1.Targeted Therapy for Repeat Expansion Diseases
JOURNAL OF RARE DISEASES 2026;5(2):125-133
Repeat expansion diseases(REDs) are a group of genetic disorders caused by the pathological expansion of specific short tandem repeats(STRs) in genomic DNA. They are characterized by significant clinical and genetic heterogeneity. Owing to the complexity of their pathogenesis, effective treatments remain elusive. With the in-depth analysis of the pathogenesis of these diseases, along with the development and innovation of targeting tools in recent years, targeted therapy strategies have become a research hotspot, and some antisense oligonucleotide drugs have entered the clinical trial stage. This article aims to review the latest advances in basic research and clinical trial outcomes of targeted therapy at the DNA, RNA and protein levels. Currently, this field still faces key bottlenecks including a high risk of off-target effects, low delivery efficiency, and challenges in clinical translation. Future efforts should focus on the optimization and refinement of targeting tools and delivery vectors, as well as multilevel collaborative combination therapeutic strategies.Combined with precise clinical classification and staging, this will promote the fundamental transformation of REDs treatment from symptomatic supportive care to etiological intervention.
2.Effect of bufalin on lactate dehydrogenase A and regulatory T cells in the tumor microenvironment of hepatocellular carcinoma in mice
Fangjing YU ; Xinyu FU ; Bin ZHANG ; Yan DONG ; Yujun LI ; Xiaonan CUI
Journal of China Medical University 2025;54(10):876-882
Objective To detect the expression of lactate dehydrogenase A(LDHA),FoxP3,and CD4 in hepatocellular carcinoma(HCC)and to analyze the effect of bufalin on LDHA as well as on the differentiation and function of regulatory T(Treg)cells in the tumor microenvironment of HCC mice.Methods Immunohistochemical staining was performed to detect the difference in the expression of LDHA,FoxP3(Treg cell marker),and CD4 between the tumor and adjacent tissues from 91 HCC patients.Hepl-6 subcutaneous tumor-bearing mouse model was established.The mice were randomly divided into control,bufalin+pyruvic acid,oxalate,and bufalin groups(n=5 each group).The mass and volume of subcutaneous tumors were compared.Immunohistochemical staining was performed to detect the expression of LDHA,FoxP3,and CD4 in tumors of mice in each group.ELISA was used to detect the levels of transforming growth factor β(TGF-β)and interleukin-10(IL-10)in the serum of mice in each group to evaluate the immune function of Treg cells.Results Compared with adjacent tissues,HCC tissues exhibited significantly higher LDHA and FoxP3 expression and lower CD4 expression(P<0.001).The results of the correlation analysis showed that LDHA was positively correlated with FoxP3 expression and negatively correlated with CD4 expression(P<0.05).The experimental results of Hep1-6 subcutaneous tumor-bearing mice showed that the tumor volume was significantly smaller in the bufalin and oxalate groups than in the control group and was significantly larger in the bufalin+pyruvic acid group than in the bufalin group(P<0.001).The results of immunohistochemical staining showed that the expression levels of LDHA and the percentage of FoxP3+cells in the bufalin and oxalate groups were significantly lower than those in the control group,and the percentage of CD4+cells in the bufalin group was significantly higher than that in the control group(P<0.001).The expres-sion level of LDHA and the percentage of FoxP3+cells in the bufalin+pyruvic acid group were significantly higher than those in the bufalin group,while the percentage of CD4+cells was significantly lower than that in the bufalin group(P<0.001).The results of ELISA showed that the levels of TGF-β and IL-10 in the bufalin and oxalate groups were significantly lower than those in the control group(P<0.001).Conclusion Bufalin inhibits cell growth,downregulates LDHA expression,and suppresses the differentiation and proliferation of Treg cells in HCC mice.
3.Treatments of endometrial injury diseases with integrated Traditional Chinese and Western Medicine
Xinyu ZHANG ; Shuo YANG ; Ruiwen FAN ; Dong LI ; Rong LI
Chinese Journal of Reproduction and Contraception 2025;45(9):892-895
Endometrial injury diseases are an important factors in female infertility, reduced menstruation, and adverse pregnancy outcomes. Clinical characteristics include intrauterine adhesions, a thin endometrium, and reduced endometrial receptivity. Restoring the morphology of the uterine cavity and promoting endometrial reconstruction are the main goals of treatment. At present, hormone medication and surgery are the major Western medicine treatments. Traditional Chinese Medicine has an advantage in treating endometrial injury and preventing postoperative recurrence. Traditional Chinese Medicine diagnosis focuses on "kidney deficiency" as the primary condition,"blood stasis" as the secondary condition, and combined with "liver depression". Therapeutic strategies aim to "replenish kidney""nourish blood""dispel blood stasis", and improve the endometrium. By means of combination of disease and syndrome, classical prescription addition and subtraction, clinical effective experience, combination of acupuncture and medicine and external treatment of Traditional Chinese Medicine can improve the effect and prognosis of patients with endometrial injury diseases. This article reviews the progress of combined Traditional Chinese and Western Medicine treatment of endometrial injury diseases to provide reference for its clinical treatment.
4.Visual analysis of the application of wearable devices in nursing care both domestically and internationally
Qing DONG ; Shujun XING ; Xianghuan LI ; Jing ZHAI ; Xinyu WANG ; Jiaqi LIU ; Jinlan LI ; Xiaoru GAO ; Yu TANG
China Modern Doctor 2025;63(30):1-4,68
Objective To analyze the research status,hotspots,and trends of wearable devices in nursing applications both domestically and internationally.Methods Using China National Knowledge Infrastructure,Wanfang Data Knowledge Service Platform,and Embase core databases as data sources,VOSviewer was used to visualize and analyze the publication time,keywords,and other relevant literature.Results Total of 428 articles were included,including 196 Chinese articles and 232 English articles.The overall publication volume showed an upward trend.Domestic research focuses on chronic diseases,artificial intelligence,and nursing,with the main research subjects being the elderly;Foreign research focuses on smart devices,self-monitoring,and quality of life,with the main research subjects being adults.Conclusion Currently,the number of publications on the application of wearable devices in nursing is relatively small,but the overall research heat is on the rise,mainly used for chronic diseases and self-monitoring.In the future,the application scope of wearable devices should be expanded and their potential value should be explored to promote the innovation and progress of nursing models.
5.Effect of bufalin on lactate dehydrogenase A and regulatory T cells in the tumor microenvironment of hepatocellular carcinoma in mice
Fangjing YU ; Xinyu FU ; Bin ZHANG ; Yan DONG ; Yujun LI ; Xiaonan CUI
Journal of China Medical University 2025;54(10):876-882
Objective To detect the expression of lactate dehydrogenase A(LDHA),FoxP3,and CD4 in hepatocellular carcinoma(HCC)and to analyze the effect of bufalin on LDHA as well as on the differentiation and function of regulatory T(Treg)cells in the tumor microenvironment of HCC mice.Methods Immunohistochemical staining was performed to detect the difference in the expression of LDHA,FoxP3(Treg cell marker),and CD4 between the tumor and adjacent tissues from 91 HCC patients.Hepl-6 subcutaneous tumor-bearing mouse model was established.The mice were randomly divided into control,bufalin+pyruvic acid,oxalate,and bufalin groups(n=5 each group).The mass and volume of subcutaneous tumors were compared.Immunohistochemical staining was performed to detect the expression of LDHA,FoxP3,and CD4 in tumors of mice in each group.ELISA was used to detect the levels of transforming growth factor β(TGF-β)and interleukin-10(IL-10)in the serum of mice in each group to evaluate the immune function of Treg cells.Results Compared with adjacent tissues,HCC tissues exhibited significantly higher LDHA and FoxP3 expression and lower CD4 expression(P<0.001).The results of the correlation analysis showed that LDHA was positively correlated with FoxP3 expression and negatively correlated with CD4 expression(P<0.05).The experimental results of Hep1-6 subcutaneous tumor-bearing mice showed that the tumor volume was significantly smaller in the bufalin and oxalate groups than in the control group and was significantly larger in the bufalin+pyruvic acid group than in the bufalin group(P<0.001).The results of immunohistochemical staining showed that the expression levels of LDHA and the percentage of FoxP3+cells in the bufalin and oxalate groups were significantly lower than those in the control group,and the percentage of CD4+cells in the bufalin group was significantly higher than that in the control group(P<0.001).The expres-sion level of LDHA and the percentage of FoxP3+cells in the bufalin+pyruvic acid group were significantly higher than those in the bufalin group,while the percentage of CD4+cells was significantly lower than that in the bufalin group(P<0.001).The results of ELISA showed that the levels of TGF-β and IL-10 in the bufalin and oxalate groups were significantly lower than those in the control group(P<0.001).Conclusion Bufalin inhibits cell growth,downregulates LDHA expression,and suppresses the differentiation and proliferation of Treg cells in HCC mice.
6.Treatments of endometrial injury diseases with integrated Traditional Chinese and Western Medicine
Xinyu ZHANG ; Shuo YANG ; Ruiwen FAN ; Dong LI ; Rong LI
Chinese Journal of Reproduction and Contraception 2025;45(9):892-895
Endometrial injury diseases are an important factors in female infertility, reduced menstruation, and adverse pregnancy outcomes. Clinical characteristics include intrauterine adhesions, a thin endometrium, and reduced endometrial receptivity. Restoring the morphology of the uterine cavity and promoting endometrial reconstruction are the main goals of treatment. At present, hormone medication and surgery are the major Western medicine treatments. Traditional Chinese Medicine has an advantage in treating endometrial injury and preventing postoperative recurrence. Traditional Chinese Medicine diagnosis focuses on "kidney deficiency" as the primary condition,"blood stasis" as the secondary condition, and combined with "liver depression". Therapeutic strategies aim to "replenish kidney""nourish blood""dispel blood stasis", and improve the endometrium. By means of combination of disease and syndrome, classical prescription addition and subtraction, clinical effective experience, combination of acupuncture and medicine and external treatment of Traditional Chinese Medicine can improve the effect and prognosis of patients with endometrial injury diseases. This article reviews the progress of combined Traditional Chinese and Western Medicine treatment of endometrial injury diseases to provide reference for its clinical treatment.
7.From"insufficiency of ZhiYi"to anxiety onset:a preliminary construction of the emotion-pathogenesis hypothesis based on body-spirit integration theory
Mingzhou GAO ; Minghui HU ; Hongwei DONG ; You LI ; Yue ZHAO ; Xinyu WANG ; Zifa LI ; Xiwen GENG ; Sheng WEI ; Hao ZHANG
Acta Laboratorium Animalis Scientia Sinica 2025;33(9):1320-1328
Anxiety is a major emotional disorder manifested in the individual's expectation of future threats.The incidence rate of anxiety is about 7.3%,with the highest lifetime prevalence rate among mental health conditions.The mechanism of anxiety overlaps with depression,and anxiety is a typical symptom of various mental diseases or emotional disorders in traditional Chinese medicine.The high rates of comorbidity and disability pose serious threats to people's health.Animal models are important tools for studying anxiety and are of great use for deciphering the pathogenesis of anxiety and for developing drugs.The traditional paradigm of stress-induced anxiety,however,is relatively limited.Based on traditional theory combined with clinical and animal experimental data,we propose a new hypothesis of"insufficiency of ZhiYi'causing anxiety,defined as"an anxiety state induced by the inability of an individual to meet their own needs,limited or lacking after multiple attempts,rendered hindered and powerless by an inability to meet their desires".This hypothesis is more in line with the typical manifestations of despair,lack of pleasure,and social withdrawal in clinical patients,and is supported by traditional theory and experimental data showing"hunger but unable to eat,food but unable to obtain,and gain but not full".Based on this,the established modeling paradigm is easy to apply,with good repeatability and low cost,and can be used to establish anxiety models in rats and mice,to provide a theoretical and model basis for the development and pharmacological evaluation of anti-anxiety drugs.
8.Investigation and characteristics of extended high frequency hearing in young adults
Xinyu DONG ; Ying LIN ; Qianjin GAO ; Ziqi WU ; Pengfei HANG ; Xiaoqing FAN ; Zhemaiwei ZHAO ; Liu QI ; Jun CHEN ; Dingjun ZHA
Journal of Audiology and Speech Pathology 2025;33(2):156-160
Objective To investigate extended high-frequency hearing in young adults and to analyse its char-acteristics.Methods A total of 230 freshmen(101 males and 129 females,aged 17-19 years old)from the class of 2023 at the Air Force Medical University underwent audiometric tests,including acoustic impedance,conventional frequency and extended high-frequency audiometry,and distortion product otoacoustic emissions(DPOAE).Ac-cording to the results of extended high-frequency audiometry,the students were divided into normal and abnormal groups,and the hearing thresholds at conventional frequencies were compared between the two groups.Results Of the 230 students,47.83%(110/230)showed abnormal extended high-frequency hearing.The hearing thresholds of the right ear were 1 to 3 dB higher than those of the left ear at most frequencies.The hearing thresholds of the ab-normal group were higher than those of the normal group in the conventional frequencies(P<0.05).The difference in extended high-frequency thresholds between the two groups increased with higher frequency.Conclusion Ex-tended high-frequency hearing loss occurs earlier,and has a higher prevalence in young adults,and right ear hearing is worse than that of left ear.Extended high-frequency audiometry can be used as a predictive tool for detecting con-ventional frequency hearing loss.
9.A single-center validation study of CSCO AI clinical decision support system for colorectal cancer patients
Yuqi JIN ; Xinyu LI ; Yinuo TAN ; Hanguang HU ; Caixia DONG ; Yingyun LI ; Ying YUAN ; Suzhan ZHANG
Practical Oncology Journal 2025;40(4):339-347
Objective To evaluate the applicability and guideline concordance of the Chinese Society of Clinical Oncology(CSCO)arti-ficial intelligence(AI)system in clinical decision-making for colorectal cancer(CRC)patients,and to explore its feasibility in real-world clinical applications.Methods A total of 972 CRC patients diagnosed and treated at the Second Affiliated Hospital,Zhejiang University School of Medicine,from January 2010 to December 2021,were included.Patient data were analyzed by the CSCO AI system to gener-ate treatment decisions,and decision concordance was assessed by a blinded independent central review(BICR)panel.The applicability and guideline concordance rates of the CSCO AI system were calculated for different treatment stages,and a logistic regression model was used to analyze factors influencing the system's decision discrepancies with actual treatments.Results The overall applicability rate of the CSCO AI system was 96.2%,and the overall guideline concordance rate was 94.9%.In the adjuvant and palliative treatment stages,the system's applicability rates were 95.8%and 96.7%,respectively,and the guideline concordance rates were 95.0%and 94.9%,respective-ly.Multivariate logistic regression analysis showed that age≥65 years and high-risk stage Ⅱ treatment were significant factors affecting guideline concordance in the adjuvant treatment stage(both P<0.05).Conclusions The CSCO AI system demonstrated high applicability and guideline concordance in the adjuvant and palliative treatment stages for CRC.The system's clinical decision-making potential is sig-nificant,and it can be further optimized for specific clinical scenarios and promoted for use across various medical institutions.
10.Investigation and characteristics of extended high frequency hearing in young adults
Xinyu DONG ; Ying LIN ; Qianjin GAO ; Ziqi WU ; Pengfei HANG ; Xiaoqing FAN ; Zhemaiwei ZHAO ; Liu QI ; Jun CHEN ; Dingjun ZHA
Journal of Audiology and Speech Pathology 2025;33(2):156-160
Objective To investigate extended high-frequency hearing in young adults and to analyse its char-acteristics.Methods A total of 230 freshmen(101 males and 129 females,aged 17-19 years old)from the class of 2023 at the Air Force Medical University underwent audiometric tests,including acoustic impedance,conventional frequency and extended high-frequency audiometry,and distortion product otoacoustic emissions(DPOAE).Ac-cording to the results of extended high-frequency audiometry,the students were divided into normal and abnormal groups,and the hearing thresholds at conventional frequencies were compared between the two groups.Results Of the 230 students,47.83%(110/230)showed abnormal extended high-frequency hearing.The hearing thresholds of the right ear were 1 to 3 dB higher than those of the left ear at most frequencies.The hearing thresholds of the ab-normal group were higher than those of the normal group in the conventional frequencies(P<0.05).The difference in extended high-frequency thresholds between the two groups increased with higher frequency.Conclusion Ex-tended high-frequency hearing loss occurs earlier,and has a higher prevalence in young adults,and right ear hearing is worse than that of left ear.Extended high-frequency audiometry can be used as a predictive tool for detecting con-ventional frequency hearing loss.

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