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.

ObjectiveTo observe the effect of modified Huanglian Wendantang on oxidative stress in metabolic syndrome. MethodsA total of 180 patients with metabolic syndrome treated in the outpatient clinics and wards of the First Affiliated Hospital of Heilongjiang University of Traditional Chinese Medicine from October 2023 to May 2025 were enrolled in this study. According to the randomized numerical table method， the patients were assigned into two groups （90 cases）. The basic treatment of the two groups was the same， and the observation group was additionally treated with modified Huanglian Wendantang. The course of treatment was 3 months. The two groups were compared in terms of traditional Chinese medicine （TCM） efficacy， obesity degree ［waist circumference （WC）， body mass index （BMI）， waist-to-hip ratio （WHR）， waist-to-height ratio （WHtR）］， blood pressure indicators ［systolic blood pressure （SBP） and diastolic blood pressure （DBP）］， lipids and glucose indicators ［total cholesterol （TC）， triglycerides （TG）， high-density lipoprotein cholesterol （HDL-C）， low-density lipoprotein cholesterol （LDL-C）， fasting insulin （FINS）， fasting glucose （FPG）， 2-hour postprandial glucose （2 h PG）， and glycosylated hemoglobin （HbA1c）］， insulin resistance indicators ［homeostatic model assessment for insulin resistance （HOMA-IR）， triglyceride-glucose index （TYG index）， triacylglycerol-to-high-density lipoprotein cholesterol （TG/HDL） ratio］， oxidative stress indicators ［malondialdehyde （MDA）， superoxide dismutase （SOD）， glutathione （GSH）， glutathione peroxidase （GSH-Px）， catalase （CAT）， and reactive oxygen species （ROS）］， and the safety of treatment. ResultsIn terms of TCM efficacy， the treatment in the observation group was significantly effective in 46 cases， effective in 30 cases， and ineffective in 10 cases， with the total effective rate of 88.4%. The treatment in the control group was significantly effective in 33 cases， effective in 28 cases， and ineffective in 23 cases， with the total effective rate of 72.6%. The observation group had higher total effective rate than the control group （χ²=11.26，P<0.05）. After treatment， both groups showed declined levels of WC， BMI， WHR， WHtR， SBP， DBP， TC， TG， LDL-C， FPG， FINS， 2 h PG， HbA1c， HOMA-IR， TG/HDL ratio， TYG index， MDA， and ROS and elevated levels of HDL-C， SOD， GSH， GSH-Px， and CAT （P<0.05）. After treatment， the observation group showed lower levels of WC， BMI， WHR， WHtR， TC， TG， LDL-C， FPG， FINS， 2 h PG， HbA1c， HOMA-IR， TG/HDL ratio， TYG index， MDA， and ROS and higher levels of HDL-C， SOD， GSH， GSH-Px， and CAT than the control group （P<0.05）. However， after treatment， there was no significant difference in SBP or DBP between the observation group and the control group. No significant adverse reactions were observed in either group. ConclusionModified Huanglian Wendantang can significantly alleviate metabolic syndrome symptoms and reduce oxidative stress， exhibiting antioxidant effects. Moreover， it does not induce adverse reactions， demonstrating safety.

ObjectiveTo observe the effect of modified Huanglian Wendantang on oxidative stress in metabolic syndrome. MethodsA total of 180 patients with metabolic syndrome treated in the outpatient clinics and wards of the First Affiliated Hospital of Heilongjiang University of Traditional Chinese Medicine from October 2023 to May 2025 were enrolled in this study. According to the randomized numerical table method， the patients were assigned into two groups （90 cases）. The basic treatment of the two groups was the same， and the observation group was additionally treated with modified Huanglian Wendantang. The course of treatment was 3 months. The two groups were compared in terms of traditional Chinese medicine （TCM） efficacy， obesity degree ［waist circumference （WC）， body mass index （BMI）， waist-to-hip ratio （WHR）， waist-to-height ratio （WHtR）］， blood pressure indicators ［systolic blood pressure （SBP） and diastolic blood pressure （DBP）］， lipids and glucose indicators ［total cholesterol （TC）， triglycerides （TG）， high-density lipoprotein cholesterol （HDL-C）， low-density lipoprotein cholesterol （LDL-C）， fasting insulin （FINS）， fasting glucose （FPG）， 2-hour postprandial glucose （2 h PG）， and glycosylated hemoglobin （HbA1c）］， insulin resistance indicators ［homeostatic model assessment for insulin resistance （HOMA-IR）， triglyceride-glucose index （TYG index）， triacylglycerol-to-high-density lipoprotein cholesterol （TG/HDL） ratio］， oxidative stress indicators ［malondialdehyde （MDA）， superoxide dismutase （SOD）， glutathione （GSH）， glutathione peroxidase （GSH-Px）， catalase （CAT）， and reactive oxygen species （ROS）］， and the safety of treatment. ResultsIn terms of TCM efficacy， the treatment in the observation group was significantly effective in 46 cases， effective in 30 cases， and ineffective in 10 cases， with the total effective rate of 88.4%. The treatment in the control group was significantly effective in 33 cases， effective in 28 cases， and ineffective in 23 cases， with the total effective rate of 72.6%. The observation group had higher total effective rate than the control group （χ²=11.26，P<0.05）. After treatment， both groups showed declined levels of WC， BMI， WHR， WHtR， SBP， DBP， TC， TG， LDL-C， FPG， FINS， 2 h PG， HbA1c， HOMA-IR， TG/HDL ratio， TYG index， MDA， and ROS and elevated levels of HDL-C， SOD， GSH， GSH-Px， and CAT （P<0.05）. After treatment， the observation group showed lower levels of WC， BMI， WHR， WHtR， TC， TG， LDL-C， FPG， FINS， 2 h PG， HbA1c， HOMA-IR， TG/HDL ratio， TYG index， MDA， and ROS and higher levels of HDL-C， SOD， GSH， GSH-Px， and CAT than the control group （P<0.05）. However， after treatment， there was no significant difference in SBP or DBP between the observation group and the control group. No significant adverse reactions were observed in either group. ConclusionModified Huanglian Wendantang can significantly alleviate metabolic syndrome symptoms and reduce oxidative stress， exhibiting antioxidant effects. Moreover， it does not induce adverse reactions， demonstrating safety.

ObjectiveTo clarify the independent and synergistic effects of dyslipidemia in the progression of hepatic steatosis in metabolic dysfunction-associated fatty liver disease （MAFLD）. MethodsA total of 7 697 participants who underwent physical examination in Beijing Friendship Hospital， Capital Medical University， from January 2022 to December 2024 were enrolled， and finally 2 177 patients with MAFLD were enrolled as subjects. Transient elastography was used to quantify the severity of hepatic steatosis （grades S1-S3）. The multivariable ordinal Logistic regression analysis was used to investigate the independent and synergistic associations of serum triglyceride （TG）， high-density lipoprotein cholesterol （HDL-C）， and low-density lipoprotein cholesterol （LDL-C） with the severity of hepatic steatosis， and their interactions and potential nonlinear relationships with metabolic factors were also examined. One-way analysis of variance or Kruskal-Wallis H test was used for comparison of continuous data between groups， and chi-square test was used for comparison of categorical data between groups. ResultsAn increase in TG （odds ratio ［OR］=1.77， 95% confidence interval ［CI］： 1.48 — 2.10， P<0.001） and a reduction in HDL-C （OR=1.35， 95%CI： 1.11 — 1.65， P=0.003） were independently associated with a greater severity of hepatic steatosis， with the strongest association when both abnormalities coexisted （OR=2.40， 95%CI： 1.87 — 3.07， P<0.001）. The dose-response relationship analysis further revealed a nonlinear threshold effect of TG on hepatic steatosis at the threshold of 1.51 mmol/L （P_nonlinearity=0.001）， below which the severity of steatosis increased more rapidly with the increase in TG concentration （P=0.001）. The subgroup analysis showed that the association between the reduction in HDL-C and the severity of steatosis was observed only in males， young adults （aged <45 years）， and metabolically healthier subgroups （without diabetes， obesity， hyperuricemia or hypertension）. Significant interactions were observed between the presence or absence of obesity and the abnormal levels of TG and HDL‑C （both P_interaction<0.05）. The association of the increase in LDL-C with steatosis was confined to specific subgroups （without obesity or hyperuricemia）. ConclusionThe increase in TG and the reduction in HDL-C are independently associated with the severity of hepatic steatosis in MAFLD. The synergistic effect of blood lipids and their interactions with metabolic factors may further refine risk stratification， so as to provide a basis for precise management of MAFLD.

Objective To evaluate and improve missing data imputation methods to enhance the performance of binary classification prediction model.Methods By simulating data missing scenes,the effects of direct elimination,mean imputation,random forest(RF)imputation algorithm,and multiple imputation-random forest(MI-RF)on the performance of the prediction model were jointly evaluated by receiver operating characteristic area under curve(AUC)and root mean square error(RMSE).Bayesian Network was introduced for the random forest imputation algorithm to optimize the imputation method using the correlations between variables.Results Under different missing proportions,both AUC and RMSE indicated that Bayesian network optimized random forest(BN-RF)imputation algorithm was better.In addition,when the missing proportion was 10％-20％,various imputation methods had roughly the same improvement effect for the prediction model;when the proportion of missing data was 30％-40％,compared to the mean imputation,except for the BN-RF,RF was more effective and its effect was slightly better than MI-RF;however,when the proportion of missing data was close to 50％,even if the model performance was still appropriate,the imputation data gradually deviated from the true data features,resulting in a decrease in the usability of the model.Conclusion The overall effect of BN-RF is satisfactory,and it should be chosen when random missing was 30％-40％.

Objective:To explore the mechanism of modified Shaoyao Decoction with Astragali Radix and Houttuynize Herba in regulating PI3K/Akt/NF-κB pathway against intestinal mucosal barrier injury in ulcerative colitis (UC) rats.Methods:Totally 72 Wistar rats were randomly divided into a blank control group, a model group, a mesalazine group, and modified Shaoyao Decoction high-, medium-, and low-dose groups using a random number table method. After successful modeling, the mesalazine group was given 0.2 g/kg of mesalazine suspension by gavage, while modified Shaoyao Decoction high-, medium-, and low-dose groups were given 44.5, 22.3, and 11.1 g/kg of modified Shaoyao Decoction by gavage, once a day, for a total of 4 weeks. The pathological changes of colon tissue were observed using HE staining; immunofluorescence assay was used to detect the expressions of tight junction protein (ZO-1), cytoskeletal protein (F-actin), and vascular endothelial cadherin (VE cadherin) in colon tissue; Western blot was used to detect the protein expressions of PI3K, Akt, NF-κB, VEGF, and cyclooxygenase (COX-2) in colon tissue; QRT PCR was used to detect the expressions of PI3K and Akt mRNA in colon tissue; ELISA method was used to detect the levels of serum TNF-α and endothelin (ET).Results:Compared with the model group, the DAI scores of the mesalazine group and modified Shaoyao Decoction high-dosage group decreased significantly on the 7th, 14th, 21st and 28th day after modeling ( P<0.05 or P<0.01). In mesalazine group and modified Shaoyao Decoction high-, medium-, and low-dose groups, the pathological injury score of colon tissue decreased ( P<0.01), the immunofluorescence intensity of ZO-1, F-actin and VE-cadherin protein expression in colon tissue increased ( P<0.05 or P<0.01), and the expressions of PI3K, Akt, NF-κB and VEGF protein decreased ( P<0.01). The expression of COX-2 protein and the levels of PI3K mRNA and Akt mRNA decreased in the mesalazine group and modified Shaoyao Decoction high- and medium groups ( P<0.05 or P<0.01). Conclusion:Modified Shaoyao Decoction can antagonize the intestinal barrier injury of UC by inhibiting PI3K/Akt/NF-κB pathway and promote the healing of intestinal mucosal ulcer.

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.

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.

Poly(ADP-ribosyl)ation (PARylation) is a specific form of post-translational modification (PTM) predominantly triggered by the activation of poly-ADP-ribose polymerase 1 (PARP1). However, the role and mechanism of PARylation in the advancement of acute kidney injury (AKI) remain undetermined. Here, we demonstrated the significant upregulation of PARP1 and its associated PARylation in murine models of AKI, consistent with renal biopsy findings in patients with AKI. This elevation in PARP1 expression might be attributed to trimethylation of histone H3 lysine 4 (H3K4me3). Furthermore, a reduction in PARylation levels mitigated renal dysfunction in the AKI mouse models. Mechanistically, liquid chromatography-mass spectrometry indicated that PARylation mainly occurred in receptor for activated C kinase 1 (RACK1), thereby facilitating its subsequent phosphorylation. Moreover, the phosphorylation of RACK1 enhanced its dimerization and accelerated the ubiquitination-mediated hypoxia inducible factor-1α (HIF-1α) degradation, thereby exacerbating kidney injury. Additionally, we identified a PARP1 proteolysis-targeting chimera (PROTAC), A19, as a PARP1 degrader that demonstrated superior protective effects against renal injury compared with PJ34, a previously identified PARP1 inhibitor. Collectively, both genetic and drug-based inhibition of PARylation mitigated kidney injury, indicating that the PARylated RACK1/HIF-1α axis could be a promising therapeutic target for AKI treatment.

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.