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.

Objective:To analyze the risk factors of contralateral central lymph node metastasis in papillary thyroid carcinoma (PTC) patients with established ipsilateral central lymph node metastasis, and to provide a basis for clinical decision-making on whether to perform contralateral central lymph node dissection.Method:The clinical data of 348 PTC patients who underwent surgery at Jiangsu Provincial People's Hospital from Jun 2018 to Aug 2024 were retrospectively analyzed. Univariate analysis and multivariate Logistic regression analysis were used to determine the independent risk factors affecting the contralateral central lymph node metastasis of PTC with existing ipsilateral central lymph node metastasis.Results:Tumor size was positively correlated with the risk of metastasis. For every one-unit increase in the metastasis rate of the ipsilateral central lymph nodes, the risk of metastasis in the contralateral central region increases by 13.31 times ( P<0.001). Patients with ipsilateral lateral cervical metastasis have a higher risk of contralateral central metastasis ( P=0.026). The contralateral lymph node metastasis rate of patients with Hashimoto was 24%, while that of patients without Hashimoto was 76%( P<0.001). When the tumor was located at the upper pole, the metastasis rate of the contralateral central lymph nodes was 18%; when it was located at the middle pole, it was 29.6%; and when it was located at the lower pole, it was 42.6%( P=0.016). Conclusions:Tumor size, contralateral lateral cervical lymph node metastasis, and the intensity of ipsilateral central lymph node metastasis are independent risk factors for contralateral central lymph node metastasis in PTC patients with existing ipsilateral central lymph node metastasis. Tumor location at the upper pole and the presence of Hashimoto are protective factors.

Objective:To analyze the risk factors of contralateral central lymph node metastasis in papillary thyroid carcinoma (PTC) patients with established ipsilateral central lymph node metastasis, and to provide a basis for clinical decision-making on whether to perform contralateral central lymph node dissection.Method:The clinical data of 348 PTC patients who underwent surgery at Jiangsu Provincial People's Hospital from Jun 2018 to Aug 2024 were retrospectively analyzed. Univariate analysis and multivariate Logistic regression analysis were used to determine the independent risk factors affecting the contralateral central lymph node metastasis of PTC with existing ipsilateral central lymph node metastasis.Results:Tumor size was positively correlated with the risk of metastasis. For every one-unit increase in the metastasis rate of the ipsilateral central lymph nodes, the risk of metastasis in the contralateral central region increases by 13.31 times ( P<0.001). Patients with ipsilateral lateral cervical metastasis have a higher risk of contralateral central metastasis ( P=0.026). The contralateral lymph node metastasis rate of patients with Hashimoto was 24%, while that of patients without Hashimoto was 76%( P<0.001). When the tumor was located at the upper pole, the metastasis rate of the contralateral central lymph nodes was 18%; when it was located at the middle pole, it was 29.6%; and when it was located at the lower pole, it was 42.6%( P=0.016). Conclusions:Tumor size, contralateral lateral cervical lymph node metastasis, and the intensity of ipsilateral central lymph node metastasis are independent risk factors for contralateral central lymph node metastasis in PTC patients with existing ipsilateral central lymph node metastasis. Tumor location at the upper pole and the presence of Hashimoto are protective factors.

OBJECTIVE To evaluate the effictiveness and safety of recombinant human endostatin combined with afatinib and teggio in the treatment of advanced lung squamous cell carcinoma. METHODS A total of 25 patients with driver-negative advanced lung squamous cell carcinoma were included in this single-arm prospective study, and the enrolled patients were treated with recombinant human endostatin combined with afatinib and teggio as scheduled. Progression-free survival(PFS), overall survival(OS), disease control rate(DCR), objective response rate(ORR), and adverse reactions(AR) were observed and analyzed. RESULTS The 25 enrolled patients received at least 2 cycles of second-line treatment, and were followed up as of March 31, 2023. Among them, 4 patients had partial remission, 17 patients had stable disease, and 4 patients experienced progressive disease. The ORR confirmed by the researchers was 16%(95%CI, 4.5%−36.1%), DCR was 84%(95%CI, 63.9%−95.5%), and median PFS was 5.3 months(95%CI, 3.5−6.9 months). The median OS had not yet been achieved. The entire group of patients had good treatment tolerance, and the most common level Ⅲ or Ⅳ adverse events related to treatment were leukopenia(20%) and rash(12%), with no reported treatment-related deaths. CONCLUSION Recombinant human endostatin combined with afatinib and teggio in the second line treatment of advanced lung squamous cell carcinoma can prolong the progression free survival period of patients and is relatively safe, which is worth further exploration and promotion.

Objective:To investigate the assessment value of X-ray angiography in postoperative recurrence,curative effect and reduction of the perfusion of liver tumor of interventional transarterial chemoembolization(TACE)for liver cancer.Methods:A total of 59 patients with liver cancer who were treated in The Third the People's Hospital of Bengbu from January 2015 to December 2020 were selected.All patients underwent the examination of routine X-ray angiography one week before surgery and four weeks after surgery.The obtained image sequences were imported into the workstation equipped with imaging technology software of color coded digital subtraction angiography(ccDSA)to conduct analysis.The region of interest(ROI)was manually defined on the ccDSA images before and after TACE.And then,the time intensity curve was obtained,and the quantitative perfusion parameters included the time to peak(TTP),area under curve(AUC),maximum slope(MS)were exported from that.The receiver operating characteristics(ROC)curve was drawn,and the area under curve(AUC)of that was calculated to analyze the assessment efficacy of perfusion parameters on the postoperative recurrence,curative effect and reduction of the perfusion of liver tumor of TACE for liver cancer.Results:In the 59 patients who were included in the study,39 cases occurred postoperative recurrence and 20 cases did not occurred postoperative recurrence according to the definition of postoperative recurrence,and the perfusion TTP(7.38±1.22)s of patients with postoperative recurrence was significantly lower than that(9.03±1.01)s of patients without postoperative recurrence,and the difference of that between them was significant(t=5.198,P<0.05).The AUC and MS of patients with postoperative recurrence were significantly lower than those of patients without postoperative recurrence(t=2.868,31.499,P<0.05),respectively.There were not significant differences in TTP,AUC and MS between patients with and without postoperative recurrence before surgery(P>0.05).According to the determination criteria of curative effect,35 cases were effectiveness,and 24 cases were ineffectiveness,and the postoperative TTP(9.09±1.08)s of patients with effectiveness was significantly higher than that(7.84±2.07)s of patients without effectiveness(t=3.029,P<0.05),and AUC and MS of patients with effectiveness were significantly higher than those of patients without ineffectiveness(t=3.852,54.366,P<0.05),and there were not significant differences in preoperative TTP,AUC and MS between patients with and without effectiveness(P>0.05),and the values of TTP,AUC and MS of the group with effectiveness and group without effectiveness after surgery were significantly higher than those before surgery,and the differences of them between two groups were significant(t=3.029,3.852,54.366,P<0.05),respectively.According to the grading criteria of subjective angiographic endpoints(SACE),33 cases were grade Ⅲ,and 26 cases were grade Ⅳ,and there were not significant in TTP,AUC and MS between patients with grade Ⅲ and patients with grade IV(P>0.05).The postoperative TTP,AUC and MS of patients with grade Ⅳ were significantly lower than those of patients with grade Ⅲ(t=7.679,3.498,58.968,P<0.05),respectively.The sensitivities of TTP,AUC and MS were respectively 66.70%,89.70% and 59.00% in assessing postoperative recurrence of interventional TACE for liver cancer,and the specificities of them were respectively 55.00%,55.00% and 55.00%,and the AUC values of them were respectively 0.629(95% CI:0.478-0.779),0.827(95% CI:0.723-0.931)and 0.512(95% CI:0.356-0.667).The sensitivities of TTP,AUC and MS were respectively 64.10%,79.50% and 61.50% in assessing postoperatively curative effect of interventional TACE for liver cancer,and the specificities of them were respectively 55.00%,65.00% and 55.00%,and the AUC values of them were respectively 0.609(95% CI:0.462-0.756),0.808(95% CI:0.698-0.918)and 0.580(95% CI:0.413-0.747).The sensitivities of TTP,AUC and MS were respectively 69.20%,82.10% and 53.80% in assessing the postoperative reduction of the perfusion of liver tumor of interventional TACE for liver cancer,and the specificities of them were respectively 70.00%,75.00% and 55.00%,and the AUC values of them were respectively 0.745(95% CI:0.613-0.877),0.842(95% CI:0.724-0.960)and 0.507(95% CI:0.360-0.654).Conclusion:The TTP,AUC and MS of perfusion parameters that are obtained by ccDSA quantitative analysis for the data after X-ray angiography examination have a certain application value in assessing the postoperative recurrence,curative effect and the reduction of the perfusion of liver tumor of interventional TACE for liver cancer.

Objective To discuss the application of mind map in self-management of elderly patients after receiving mitral valve transcatheter edge-to-edge repair(M-TEER).Methods A total of 66 patients,who underwent M-TEER at Nanjing Hospital of Nanjing Medical University from August 2021 to October 2022,were enrolled in this study.Using the envelope concealment method,a total of 66 data analysis samples were included in the analysis.There were 33 patients each in the study group and control group.Routine health education was adopted for the patients of the control group,while the responsible nurse conducted health education for the patients of the study group under the guidance of the mind map that was designed by a multidisciplinary specialized nurses.Results There was a significant difference in postoperative medication compliance between the study group and the control group(P＜0.05),i.e.the degree of compliance,including taking medicine on time,insisting on taking medicine and taking medicine as prescribed,in the study group was obviously higher than that in the control group.The postoperative 6-min walking test,which was regarded as one of the indicators of cardiac functions,in the study group was remarkably better than that in the control group,the difference was statistically significant(P＜0.05).The postoperative quality of life(including daily activity ability,frailty degree,social support,and incidence of hospitalization for heart failure within one year after treatment)in the study group was strikingly better than that in the control group(P＜0.05).Conclusion The use of mind map in self-management of elderly patients after receiving M-TEER can effectively improve the medication compliance of the patients after discharge,improve the quality of life of patients,and reduce the incidence of hospitalization due to heart failure.

Objective:To assess the clinical features and effectiveness of antiviral therapy in newborns with sensorineural hearing loss (SNHL) caused by congenital congenital cytomegalovirus (cCMV) infection, and to speculate the risk factors for poor hearing outcomes.Methods:A multicenter prospective cohort study wasconducted, enrolling 176 newborns diagnosed with cCMV at four research centers in Zhejiang Province from March 1, 2021, to April 30, 2024. Clinical characteristics at birth were recorded and hearing was followed up. The children were divided into groups based on their condition at birth, specifically into asymptomatic, mild symptom, and moderate to severe symptom groups. Additionally, they were divided into SNHL and normal hearing groups based on the results of air conduction brainstem audiometry at birth. And they were also divided into treatment and untreated groups according to antiviral treatment. Mann Whitney U test, and chi square test were used for inter group comparison to analyze the differences in clinical features between different disease groups, and to analyze the effects of clinical features, antiviral therapy, and other factors on hearing improvement. Logistic regression analysis was employed to identify the risk factors influencing hearing outcomes. Results:Among the cohort of 176 children diagnosed infection with cCMV, 90 cases were male and 86 cases were female. Of these, 79 cases were asymptomatic, 12 cases classified as mild cCMV and 85 cases as moderate to severe cCMV. Fifty cases belonged to SNHL group, with different degrees of severity, including 30 cases of mild, 9 cases of moderate, 5 cases of severe, and 6 cases of extremely severe SNHL. Among the 121 cases in the normal hearing group, 2 cases (1.7%) exhibited late-onset hearing loss despite having normal hearing at birth. Among 81 cases (46.0%) who completed the hearing follow-up, 71 cases (87.7%) had good hearing outcomes and 10 cases (12.3%) had poor hearing outcomes. Among the 81 children, 29 cases (35.8%) had SNHL at birth. During follow-up, the hearing threshold improved in 19 cases (65.5%), remained stable in 7 cases (24.1%) and progressed in 3 cases (10.3%). A total of 26 cases in the treatment group and 55 cases in the untreated group completed the hearing follow-up assessment. The rate of hearing improvement in the treatment group was found to be higher compared to the untreated group (13 cases (50.0%) vs. 6 cases (10.9%), χ2=15.00, P<0.01), with individuals in the treatment group having a 4.58 times greater likelihood of experiencing hearing improvement ( RR=4.58,95% CI 1.96-10.70, P<0.05). However, no statistically significant difference was observed in hearing outcomes between the antiviral treatment group and the untreated group ( RR=0.90, 95% CI 0.57-1.41, P=0.517). Multivariate analysis further confirmed SNHL ( OR=11.58, 95% CI 2.10-63.93, P=0.005) and preterm birth ( OR=4.98, 95% CI 1.06-23.41, P=0.042) as independent risk factors for poor hearing outcomes. Conclusions:SNHL resulting from cCMV infection presents symptoms at birth and can be improved by antiviral therapy. Poor hearing outcomes are associated with SNHL and prematurity.

Purpose To investigate the evaluation value of right-to-left shunt in atrial septal aneurysm(ASA)via contrast-enhanced transcranial Doppler,and analyze its clinical significance.Materials and Methods Forty patients with ASA who were performed on contrast-enhanced transcranial Doppler in Jiaozuo People's Hospital from June 2020 to July 2021,and 242 patients without ASA during the same period were enrolled.The overall incidence of right-to-left shunt was compared between the two groups in resting state and after Valsalva maneuver.All patients with right-to-left shunt were divided into small shunt group and large shunt group according to the number of microbubbles detected,comparing the incidence of small and big shunt,as well as alterations of shunt after Valsalva maneuver between the two groups.Results Contrast-enhanced transcranial Doppler in resting state:positive rate of ASA patients with right-to-left shunt was significantly higher than that of non-ASA patients via contrast-enhanced transcranial Doppler in resting state[47.5%(19/40)vs.29.8%(72/242);χ2=4.95,P=0.03].There were 14 ASA patients(73.7%)with small shunt and five ASA patients(26.3%)with large shunt.There were 61 non-ASA patients(84.7%)with small shunt and 11 non-ASA patients(15.3%)with large shunt.In resting state,there was no significant difference in ratio between small and large shunts,though there were mainly small shunt patients between the two groups(χ2=1.26,P=0.264).The positive rate of patients with or without ASA were significantly higher after Valsalva maneuver than those in resting state(positive rate of ASA patients was 77.5%,χ2=8.64,P=0.002;positive rate of non-ASA patients was 48.8%,χ2=80.49,P<0.001).The number of cases with massive shunt in ASA group were significantly higher than those in non-ASA group[64.5%(20/31)vs.47.5%(56/118);χ2=12.58,P<0.001].Conclusion ASA is often accompanied by right-to-left shunt,especially those with a substantial right-to-left shunt can trigger by the Valsalva maneuver.Therefore,attention should be paid to patients with ASA in clinical practice with standardized diagnosis and treatment.

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.