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:The femorofibular angle is a commonly used reference angle for mechanical axis correction in high tibial osteotomy on a single plane,but there has been no in-depth study on the application of this angle in high tibial osteotomy on a single plane.OBJECTIVE:To explore the application effect of the femorofibular angle as a reference for mechanical axis correction in high tibial osteotomy on a single plane.METHODS:A retrospective analysis was conducted on 64 cases of knee osteoarthritis patients who underwent high tibial osteotomy on a single plane at Third Affiliated Hospital of Beijing University of Chinese Medicine from January 2023 to January 2024.The patients were grouped according to the intraoperative mechanical axis correction reference method.The observation group consisted of 32 cases,which used the femorofibular angle as a reference for mechanical axis correction during surgery.The control group consisted of 32 cases,which used electrocautery line measurement as a reference for mechanical axis correction during surgery.Both groups received the same perioperative treatment and management.The lower limb mechanical axis ratio,hip-knee-ankle angle,proximal medial tibial angle,and femorofibular angle were recorded before and after surgery to assess changes in the lower limb mechanical state.The operation time and number of fluoroscopies were recorded.The visual analog scale score and Lysholm score for pain and knee function were recorded before surgery and at 1 and 3 months after surgery to evaluate changes in knee pain and function.RESULTS AND CONCLUSION:(1)All patients completed the treatment and follow-up,and no serious adverse events occurred.(2)Before surgery,there was no statistically significant difference in the lower limb mechanical axis ratio,proximal medial tibial angle,hip-knee-ankle angle,and femorofibular angle between the two groups(P＞0.05).At 3 months after surgery,the lower limb mechanical axis ratio,proximal medial tibial angle,hip-knee-ankle angle,and femorofibular angle were significantly improved in both groups compared to before surgery,with statistically significant differences(P＜0.05).There was no significant difference between the two groups(P＞0.05).(3)During surgery,the operation time and number of fluoroscopies in the observation group were less than those in the control group,with statistically significant differences(P＜0.05).(4)At each follow-up point before and after surgery,there was no statistically significant difference in the visual analog scale score and Lysholm score between the two groups(P＞0.05).With the passage of time after surgery,the visual analog scale score and Lysholm score in both groups were significantly improved compared to before surgery(P＜0.05).(5)It is suggested that the application of the femorofibular angle as a reference for mechanical axis correction in high tibial osteotomy on a single plane can accurately locate the range of lower limb mechanical axis correction,is simple and reliable,and reduces the number of fluoroscopies and operation time compared to traditional electrocautery line measurement.

BACKGROUND:The femorofibular angle is a commonly used reference angle for mechanical axis correction in high tibial osteotomy on a single plane,but there has been no in-depth study on the application of this angle in high tibial osteotomy on a single plane.OBJECTIVE:To explore the application effect of the femorofibular angle as a reference for mechanical axis correction in high tibial osteotomy on a single plane.METHODS:A retrospective analysis was conducted on 64 cases of knee osteoarthritis patients who underwent high tibial osteotomy on a single plane at Third Affiliated Hospital of Beijing University of Chinese Medicine from January 2023 to January 2024.The patients were grouped according to the intraoperative mechanical axis correction reference method.The observation group consisted of 32 cases,which used the femorofibular angle as a reference for mechanical axis correction during surgery.The control group consisted of 32 cases,which used electrocautery line measurement as a reference for mechanical axis correction during surgery.Both groups received the same perioperative treatment and management.The lower limb mechanical axis ratio,hip-knee-ankle angle,proximal medial tibial angle,and femorofibular angle were recorded before and after surgery to assess changes in the lower limb mechanical state.The operation time and number of fluoroscopies were recorded.The visual analog scale score and Lysholm score for pain and knee function were recorded before surgery and at 1 and 3 months after surgery to evaluate changes in knee pain and function.RESULTS AND CONCLUSION:(1)All patients completed the treatment and follow-up,and no serious adverse events occurred.(2)Before surgery,there was no statistically significant difference in the lower limb mechanical axis ratio,proximal medial tibial angle,hip-knee-ankle angle,and femorofibular angle between the two groups(P＞0.05).At 3 months after surgery,the lower limb mechanical axis ratio,proximal medial tibial angle,hip-knee-ankle angle,and femorofibular angle were significantly improved in both groups compared to before surgery,with statistically significant differences(P＜0.05).There was no significant difference between the two groups(P＞0.05).(3)During surgery,the operation time and number of fluoroscopies in the observation group were less than those in the control group,with statistically significant differences(P＜0.05).(4)At each follow-up point before and after surgery,there was no statistically significant difference in the visual analog scale score and Lysholm score between the two groups(P＞0.05).With the passage of time after surgery,the visual analog scale score and Lysholm score in both groups were significantly improved compared to before surgery(P＜0.05).(5)It is suggested that the application of the femorofibular angle as a reference for mechanical axis correction in high tibial osteotomy on a single plane can accurately locate the range of lower limb mechanical axis correction,is simple and reliable,and reduces the number of fluoroscopies and operation time compared to traditional electrocautery line measurement.

ObjectiveTo examine the impact of Toll-like receptor 4 （TLR4）-mediated neutrophil extracellular traps （NETs） formation on isoproterenol （ISO）-induced heart failure （HF） in aged mice. MethodsThe mice were randomly divided into Control group， Model group， TAK-242 （TLR4 inhibitor） group， LPS （TLR4 agonist） group and LPS+DNaseⅠ （NETs inhibitor） group， with 8 mice in each group. The HF model was established by continuous infusion of ISO through an osmotic pump， and TAK-242， LPS， and LPS+DNaseⅠ interventions were administered during the last week of infusion for 7 consecutive days. ELISA was used to detect the N-terminal pro-B-type natriuretic peptide （NT-pro BNP）， cardiac troponin I （cTnI）， interleukin-1β （IL-1β）， interleukin-6 （IL-6）， tumor necrosis factor-α （TNF-α）， and serum and myocardial tissue myeloperoxidase-DNA （MPO-DNA） and neutrophil elastase-DNA （NE-DNA） levels. HE staining was used to observe the pathological changes of myocardial tissue. Masson staining was used to observe the deposition of collagen fibers in myocardial tissue. Immunofluorescence was used to observe the colocalization of Ly6G and MPO in myocardial tissue. The protein expressions of TLR4， MPO， NE and cit-H3 in myocardial tissue were detected by Western blot. ResultsCompared with the Control group， the end-diastolic interventricular septal thickness （IVSD）， left ventricular end-diastolic diameter （LVEDD） and left ventricular end-systolic diameter （LVESD） in the Mode group significantly increased （P<0.01）， fractional shortening （FS） and ejection fraction （EF） significantly decreased （P<0.01）， and the myocardial structure was significantly damaged. The myocardial collagen fiber precipitation， serum NT-pro BNP， cTnI， IL-1β， IL-6 and TNF-α contents， MPO-DNA and NE-DNA contents in serum and myocardial tissue significantly increased （P<0.01）. The co-localization of Ly6G and MPO and the expression of TLR4， MPO， NE and cit-H3 proteins in myocardial tissue significantly increased （P<0.01）. After TAK-242 intervention， the above indicators were significantly reversed， while the injury was further aggravated in LPS group. DNaseⅠ treatment could partially alleviate the deterioration of myocardial structure and function induced by LPS. ConclusionTLR4 and NETs are abnormally elevated in the myocardial tissue of aged HF mice. Treatment with the TLR4 inhibitor TAK-242 effectively suppresses NET formation， attenuates inflammatory responses， and enhances cardiac function in aged HF mice.

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 investigate the effect and mechanism of Tangzhi formula（TZF） on improving glucose and lipid metabolism disorders in type 2 diabetes mellitus （T2DM） rats.METHODS Thirty SPF-grade SD rats were used to establish a T2DM rat model through high-fat diet feeding combined with intraperitoneal injection of streptozotocin. After successful modeling， the rats were divided into the model group， metformin group （positive control， 0.18 g/kg）， and TZF low-， medium-， and high-dose groups （5， 10， and 20 g/kg）， with 6 rats in each group. An additional 6 rats were selected as the blank group. The rats in each group were orally administered the corresponding volume of drug solution or saline， and continuous dosing was performed for 6 weeks， once daily. Fasting blood glucose （FBG）， area under the curve of oral glucose tolerance test （OGTT-AUC）， area under the curve of intraperitoneal insulin tolerance test （IPITT-AUC）， serum total cholesterol （TC）， triglyceride （TG）， low-density lipoprotein cholesterol （LDL-C）， and high-density lipoprotein cholesterol （HDL-C） levels were measured. Hematoxylin-eosin （HE） staining and oil red O staining were used to observe hepatic pathological morphology and lipid deposition. Differentially expressed proteins in liver tissues were screened by proteomics analysis， and key proteins in signaling pathways were verified by Western blot and immunofluorescence staining.RESULTS Compared with the blank group， the levels of FBG， OGTT-AUC， IPITT-AUC， LDL-C， TG， and TC in the model group were significantly increased （ P ＜0.05）， while HDL-C level was significantly decreased （ P ＜0.05）； the liver tissues showed disordered hepatic cords， punctate necrosis of hepatocytes， and significant lipid deposition， the NAFLD activity score and positive area of lipid droplets were significantly increased（ P ＜0.05）. Compared with the model group， the above indicators in TZF low-， medium-， and high-dose groups and metformin group were significantly reversed （ P ＜0.05）； hepatic pathological injury and lipid deposition were alleviated. Proteomics results showed that a total of 442 differentially expressed proteins were screened between the model group and the blank group， and 358 differentially expressed proteins were screened between the TZF high-dose group and the model group. Among these differentially expressed proteins， multiple proteins closely related to glucose and lipid metabolism showed a reversal trend after TZF intervention. Kyoto Encyclopedia of Genes and Genomes pathway enrichment analysis showed that the peroxisome proliferator-activated receptor （PPAR） signaling pathway was significantly enriched. The validation experiment results showed that TZF could significantly up-regulate the expression of PPARα， PPARγ， and apolipoprotein A1 （ApoA1） in rat liver tissues （ P ＜0.05）， and down-regulate the expression of stearoyl-CoA desaturase 1 （SCD1） and perilipin 2 （PLIN2） （ P ＜0.05）.CONCLUSIONS TZF can improve glucose and lipid metabolism disorders in T2DM rats； its mechanism may be related to the activation of the PPAR signaling pathway and the regulation of downstream lipid metabolism-related proteins SCD1， PLIN2， and ApoA1.

Acute cerebral infarction predominantly occurs in middle-aged and elderly individuals with multiple underlying diseases， and it is often accompanied by atherosclerosis or heart diseases. It has a low incidence rate in children and adolescents， who tend to have atypical symptoms in the early stage， leading to misdiagnosis or missed diagnosis. With the continuous development of imaging technology， the diagnosis of cerebral infarction has become more precise， which helps to further clarify the etiology of cerebral infarction and identify an increasing number of patients with different subtypes of cerebral infarction in clinical practice. This article reports a rare case of a pediatric patient with acute cerebral infarction caused by primary central nervous system vasculitis， which led to neurological dysfunction， in order to improve the awareness of cerebral infarction in children among clinicians.
Vasculitis

Retinal vein occlusion(RVO)is the second most common blinding retinal vascular disease, and its secondary macular edema(ME)is an important cause of visual function impairment in patients. Intravitreal injection of anti-vascular endothelial growth factor(VEGF)drugs serves as the first-line treatment, yet it is confronted with such issues as the need for repeated injections and non-response in some patients. Imaging and laboratory biomarkers play a crucial role in the early accurate diagnosis, prediction of disease progression, and evaluation of visual prognosis of RVO-ME. This study systematically reviews the research progress of imaging and laboratory biomarkers related to the prognosis of RVO-ME after anti-VEGF treatment in recent years, covering imaging biomarkers like central retinal thickness and ellipsoid zone integrity, as well as laboratory biomarkers such as serum APLN and aqueous humor IL-6. It summarizes the associations between different biomarkers and the prognosis of anti-VEGF therapy, aiming to provide a basis for the early accurate assessment and optimization of individualized treatment for RVO-ME patients, which holds significant clinical reference value.

ObjectiveTo establish a method for the identification of Haliotidis Concha and its counterfeits， and to improve its quality evaluation method. MethodsA total of 17 batches of Haliotis discus hannai， 4 batches of H. ruber， 3 batches of H. laevigata， 3 batches of H. ovina， 3 batches of H. diversicolor， 3 batches of H. asinina， 3 batches of H. iris were collected. Ultra-high performance liquid chromatography-quadrupole/electrostatic field orbitrap high-resolution mass spectrometry（UPLC-Q-Exactive-Orbitrap-MS/MS） was used to analyze the hydrolysates of different original Haliotidis Concha and its counterfeits， and the potential characteristic ions of each species were screened by Venn diagram. UPLC-triple quadrupole tandem mass spectrometry（UPLC-QqQ-MS/MS） was used to validate the characteristic ions， and the specific detection method of the characteristic ions was established. ResultsA total of 1 182， 167， 47， 89， 104， 203， 424 potential characteristic ions were screened from H. discus hannai， H. ruber， H. laevigata， H. ovina， H. diversicolor， H. asinina and H. iris， respectively. And 9 characteristic ions were selected. The precision， stability and repeatability of the 9 characteristic ions in the established identification method met the requirements. Different original Haliotidis Concha and its counterfeits could detect their own characteristic ions， including m/z 631.83-886.48（double charge） and m/z 631.83-443.74（double charge） of H. discus hannai， m/z 699.28-232.11（double charge） and m/z 699.28-544.27（double charge） of H. ruber， m/z 535.76-752.37（double charge） and m/z 535.76-548.28（double charge） of H. laevigata， m/z 708.35-442.28（double charge） and m/z 708.35-215.14（double charge） of H. ovina， m/z 561.33-614.86（triple charge）， m/z 561.33-468.28（triple charge）， m/z 608.29-618.32（double charge） and m/z 608.29-390.21（double charge） of H. diversicolor， m/z 769.85-274.10（double charge）， m/z 769.85-532.75（double charge）， m/z 827.43-646.36（single charge）， m/z 827.43-257.12（single charge） of H. asinina， and m/z 468.24-576.29（double charge） and m/z 468.24-505.26（double charge） of H. iris. ConclusionIn this study， a total of 9 characteristic ions are screened from 6 kinds of original Haliotidis Concha and its counterfeits， and a specific identification method is established， which is helpful to solve the limitations of the existing quality evaluation methods of Haliotidis Concha， and provide a basis for the production， circulation and medication quality.