BACKGROUND:H uman pluripotent stem cell-derived cardiomyocytes offer an ideal cellular resource for studying heart diseases,conducting drug screening,developing in vitro heart models,and exploring potential cell therapies.However,human pluripotent stem cell-derived cardiomyocytes are characterized by immaturity with limited specific gene expression,low Ca2+processing levels,and underdeveloped structural,metabolic,and electrophysiological features.These limitations significantly impede the application of human pluripotent stem cell-derived cardiomyocytes.OBJECTIVE:To review the academic progress and clinical application of promoting the maturation of human pluripotent stem cell-derived cardiomyocytes by in vitro synthetic microenvironment.METHODS:CNKI,WanFang,VIP,PubMed,Web of Science,and Medline databases were searched,with"human pluripotent stem cells,human myocardial cells,hPSC-CMs,mature,OA,human pluripotent stem cell-derived cardiomyocytes,hPSC-CMs"as English search terms and"human pluripotent stem cells,cardiomyocytes,mature,OA,hPSC-CMs"as Chinese search terms.All relevant literature published from January 2002 to July 2024 was retrieved and 82 articles were included in the review.RESULTS AND CONCLUSION:(1)In recent years,in vitro synthetic microenvironments have attracted extensive attention due to their excellent intrinsic properties such as stiffness,plasticity,nanoscale morphology,and chemical functionality.(2)Human pluripotent stem cell-derived cardiomyocytes can be used as an effective platform for the treatment of cardiovascular diseases.(3)Mechanical stimulation,electrical stimulation,addition of biochemical molecules,and three-dimensional culture methods are effective methods to promote the maturation of human pluripotent stem cell-derived cardiomyocytes,which can further promote the clinical application of human pluripotent stem cell-derived cardiomyocytes.

Prostate cancer is one of the most common male urological malignancies,in which bone metastasis of desmo-plasia-resistant prostate cancer is an important stage in the progression of the disease,which seriously affects the quality of life and survival of patients.With the development of nuclide therapy technology in recent years,223-Ra,as a new type of alpha-targeted therapy,has shown good efficacy in the treatment of desmoplasia-resistant prostate cancer bone metastasis.The purpose of this pa-per is to review the characteristics,mechanism of action,treatment,and the main research results of its treatment of desmoplasia-resistant prostate cancer bone metastasis,and provide a comprehensive review of the clinical application of 223-Ra in the treatment of desmoplasia-resistant prostate cancer bone metastasis for the clinical application of 223-Ra in prostate cancer bone metastasis.

OBJECTIVE: To evaluate the efficacy and safety of Shexiang Tongxin Dropping Pill (STDP) in treating stable angina patients with phlegm-heat and blood-stasis syndrome by exercise duration and metabolic equivalents. METHODS: This multicenter, randomized, double-blind, placebo-controlled clinical trial enrolled stable angina patients with phlegm-heat and blood-stasis syndrome from 22 hospitals. They were randomized 1:1 to STDP (35 mg/pill, 6 pills per day) or placebo for 56 days. The primary outcome was the exercise duration and metabolic equivalents (METs) assessed by the standard Bruce exercise treadmill test after 56 days of treatment. The secondary outcomes included the total angina symptom score, Chinese medicine (CM) symptom scores, Seattle Angina Questionnaire (SAQ) scores, changes in ST-T on electrocardiogram and adverse events (AEs). RESULTS: This trial enrolled 309 patients, including 155 and 154 in the STDP and placebo groups, respectively. STDP significantly prolonged exercise duration with an increase of 51.0 s, compared to a decrease of 12.0 s with placebo (change rate: -11.1% vs. 3.2%, P<0.01). The increase in METs was significantly greater in the STDP group than in the placebo group (change: -0.4 vs. 0.0, change rate: -5.0% vs. 0.0%, P<0.01). The improvement of total angina symptom scores (25.0% vs. 0.0%), CM symptom scores (38.7% vs. 11.8%), reduction of nitroglycerin consumption (100.0% vs. 11.3%), and all domains of SAQ, were significantly greater with STDP than placebo (all P<0.01). The changes in Q-T intervals at 28 and 56 days from baseline were similar between the two groups (both P>0.05). Twenty-five participants (16.3%) with STDP and 16 (10.5%) with placebo experienced AEs (P=0.131), with no serious AEs observed. CONCLUSION STDP could improve exercise tolerance in patients with stable angina and phlegm-heat and blood stasis syndrome, with a favorable safety profile. (Registration No. ChiCTR-IPR-15006020).
Humans ; Double-Blind Method ; Drugs, Chinese Herbal/adverse effects* ; Male ; Female ; Middle Aged ; Angina, Stable/physiopathology* ; Aged ; Syndrome ; Treatment Outcome ; Placebos ; Tablets

OBJECTIVE: To evaluate the dynamic changes of glucocorticoid (GC) dose and the feasibility of GC discontinuation in rheumatoid arthritis (RA) patients under the background of Chinese medicine (CM). METHODS: This multicenter retrospective cohort study included 1,196 RA patients enrolled in the China Rheumatoid Arthritis Registry of Patients with Chinese Medicine (CERTAIN) from September 1, 2019 to December 4, 2023, who initiated GC therapy. Participants were divided into the Western medicine (WM) and integrative medicine (IM, combination of CM and WM) groups based on medication regimen. Follow-up was performed at least every 3 months to assess dynamic changes in GC dose. Changes in GC dose were analyzed by generalized estimator equation, the probability of GC discontinuation was assessed using Kaplan-Meier curve, and predictors of GC discontinuation were analyzed by Cox regression. Patients with <12 months of follow-up were excluded for the sensitivity analysis. RESULTS: Among 1,196 patients (85.4% female; median age 56.4 years), 880 (73.6%) received IM. Over a median 12-month follow-up, 34.3% (410 cases) discontinued GC, with significantly higher rates in the IM group (40.8% vs. 16.1% in WM; P<0.05). GC dose declined progressively, with IM patients demonstrating faster reductions (median 3.75 mg vs. 5.00 mg in WM at 12 months; P<0.05). Multivariate Cox analysis identified age <60 years [P<0.001, hazard ratios (HR)=2.142, 95% confidence interval (CI): 1.523-3.012], IM therapy (P=0.001, HR=2.175, 95% CI: 1.369-3.456), baseline GC dose ⩽7.5 mg (P=0.003, HR=1.637, 95% CI: 1.177-2.275), and absence of non-steroidal anti-inflammatory drugs use (P=0.001, HR=2.546, 95% CI: 1.432-4.527) as significant predictors of GC discontinuation. Sensitivity analysis (545 cases) confirmed these findings. CONCLUSIONS RA patients receiving CM face difficulties in following guideline-recommended GC discontinuation protocols. IM can promote GC discontinuation and is a promising strategy to reduce GC dependency in RA management. (Trial registration: ClinicalTrials.gov, No. NCT05219214).
Adult ; Aged ; Female ; Humans ; Male ; Middle Aged ; Arthritis, Rheumatoid/drug therapy* ; Glucocorticoids/therapeutic use* ; Medicine, Chinese Traditional ; Retrospective Studies

BACKGROUND:H uman pluripotent stem cell-derived cardiomyocytes offer an ideal cellular resource for studying heart diseases,conducting drug screening,developing in vitro heart models,and exploring potential cell therapies.However,human pluripotent stem cell-derived cardiomyocytes are characterized by immaturity with limited specific gene expression,low Ca2+processing levels,and underdeveloped structural,metabolic,and electrophysiological features.These limitations significantly impede the application of human pluripotent stem cell-derived cardiomyocytes.OBJECTIVE:To review the academic progress and clinical application of promoting the maturation of human pluripotent stem cell-derived cardiomyocytes by in vitro synthetic microenvironment.METHODS:CNKI,WanFang,VIP,PubMed,Web of Science,and Medline databases were searched,with"human pluripotent stem cells,human myocardial cells,hPSC-CMs,mature,OA,human pluripotent stem cell-derived cardiomyocytes,hPSC-CMs"as English search terms and"human pluripotent stem cells,cardiomyocytes,mature,OA,hPSC-CMs"as Chinese search terms.All relevant literature published from January 2002 to July 2024 was retrieved and 82 articles were included in the review.RESULTS AND CONCLUSION:(1)In recent years,in vitro synthetic microenvironments have attracted extensive attention due to their excellent intrinsic properties such as stiffness,plasticity,nanoscale morphology,and chemical functionality.(2)Human pluripotent stem cell-derived cardiomyocytes can be used as an effective platform for the treatment of cardiovascular diseases.(3)Mechanical stimulation,electrical stimulation,addition of biochemical molecules,and three-dimensional culture methods are effective methods to promote the maturation of human pluripotent stem cell-derived cardiomyocytes,which can further promote the clinical application of human pluripotent stem cell-derived cardiomyocytes.

Prostate cancer is one of the most common male urological malignancies,in which bone metastasis of desmo-plasia-resistant prostate cancer is an important stage in the progression of the disease,which seriously affects the quality of life and survival of patients.With the development of nuclide therapy technology in recent years,223-Ra,as a new type of alpha-targeted therapy,has shown good efficacy in the treatment of desmoplasia-resistant prostate cancer bone metastasis.The purpose of this pa-per is to review the characteristics,mechanism of action,treatment,and the main research results of its treatment of desmoplasia-resistant prostate cancer bone metastasis,and provide a comprehensive review of the clinical application of 223-Ra in the treatment of desmoplasia-resistant prostate cancer bone metastasis for the clinical application of 223-Ra in prostate cancer bone metastasis.

[Objective]To investigate the difference of ultrasound characteristics between pure mucinous carcinoma(PMC)and fibroadenoma(FA)of the breast.[Methods]Ultrasound data of 50 continuous patients with breast PMC from January 2012 to January 2021 and 100 continuous patients with breast FA from June 2018 to January 2019 in Sun Yat-sen Memorial Hospital of Sun Yat-sen University were retrospectively reviewed.The ultrasound characteristics of the two groups were evaluated according to the 2013 BI-RADS Ultrasound Atlas,and the differences in age,maximum diameter and ultrasound characteristics between the two groups were compared.[Results]The median age of PMC patients was 47 years and that of FA patients was 33 years.The age of PMC patients was higher than that of the FA group,and the differ-ence between the two groups of patients was statistically significant(P<0.001).The median maximum diameter of PMC pa-tients was 2.4 cm,which was greater than that of the FA group(1.8 cm),and the difference was statistically significant(P=0.001).Of the PMC,70%(35/50)were irregular,82%(41/50)were parallel to the skin,92%(46/50)had no circum-scribed margin,72%(36/50)were hypoechoic,and 68%(34/50)had enhanced posterior echo.Of the FA,69%(69/100)were oval or round,98%(98/100)were parallel to the skin,54%(54/100)had circumscribed margin,98%(98/100)were hypoechoic,and 75%(75/100)had no posterior features.The differences in the above ultrasound characteris-tics between the PMC and FA groups were statistically significant(P<0.001,P=0.001,P<0.001,P<0.001,P<0.001).There was no significant difference between calcifications and blood flow.[Conclusions]Compared with the FA group,pa-tients with PMC are older and the diameter of the lesions are larger.On ultrasound,the morphology and margin of most breast PMC still show the growth characteristics of invasive cancer.Meanwhile,the posterior echo of PMC is enhanced,which is a unique manifestation.

Background and purpose:Long non-coding RNA(lncRNA)LINC01410,with a length of 647 bp,participates in a variety of tumor biological processes.However,the role and mechanism of LINC01410 involved in esophageal squamous cell carcinoma(ESCC)remain unclear.This study aimed to explore the potential mechanism of LINC01410 promoting ESCC proliferation and invasion,to provide a potential prognostic indicator and therapeutic target for individuals with ESCC.Methods:Gene Expression Profiling Interactive Analysis 2(GEPIA2)databases were used to analyze the expression of LINC01410 and overall survival in esophageal squamous cell carcinoma data set in the Cancer Genome Atlas(TCGA).Gene Set Enrichment Analysis(GSEA)was performed to identify the underlying signaling pathways involved in the biological effects of LINC01410 in ESCC.A total of 62 pairs of ESCC tissues and paracancerous tissues from ESCC patients who underwent radical surgery in the Department of Thoracic Surgery at the First Affiliated Hospital of Xinxiang Medical College and the First People's Hospital of Pingdingshan City from January 2020 to December 2021 were collected.This project has been approved by the Hospital Ethics Committee(First Affiliated Hospital of Xinxiang Medical College,No.2018036;First People's Hospital of Pingdingshan City,No.2019-018).The expression of LINC01410 in ESCC tissues was detected by real-time fluorescence quantitative polymerase chain reaction(RTFQ-PCR).We transfected EC109 cells with LV-NC or LV-over/LINC01410 and EC9706 cells with shRNA-NC or shRNA-LINC01410.Stable transfected cells(EC109/NC,EC109/OE,EC9706/NC and EC9706/KD)were selected in primary cell culture medium containing puromycin.The expression of LINC01410 was detected by RTFQ-PCR.The impact of LINC01410 on ESCC cell proliferation was determined by 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide(MTT)and colony formation assays.The effect of LINC01410 on ESCC cell invasion was detected by transwell migration assay.T cell factor/lymphoid enhancer factor 1(TCF/LEF1)luciferase reporter assay was performed to validate the effect of LINC01410 on the activity of canonical Wnt/β-catenin signaling pathway.The expressions of Wnt/β-catenin and epithelial-mesenchymal transition(EMT)signal pathway related proteins in ESCC cells were detected by Western blot.Results:By analyzing the LINC01410 expression from ESCC samples in TCGA by GEPIA2,we found LINC01410 was consistently increased in ESCC tumors compared with normal tissues(P＜0.05),and high LINC01410 expression was associated with poorer overall survival(OS).RTFQ-PCR assay showed that expressions of LINC01410 were higher in esophageal cancer tissues and esophageal cancer cells(EC109 and EC9706)than in precancerous tissues and HEEC cells(P＜0.05).The expression level of LINC01410 was significantly correlated with invasion range,lymph node metastasis and TNM stage in ESCC patients(P＜0.01).LINC01410 expression was also upregulated in EC109/OE,however the expression of LINC01410 in EC9706/KD was decreased(P＜0.01).MTT assay showed overexpression of LINC01410 increased the viability of EC109 cells,while knockdown of LINC01410 decreased the viability of EC9706 cells(P＜0.01).Colony formation assay indicated that overexpression of LINC01410 enhanced the clonogenic ability of ESCC cells,while knockdown of LINC01410 reduced colony formation(P＜0.01).Transwell migration assay showed that LINC01410 overexpression drastically increased the number of migratory cells,while silencing of LINC01410 suppressed the migration in EC9706 cells(P＜0.01).GSEA revealed that Wnt/β-catenin and EMT pathways were significantly enriched in ESCC samples with a high level of LINC01410.TCF/LEF1 luciferase reporter assay showed higher levels of Wnt-dependent activities were observed in EC109/OE cells,whereas silenced LINC01410 in EC9706 cells led to contrary results(P＜0.01).Western blot analysis showed that overexpression of LINC01410 in EC109 cell significantly increased the expression levels of N-cadherin,β-catenin,cyclin D1,c-Myc and decreased E-cadherin expression,while knockdown LINC01410 resulted in opposite results.Conclusion:LINC01410 promotes proliferation and metastasis of ESCC,which might be caused by activation of Wnt/β-catenin and EMT signaling pathways.

Objective:To explore the current status of cognitive function of the older adults in Beijing,and to analyze the factors affecting their cognitive function.Methods:It was a cross-sectional study.A questionnaire survy was conducted in 2023 among the older adults in Beijing.The cognitive function of the older adults was assessed with the Hong Kong brief cognitive test(HKBC)scale,a simple cognitive assessment tool.Using SPSS 27.0 to perform the descriptive analysis and multiple linear regression analy-sis of factors,which affect cognitive function among the older adults.Results:Totally 349 older adults were recruited,with the highest percentage of respondents aged 60-69 years(41.3％),of whom 58.7％were female,88.0％of the respondents had a junior high school or above education level.Most of the older adults(68.8％)worked 35-48 h/week before they retired,and 14.0％of the older adults had a family history of dementia.After controlling age and gender,the linear regression analysis showed that marital status married(β=0.501,95％CI:0.144-0.859)and 3-4 times physical activity per week(β=0.617,95％CI:0.087-1.148)were protective factors of cognitive function in the older adults,and depressive symptoms were a risk factor(β=-0.723,95％CI:-1.198 to-0.247)of cognitive function for the older adults.Conclusion:In this study,the factors influencing cognitive function among the older adults was analyzed based on a life-cycle perspective.Lack of physical activity and depressive symptoms were risk factors for cognitive function among the older adults.It was suggested that strengthening physical activity,improving mental health of the older adults,as well as conducting preventive intervention in early stages of the life-cycle will be benefit for preventing and slowing cognitive decline in the older adults.

Objective To investigate the prognosis of patients with hepatitis B virus(HBV)-related intrahepatic cholangiocarcinoma(ICC)whose HBV DNA was negative before surgical.Methods A retrospective analysis was conducted on the clinical data of 97 ICC patients who underwent surgery resection at the Fifth Medical Center of Chinese PLA General Hospital between October 2010 and January 2017.All patients were divided into HBV-related ICC(HBV-ICC)group(n=62)and non-HBV-related ICC(Con-ICC)group(n=35).HBV-ICC group included 34 patients with HBV core antigen positive(HBcAb+)and HBV surface antigen positive(HBsAg+),and 28 patients with HBcAb positive and HBsAg negative.Kaplan-Meier analysis was used to plot survival curves and compare the overall survival(OS)and postoperative recurrence-free survival(RFS)among patients in Con-ICC,ICC patients with HBsAg+/HBcAb+,and ICC patients with HBsAg-/HBcAb+.Univariate and multivariate Cox proportional hazard models were used to analyze independent influencing factor for OS,RFS and early postoperative recurrence among gender,age,pathogenic factor,liver cirrhosis,Child-Pugh grade,carbohydrate antigen 19-9(CA199),alpha-fetoprotein(AFP),glutamine transferase(GGT),alkaline phosphatase(ALP),total bilirubin(TBil),direct bilirubin(DBil),American Joint Committee on Cancer(AJCC)stage,tumor size,tumor number,tumor differentiation,microvascular invasion,lymph node metastasis,hepatectomy procedure,cholecystectomy,and follow-up treatment.Results Of the 97 patients,the median age was 56 years,and 79(81.4%)of them were male.The median follow-up time was 92.2 months.Eighty-eight(90.7%)patients presented with tumor recurrence and 73(75.3%)died.In multivariate analyses,HBV-ICC and CA199>37 kU/L were independent predictors of OS(HR=0.45,95%CI 0.26-0.77,P=0.003;HR=2.10,95%CI 1.24-3.57,P=0.006),RFS(HR=0.43,95%CI 0.27-0.68,P<0.001;HR=1.78,95%CI 1.12-2.81,P=0.014),and postoperative early recurrence(HR=0.42,95%CI 0.26-0.70,P=0.001;HR=2.02,95%CI 1.20-3.39,P=0.008).AJCC stage Ⅲ was an independent risk factor for postoperative RFS(HR=1.81,95%CI 1.04-3.14,P=0.037).Multiple tumor lesions was an independent risk factor for postoperative RFS and early recurrence(HR=1.73,95%CI 1.07-2.77,P=0.024;HR=1.90,95%CI 1.12-3.24,P=0.017).There was no statistically significant difference in OS,RFS,and early recurrence between HBV-ICC patients with HBsAg-/HBcAb+and Con-ICC patients(P<0.05),whereas HBsAg+/HBcAb+was a significant factor affecting postoperative OS(HR=0.32,95%CI 0.16-0.62,P=0.001),RFS(HR=0.32,95%CI 0.18-0.55,P<0.001),and early recurrence(HR=0.29,95%CI 0.15-0.54,P<0.001)in ICC patients.Conclusions The prognosis of HBV-ICC patients with preoperative HBV-DNA-is better than that of Con-ICC patients.The prognosis of HBV-ICC patients with HBcAb+/HBsAg-is worse than that of HBV-ICC patients with HBcAb+/HBsAg+,but similar to Con-ICC patients.Therefore,the postoperative stratified management of HBV-ICC patients should be emphasized.