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.

ObjectiveTo characterize the seasonal patterns of influenza in Kunming City, Yunnan Province before, during, and after the COVID-19 pandemic, and provide scientific evidence for optimizing influenza prevention and control strategies. MethodsInfluenza-like illness (ILI) and etiological surveillance data for influenza from the 14^th week of 2010 to the 13^th week of 2024 in Kunming City of Yunnan Province were collected. Harmonic regression models were constructed to analyze the epidemic characteristics and seasonal patterns of influenza before (2010/2011‒2019/2020 influenza seasons), during (2020/2021‒2022/2023 influenza seasons), and after (2023/2024 influenza season) the COVID-19 pandemic. ResultsBefore the COVID-19 pandemic, influenza in Kunming City mainly exhibited an annual cyclic pattern without a significant semi-annual periodicity, peaking from December to February of the next year, with an epidemic duration of 20‒30 weeks. During the pandemic, influenza seasonality shifted, with an increase in semi-annual periodicity and an approximate one month delay in annual peaks. However, after the pandemic, the annual amplitude of influenza increased compared with that before the pandemic, and the epidemic duration extended by about one month. Although the annual peak largely reverted to the pre-pandemic levels, the annual peaks for different influenza subtypes/lineages had not fully recovered. ConclusionInfluenza seasonality in Kunming City underwent substantial alterations following the COVID-19 pandemic and has not yet fully reverted to pre-pandemic levels. Continuous surveillance on different subtypes/lineages of influenza viruses remains essential, and prevention and control strategies should be adjusted and optimized in a timely manner based on current epidemic trends.

Objective To explore the short-term efficacy and safety of AngioJet mechanical thrombus removal,large lumen cathe-ter thrombus aspiration,and simple catheter-directed thrombolysis(CDT)for the treatment of acute deep venous thrombosis(DVT)of lower extremity.Methods A total of 75 patients with acute lower extremity DVT received interventional therapy were analyzed retrospectively,including 22 patients in AngioJet mechanical thrombus removal(group A),32 patients in large lumen catheter thrombus aspiration(group B),and 21 patients in simple CDT(group C).The short-term efficacy,health economics index,laboratory index and complications of the three groups were compared.Results The success rate of the three groups was 100％.Group A had superior thrombus clearance rates,lower dosages of urokinase,shorter thrombolysis durations,and shorter hospital stays compared to groups B and C.However,the hospitalization costs in group A were significantly higher than those in groups B and C,with statistically significant differences(P＜0.05).No significant renal dysfunction and severe complications were observed in the three groups.Post-operative creatinine levels in group A were higher than those in groups B and C,with statistically significant differences(P＜0.05).Both groups A and B experienced significant decreases in hematocrit postoperatively,and the absolute decrease and percentage decrease in hematocrit in group A were significantly greater than those in group C,with statistically significant differences(P＜0.05).Conclusion Compared to large lumen catheter thrombus aspiration and simple CDT treatment,AngioJet mechanical thrombus removal demonstrates higher efficiency in thrombus clearance rate but is associated with higher costs and risks of renal dysfunction.Postoperative care should focus on protecting renal function.

Objective:To explore the diagnostic value of blood flow parameters of carotid ultrasound combined with serum Sortilin and paraoxonase-1 (PON-1) for stability of carotid atherosclerotic plaque (CAP). Methods:A total of 100 CAP patients who admitted to Rugao Hospital of Traditional Chinese Medicine from January 2021 to December 2023 were selected,and they were divided into a stable plaque group (n=54) and a unstable plaque group (n=46). Enzyme linked immunosorbent assay (ELISA) was adopted to determine the expression levels of serum Sortilin and PON-1 of patients in two groups. Multi factor logistic regression was implemented to analyze the influencing factors on CAP stability. The receiver operating characteristic (ROC) curves were drawn to analyze the diagnostic efficiency of blood flow parameters of carotid ultrasound combined with Sortilin and PON-1 on CAP stability. Results:Compared with the end diastolic blood flow velocity (EDV) and intima-media thickness (IMT) of stable plaque group,unstable plaque group showed increased EDV and IMT,and decreased PSV,and the differences were significant (t=7.536,4.680,5.487,P<0.05),respectively. Compared with stable plaque group,the serum Sortilin level in unstable plaque group significantly increased,while the PON-1 level significantly decreased,and the differences of them were significant (t=8.362,5.581,P<0.05),respectively. Multivariate logistic analysis found that Sortilin was a risk factor that affected CAP stability (OR=3.165,P<0.05),while PON-1 was a protective factor that affected CAP stability (OR=0.765,P<0.05). ROC curve analysis indicated that the area under curve (AUC) values of single Sortilin,PON-1,EDV,IMT,PSV,and the combination of them were respectively 0.788 (95％CI:0.695-0.864),0.814 (95％CI:0.724-0.885),0.847 (95％ CI:0.761-0.911),0.767 (95％ CI:0.672-0.846),0.707 (95％ CI:0.607-0.793) and 0.963 (95％ CI:0.839-0.907). The AUC value of the combination of above 5 indicators was highest,which was better than that of each single indicator,and its sensitivity and specificity were respectively 95.65％ and 83.33％. Conclusion:The EDV,IMT and PSV of blood flow parameters of ultrasound can provide CAP information of morphology and hemodynamics,and serum Sortilin level and PON-1 level can reflect the biological processes of formation and development of CAP. The combined detection of the five indicators can better diagnose CAP stability.

Objective:To explore the diagnostic value of blood flow parameters of carotid ultrasound combined with serum Sortilin and paraoxonase-1 (PON-1) for stability of carotid atherosclerotic plaque (CAP). Methods:A total of 100 CAP patients who admitted to Rugao Hospital of Traditional Chinese Medicine from January 2021 to December 2023 were selected,and they were divided into a stable plaque group (n=54) and a unstable plaque group (n=46). Enzyme linked immunosorbent assay (ELISA) was adopted to determine the expression levels of serum Sortilin and PON-1 of patients in two groups. Multi factor logistic regression was implemented to analyze the influencing factors on CAP stability. The receiver operating characteristic (ROC) curves were drawn to analyze the diagnostic efficiency of blood flow parameters of carotid ultrasound combined with Sortilin and PON-1 on CAP stability. Results:Compared with the end diastolic blood flow velocity (EDV) and intima-media thickness (IMT) of stable plaque group,unstable plaque group showed increased EDV and IMT,and decreased PSV,and the differences were significant (t=7.536,4.680,5.487,P<0.05),respectively. Compared with stable plaque group,the serum Sortilin level in unstable plaque group significantly increased,while the PON-1 level significantly decreased,and the differences of them were significant (t=8.362,5.581,P<0.05),respectively. Multivariate logistic analysis found that Sortilin was a risk factor that affected CAP stability (OR=3.165,P<0.05),while PON-1 was a protective factor that affected CAP stability (OR=0.765,P<0.05). ROC curve analysis indicated that the area under curve (AUC) values of single Sortilin,PON-1,EDV,IMT,PSV,and the combination of them were respectively 0.788 (95％CI:0.695-0.864),0.814 (95％CI:0.724-0.885),0.847 (95％ CI:0.761-0.911),0.767 (95％ CI:0.672-0.846),0.707 (95％ CI:0.607-0.793) and 0.963 (95％ CI:0.839-0.907). The AUC value of the combination of above 5 indicators was highest,which was better than that of each single indicator,and its sensitivity and specificity were respectively 95.65％ and 83.33％. Conclusion:The EDV,IMT and PSV of blood flow parameters of ultrasound can provide CAP information of morphology and hemodynamics,and serum Sortilin level and PON-1 level can reflect the biological processes of formation and development of CAP. The combined detection of the five indicators can better diagnose CAP stability.

Objective To explore the short-term efficacy and safety of AngioJet mechanical thrombus removal,large lumen cathe-ter thrombus aspiration,and simple catheter-directed thrombolysis(CDT)for the treatment of acute deep venous thrombosis(DVT)of lower extremity.Methods A total of 75 patients with acute lower extremity DVT received interventional therapy were analyzed retrospectively,including 22 patients in AngioJet mechanical thrombus removal(group A),32 patients in large lumen catheter thrombus aspiration(group B),and 21 patients in simple CDT(group C).The short-term efficacy,health economics index,laboratory index and complications of the three groups were compared.Results The success rate of the three groups was 100％.Group A had superior thrombus clearance rates,lower dosages of urokinase,shorter thrombolysis durations,and shorter hospital stays compared to groups B and C.However,the hospitalization costs in group A were significantly higher than those in groups B and C,with statistically significant differences(P＜0.05).No significant renal dysfunction and severe complications were observed in the three groups.Post-operative creatinine levels in group A were higher than those in groups B and C,with statistically significant differences(P＜0.05).Both groups A and B experienced significant decreases in hematocrit postoperatively,and the absolute decrease and percentage decrease in hematocrit in group A were significantly greater than those in group C,with statistically significant differences(P＜0.05).Conclusion Compared to large lumen catheter thrombus aspiration and simple CDT treatment,AngioJet mechanical thrombus removal demonstrates higher efficiency in thrombus clearance rate but is associated with higher costs and risks of renal dysfunction.Postoperative care should focus on protecting renal function.

ObjectiveTo investigate the effect of Yishen Tongluo prescription （YSTLP） on apoptosis of renal tubular epithelial cells and explore the mechanism based on endoplasmic reticulum stress pathway of protein kinase R-like endoplasmic reticulum kinase （PERK）/activating transcription factor 4 （ATF4）/transcription factor C/EBP homologous protein （CHOP）. MethodThe db/db mice were randomly divided into model group， valsartan group （10 mg·kg^-1）， and low， middle， high-dose YSTLP groups （1， 2.5， 5 g·kg^-1）. Samples were collected after eight weeks of drug intervention. In addition， db/m mice in the same litter served as the control group. Human renal tubular epithelial cells （HK-2） were cultured in vitro and divided into the control group， advanced glycated end-product （AGE） group， and AGE + low， middle， and high-dose YSTLP groups （100， 200， 400 mg·L^-1）. TdT-mediated dUTP nick end labeling （TUNEL） staining was used to detect the apoptosis rate of HK-2 cells. Methylthiazolyldiphenyl-tetrazolium bromide （MTT） assay was conducted to detect the viability of HK-2 cells. Calcium fluorescence probe staining and luciferase reporter gene method were adopted to detect the luciferase activity of folded protein response element （UPRE） and endoplasmic reticulum stress. Immunohistochemical （IHC） analysis was carried out to measure the protein expressions of phosphorylated PKR （p-PERK）， CHOP， and ATF4. Real-time polymerase chain reaction （Real-time PCR） was used to measure the mRNA expression levels of CHOP and X-box binding protein 1 （XBP1） in mouse kidney and HK-2 cells. Western blot was used to detect the protein expression level of p-PERK， PERK， CHOP， ATF4， B-cell lymphoma-2 （Bcl-2）， Bcl-2 associated X protein （Bax）， and cleaved Caspase-3 in mouse kidney and HK-2 cells. ResultIn the cellular assay， HK-2 cell viability was significantly reduced， and the apoptosis rate was elevated in the AGE group compared with the control group （P<0.01）. The mRNA and protein expression levels of apoptosis-related factor Bcl-2 were significantly reduced （P<0.01）， and those of Bax were significantly increased （P<0.01）. The protein expression level of cleaved Caspase-3 was significantly increased （P<0.01）. Compared with the AGE group， YSTLP administration treatment resulted in elevated cell viability and reduced apoptosis rate （P<0.01）. The mRNA and protein expression levels of Bcl-2 were significantly elevated in a time- and dose-dependent manner （P<0.01）， and those of Bax were significantly reduced in a time- and dose-dependent manner. The protein expression level of cleaved Caspase-3 was significantly reduced in a time- and dose-dependent manner （P<0.01）. The intracellular Ca²⁺ imbalance and UPRE luciferase fluorescence intensity were increased in the AGE group compared with the control group （P<0.01）. The mRNA levels of endoplasmic reticulum stress-related factors CHOP and XBP1 were significantly increased （P<0.01）， and the protein expression levels of p-PERK， CHOP， and ATF4 were significantly increased （P<0.05）. Compared with the AGE group， YSTLP effectively improved intracellular Ca²⁺ imbalance in HK-2 cells and decreased UPRE luciferase fluorescence intensity in a dose-dependent manner （P<0.01）. It reduced the mRNA levels of endoplasmic reticulum stress-related factors CHOP and XBP1 （P<0.01） and the protein expression levels of intracellular p-PERK， CHOP， and ATF4 in a dose- and time-dependent manner （P<0.01）. In animal experiments， the protein expression level of Bcl-2 was significantly reduced（P<0.01）， and that of cleaved Caspase-3 and Bax was significantly increased in the model group compared with the control group （P<0.05）. The protein expression level of Bcl-2 was dose-dependently elevated， and that of cleaved Caspase-3 and Bax was dose-dependently decreased in the YSTLP groups compared with the model group （P<0.01）. Compared with the control group， the mRNA expression levels of CHOP and XBP1 were significantly elevated in the model group （P<0.05， P<0.01）， and the protein expression levels of p-PERK， CHOP， and ATF4 were significantly increased （P<0.05）. Compared with the model group， YSTLP significantly decreased the mRNA expression levels of CHOP and XBP1 （P<0.01） and the protein expression levels of p-PERK， CHOP， and ATF4 （P<0.01）. ConclusionYSTLP can effectively inhibit endoplasmic reticulum stress and improve apoptosis of renal tubular epithelial cells， and its mechanism may be related to the regulation of the PERK/AFT4/CHOP pathway.

Objective:To investigate the effects of Schisandrin A on the proliferation and apoptosis of prostate cancer cell and its mechanism.Methods:Human prostate cancer DU145 cell were cultured in vitro and grouped into DU145 group (normal culture), Schisandrin A L group (50 μmol/L Schisandrin A was added), Schisandrin A M group (100 μmol/L Schisandrin A was added), Schisandrin A H group (150 μmol/L Schisandrin A was added) and Simvastatin group (50 μmol/L Simvastatin was added). Cell morphology of each group was observed under microscope, cell proliferation ability was detected by CCK8 method, cell migration ability was detected by cell scratch assay, cell invasion ability was detected by Transwell assay, and cell apoptosis was detected by flow cytometry, the expression of phosphorylation (p) - mammalian STE20-like protein kinase 1 (MST1), MST1, p-large tumor suppressor 1 (LATS1), LATS1, p-Yes associated protein (YAP) and YAP protein were detected by Western blotting. Measurement data were expressed as mean± standard deviation ( ± s), one-way ANOVA for comparisons between multiple groups, and t-test for comparisons between two groups. Results:Compared with DU145 group, the number of cells in Schisandrin A L, M, H groups and Simvastatin group decreased, and the cells gradually shrunk and the spacing became larger, the cell survival rate [(100.00±0.00)%, (88.41±9.36)%, (62.34±7.31)%, (42.57±5.01)%, (45.47±5.65)%], migration [(90.11±13.43)%, (74.16±8.08)%, (57.53±7.34)%, (41.34±6.79)%, (43.44±5.26)%] and invasion [(89.01±10.31)%, (73.11±9.23)%, (55.62±7.67)%, (41.13±6.35)%, (40.36±5.68)%], and the expression of p-YAP/YAP protein (0.98±0.08, 0.83±0.11, 0.69±0.07, 0.55±0.07, 0.53±0.05) were significantly decreased, the apoptosis rate [(2.88±0.34)%, (5.20±0.57)%, (8.37±0.94)%, (12.71±1.58)%, (12.03±2.21)%] and the expression of p-MST1/MST1 (0.41±0.04, 0.53±0.07, 0.75±0.07, 0.89±0.08, 0.88±0.07] and p-LATS1/LATS1 protein (0.40±0.04, 0.52±0.06, 0.64±0.06, 0.77±0.08, 0.79±0.08) were significantly increased, and the differences were statistically significant ( P<0.05). Conclusion:Schisandrin A may inhibit the proliferation of prostate cancer cell and promote cell apoptosis by inhibiting Hippo-YAP signaling pathway.

Objective To discuss the clinical efficacy and safety of hepatic arterial infusion chemotherapy(HAIC)combined with carrelizumab and sorafenib in treating advanced hepatocellular carcinoma(HCC).Methods The clinical data of 36 HCC patients,who were admitted to the Affiliated Nantong Third Hospital of Nantong University of China to receive HAIC combined with carrelizumab and sorafenib from August 2019 to August 2020,were collected.According to modified Response Evaluation Criteria in Solid Tumors(mRECIST),the objective response rate(ORR)and disease control rate(DCR)of the combination therapy were evaluated.The Common Terminology Criteria Adverse Events Version 5.0 developed by American National Cancer Institute was used to evaluate the clinical safety.Results After receiving 4 cycles of FOLFOX-HAIC,the ORR and DCR of the patients were 38.9％and 77.8％respectively.The patients were followed up for 30 months.The median progression-free survival(mPFS)was 306 days(95％CI:242.7-369.3),and the median overall survival(mOS)was 515 days(95％CI:2 482.5-547.5).After HAIC treatment,one patient was successfully changed to surgical operation.The overall incidence of adverse events were 100％.There were 9 adverse events(25％)above grade m,including severe abdominal pain(n=2,5.6％),nausea(n=1,2.8％),vomiting(n=1,2.8％),elevated alanine aminotransferase(n=3,8.3％),elevated aspartate aminotransferase(n=1,2.8％),and death due to pulmonary failure caused by severe immune-induced pneumonia(n=1,2.8％).Conclusion For the treatment of advanced HCC,HAIC combined with carrelizumab and sorafenib has better ORR and DCR with controllable safety,which provides a new option for the treatment of advanced HCC.However,studies with large sample size need to be conducted before its long-term survival benefit of patients can be further validated.

Objective To explore the difference of transfer RNA-derived small RNA(tsRNA)expression profile before and after acute myocardial infarction(AMI)and the diagnostic value of tsRNA for AMI.Methods Age-and weight-matched male C57 mice(8-10 weeks)were randomly divided into MI group and Sham group,with 4 in each group.AMI model was surgically induced in mice in MI group.After 24 h of modeling,RNA was extracted from left ventricular myocardial tissue.After removing modifications,total RNA of each sample was sequentially ligated to 3'and 5'small RNA adapters.Subsequently,reverse transcription PCR was performed.cDNA was then synthesized and amplified.The amplified products corresponding to the size of 15-40 nt RNA were screened to construct a library for sequencing.The sequencing results were compared with the mature tRNA and tRNA precursor sequences in GtRNAdb database.Differentially expressed tsRNA profiles before and after AMI were obtained.The alterations of the cleaved patterns of tRNA corresponding to the same codon before and after AMI were analyzed.According to the profile of differentially expressed tsRNA before and after AMI,tsRNA only abundantly expressed in MI group were selected and verified in myocardial tissue and plasma of mice to explore the potential of these tsRNAs as diagnostic markers of AMI.Results tsRNA profile showed good repeatability within the same group and great distinctiveness between the different groups.After AMI occurred,the cleaved patterns of a variety of tRNAs changed,including tRNA Asn-GTT,Glu-TTC,Gly-ACC,Gly-GCC,His-GTG,Ile-AAT,Ile-GAT,Pro-TGG,Ser-AGA,and Trp-CCA.Compared with the Sham group,268 tsRNAs significantly up-regulated and 1 228 tsRNAs down-regulated in MI group,and 64 tsRNAs were uniquely expressed in MI group.tRF-Gly-CCC-2-31,tiRNA-Val-CAC-1-32,tiRNA-Val-AAC-2-32,tiRNA-Glu-TTC-2-32,and tiRNA-Lys-TTT-1-34 were specifically expressed in cardiac tissue on the 1st day post AMI.Among them,tiRNA-Val-AAC-2-32 and tiRNA-Lys-TTT-1-34 showed specifically abundant levels in plasma from MI group and dynamically changed with AMI duration.Conclusions The expression profile of tsRNA is significantly different before and after AMI.tiRNA-Val-AAC-2-32 and tiRNA-Lys-TTT-1-34 are uniquely highly expressed in myocardial tissue and plasma from AMI mice,and might have the potential as diagnostic markers of AMI.