A mounting body of research suggests that circRNAs significantly contribute to the develop-ment of myocardial fibrosis.The microarray results of human circular RNA expression profile indicated that circHERC4_041 expression increased in the myocardium of patients with heart failure,RT-qPCR a-nalysis confirmed that the myocardial expression level of circHERC4_041 in individuals with heart failure were considerably elevated compared to that in healthy organ donors.Fluorescence in situ hybridization(FISH)confirmed that circHERC4_041 was abundant in the cytoplasm of human cardiomyocyte AC16.Overexpression of circHERC4_041 in mouse myocardial fibroblasts(mCFs)mediated by adenovirus in-hibited the expression of fibrosis-related proteins in mCFs.Experiments involving cell proliferation,wound healing,and Transwell assays demonstrated that overexpression of circHERC4_041 suppressed the growth and mobility of mCFs(P＜0.001).Sequence analysis results suggested that circHERC4_041 con-tains potential ribosome entry sequence(IRES)and open reading frame(ORF).Western blot confirmed that circHERC4_041 could translate the 516 amino acid HERC4-516aa protein,which was mainly located in the cytoplasm of the cell.Cell functional experiments confirmed that circHERC4_041 inhibited the fi-brotic phenotype of mCFs by specifically translating HERC4-516aa(P＜0.05).The specific interaction between HERC4-516aa and transglutaminase 2(TGM2)was confirmed by IP-MS screening and Co-IP i-dentification.Further results found that the degradation of TGM2 was promoted through proteasome path-way.The overexpression of TGM2 in mCFs facilitated by adenoviral vectors could counteract the suppres-sive effects of HERC4-516aa on the fibrotic phenotype of mCFs.Therefore,this study confirmed that the HERC4-516aa protein translated by circHERC4_041 can specifically bind to TGM2 to inhibit the fibrotic phenotype of myocardial fibroblasts.

Objective:To investigate the efficacy and toxicity of blinatumomab in the first-line and second-line treatment of pediatric B-cell acute lymphoblastic leukemia (B-ALL).Methods:A multi-center retrospective cohort study was conducted to analyze clinical data from 323 pediatric B-ALL patients treated with blinatumomab across 14 hospitals in China from May 2021 to July 2023. Patients were divided into four groups based on the treatment phase and disease status when blinatumomab was used: relapsed/refractory group, post-consolidation minimal residual disease (MRD)-positive group, early MRD-positive group, and MRD-negative group. Blinatumomab for the relapsed/refractory group was considered as second-line treatment, while the other 3 groups as first-line treatment. The MRD negativity rate after treatment, the survival rates and the incidence of severe adverse events were compared across these groups. Patients who received blinatumomab for more than 7 days were included in the efficacy analysis. Survival analysis was performed using the Kaplan-Meier method, and Log-Rank test was used to compare the survival rates among groups.Results:Among the 323 patients, 191 (59.1%) were male, with the age of 6.2 (3.9, 10.5) years. There were 117 patients in the relapsed/refractory group, 62 cases in the post-consolidation MRD-positive group, 43 cases in the early MRD-positive group, and 101 cases in the MRD negative group. In the relapsed/refractory group, the complete remission rate and MRD negativity rate after one course of blinatumomab were 71.4% (35/49) and 81.5% (75/92) for the 49 children without complete remission and the 92 children with flow cytometry-positive MRD, respectively. In the post-consolidation MRD-positive group, the MRD negativity rates after one course of blinatumomab were 100.0% (27/27), 12/16 and 9/19 for patients with MRD positivity detected by flow cytometry, polymerase chain reaction and next-generation sequencing, respectively. In the early MRD-positive group, the MRD negativity rates were 96.7% (29/30) and 9/9 for flow cytometry and next-generation sequencing, respectively. The 2-year overall survival rate and event-free survival rate for the 319 children evaluable for efficacy were (90.6±1.7)% and (87.6±1.9)%, respectively, with the relapsed/refractory group showing significantly lower overall survival rates and event-free survival rate compared to the other groups ( χ2=21.40, 26.21,both P<0.001). Grade 3 or higher adverse events occurred in 128 cases (39.6%), with hematological toxicity observed in 101 cases, while cytokine release syndrome (CRS), infection, and neurotoxicity occurred in 11, 26 and 8 cases, respectively. In addition, there were statistically significant differences in the grade 3 or higher CRS among the four groups ( χ2=8.03, P<0.05). Conclusion:Blinatumomab can clear MRD more effectively and achieve superior survival outcomes when used as first-line treatment for pediatric B-ALL, with less CRS.

A mounting body of research suggests that circRNAs significantly contribute to the develop-ment of myocardial fibrosis.The microarray results of human circular RNA expression profile indicated that circHERC4_041 expression increased in the myocardium of patients with heart failure,RT-qPCR a-nalysis confirmed that the myocardial expression level of circHERC4_041 in individuals with heart failure were considerably elevated compared to that in healthy organ donors.Fluorescence in situ hybridization(FISH)confirmed that circHERC4_041 was abundant in the cytoplasm of human cardiomyocyte AC16.Overexpression of circHERC4_041 in mouse myocardial fibroblasts(mCFs)mediated by adenovirus in-hibited the expression of fibrosis-related proteins in mCFs.Experiments involving cell proliferation,wound healing,and Transwell assays demonstrated that overexpression of circHERC4_041 suppressed the growth and mobility of mCFs(P＜0.001).Sequence analysis results suggested that circHERC4_041 con-tains potential ribosome entry sequence(IRES)and open reading frame(ORF).Western blot confirmed that circHERC4_041 could translate the 516 amino acid HERC4-516aa protein,which was mainly located in the cytoplasm of the cell.Cell functional experiments confirmed that circHERC4_041 inhibited the fi-brotic phenotype of mCFs by specifically translating HERC4-516aa(P＜0.05).The specific interaction between HERC4-516aa and transglutaminase 2(TGM2)was confirmed by IP-MS screening and Co-IP i-dentification.Further results found that the degradation of TGM2 was promoted through proteasome path-way.The overexpression of TGM2 in mCFs facilitated by adenoviral vectors could counteract the suppres-sive effects of HERC4-516aa on the fibrotic phenotype of mCFs.Therefore,this study confirmed that the HERC4-516aa protein translated by circHERC4_041 can specifically bind to TGM2 to inhibit the fibrotic phenotype of myocardial fibroblasts.

Objective To analyze the spatiotemporal evolution patterns of mortality and disease burden of smoking-related prostate cancer(PCa)from 1990 to 2021 and to predict the future trends,so as to provide evidence-based insights for optimizing regional PCa prevention policies and smoking cessation interventions.Methods Based on data from the Global Burden of Disease Study(GBD)2021,annual mortality,disability-adjusted life years(DALYs),years of life lost(YLLs),years lived with disability(YLDs),and age-standardized rates(ASRs)for PCa across 204 countries and 21 regions from 1990 to 2021 were obtained.Estimated annual percentage change(EAPC)was used to assess the disease burden and mortality of smoking-related PCa across global,regional,socio-demographic index(SDI),and age groups.An autoregressive integrated moving average(ARIMA)model was employed to predict trends in these indicators up to 2050.Results In 2021,smoking-related PCa caused 12 992 global deaths,a 30.74％increase compared to 1990.However,from 1990 to 2021,the global age-standardized mortality rate(ASMR),age-standardized DALYs rate(ASDR),age-standardized YLDs rate(ASYR),and age-standardized YLLs rate(ASLR)for smoking-related PCa declined,with EAPCs being-1.43(95％CI:-1.77--1.12),-1.39(95％CI:-1.66--1.12),-0.41(95％CI:-0.67--0.15)and-1.51(95％CI:-1.78--1.23).In 2021,the region with the highest number of deaths from PCa was Asia(4663 deaths),followed by Europe(4647 deaths),and Oceania had the lowest number of deaths(9 deaths).From 1990 to 2021,the mortality rate of PCa in most regions generally showed a downward trend.High SDI regions showed the most significant declines in ASMR,ASDR,and ASLR[EAPCs:-3.17(95％CI:-3.31--3.02),-2.91(95％CI:-3.02--2.83),and-3.22(95％CI:-3.35--3.09)].For ASYR,only high-SDI regions exhibited a decline,whereas low-middle-SDI regions saw the largest increase[EAPC:1.26(95％CI:1.19-1.33)].In 2021,the number of PCa deaths was more concentrated in the age groups of 70-74 and 75-79,with 2312 and 2278 deaths,respectively.From 1990 to 2021,ASMR,ASDR,and ASLR showed an overall downward trend,EAPC were-2.84(95％CI:-3.21--1.83),-2.77(95％CI:-3.13--1.75),and-2.84(95％CI:-3.14--1.71),with the most significant decline observed in individuals aged 35-39.Projections to 2050 indicated continuing declines in all burden metrics,which would stabilize in later years.Conclusion Despite a global decline in smoking-related PCa burden over the past three decades,significant regional disparities persist,with low-and middle-income countries facing ongoing challenges.Implementing stricter tobacco control policies is critical to mitigating smoking-related health risks.

Objective To analyze the risk factors of permanent hypoparathyroidism(pHPP)after total thyroidectomy in patients with thyroid cancer and establish a nomogram prediction model.Methods A total of 245 patients with thyroid cancer who received total thyroidectomy in our hospital were enrolled between January 2020 and January 2024.According to presence or absence of postoperative pHPP,patients were divided into the pHPP group and the non-pHPP group.The influencing factors of postoperative pHPP in patients with thyroid cancer were analyzed by univariate and multivariate Logistic regression analysis.The nomogram prediction model for postoperative pHPP in patients with thyroid cancer was constructed and varified,and efficiency of the model was evaluated.Results In 245 patients with thyroid cancer,the incidence of pHPP within 6 months after surgery was 10.20%(25/245).Univariate analysis showed that there were significant differences in tumor size,surgical method,central lymph node dissection,use of nano carbon tracer,envelope invasion,parathyroid excision by mistake,Hashimoto thyroiditis,serum calcium and parathyroid hormone at 1 d after surgery between the two groups(P＜0.05),but there were no significant differences in gender,age,smoking,drinking,extraglandular invasion,parathyroid autologous transplantation,preoperative vitamin D or serum phosphorus at 1 d after surgery between the two groups(P＞0.05).Multivariate analysis showed that maximum tumor diameter≥4 cm,routine and open total thyroidectomy,central lymph node dissection,no use of nano carbon tracer and parathyroid excision by mistake were all independent risk factors for postoperative pHPP in patients with thyroid cancer(P＜0.05).Results of nomogram prediction model showed that C-index was 0.921,the corrected curve was close to ideal curve,and AUC of nomogram model for predicting postoperative pHPP was 0.926(95%CI:0.871-0.981).Conclusion The nomogram prediction model constructed based on independent risk factors of postoperative pHPP has good predictive efficiency in patients with thyroid cancer.

Objective To analyze the spatiotemporal evolution patterns of mortality and disease burden of smoking-related prostate cancer(PCa)from 1990 to 2021 and to predict the future trends,so as to provide evidence-based insights for optimizing regional PCa prevention policies and smoking cessation interventions.Methods Based on data from the Global Burden of Disease Study(GBD)2021,annual mortality,disability-adjusted life years(DALYs),years of life lost(YLLs),years lived with disability(YLDs),and age-standardized rates(ASRs)for PCa across 204 countries and 21 regions from 1990 to 2021 were obtained.Estimated annual percentage change(EAPC)was used to assess the disease burden and mortality of smoking-related PCa across global,regional,socio-demographic index(SDI),and age groups.An autoregressive integrated moving average(ARIMA)model was employed to predict trends in these indicators up to 2050.Results In 2021,smoking-related PCa caused 12 992 global deaths,a 30.74％increase compared to 1990.However,from 1990 to 2021,the global age-standardized mortality rate(ASMR),age-standardized DALYs rate(ASDR),age-standardized YLDs rate(ASYR),and age-standardized YLLs rate(ASLR)for smoking-related PCa declined,with EAPCs being-1.43(95％CI:-1.77--1.12),-1.39(95％CI:-1.66--1.12),-0.41(95％CI:-0.67--0.15)and-1.51(95％CI:-1.78--1.23).In 2021,the region with the highest number of deaths from PCa was Asia(4663 deaths),followed by Europe(4647 deaths),and Oceania had the lowest number of deaths(9 deaths).From 1990 to 2021,the mortality rate of PCa in most regions generally showed a downward trend.High SDI regions showed the most significant declines in ASMR,ASDR,and ASLR[EAPCs:-3.17(95％CI:-3.31--3.02),-2.91(95％CI:-3.02--2.83),and-3.22(95％CI:-3.35--3.09)].For ASYR,only high-SDI regions exhibited a decline,whereas low-middle-SDI regions saw the largest increase[EAPC:1.26(95％CI:1.19-1.33)].In 2021,the number of PCa deaths was more concentrated in the age groups of 70-74 and 75-79,with 2312 and 2278 deaths,respectively.From 1990 to 2021,ASMR,ASDR,and ASLR showed an overall downward trend,EAPC were-2.84(95％CI:-3.21--1.83),-2.77(95％CI:-3.13--1.75),and-2.84(95％CI:-3.14--1.71),with the most significant decline observed in individuals aged 35-39.Projections to 2050 indicated continuing declines in all burden metrics,which would stabilize in later years.Conclusion Despite a global decline in smoking-related PCa burden over the past three decades,significant regional disparities persist,with low-and middle-income countries facing ongoing challenges.Implementing stricter tobacco control policies is critical to mitigating smoking-related health risks.

The auxin/indole-3-acetic acid (Aux/IAA) gene family is an important regulator for plant growth hormone signaling, involved in plant growth, development, as well as response to environmental stresses. In the present study, we identified SmIAA7 which is potentially associated with Salvia miltiorrhiza leaf development through comparatively analyzed the transcriptome data from different pinnate leaves. SmIAA7 was successfully isolated from S. miltiorrhiza using the specific primers. Then subsequent bioinformatic analysis, prokaryotic expression and purification, subcellular localization, and induction expression analysis under auxin and abiotic stress were performed. The full-length of SmIAA7 contained an ORF of 684 bp encoding a protein of 227 amino acid with a molecular weight of 25.3 kD. Conserved domain analysis showed that SmIAA7 contains the conserved Aux_IAA domain (pfam02309). Sequence analysis and phylogenetic tree analysis results indicated SmIAA7 was phylogenetically close to IAA7 and IAA14 from other plants, suggesting SmIAA7 involved in plant growth and development as well as response to environmental stresses. The prokaryotic expression vector pET28a-SmIAA7 was constructed and SmIAA7 recombinant protein was successfully expressed in E. coli Rosetta (DE3) strain. Subcellular localization experiment demonstrated that SmIAA7 localized in the nucleus of plant cells. Real-time fluorescence quantitative PCR results showed that the expression level of SmIAA7 was upregulated in response to auxin. Drought, low temperature, and salt stress significantly increased the transcript level of SmIAA7 gene. This study lays a foundation for further elucidating the role of SmIAA7 in leaf development, signal transduction, and stress defense in S. miltiorrhiza.

Objective To analyze the prevalence status of cardiometabolic risk factor (CMRF) and its aggregation among workers engaged in new forms of employment. Methods A total of 5 429 new employment workers (including couriers, online food delivery workers, and ride hailing drivers) who underwent health medical examinations at a tertiary hospital in Beijing City were selected as the research subjects using the judgment sampling method. Data on waist circumference, blood pressure, blood glucose, and blood lipid levels were collected to analyze their CMRF [central obesity, elevated blood pressure, elevated blood glucose, elevated triglycerides, and reduced high-density lipoprotein cholesterol (HDL-C)] and their aggregation (with ≥ 2 of the above 5 risk factors) status. Results The detection rates of central obesity, elevated blood pressure, elevated blood glucose, elevated triglycerides, and reduced HDL-C were 61.2%, 38.2%, 29.5%, 40.9% and 22.6%, respectively. The detection rates of CMRF aggregation was 57.8%. The result of multivariable logistic regression analysis showed that male, age ≥45 years, smoking, overweight, and obesity were risk factors for CMRF aggregation (all P<0.05). Conclusion The detection rate of CMRF and its aggregation among workers with new forms of employment in Beijing City is relatively high. Targeted prevention and control efforts should be strengthened for high-risk populations, especially males, workers aged ≥45 years, smokers, and those who are overweight or obese.

Functional dyspepsia (FD), characterized by persistent or recurrent dyspeptic symptoms without identifiable organic, systemic or metabolic causes, is an increasingly recognized global health issue. The objective of this guideline is to equip clinicians and nursing professionals with evidence-based strategies for the management and treatment of adult patients with FD using traditional Chinese medicine (TCM). The Guideline Development Group consulted existing TCM consensus documents on FD and convened a panel of 35 clinicians to generate initial clinical queries. To address these queries, a systematic literature search was conducted across PubMed, EMBASE, the Cochrane Library, China National Knowledge Infrastructure (CNKI), VIP Database, China Biology Medicine (SinoMed) Database, Wanfang Database, Traditional Medicine Research Data Expanded (TMRDE), and the Traditional Chinese Medical Literature Analysis and Retrieval System (TCMLARS). The evidence from the literature was critically appraised using the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) approach. The strength of the recommendations was ascertained through a consensus-building process involving TCM and allopathic medicine experts, methodologists, pharmacologists, nursing specialists, and health economists, leveraging their collective expertise and empirical knowledge. The guideline comprises a total of 43 evidence-informed recommendations that span a range of clinical aspects, including the pathogenesis according to TCM, diagnostic approaches, therapeutic interventions, efficacy assessments, and prognostic considerations. Please cite this article as: Zhang SS, Zhao LQ, Hou XH, Bian ZX, Zheng JH, Tian HH, Yang GH, Hong WS, He YY, Liu L, Shen H, Li YP, Xie S, Shu J, Zeng BF, Li JX, Liu Z, Xiao ZH, Xiao JD, Zheng PY, Huang SG, Chen SL, Fei GJ. International clinical practice guideline on the use of traditional Chinese medicine for functional dyspepsia (2025). J Integr Med. 2025; 23(5):502-518.
Dyspepsia/drug therapy* ; Humans ; Medicine, Chinese Traditional/methods* ; Practice Guidelines as Topic ; Drugs, Chinese Herbal/therapeutic use*

Objective:To investigate the efficacy and toxicity of blinatumomab in the first-line and second-line treatment of pediatric B-cell acute lymphoblastic leukemia (B-ALL).Methods:A multi-center retrospective cohort study was conducted to analyze clinical data from 323 pediatric B-ALL patients treated with blinatumomab across 14 hospitals in China from May 2021 to July 2023. Patients were divided into four groups based on the treatment phase and disease status when blinatumomab was used: relapsed/refractory group, post-consolidation minimal residual disease (MRD)-positive group, early MRD-positive group, and MRD-negative group. Blinatumomab for the relapsed/refractory group was considered as second-line treatment, while the other 3 groups as first-line treatment. The MRD negativity rate after treatment, the survival rates and the incidence of severe adverse events were compared across these groups. Patients who received blinatumomab for more than 7 days were included in the efficacy analysis. Survival analysis was performed using the Kaplan-Meier method, and Log-Rank test was used to compare the survival rates among groups.Results:Among the 323 patients, 191 (59.1%) were male, with the age of 6.2 (3.9, 10.5) years. There were 117 patients in the relapsed/refractory group, 62 cases in the post-consolidation MRD-positive group, 43 cases in the early MRD-positive group, and 101 cases in the MRD negative group. In the relapsed/refractory group, the complete remission rate and MRD negativity rate after one course of blinatumomab were 71.4% (35/49) and 81.5% (75/92) for the 49 children without complete remission and the 92 children with flow cytometry-positive MRD, respectively. In the post-consolidation MRD-positive group, the MRD negativity rates after one course of blinatumomab were 100.0% (27/27), 12/16 and 9/19 for patients with MRD positivity detected by flow cytometry, polymerase chain reaction and next-generation sequencing, respectively. In the early MRD-positive group, the MRD negativity rates were 96.7% (29/30) and 9/9 for flow cytometry and next-generation sequencing, respectively. The 2-year overall survival rate and event-free survival rate for the 319 children evaluable for efficacy were (90.6±1.7)% and (87.6±1.9)%, respectively, with the relapsed/refractory group showing significantly lower overall survival rates and event-free survival rate compared to the other groups ( χ2=21.40, 26.21,both P<0.001). Grade 3 or higher adverse events occurred in 128 cases (39.6%), with hematological toxicity observed in 101 cases, while cytokine release syndrome (CRS), infection, and neurotoxicity occurred in 11, 26 and 8 cases, respectively. In addition, there were statistically significant differences in the grade 3 or higher CRS among the four groups ( χ2=8.03, P<0.05). Conclusion:Blinatumomab can clear MRD more effectively and achieve superior survival outcomes when used as first-line treatment for pediatric B-ALL, with less CRS.