Objective To explore the functional impact of A-to-I editing in the seed region of miR-411 during post-myocardial infarction (MI) fibrosis and elucidate its therapeutic potential. Methods Integrating GEO database with myocardial RNA-seq data from MI mouse models, we identified dynamic A-to-I RNA editing in small noncoding RNAs across MI progression (1 day to 8 weeks post-MI). Four miRNAs exhibited differential editing rates between MI and controls, with miR-411 showing progressive editing enhancement at seed region position 4 (P＜0.01). This editing event was validated in both murine MI models and human heart failure specimens. Results The A-to-I editing ratio change of the 4th nucleotide in the seed region of miR-411 mainly occurs in cardiac fibroblasts rather than cardiomyocytes, and the editing at this site depends on ADAR2 rather than ADAR1. Edited miR-411 (ED-miR-411) diverged from wild-type miR-411 (WT-miR-411) in suppressing collagen-related pathways (extracellular matrix [ECM]-receptor interaction, collagen-containing ECM, ECM organization; P＜0.01) in cardiac fibroblasts. Mechanistically, dual-luciferase assays confirmed ED-miR-411 directly targeted the 3′UTR and suppressed expression of type Ⅱ transforming growth factor (TGF)-beta receptor (TGFBR2) and CD44, which were key drivers of TGF-β-mediated fibroblast activation. ED-miR-411 overexpression blunted TGF-β-induced collagen synthesis and myofibroblast proliferation (P＜0.05). In vivo, intramyocardial delivery of ED-miR-411 mimics at 1 week post-MI reduced fibrosis by 40% and improved ejection fraction by 15% (P＜0.01 vs controls), whereas WT-miR-411 showed no therapeutic effect. Conclusions A-to-I editing of miR-411 emerges as an endogenous anti-fibrotic mechanism by repressing TGFBR2 and CD44, thereby disrupting TGF-β signaling and ECM dysregulation. Our findings highlight ED-miR-411 as a novel RNA-based therapeutic candidate to mitigate post-infarction cardiac remodeling.

Background/Aims: Hepatocellular carcinoma (HCC) is one of the leading causes of cancer-related mortality worldwide and is driven by metabolic reprogramming that supports tumor growth and progression. A common missense genetic variant (rs2642438, p.A165T) in mitochondrial amidoxime reducing component 1 (MTARC1), identified as protective against liver disease, has been recently associated with lower prevalence of steatosis, cirrhosis, and HCC. However, the mechanistic role of MTARC1 in HCC is unclear. Therefore, we sought to decipher the role of MTARC1 in HCC. Methods: We investigated the role of MTARC1 in HCC by performing siRNA-mediated knockdown across human immortalized HCC cell lines (Hep3B2, HuH7, HepG2 and HepaRG) homozygous for the risk allele (p.A165) and by generating stable CRISPR-Cas9 knockout (KO) models. Next, we assessed the effect of MTARC1 loss on cell proliferation, migration, lipid metabolism, and fatty acid oxidation in vitro, as well as tumor aggressiveness in a subcutaneous xenograft mouse model. Additionally, we performed global proteomics in both in vitro and xenograft models. Results: Transient knockdown of MTARC1 p.A165 reduced proliferation in HCC cell lines. CRISPR-Cas9-mediated stable MTARC1 p.A165 KO in Hep3B2 cells led to decreased neutral lipid intracellular accumulation, enhanced β-oxidation and reduced cell migration. An MTARC1 KO xenograft model had reduced tumor volume. Proteomic analyses of both in vitro HCC cells and xenograft tumors revealed inhibition of oncogenic pathways and activation of anti-proliferative proteins. Conclusions Downregulation of MTARC1 p.A165 inhibits lipid accumulation, dampens tumor-promoting pathways and restricts tumor growth, highlighting MTARC1 as a promising therapeutic target for HCC.

ObjectiveTo investigate the value of liver stiffness measurement （LSM） and spleen stiffness measurement （SSM） measured by two-dimensional shear wave elastography （2D-SWE） in the diagnosis of severe portal hypertension （SPH） and high-risk varices （HRV）， and to provide a basis for noninvasive assessment of portal hypertension. MethodsA prospective study was conducted among 78 patients with cirrhotic portal hypertension who were treated in Liver Research Center of Beijing Friendship Hospital， Capital Medical University， from December 2019 to April 2023. According to hepatic venous pressure gradient （HVPG）， the patients were divided into 6 mmHg≤HVPG<12 mmHg group， 12 mmHg≤HVPG<20 mmHg group， and HVPG ≥20 mmHg group. All patients underwent gastroscopy and 2D-SWE within 1 week after HVPG measurement， and SWE-LSM and SWE-SSM measured by 2D-SWE were recorded. A one-way analysis of variance or the Kruskal-Wallis H test was used for comparison of continuous data between multiple groups， and the chi-square test or the Fisher’s exact test was used for comparison of categorical data between groups. With HVPG and gastroscopy findings as the gold standard， the receiver operating characteristic （ROC） curve was plotted and the area under the ROC curve （AUC） was calculated to evaluate diagnostic performance， while the DeLong test was used for comparison of AUC. The Pearson or Spearman correlation analysis was used to investigate the correlation between variables， and the linear regression analysis and the Logistic regression analysis were used to investigate the influencing factors for HVPG and HRV. ResultsThe mean HVPG was 18.1±6.4 mmHg for the patients enrolled in this study， and HRV was observed in 62 patients （79.5%）. Both SWE-LSM and SWE-SSM were significantly positively correlated with HVPG （r=0.413 and 0.633， both P<0.001）， with an AUC of 0.812 and 0.902， respectively， in the diagnosis of HVPG≥12 mmHg and an AUC of 0.804 and 0.789， respectively， in the diagnosis of HVPG≥20 mmHg （all P>0.05）. The multivariate linear regression analysis showed that SWE-SSM was an independent influencing factor for HVPG （β=0.17， P<0.001）. In the diagnosis of HRV， only SWE-SSM showed a significant positive correlation with HRV （r=0.432， P<0.001）， with a better diagnostic performance than SWE-LSM in terms of AUC （0.808 vs 0.642， Z=2.775， P=0.006）. The multivariate Logistic regression analysis showed that platelet count was an independent influencing factor for HRV （odds ratio=0.97， P=0.014）. ConclusionSWE-SSM is closely correlated with both HVPG and HRV， showing a good performance in the diagnosis of SPH and HRV， and therefore， it is expected to become an effective noninvasive tool for assessing portal hypertension.

Objective:To identify the serotype and genotype characteristics of the first cluster infection of Brucella in Nujiang Lisu Autonomous Prefecture of Yunnan Province. Methods:The information of seven suspected cluster brucellosis cases reported in Lanping County, Nujiang Lisu Autonomous Prefecture in April 2023 were collected, blood samples were collected, and the strains were isolated and cultured. Serological methods were employed for brucellosis diagnosis, bacterial species identification was performed using BCSP31-PCR and AMOS-PCR. Multilocus locus variable-number tandem repeat analysis (MLVA) was conducted for strain genotyping, followed by phylogenetic analysis comparing the strains with those from other regions of China.Results:All seven cases were diagnosed with brucellosis, they were all villagers from the same village and had daily contact with sheeps. Four suspected Brucella strains were isolated, identified as Brucella melitensis biotype by BCSP31-PCR and AMOS-PCR. The four isolated strains exhibited identical MLVA-16 genotype, with MLVA-8 genotype 42 and MLVA-11 genotype 180, belonging to the Eastern Mediterranean lineage. Compared with the MLVA-16 of the isolated strains from other regions of China, the four isolated strains formed an independent cluster. Conclusion:The first cluster infection of Brucella in Nujiang Lisu Autonomous Prefecture of Yunnan Province is caused by Brucella melitensis biotype, and the four isolated strains have showed unique MLVA genotype.

Objective:To learn about the geographical distribution and bio-tying diversity characteristics of Brucella strains isolated in Yunnan Province. Methods:From March 2017 to December 2023, 516 suspected Brucella strains were collected from brucellosis surveillance sites and hospitals in Yunnan Province, and Yunnan Institute of Endemic Disease Control and Prevention. The Brucella isolates were confirmed to genus level by BCSP31-PCR, and subsequently identified to species and biovar level using conventional biotyping methods and AMOS-PCR. The geographical distribution of the strains was visualized using ArcGIS 10.8 software, simultaneously analyze the general characteristics of brucellosis patients. Results:Among the 516 suspected Brucella strains, 514 strains were isolated from patient blood samples and 2 strains were isolated from sheep blood samples. BCSP31-PCR identification showed that all strains were Brucella spp. The results of conventional biotyping and AMOS-PCR identification revealed that the isolates comprised 514 Brucella melitensis strains (16 strains of Brucella melitensis biovar 1 and 498 strains of Brucella melitensis biovar 3), one Brucella abortus (biovar 1) strain, and one Brucella canis strain. The strain was distributed in 69 counties/cities of 13 prefectures/cities in Yunnan Province, involving 390 administrative villages in 186 townships. Brucella melitensis was the dominant epidemic strain, and the largest number of Brucella melitensis was distributed in Kunming City( n = 205), followed by Honghe Hani and Yi Autonomous Prefecture ( n = 98) and Qujing City ( n = 72). Brucella abortus was only distributed in Lincang City ( n = 1), and Brucella canis was distributed Wenshan Zhuang and Miao Autonomous Prefecture ( n = 1). The age range of 514 brucellosis patients ranged from 10 months to 88 years, with the majority being between 40 and 60 years old (52.72%, 271/514). The predominant occupational group was farmers (89.11%, 458/514), followed by students (5.06%, 26/514). Conclusion:Brucella exhibits a wide distribution and species/biovar diversity in Yunnan Province, with infection among the farming population emerging as a serious public health problem in the area.

Objective To investigate the diagnostic value of serum soluble growth stimulation expressed gene 2(sST2),decoy receptor 3(DcR3)and dynamic electrocardiogram(DCG)for asymptomatic myocardial ischemia(SMI).Methods Eighty-five patients with coronary heart disease were selected as observation subjects(the observation group).Sixty-one SMI patients were confirmed by coronary angiography(the SMI group).Among them,there were 24 cases with symptomatic myocardial ischemia(the symptomatic myocardial ischemia group).During the same period,84 patients with unexplained chest pain who were examined in our hospital and without coronary heart disease were selected as the control group.ELISA was applied to detect serum levels of sST2 and DcR3.ROC was used to analyze the diagnostic value of serum sST2,DcR3 and DCG for SMI.Multivariate Logistic regression was applied to analyze the influencing factors of SMI.Results The serum level of sST2 was higher in the observation group than that in the control group[(55.61±7.12)μg/L vs.(14.22±3.64)μg/L],while the level of DcR3 was lower than that in the control group[(0.68±0.11)μg/L vs.(1.24±0.21)μg/L](P＜0.05).The serum level of sST2 was higher in the SMI group than that in the symptomatic myocardial ischemia group[(59.28±7.12)μg/L vs.(46.28±8.15)μg/L],while the level of DcR3 was lower than that in the symptomatic myocardial ischemia group[(0.63±0.11)μg/L vs.(0.81±0.14)μg/L](P＜0.05).The heart rate of the SMI group was higher than that of the symptomatic myocardial ischemia group,and the duration of ischemia and the decrease in ST segment were lower than those of the symptomatic myocardial ischemia group(P＜0.05).ROC curve results showed that the AUC values of serum sST2,DcR3 and DCG alone and in their combination for diagnosing SMI in patients with coronary heart disease were 0.826,0.882,0.773,and 0.958,respectively,and the combined diagnosis of SMI was superior to individual diagnosis(Z=3.188,2.225,2.770,P＜0.05).sST2 and DcR3 were influencing factors of SMI occurrence(P＜0.05).Conclusion The increased serum sST2 and the decreased DcR3 are closely related to the occurrence of SMI,and the combination of serum sST2 and DcR3 with DCG has certain diagnostic value for SMI.

Objective This study aims to observe the impact of warm moxibustion on menstrual pain in college students with primary dysmenorrhea and explore its potential mechanism.Methods College students with primary dysmenorrhea were recruited and treated with warm moxibustion at Shenque acupoint for three consecutive menstrual cycles.Healthy subjects were also recruited for comparison.Pain scale,uterine artery hemodynamics,and related inflammatory factors were assessed before and after treatment.Results ①The results of scale study showed that the severity and duration of dysmenorrhea were gradually alleviated with the prolongation of treatment time through the analysis of variance of repeated measurements of the total scores of McGill pain inquiry scale and CMSS dysmenorrhea symptom scale before and after 3 treatments.The results of variance analysis and pairwise comparison of repeated measurements of PRI,VAS and PPI of McGill pain inquiry scale before and after 3 times treatment in warm moxibustion group also showed that each index decreased gradually with the prolongation of treatment time.The comparison of the scores of each item of CMSS scale showed that the severity and duration of low back before treatment were significantly different from those in the healthy group(P<0.001),but the difference was weakened after the third treatment.The severity of vomiting,the duration of vomiting,the severity of diarrhea and the duration of diarrhea were significantly different from those in the healthy group before treatment(P<0.001),but they were still higher than those in the healthy group after the third treatment.but the difference was not statistically significant.②Prior to treatment,PD college students exhibited significantly higher S/D and PI values on both sides compared to healthy subjects,with a statistically significant difference observed for PI on the left side(P<0.001).Following treatment,all aforementioned indexes decreased significantly,particularly PI on the left side which showed a significant difference from pre-treatment levels(P<0.001).③Before treatment,the levels of serum IL-1β,TNF-α,and CRP in PD college students were significantly higher compared to those in the healthy group.The difference in IL-1β level was statistically significant(P<0.001).After treatment,there was a noticeable decrease in the levels of IL-1β,TNF-α,and CRP.Specifically,IL-1β showed a significant reduction(P<0.01),and this time the comparison with the healthy group did not reveal any significant difference in IL-1β levels.Conclusion The application of warm moxibustion at the Shenque acupoint demonstrates a significant improvement in both the dysmenorrhea pain rating index and severity among college students with primary dysmenorrhea,while also alleviating the severity and duration of associated symptoms.These positive effects may be attributed to warm moxibustion's ability to enhance uterine microcirculation in individuals with primary dysmenorrhea,and ameliorating inflammatory conditions.

Objective:To study the effects of remimazolam on stress response index, T lymphocyte subsets and postoperative delirium in patients undergoing modified radical mastectomy.Methods:A total of 120 patients with breast cancer who underwent modified radical mastectomy in our hospital from Aug. 2024 to Dec. 2024 were separated into the control group (n=60, anesthetic induction and maintenance with Propofol) and the observation group (n=60, anesthetic induction and maintenance with remimazolam) according to random number table method, and the other anesthetic drugs were the same. The operation time, anesthesia recovery time, postoperative delirium and cognitive dysfunction of the two groups were observed, and the changes of stress response indexes and T lymphocyte subsets indexes at different time points were compared, and the adverse reactions after anesthesia were counted.Results:The incidence of postoperative delirium and cognitive dysfunction in the observation group was lower than that in the control group ( x2=4.62, 5.18, P < 0.05), and there was no statistically significant difference in operation time or anesthesia recovery time between the two groups ( t=0.43, 1.71, P > 0.05). The observation group had lower serum cortisol (Cor), norepinephrine (NE) and epinephrine (E) levels 30 min after anesthesia induction (T 1) and immediately after surgery (T 2) ( t=5.53, 6.71, 9.33, 6.74, 7.26, 8.77, P < 0.05), while the comparison of those indexes before surgery (T 0) and 12 h after surgery (T 3) showed no statistically significant difference ( t=1.19, 1.85, 0.90, 1.55, 1.64, 1.81, P > 0.05). The levels of CD3 +T, CD4 +T and CD4 +/CD8 + in the observation group were higher than those in the control group at T 1, T 2 and T 3 ( t=2.21, 4.94, 4.77, 4.44, 6.24, 7.07, 2.11, 2.56, 2.15, P < 0.05), and there was no statistically significant difference in those indexes between the two groups at T 0 ( t=0.76, 0.79, 1.51, P > 0.05). The incidence of adverse reactions after anesthesia showed no statistically significant difference between the two groups [25.00% (15/60) and 33.33% (20/60) ] ( χ2=1.008, P > 0.05) . Conclusion:The induction and maintenance of remimazolam anesthesia can effectively reduce the incidence of postoperative delirium and cognitive dysfunction in patients with modified radical mastectomy, relieve the body stress response of patients, and effectively reduce the influence of anesthesia on T lymphocytes.

Objective:To study the effects of remimazolam on stress response index, T lymphocyte subsets and postoperative delirium in patients undergoing modified radical mastectomy.Methods:A total of 120 patients with breast cancer who underwent modified radical mastectomy in our hospital from Aug. 2024 to Dec. 2024 were separated into the control group (n=60, anesthetic induction and maintenance with Propofol) and the observation group (n=60, anesthetic induction and maintenance with remimazolam) according to random number table method, and the other anesthetic drugs were the same. The operation time, anesthesia recovery time, postoperative delirium and cognitive dysfunction of the two groups were observed, and the changes of stress response indexes and T lymphocyte subsets indexes at different time points were compared, and the adverse reactions after anesthesia were counted.Results:The incidence of postoperative delirium and cognitive dysfunction in the observation group was lower than that in the control group ( x2=4.62, 5.18, P < 0.05), and there was no statistically significant difference in operation time or anesthesia recovery time between the two groups ( t=0.43, 1.71, P > 0.05). The observation group had lower serum cortisol (Cor), norepinephrine (NE) and epinephrine (E) levels 30 min after anesthesia induction (T 1) and immediately after surgery (T 2) ( t=5.53, 6.71, 9.33, 6.74, 7.26, 8.77, P < 0.05), while the comparison of those indexes before surgery (T 0) and 12 h after surgery (T 3) showed no statistically significant difference ( t=1.19, 1.85, 0.90, 1.55, 1.64, 1.81, P > 0.05). The levels of CD3 +T, CD4 +T and CD4 +/CD8 + in the observation group were higher than those in the control group at T 1, T 2 and T 3 ( t=2.21, 4.94, 4.77, 4.44, 6.24, 7.07, 2.11, 2.56, 2.15, P < 0.05), and there was no statistically significant difference in those indexes between the two groups at T 0 ( t=0.76, 0.79, 1.51, P > 0.05). The incidence of adverse reactions after anesthesia showed no statistically significant difference between the two groups [25.00% (15/60) and 33.33% (20/60) ] ( χ2=1.008, P > 0.05) . Conclusion:The induction and maintenance of remimazolam anesthesia can effectively reduce the incidence of postoperative delirium and cognitive dysfunction in patients with modified radical mastectomy, relieve the body stress response of patients, and effectively reduce the influence of anesthesia on T lymphocytes.

Objective To investigate the diagnostic value of serum soluble growth stimulation expressed gene 2(sST2),decoy receptor 3(DcR3)and dynamic electrocardiogram(DCG)for asymptomatic myocardial ischemia(SMI).Methods Eighty-five patients with coronary heart disease were selected as observation subjects(the observation group).Sixty-one SMI patients were confirmed by coronary angiography(the SMI group).Among them,there were 24 cases with symptomatic myocardial ischemia(the symptomatic myocardial ischemia group).During the same period,84 patients with unexplained chest pain who were examined in our hospital and without coronary heart disease were selected as the control group.ELISA was applied to detect serum levels of sST2 and DcR3.ROC was used to analyze the diagnostic value of serum sST2,DcR3 and DCG for SMI.Multivariate Logistic regression was applied to analyze the influencing factors of SMI.Results The serum level of sST2 was higher in the observation group than that in the control group[(55.61±7.12)μg/L vs.(14.22±3.64)μg/L],while the level of DcR3 was lower than that in the control group[(0.68±0.11)μg/L vs.(1.24±0.21)μg/L](P＜0.05).The serum level of sST2 was higher in the SMI group than that in the symptomatic myocardial ischemia group[(59.28±7.12)μg/L vs.(46.28±8.15)μg/L],while the level of DcR3 was lower than that in the symptomatic myocardial ischemia group[(0.63±0.11)μg/L vs.(0.81±0.14)μg/L](P＜0.05).The heart rate of the SMI group was higher than that of the symptomatic myocardial ischemia group,and the duration of ischemia and the decrease in ST segment were lower than those of the symptomatic myocardial ischemia group(P＜0.05).ROC curve results showed that the AUC values of serum sST2,DcR3 and DCG alone and in their combination for diagnosing SMI in patients with coronary heart disease were 0.826,0.882,0.773,and 0.958,respectively,and the combined diagnosis of SMI was superior to individual diagnosis(Z=3.188,2.225,2.770,P＜0.05).sST2 and DcR3 were influencing factors of SMI occurrence(P＜0.05).Conclusion The increased serum sST2 and the decreased DcR3 are closely related to the occurrence of SMI,and the combination of serum sST2 and DcR3 with DCG has certain diagnostic value for SMI.