect of picroside Ⅱ on their tumor mass and volume. RESULTS Compared with the control group， the OD450 values， EdU-positive cell rates， scratch healing rates， cell invasion number， and the relative expression levels of PCNA， MMP-2， MMP-9， SPHK1， S1PR3 and ERK1/2 protein in the low-， medium- and high-concentration groups of picroside Ⅱ were significantly decreased. Compared with the nude mouse-control group， the tumor mass and volume in the nude mouse-low-， medium- and high-dose groups of picroside Ⅱ were significantly decreased or shrunk. The changes of above indicators were concentration/dose-dependent （P＜0.05）. The changing trend of the corresponding indicators in the K6PC-5 ZYTS181） group and the nude mouse-K6PC-5 group was opposite （P＜0.05）. Compared with the picroside Ⅱ high-concentration group or the nude mice-picroside Ⅱ high-dose group， the above quantitative indicators in the picroside Ⅱ high- concentration+K6PC-5 group cells and the nude mouse-picroside Ⅱ high-dose+K6PC-5 group nude mice were significantly increased or enlarged （P＜0.05）. CONCLUSIONS Picroside Ⅱ may inhibit the malignant progression of NSCLC by inhibiting SPHK1/sphingosine-1-phosphate/S1PR3 signaling pathway.

ObjectiveTo investigate the clinical efficacy of Gandouling tablet （GDL） on abnormal lipid metabolism in Wilson's disease （WD） and the correlation between the prediction model of hepatic steatosis and the related indexes of lipid metabolism in WD. MethodA total of 86 patients with abnormal lipid metabolism in WD were selected. The 24-hour urine copper， alanine aminotransferase （ALT）， aspartate aminotransferase （AST）， serum triglyceride （TG）， total cholesterol （TC）， apolipoprotein B （ApoB）， low density lipoprotein cholesterol （LDL-C）， bile acid （BA）， γ-glutamyl transferase （GGT）， prediction model of hepatic steatosis ［hepatic steatosis index （HSI） and Zhejiang University index （ZJU index）］， ultrasonic attenuation coefficient imaging （ATT）， and traditional Chinese medicine （TCM） syndrome score were statistically analyzed before treatment. Pearson correlation test was used to analyze the correlation between TG， TC， LDL-C， ApoB， ALT， AST， ALT/AST， BA， GGT， TCM syndrome score， ATT， and HIS and ZJU. The patients were divided into an observation group and a control group by random number table method， with 43 cases in each group. The observation group was treated with GDL combined with sodium dimercaptopropane sulfonate （DMPS）， while the control group was only treated with DMPS as a control. After six courses of treatment， 24-hour urine copper， TC， TG， LDL-C， ApoB， HSI， ZJU， ATT， TCM syndrome score， and clinical efficiency before and after treatment were observed and compared between the two groups. The correlation between HSI and ZJU and serum TC， TG， LDL-C， ApoB， ALT， AST， ALT/AST， BA， GGT， TCM syndrome scores， and ATT was analyzed. ResultPearson correlation analysis showed that serum TC （r = 0.811）， TG （r = 0.826）， LDL-C （r = 0.802）， ApoB （r = 0.820）， ALT （r = 0.497）， ALT/AST （r = 0.826）， TCM syndrome score （r = 0.716）， and ATT （r = 0.736） were positively correlated with HSI （P<0.01）， while AST， BA， and GGT had no significant correlation with HSI. TC （r = 0.718）， TG （r = 0.765）， LDL-C （r = 0.667）， ApoB （r = 0.699）， ALT/AST （r = 0.403）， TCM syndrome score （r = 0.666）， and ATT （r = 0.684） were positively correlated with ZJU （P<0.01）. ALT， AST， BA， and GGT had no significant correlation with ZJU. The total effective rate of the observation group was 86.05 （37/43）， and that of the control group was 72.09% （31/43）. The total effective rate of the observation group was higher than that of the control group （Z = -2.301， P<0.05）. After treatment， the 24-hour urine copper of the two groups increased significantly. The levels of TC， TG， LDL-C， and ApoB were significantly decreased， and the HSI， ZJU， and ATT were significantly decreased （P<0.01）. Compared with those in the control group after treatment， the above indexes improved better in the observation group （P<0.05， P<0.01）. ConclusionGDL can effectively improve the level of copper and lipid metabolism in patients with WD， with high clinical safety and good clinical application value. The prediction model of hepatic steatosis can effectively reflect the degree of abnormal lipid metabolism in WD.

BACKGROUND:As tissue engineering brings new hope to the worldwide problem of articular cartilage repair,the construction of light-curing 3D printed hydrogel scaffolds with biomimetic composition is of great significance for cartilage tissue engineering. OBJECTIVE:To construct a biomimetic methacryloylated hyaluronic acid/acellular Wharton's jelly composite hydrogel scaffold by digital light processing 3D printing technology,and to evaluate its biocompatibility. METHODS:Wharton's jelly was isolated and extracted from human umbilical cord,then decellulated,freeze-dried,ground into powder,and dissolved in PBS to prepare 50 g/L acellular Wharton's jelly solution.Methylallylated hyaluronic acid was prepared,lyophilized and dissolved in PBS to prepare 50 g/L methylallylated hyaluronic acid solution.Acellular Wharton's jelly solution was mixed with methacrylyacylated hyaluronic acid solution at a volume ratio of 1:1,and was used as bio-ink after adding photoinitiator.Methylacrylylated hyaluronic acid hydrogel scaffolds(labeled as HAMA hydrogel scaffolds)and methylacrylylated hyaluronic acid/acellular Wharton's jelly gel scaffolds(labeled as HAMA/WJ hydrogel scaffolds)were prepared by digital light processing 3D printing technology,and the microstructure,swelling performance,biocompatibility,and cartilage differentiation performance of the scaffolds were characterized. RESULTS AND CONCLUSION:(1)Under scanning electron microscope,the two groups of scaffolds showed a three-dimensional network structure,and the fiber connection of HAMA/WJ hydrogel scaffold was more uniform.Both groups achieved swelling equilibrium within 10 hours,and the equilibrium swelling ratio of HAMA/WJ hydrogel scaffold was lower than that of HAMA hydrogel scaffold(P＜0.05).(2)CCK-8 assay showed that HAMA/WJ hydrogel scaffold could promote the proliferation of bone marrow mesenchymal stem cells compared with HAMA hydrogel scaffold.Dead/live staining showed that bone marrow mesenchymal stem cells grew well on the two groups of scaffolds,and the cells on the HAMA/WJ hydrogel scaffolds were evenly distributed and more cells were found.Phalloidine staining showed better adhesion and spread of bone marrow mesenchymal stem cells in HAMA/WJ hydrogel scaffold than in HAMA.(3)Bone marrow mesenchymal stem cells were inoculated into the two groups for chondrogenic induction culture.The results of qRT-PCR showed that the mRNA expressions of agglutinoglycan,SOX9 and type Ⅱ collagen in the HAMA/WJ hydrogel scaffold group were higher than those in the HAMA hydrogel scaffold group(P＜0.05,P＜0.01).(4)These findings indicate that the digital light processing 3D bioprinting HAMA/WJ hydrogel scaffold can promote the proliferation,adhesion,and chondrogenic differentiation of bone marrow mesenchymal stem cells.

Objective To investigate the prognostic value of preoperative serum albumin-to-globulin ratio (AGR) and neutrophil-lymphocyte ratio (NLR) in the overall survival (OS) of patients with esophageal squamous cell carcinoma (ESCC), and to establish an individualized nomogram model and evaluate its efficacy, in order to provide a possible evaluation basis for the clinical treatment and postoperative follow-up of ESCC patients. Methods AGR, NLR, clinicopathological and follow-up data of ESCC patients diagnosed via pathology in the Department of Thoracic Surgery, The First Affiliated Hospital of Xinjiang Medical University from 2010 to 2017 were collected. The correlation between NLR/AGR and clinicopathological data were analyzed. Kaplan-Meier analysis and log-rank test were used for survival analysis. The optimal cut-off values of AGR and NLR were determined by X-tile software, and the patients were accordingly divided into a high-level group and a low-level group. At the same time, univariate and multivariate Cox regression analyses were used to identify independent risk factors affecting OS in the ESCC patients, and a nomogram prediction model was constructed and internally verified. The diagnostic efficacy of the model was evaluated by receiver operating characteristic (ROC) curve and calibration curve, and the clinical application value was evaluated by decision curve analysis. Results A total of 150 patients were included in this study, including 105 males and 45 females with a mean age of 62.3±9.3 years, and the follow-up time was 1-5 years. The 5-year OS rate of patients in the high-level AGR group was significantly higher than that in the low-level group (χ2=6.339, P=0.012), and the median OS of the two groups was 25 months and 12.5 months, respectively. The 5-year OS rate of patients in the high-level NLR group was significantly lower than that in the low-level NLR group (χ2=5.603, P=0.018), and the median OS of the two groups was 18 months and 39 months, respectively. Multivariate Cox analysis showed that AGR, NLR, T stage, lymph node metastasis, N stage, and differentiation were independent risk factors for the OS of ESCC patients. The C-index of the nomogram model was 0.689 [95%CI (0.640, 0.740)] after internal validation. The area under the ROC curve of predicting 1-, 3-, and 5-year OS rate was 0.773, 0.724 and 0.725, respectively. At the same time, the calibration curve and the decision curve suggest that the model had certain efficacy in predicting survival and prognosis. Conclusion Preoperative AGR and NLR are independent risk factors for ESCC patients. High level of AGR and low level of NLR may be associated with longer OS in the patients; the nomogram model based on AGR, NLR and clinicopathological features may be used as a method to predict the survival and prognosis of ESCC patients, which is expected to provide a reference for the development of personalized treatment for patients.

Objective To understand the proficiency level and sources of Traditional Chinese Medicine(TCM)health education among hemodialysis patients,in order to provide the basis for promoting the application of TCM nursing in hemodialysis patients.Methods Utilizing a convenience sampling approach,we conducted a survey from April to May 2023 involving hemodialysis patients from 7 tertiary TCM hospitals across Beijing,Hebei Province,Sichuan Province,and other regions.Custom-made questionnaires were utilized,gathering general information,respons-es conceming the level of mastery on TCM health education,and their primary sources of such knowledge.Results A total of 413 questionnaires were disseminated,and 392 proved valid,yielding a valid response rate of 94.92％.The score of patient's knowledge on TCM health education averaged(8.25±3.73),and an average score rate of 48.53％was obtained.In the patients undergoing hemodialysis,a relatively larger number of people possess knowl-edge of TCM health knowledge about relieving symptoms(50.8％～55.9％)and traditional Chinese daily life routines(56.4％～90.1％).However,fewer people are aware of how to use the five-tone therapy method for emotional inter-vention(40.8％)and principle of taking restorative Traditional Chinese Medicine(24.5％～36.7％),the dietary prin-ciples of"nurturing yang in spring and summer,and nurturing yin in autumn and winter"(14.3％),and theories of TCM kidney functions(9.9％).Approximately 23.0％of the patients sourced their TCM health education knowledge from new media platforms.Compared with new media method alone,patients who utilized only traditional education-al platforms(P=0.020),and those who combined both new media and traditional methods(P=0.018)demonstrated higher proficiency in TCM health education.Conclusion Hemodialysis caregivers are urged to develop a TCM health education framework that emphasizes emotional well-being and traditional wellness concepts,thereby fostering patient-centric TCM health ideologies.Hemodialysis education personnel are encouraged to leverage new media whilst ensuring education quality and effective outcomes.

Objective To investigate the progress of two-dimensional echocardiographic parameters in patients with different severity of aortic stenosis.Methods A retrospective analysis was per-formed on 96 patients diagnosed with aortic stenosis with at least 2 times of transthoracic echo-cardiography(interval ≥1 year)in Department of Cardiology,Fourth Medical Center of Chinese PLA General Hospital from March 2017 to December 2023.According to aortic stenosis severity,they were divided into a mild group(72 cases),a moderate group(14 cases)and a severe group(10 cases).Peak pressure gradient(PPG)across aortic valve,Vmax,mean aortic valve pressure gradient(ΔPm),pulmonary artery systolic pressure(PASP)were collected,and the changes and annual progress of these echocardiographic parameters at baseline and before and after follow-up were analyzed.Results The values of IVST,LVPWT,Vmax,aortic valve PPG and ΔPm were sig-nificantly increased in the mild,moderate and severe stenosis groups in turn(P＜0.05,P＜0.01).The values of Vmax,PPG and ΔPm were significantly lower in the mild stenosis group than the moderate and severe stenosis groups,and the LVPWT value was obviously lower in the mild ste-nosis group than the severe stenosis group(P＜0.05).The aortic valve PPG and ΔPm values at follow-up were significantly higher than those before the follow-up in the three stenosis groups(P＜0.05,P＜0.01).After follow-up,the Vmax values in mild and moderate stenosis groups were notably higher than before(P＜0.01).The PASP value at follow-up was significantly higher than before in the severe stenosis group(P＜0.05).The annual progression rate of Vmax,PASP,LVEF were gradually increased in the mild,moderate,and severe stenosis groups(P＞0.05).The annual progression rate of ΔPm was gradually increased in the three groups in turn(2.30±1.77 mm Hg/year vs 2.40±1.18 mm Hg/year vs 6.08±1.70 mm Hg/year,P＜0.05).Conclusion As the severity of baseline aortic stenosis increases,obvious changes are observed in cardiac structure and function.Before and after follow-up,the serious the aortic stenosis severity is,the faster the annual progression rates of Vmax,PPG,LVEF and PASP are.

Insufficient myocardial perfusion is a common pathological feature in the early stage of various heart diseases,and quantitative evaluation of myocardial perfusion is of great significance for diagnosing and treating diseases and evaluating prognosis.Cardiac MR(CMR)perfusion imaging is non radiative,having high spatial resolution and being sensitive to local myocardial ischemia.Numerical simulation technology combined with computational biomechanics could simulate the process of myocardial blood flow perfusion.The research progresses of CMR and numerical simulation for quantitative evaluation of myocardial perfusion were reviewed in this article.

Objective:To evaluate the diagnostic value of urine proteomics in interstitial lung disease.Methods:A case control study was conducted. 10 patients (age 56.70±14.78 years) with interstitial lung disease, 9 patients (age 51.30±23.26 years) with pulmonary infection and 10 healthy controls (age 50.20±6.07 years) from the physical examination center were selected from China-Japan Friendship Hospital from March 12 to April 15, 2023. The urine proteomics of three groups of people were studied using Liquid chromatography-mass spectrometry proteomics technology. Based on Data-Independent Acquisition mass spectrometry quantitative technology, three groups of people were compared, and t-test was performed between groups and relevant functional analysis was conducted.Results:A total of 2 730 proteins were identified. Three groups of people can be clearly distinguished by urine proteome using partial least squares discriminant analysis based on orthogonal signal correction. Quantitative comparison of proteins was conducted by the screening criteria for differential proteins with P<0.05 and protein abundance fold changes of>3/2 or<2/3. 49 proteins between interstitial lung disease patients and healthy people, as well as 57 proteins between interstitial lung disease patients and infectious diseases patients, were significantly changed. ECM receptor interaction and complement-coagulation cascade pathways were enriched by GO enrichment and KEGG analysis on differentially expressed proteins. Conclusions:Urinary proteomics can effectively distinguish patients with interstitial lung disease from those with pulmonary infections and the normal population. The differential proteins identified in this experiment have certain diagnostic performance (AUC value 0.68-1.00) and can be used as potential disease markers for the diagnosis of interstitial lung disease.

Objective: This study aimed to determine the predictive performance of non-contrast CT (NCCT) signs for hemorrhagic growth after intracerebral hemorrhage (ICH) when stratified by onset-to-imaging time (OIT). Materials and Methods: 1488 supratentorial ICH within 6 h of onset were consecutively recruited from six centers between January 2018 and August 2022. NCCT signs were classified according to density (hypodensities, swirl sign, black hole sign, blend sign, fluid level, and heterogeneous density) and shape (island sign, satellite sign, and irregular shape) features. Multivariable logistic regression was used to evaluate the association between NCCT signs and three types of hemorrhagic growth: hematoma expansion (HE), intraventricular hemorrhage growth (IVHG), and revised HE (RHE). The performance of the NCCT signs was evaluated using the positive predictive value (PPV) stratified by OIT. Results: Multivariable analysis showed that hypodensities were an independent predictor of HE (adjusted odds ratio [95% confidence interval] of 7.99 [4.87–13.40]), IVHG (3.64 [2.15–6.24]), and RHE (7.90 [4.93–12.90]). Similarly, OIT (for a 1-h increase) was an independent inverse predictor of HE (0.59 [0.52–0.66]), IVHG (0.72 [0.64–0.81]), and RHE (0.61 [0.54– 0.67]). Blend and island signs were independently associated with HE and RHE (10.60 [7.36–15.30] and 10.10 [7.10–14.60], respectively, for the blend sign and 2.75 [1.64–4.67] and 2.62 [1.60–4.30], respectively, for the island sign). Hypodensities demonstrated low PPVs of 0.41 (110/269) or lower for IVHG when stratified by OIT. When OIT was ≤ 2 h, the PPVs of hypodensities, blend sign, and island sign for RHE were 0.80 (215/269), 0.90 (142/157), and 0.83 (103/124), respectively. Conclusion Hypodensities, blend sign, and island sign were the best NCCT predictors of RHE when OIT was ≤ 2 h. NCCT signs may assist in earlier recognition of the risk of hemorrhagic growth and guide early intervention to prevent neurological deterioration resulting from hemorrhagic growth.

The characteristic genetic abnormality of neuroendocrine neoplasms (NENs), a heterogeneous group of tumors found in various organs, remains to be identified. Here, based on the analysis of the splicing variants of an oncogene Focal Adhesion Kinase (FAK) in The Cancer Genome Atlas datasets that contain 9193 patients of 33 cancer subtypes, we found that Box 6/Box 7-containing FAK variants (FAK^6/7) were observed in 7 (87.5%) of 8 pancreatic neuroendocrine carcinomas and 20 (11.76%) of 170 pancreatic ductal adenocarcinomas (PDACs). We tested FAK variants in 157 tumor samples collected from Chinese patients with pancreatic tumors, and found that FAK^6/7 was positive in 34 (75.6%) of 45 pancreatic NENs, 19 (47.5%) of 40 pancreatic solid pseudopapillary neoplasms, and 2 (2.9%) of 69 PDACs. We further tested FAK splicing variants in breast neuroendocrine carcinoma (BrNECs), and found that FAK^6/7 was positive in 14 (93.3%) of 15 BrNECs but 0 in 23 non-NEC breast cancers. We explored the underlying mechanisms and found that a splicing factor serine/arginine repetitive matrix protein 4 (SRRM4) was overexpressed in FAK^6/7-positive pancreatic tumors and breast tumors, which promoted the formation of FAK^6/7 in cells. These results suggested that FAK^6/7 could be a biomarker of NENs and represent a potential therapeutic target for these orphan diseases.
Female ; Humans ; Alternative Splicing ; Breast Neoplasms/metabolism* ; Carcinoma, Pancreatic Ductal/pathology* ; Focal Adhesion Protein-Tyrosine Kinases/therapeutic use* ; Nerve Tissue Proteins/genetics* ; Neuroendocrine Tumors/genetics* ; Oncogenes ; Pancreatic Neoplasms/metabolism*