Objective To summarize and analyze the preliminary clinical outcomes of the KokaclipTM transcatheter edge-to-edge mitral valve repair system for severe degenerative mitral regurgitation (DMR). Methods This study was a single-arm, prospective, single-group target value clinical trial that enrolled patients who underwent the KokaclipTM transcatheter edge-to-edge repair (TEER) system for DMR in the Department of Heart Surgery of Guangdong Provincial People's Hospital, Guangdong Cardiovascular Institute from June 2022 to January 2023. Differences in the grade of mitral regurgitation (MR) during the perioperative and follow-up periods were compared, and the incidences of adverse events such as all-cause death, thoracotomy conversion, reoperation, and severe recurrence of MR during the study period were investigated. Results The enrolled patient population consisted of 14 (50.0%) females with a mean age of 70.9±5.4 years. Twenty-eight (100.0%) patients were preoperatively diagnosed with typeⅡ DMR, with a prolapse width of 12.5 (11.0, 16.1) mm, a degree of regurgitation 4+ leading to pulmonary venous reflux, and a New York Heart Association cardiac function class≥Ⅲ. All patients completed the TEER procedure successfully, with immediate postoperative improvement of MR to 0, 1+, and 2+ grade in 2 (7.1%), 21 (75.0%), and 5 (17.9%) patients, respectively. Mitral valve gradient was 2.5 (2.0, 3.0) mm Hg. Deaths, thoracotomy conversion, or device complications such as unileaflet clamping, clip dislodgement, or leaflet injury were negative. Twenty-eight (100.0%) patients completed at least 3-month postoperative follow-up with a median follow-up time of 5.9 (3.6, 6.8) months, during which patients had a mean MR grade of 1.0+ (1.0+, 2.0+) grade and a significant improvement from preoperative values (P<0.001). There was no recurrence of ≥3+ regurgitation, pulmonary venous reflux, reoperation, new-onset mitral stenosis, or major adverse cardiovascular events. Twenty-two (78.6%) patients’ cardiac function improved to classⅠorⅡ. Conclusion The domestic KokaclipTM TEER system has shown excellent preliminary clinical results in selected DMR patients with a high safety profile and significant improvement in MR. Additional large sample volume, prospective, multicenter studies, and long-term follow-up are expected to validate the effectiveness of this system in the future.

Objective To observe the value of radiomics models and nomogram model based on two-dimensional ultrasound and automated breast volume scanning(ABVS)for predicting molecular types of breast cancer.Methods Data of 326 female patients of single breast cancer confirmed by pathology were analyzed retrospectively.The patients were randomly divided into training set(n=260)or validation set(n=66)at the ratio of 8∶2,and further divided into Luminal subgroup and non-Luminal subgroup.Radiomics features were extracted based on two-dimensional ultrasound of breast and ABVS imaging,then model2DUS,modelABVS and modelcombined radiomics were constructed,respectively.Univariate analysis and multivariate logistic regression analysis were used to screen independent factors for predicting molecular types of breast cancer,and nomogram model(modelnomogram)was constructed combined with independent factors and radiomics Radscores.The receiver operating characteristic(ROC)curve was used to evaluate the efficacy of each model for molecular type of breast cancer.Results The maximum diameter of tumor(OR=1.029)and the retraction phenomenon(OR=0.408)were both independent predictive factors for molecular type of breast cancer(both P＜0.05).The area under the curve(AUC)of model2DUS,modelABVS.modelcombined radiomics and modelnomogram for predicting molecular type of breast cancer in validation set was 0.67,0.75,0.84 and 0.83,respectively.No significant difference of AUC of modelcombined radiomics and modelnomogram was found(P＞0.05),which were both higher than AUC of model2DUs and modelABVS(all P＜0.05).Conclusion Combined radiomics model and nomogram model based on two-dimensional ultrasound and ABVS could effectively predict molecular type of breast cancer.

Rheumatoid arthritis （RA） is an autoimmune disease involving symmetrical small joints， with clinical manifestations such as small joint swelling， morning stiffness， progressive pain， and even joint deformity and loss of function. Due to the complex immune mechanism， the pathogenesis of RA remains unclear. However， studies have shown that the pathogenesis of RA is related to abnormal immune mechanism， increased synovial inflammatory response， abnormal biological behavior of RA fibroblast-like synoviocytes （RA-FLSs）， and abnormal degradation of extracellular matrix. Mitogen-activated protein kinase （MAPK） plays a key role in the regulation of cell growth， proliferation， differentiation， and apoptosis. It is involved in the abnormal release and activation of inflammatory mediators in RA， the abnormal proliferation， migration， and invasion of RA-FLSs， synovial angiogenesis， bone erosion， and cartilage destruction. The thousands of years of practical experience show that Chinese medicine can effectively mitigate the clinical symptoms such as joint swelling， morning stiffness， and pain and delay the occurrence of joint deformity in RA patients. Moreover， the Chinese medicine treatment has the advantages of overall regulation， personalized treatment， multiple pathways and targets， high safety， few adverse reactions， and stable quality. Modern studies have confirmed that Chinese medicine can play a role in the prevention and treatment of RA by interfering in the MAPK signaling pathway， reducing pro-inflammatory cytokines， inhibiting the abnormal proliferation， migration， and invasion of RA-FLSs， regulating the apoptosis of RA-FLSs， and protecting extracellular matrix. This article elaborates on the key role of MAPK signaling pathway in the development of RA and reviews the latest research results of Chinese medicine intervention in MAPK signaling pathway for the prevention and treatment RA， aiming to provide a basis for the development of new drugs and the clinical application of Chinese medicine in the prevention and treatment of RA.

Objective To analyze the long-term outcome of modified Morrow surgery (interventricular septal cardiomyectomy) in the treatment of hypertrophic obstructive cardiomyopathy (HOCM) in children. Methods The clinical data of the children with HOCM (aged≤14 years) who underwent modified Morrow surgery from January 2010 to August 2022 in Guangdong Provincial People's Hospital were retrospectively analyzed, including changes in hospitalization status, perioperative period, and long-term 15-lead electrocardiogram and echocardiography. Results A total of 29 patients were collected, including 22 males and 7 females, aged 10.00 (5.00, 12.00) years. Five (17.9%) patients had New York Heart Association (NYHA) heart function grade Ⅲ or Ⅳ. Ventricular septal cardiomyectomy was performed in all patients. All 29 patients survived and their cardiac function recovered after operation. Before discharge, right bundle branch block was observed in 2 patients and left bundle branch block in 6 patients. After surgery, in the left ventricular septal cardiomyectomy, the left atrial diameter decreased (P＜0.001), left ventricular end-systolic diameter increased (P=0.009), the peak pressure gradient of left ventricular outflow tract decreased (P＜0.001), and the thickness of ventricular septum decreased (P＜0.001). The systolic anterior motion of mitral valve disappeared and mitral regurgitent jet area decreased (P＜0.001). The flow velocity and peak pressure gradient of right ventricular outflow tract also decreased in the patients who underwent right ventricular septal cardiomyectomy. The average follow-up of the patients was 69.03±10.60 months. All the patients survived with their NYHA cardiac function grading Ⅰ or Ⅱ. No new-onset arrythmia event was found. Echocardiography indicated that the peak pressure gradient of the left ventricular outflow tract remained low (P<0.001). Moderate mitral regurgitation occurred in 2 patients, and left ventricular outflow tract obstruction with moderate mitral regurgitation occurred in 1 patient after simple right ventricular septal cardiomyectomy. Conclusion Right ventricular or biventricular obstruction is frequent in the children with HOCM and they usually have more symptoms before surgery. Modified Morrow surgery can effectively relieve outflow tract obstruction and improve their cardiac function. The long-term outcome is satisfactory. However, the posterior wall of the left ventricle remains hypertrophic. Also, there is an increased risk of a conduction block.

BACKGROUND:Inflammation and oxidative stress contribute to the barriers of regeneration in chronic wound.Oxymatrine has various biological activities,such as anti-oxidation,anti-inflammation and so on,which may have the potential effect of promoting wound healing. OBJECTIVE:To investigate the effect of oxymatrine on wound healing and the protective effect on H2O2-induced oxidative stress injury in human keratinoid cell line HaCaT cells. METHODS:(1)In vivo experiment:Hyaluronic acid methacryloyl hydrogels containing 0,0.05,0.1,0.2 g/L oxymatrine were prepared.A full-layer skin defect model with a diameter of 12 mm was made in the back of 75 diabetic mice and randomly divided into five groups for intervention,with 15 mice in each group.The wounds of the model group were bandaged and fixed.The wounds of the hydrogel group were covered with hyaluronic acid methacryloyl hydrogel.The wounds of the low-dose,moderate-dose and high-dose oxymatrine groups were covered with hyaluronic acid methacryloyl hydrogel containing 0.05,0.1,and 0.2 g/L oxymatrine,respectively,and then bandaged and fixed after light curing.Relevant indicators were detected within 14 days.(2)In vitro experiment:Human keratinocyte line HaCaT was divided into five groups.The normal group was cultured conventionally.H2O2 group and low-,moderate-and high-concentration oxymatrine groups were treated with H2O2 for 4 hours,and then the medium was replaced with medium containing 0,0.05,0.1,and 0.2 g/L oxymatrine,respectively,and the relevant indexes were detected after 24 hours of culture. RESULTS AND CONCLUSION:(1)In vivo experiment:Compared with the model group,the wound healing rate of mice in the hydrogel group had no significant change.The wound healing rate of mice in the low-,moderate-and high-dose oxymatrine group was increased at 7 and 14 days after treatment(P<0.05).Pathological observation of wound section 14 days after treatment showed that compared with the model group,the thickness of regenerated epidermal layer,the number of microvessels,and collagen deposition in the moderate-and high-dose oxymatrine groups were increased(P<0.05).Western blot assay analysis of wound samples 7 days after surgery showed that compared with the model group,the protein expressions of tumor necrosis factor α and interleukin 6 in the moderate-and high-dose oxymatrine groups were decreased(P<0.05).(2)In vitro experiment:CCK8 assay,EdU and Ki67 staining showed that compared with the H2O2 group,the cell proliferation ability of the moderate-and high-concentration oxymatrine groups was significantly increased(P<0.05).Compared with the H2O2 group,mitochondrial membrane potential was increased(P<0.05)and reactive oxygen species content was decreased(P<0.05)in the moderate-and high-concentration oxymatrine groups.Western blot assay results showed that compared with the H2O2 group,the expression levels of Nrf2 nuclear protein,Nrf2 total protein,HO-1 protein,and superoxide dismutase 1 protein were increased in the high-concentration oxymatrine group(P<0.05).(3)These findings confirm that oxymatrine can alleviate oxidative stress damage in HaCat cells and accelerate wound healing by upregulating the levels of Nrf2 and HO-1 protein.

Objective:To conduct a scope review on the application of ICU diaries in critically ill patients, laying the foundation for further exploration and construction of ICU diary patterns and frameworks that were in line with the national conditions and tailored to different regions and cultural backgrounds.Methods:The Joanna Briggs Institute Reviewer′s Manual was used as the methodological framework, and a computer search was conducted in nine domestic and international databases, including China National Knowledge Infrastructure, Wanfang Database, China Biomedical Literature Database, Cochrane Library, PubMed, and Embase, etc. The search period was from the inception of the databases until March 13, 2023. The included literature was screened, summarized, and analyzed.Results:A total of 19 articles were included. ICU diaries were commonly recorded using a combination of text and visuals, with the involvement of both healthcare professionals and family members. Most patients received ICU diaries approximately one month after their transfer from the ICU. Out of the 15 studies, ICU diaries were found to be effective, while 4 studies indicated no significant improvement in patients′ psychological issues. However, ICU diaries were still considered acceptable by patients and their families.Conclusions:The application of ICU diaries has shown positive significance in critically ill patients, but further research and exploration are needed to investigate its impact on issues such as post-traumatic stress disorder, anxiety, depression, and quality of life. In the future, a combination of multiple forms and high-quality research designs with large samples, long periods, and structured approaches should be employed to explore its application effects and long-term outcomes on psychological problems.

ObjectiveThe antitumor activity of sesquiterpenoid M36 isolated from Myrrha against human hepatoma HepG2 cells was investigated in this study. MethodHepG2 cells were treated with M36 at different concentrations （0， 2， 4， 6， 8， 10 μmol·L^-1）. Firstly， the effects of M36 on the proliferation of human hepatoma HepG2 cells were detected by methyl thiazolyl tetrazolium （MTT）， colony formation assay， and EdU proliferation assay. Hoechst staining， flow cytometry analysis， and Western blot were used to explore the effect of M36 on the apoptosis of human hepatoma HepG2 cells. Acridine orange staining and western blotting were used to examine the effect of M36 on autophagy in HepG2 cells. Finally， Western blot was used to detect protein expression of cancer-related signaling pathways. ResultCompared with the blank group， M36 treatment significantly inhibited the proliferation of human hepatoma HepG2 cells （P<0.01）， and the half inhibitory concentration （IC₅₀） value of M36 for 48 h was 5.03 μmol·L^-1， in a dose- and time-dependent manner. M36 was also able to induce apoptosis and autophagy in human hepatoma HepG2 cells. After treatment with 8 μmol·L^-1 M36 for 48 hours， the apoptosis rate of HepG2 cells was （42.03±9.65）% （P<0.01）. Compared with the blank group， HepG2 cells treated with 4 and 8 μmol·L^-1 M36 for 48 h had a significant increase in cleaved poly ADP-ribose polymerase （cleaved-PARP） protein levels （P<0.01）. Acridine orange staining showed that autophagy was significantly activated in HepG2 cells treated with 4 and 8 μmol·L^-1 M36 for 48 h compared with the blank group （P<0.01）， which was further verified by the up-regulation of microtubule-associated protein 1 light chain 3 Ⅱ （LC3 Ⅱ）. Western blot results showed that compared with the blank group， the levels of phosphorylated extracellular regulated protein kinase （p-ERK）， phosphorylated p38 mitogen-activated protein kinase （p-p38 MAPK）， phosphorylated c-Jun N-terminal kinase （p-JNK）， and its downstream nuclear transcription factors c-Jun and p-c-Jun protein were significantly increased in M36 group （P<0.05， P<0.01）. The mechanism may be related to the up-regulation of MAPK signaling pathway. ConclusionThe sesquiterpenoid M36 isolated from Myrrha inhibits the proliferation of human hepatoma HepG2 cells and promotes apoptosis and autophagy， which may be related to the activation of the MAPK signaling pathway.

Iron is an indispensable nutritional element for human growth and development. It has a protective effect on cardiovascular. The changes and metabolism of iron can affect the physiological and pathological state of the body. Current research has confirmed that iron overload will promote the synthesis of cholesterol and increase lipid metabolism disorders. Lipid metabolic disorders in the body easily induce the occurrence and development of related metabolic diseases, and increase the hidden dangers of the outbreak of relevant risk factors. This article reviews iron and lipid metabolic and other metabolic diseases and natural products to prevent diseases through iron metabolic pathway, which aims to provide more powerful references for in-depth research on the mechanism of metabolic diseases and related diseases and target drug research and development.

ObjectiveTo identify immunogenic cell death （ICD）-related genes in hepatocellular carcinoma （HCC）， and to establish a scoring model based on these genes for predicting the prognosis and tumor microenvironment characteristics of HCC. MethodsThe Cancer Genome Atlas database was used to obtain HCC datasets， and heatmaps were used to display the expression of 57 ICD-related genes in HCC. A cluster analysis was conducted based on the expression of ICD-related genes， and two ICD subtypes （low and high ICD expression groups） were analyzed in terms of gene ontology enrichment analysis， Kyoto Encyclopedia of Genes and Genomes （KEGG） enrichment analysis， somatic mutation， and immune cell infiltration. The LASSO Cox regression risk model was constructed to evaluate its clinical application value， and a nomogram model was established to predict the 1-， 3-， and 5-year survival rates of patients. In addition， qRT-PCR was used to validate the expression levels of key genes in the model. The independent-samples t test was used for comparison between two groups， and the univariate and multivariate Cox regression analyses were used to determine prognostic factors among clinicopathological features. The Kaplan-Meier survival curve was used for prognostic analysis， and the Spearman rank correlation test was used for correlation analysis. ResultsThe low ICD expression group had a poorer prognosis， while the high ICD expression group had relatively favorable clinical outcomes （P=0.004）. Further analysis showed that the high ICD expression group was associated with an immune-active microenvironment， and the genes were mainly enriched in immune-related pathways such as immunoglobulin receptor binding， hematopoietic cell lineage， and B cell receptor. The results of somatic mutation analysis showed that the high ICD expression group had higher expression levels of CD274， CTLA4， HAVCR2， TIGIT， PDCD1， and PDCD1LG2 （all P<0.05）. A risk prediction model was established using 8 ICD-related genes， i.e.， HSP90AA1， ATG5， BAX， PPIA， HSPA4， TLR2， TREM1， and LY96， and this model showed a good predictive value across different clinical characteristics. The univariate and multivariate Cox regression analyses showed that age and risk score were independent prognostic factors for overall survival in the training set （both P<0.05）. The results of qRT-PCR showed that the relative expression levels of HSPA4 and REM1 in HCC tumor samples were significantly higher than those in adjacent tissue samples （both P<0.001）. For the patients with an increase in ICD risk score， the ICD risk score was negatively correlated with γδT cells （r=-0.29， P<0.05）， plasma cells （r=-0.3， P<0.05）， and CD8⁺T lymphocytes （r=-0.37， P<0.05） and was positively correlated with memory B cells （r=0.38， P<0.05）， resting dendritic cells （r=0.47， P<0.05）， and M0 macrophages （r=0.49， P<0.05）. ConclusionThis study identifies the ICD-related genes that are associated with the prognosis of HCC， which provides insights into the immune characteristics of different ICD expression profiles. The risk model and the nomogram model established in this study have a significant value for predicting the prognosis of HCC patients and guiding immunotherapy for HCC patients.

The canalis sinuosus,a canal containing the anterior superior alveolar nerve bundle,originates from the infraorbital canal and extends along the maxillary sinus and nasal cavity edges to the anterior maxilla.It was once regarded as an anatomical variation.However,with the widespread application of cone beam computed tomography(CBCT),the detection rate of canalis sinuosus in the population has increased.The canalis sinuosus exhibits diverse courses,branching into multiple accessory canals and terminating at the nasal floor or the anterior tooth region,with the majority traversing the palatal side of the central incisor.The anterior superior alveolar nerve bundle within the canalis sinuosus not only innervates and nourishes the maxillary anterior teeth and the corresponding soft tissues,and the maxillary sinus mucosa,but also relates to the nasal septum,lateral nasal wall,and parts of the palatal mucosa.To minimize surgical complications,strategies for preventing and treating canalis sinuosus injuries need to be investigated.Preoperatively,CBCT is used to identify the canalis sinuosus and to virtually design implant placement at a distance of more than 2 mm from the canalis sinuosus.Intraoperatively,assessing bleeding and patient comfort,complemented by precision surgical techniques such as the use of implant surgical guide plates.Postoperatively,CBCT is used to examine the relationship between the implant and the canalis sinuosus,and treatment of canalis sinuosus injuries can be tailored based on the patient's symptoms.This review summarizes the detection of canalis sinuosus in the population,its anatomical characteristics,and the physiological functions in the anterior maxilla,and discusses strategies for avoiding canalis sinuosus injuries during implant surgery,thereby enhancing clinical awareness and providing references for clinical decision-making.