Mitral valve prolapse is one of the common causes of mitral regurgitation.Mitral valve prolapse complicated with leaflet cleft is rare in clinical practice,which most often undergo surgical mitral valve repair or mitral valve replacement.We report a case of mitral valve prolapse with posterior leaflet cleft treated by transcatheter edge-to-edge mitral valve repair,in order to provide a model for similar cases.

Background and Aims:Sonodynamic therapy(SDT)is an emerging tumor treatment method that primarily utilizes low-intensity ultrasound(US)to activate sonosensitizers,leading to the production of cytotoxic reactive oxygen species(ROS)that kill cells.This study was conducted with an attempt to develop a novel nanoparticle(NPs)formulation containing a sonosensitizer and the small interfering RNA(siRRS1)of tumor-related gene RRS1 to observe its anticancer effects on colon cancer,to provide new strategies for colon cancer treatment. Methods:RRS1 RNA-Seq data were downloaded from the TCGA and GEO databases,and clinical pathological data were collected from 80 patients with colon cancer at Hunan Provincial People's Hospital.The expression of RRS1 in colon cancer and its relationship with prognosis were analyzed.The proliferation and apoptosis of colon cancer cells transfected with siRRS1 were observed.The sonosensitizer tetra(4-carboxyphenyl)porphyrin(TCPP),gene carrier DSPE-PEI,and siRRS1 were assembled into TCPP@DSPE-PEI-siRRS1 NPs(T@D-siRRS1 NPs).After structural characterization and examination of cellular uptake and ROS generation capabilities in vitro,the anticancer effects of T@D-siRRS1 NPs on colon cancer were assessed in cell experiments and tumor-bearing mouse models. Results:Both database analysis and clinical specimen testing indicated that RRS1 expression in colon cancer tissues was higher than that in adjacent normal tissues,and high expression was associated with poor prognosis(HR=1.88,95％CI=1.27-2.79,P=0.002).Univariate and multivariate analyses showed that RRS 1 mRNA expression was an independent risk factor for overall survival in colon cancer patients(HR=1.354,95％CI=1.447-2.215,P=0.031).Knockdown of RRS1 significantly reduced the proliferation capacity of colon cancer cells and increased apoptosis(both P＜0.05).Characterization results showed that the particles were uniform and stable;T@D-siRRS1 NPs entered cells through endocytosis,where TCPP could generate singlet oxygen(1O2)under ultrasound irradiation.Subsequent in vitro and in vivo experimental results demonstrated that transfection with NPs carrying siRRS1 or TCPP(T@D-control siRNA,T@D-siRRS1)combined with US resulted in varying degrees of growth inhibition in colon cancer cells,with the T@D-siRRS1 NPs+US treatment showing the strongest effect(all P＜0.05).Moreover,no significant damage was observed in the vital organs of mice treated with T@D-siRRS1 NPs+US. Conclusion:T@D-siRRS1 NPs plus US integrate SDT and gene therapy,producing an effective synergistic cytotoxic effect on colon cancer cells.Additionally,T@D-siRRS1 NPs demonstrate good safety and biocompatibility,suggesting potential for clinical application.

Objective:To investigate the effect of genetic polymorphism of MTHFR C677T (rs1801133) on methotrexate (MTX) related toxicity in pediatric mature B-cell lymphoma patients. Methods:Fifty-eight intermediate and high risk patients under 18 years of age with mature B-cell lymphoma who received 5 g/m2 MTX (24 h intravenous infusion) in Sun Yat-sen University Cancer Center from August 2014 to December 2021 were included,and their toxicity of high-dose MTX (HD-MTX) were monitored and analyzed. Results:Among the 58 pediatric patients,the number of CC,CT,and TT genotypes for MTHFR C677T was 33,19 and 6,respectively. A total of 101 courses of HD-MTX therapy were counted,of which plasma MTX level>0.2 μmol/L at 48 h post-MTX infusion were observed in 35 courses,≤0.2 μmol/L in 66 courses. Inter-group comparison showed that plasma MTX level>0.2 μmol/L at 48 h post-MTX infusion increased the risk of developing oral mucositis (P<0.05). Compared with wild-type (CC genotype),patients in the mutant group (CT+TT genotype) were more likely to develop myelosuppression,manifested as anemia,leucopenia,neutropenia and thrombocytopenia. However,plasma MTX level at 48 h was not associated with MTHFR C677T gene polymorphism. Conclusion:The risk of developing oral mucositis in children with mature B-cell lymphoma is associated with plasma MTX concentration. Polymorphism of MTHFR C677T gene is not related to plasma MTX concentration in children with mature B-cell lymphoma,but is related to grade Ⅲ to Ⅳ hematological toxicity.

Humans ; Child ; Lymphoma, Large B-Cell, Diffuse/pathology*

Objective: To study the effect of diurnal temperature range on the number of elderly inpatients with ischemic stroke in Hunan Province. Method: Demographic and disease data, meteorological data, air quality data, population, economic and health resource data of elderly inpatients with ischemic stroke were collected in 122 districts/counties of Hunan Province from January to December 2019. The relationships between the diurnal temperature range and the number of elderly inpatients with ischemic stroke were analyzed by using the distributed lag non-linear model, including the cumulative lag effect of the diurnal temperature range in different seasons, extremely high diurnal temperature range and extremely low diurnal temperature range. Results: In 2019, 152 875 person-times were admitted to the hospital for ischemic stroke in the elderly in Hunan Province. There was a non-linear relationship between the diurnal temperature range and the number of elderly patients with ischemic stroke, with different lag periods. In spring and winter, with the decrease in diurnal temperature range, the risk of admission of elderly patients with ischemic stroke increased (P_trend<0.001, P_trend=0.002);in summer, with the increase in diurnal temperature range, the risk of admission of elderly patients with ischemic stroke increased (P_trend=0.024);in autumn, the change in the diurnal temperature range would not cause a change in admission risk (P_trend=0.089). Except that the lag effect of the extremely low diurnal temperature range in autumn was not obvious, the lag effect occurred in other seasons under extremely low and extremely high diurnal temperature ranges. Conclusion: The high diurnal temperature range in summer and the low diurnal temperature range in spring and winter will increase the risk of admission of elderly patients with ischemic stroke, and the risk of admission of elderly patients with ischemic stroke will lag under the extremely low and extremely high diurnal temperature ranges in the above three seasons.
Humans ; Aged ; Temperature ; Ischemic Stroke ; Inpatients ; Cold Temperature ; Hot Temperature ; Seasons ; China/epidemiology*

Objective: To observe the clinical effect of auricle reconstruction in adult patients with microtia and summarize the experience. Methods: Clinical data of adult patients with microtia who underwent total auricle reconstruction using the modified Nagata's two stage for microtia reconstruction from June 2016 to June 2021 were analyzed. A total of 41 adult patients (42 ears) with microtia were enrolled, including 30 males and 11 females, with the median age at the time of surgery of 37 years. Autogenous costal cartilage was used as the auricular framework for all patients in this group. The first stage surgery was performed according to the modified Nagata's two stage for microtia reconstruction procedure,cartilage auricular framework carving was performed by different methods according to the ossification state of adult costal cartilage. Six months following the primary operation, ear elevation and cranioauricular angle formation, retroauricular facial flap transfer and medium-thick skin grafting were performed in the second stage. Results: All patients successfully completed two stage operation. During the follow-up of 3 months and 24 months, all the 41 patients were satisfied with the morphology of reconstructed auricle. Conclusion: According to the costal cartilage status of adult patients, different costal cartilage carving techniques can be used for total auricle reconstruction to obtain ideal surgical results.
Male ; Female ; Humans ; Adult ; Surgical Flaps ; Congenital Microtia/surgery* ; Plastic Surgery Procedures ; Ear, External/surgery* ; Ear Auricle/surgery*

Objective: To analyze and compare therapy responses, outcomes, and incidence of severe hematologic adverse events of flumatinib and imatinib in patients newly diagnosed with chronic phase chronic myeloid leukemia (CML) . Methods: Data of patients with chronic phase CML diagnosed between January 2006 and November 2022 from 76 centers, aged ≥18 years, and received initial flumatinib or imatinib therapy within 6 months after diagnosis in China were retrospectively interrogated. Propensity score matching (PSM) analysis was performed to reduce the bias of the initial TKI selection, and the therapy responses and outcomes of patients receiving initial flumatinib or imatinib therapy were compared. Results: A total of 4 833 adult patients with CML receiving initial imatinib (n=4 380) or flumatinib (n=453) therapy were included in the study. In the imatinib cohort, the median follow-up time was 54 [interquartile range (IQR), 31-85] months, and the 7-year cumulative incidences of CCyR, MMR, MR(4), and MR(4.5) were 95.2%, 88.4%, 78.3%, and 63.0%, respectively. The 7-year FFS, PFS, and OS rates were 71.8%, 93.0%, and 96.9%, respectively. With the median follow-up of 18 (IQR, 13-25) months in the flumatinib cohort, the 2-year cumulative incidences of CCyR, MMR, MR(4), and MR(4.5) were 95.4%, 86.5%, 58.4%, and 46.6%, respectively. The 2-year FFS, PFS, and OS rates were 80.1%, 95.0%, and 99.5%, respectively. The PSM analysis indicated that patients receiving initial flumatinib therapy had significantly higher cumulative incidences of CCyR, MMR, MR(4), and MR(4.5) and higher probabilities of FFS than those receiving the initial imatinib therapy (all P<0.001), whereas the PFS (P=0.230) and OS (P=0.268) were comparable between the two cohorts. The incidence of severe hematologic adverse events (grade≥Ⅲ) was comparable in the two cohorts. Conclusion: Patients receiving initial flumatinib therapy had higher cumulative incidences of therapy responses and higher probability of FFS than those receiving initial imatinib therapy, whereas the incidence of severe hematologic adverse events was comparable between the two cohorts.
Adult ; Humans ; Adolescent ; Imatinib Mesylate/adverse effects* ; Incidence ; Antineoplastic Agents/adverse effects* ; Retrospective Studies ; Pyrimidines/adverse effects* ; Leukemia, Myelogenous, Chronic, BCR-ABL Positive/drug therapy* ; Treatment Outcome ; Benzamides/adverse effects* ; Leukemia, Myeloid, Chronic-Phase/drug therapy* ; Aminopyridines/therapeutic use* ; Protein Kinase Inhibitors/therapeutic use*

Humans ; Child ; Lymphoma, Large-Cell, Anaplastic ; Neoplasm Recurrence, Local ; Prognosis ; Hodgkin Disease

Aim To observe the effect of Gupi Xiaoji Decoction (GPXJY) on the structure and function of mitochondria of human hepatoma cell HepG2 cells and explore its possible mechanism. Methods CCK8 was used to detect cell proliferation, Mito-Tracker Green fluorescence staining was used to observe the mitochondrial structure, flow cytometry was used to detect the membrane potential, Elisa was used to detect the ATP content, fluoroscopic electron microscopy was used to observe the microstructure changes, and high-content screening(HCS) was used to detect the related proteins. Results Fluorescence staining showed that GPXJY damaged the mitochondria of HepG2 cells and decreased the content of ATP. The results of flow cytometry showed that GPXJY could reduce the mitochondrial membrane potential of HepG2 cells. The results of electron microscope showed that GPXJY made the mitochondria of cancer cells swell and so on. HCS found that GPXJY significantly reduced the average fluorescence intensity of Bcl-2 in HepG2 cells, and significantly increased the average fluorescence intensity of apoptosis promoting proteins Bax, cytochrome-c, caspase-3 and cleaved-caspase-3, which was statistically significant. Conclusion GPXJY can regulate the structure and function of mitochondria in HepG2 cells.

ObjectiveTo screen the active antitumor components of Gupi Xiaoji decoction by network pharmacology and molecular docking based on the pyroptosis mediated by cysteinyl aspartate-specific protease 1 （Caspase-1） and explore its molecular mechanism in intervening in the pyroptosis of HepG2.2.15 cells through in vitro experiments. MethodThe compounds and targets of Gupi Xiaoji decoction were screened out by Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform（TCMSP） to obtain the corresponding gene symbols. The targets of Caspase-1 were collected from GeneCards，online mendelian inheritance in man（OMIM），PharmGKB，and TTD，and the compound-gene target regulatory network was constructed by Cytoscape. The protein-protein interaction（PPI） network was established and analyzed by STRING. The mechanism of the effective components of Gupi Xiaoji decoction on Caspase-1 was predicted by gene ontology（GO） functional enrichment and Kyoto Encyclopedia of Genes and Genomes（KEGG） pathway enrichment analyses. The molecular docking was verified with AutoDock Vina. The plasma medicated with Gupi Xiaoji Decoction was prepared and HepG2.2.15 cells were cultured in vitro. HepG2.2.15 cells were divided into a blank plasma group，a VX-765 group，a VX-765+medicated plasma group， and a medicated plasma group. After 48 hours of intervention with 15% medicated plasma， the expression and distribution of gasdermin D-N （GSDMD-N） on the surface of the cell membrane were detected by immunofluorescence staining. The release of lactic dehydrogenase （LDH）， interleukin（IL）-1β，and IL-18 in the cell supernatant was measured by enzyme-linked immunosorbent assay（ELISA） kits. The expression of Caspase-1 and GSDMD-N was measured by Western blot. ResultThe mitogen-activated protein kinase 14 （MAPK14），MAPK1，protein kinase B1 （Akt1）， MAPK8， V-Jun sarcoma virus oncogene homolog （JUN）， and TP53 screened by network pharmacology were the main targets. The compounds 7-hydroxy-5，8-dimethoxy-2-phenyl-chromone，wogonin，rhamnazin，moslosooflavone，isorhamnetin，7-O-methylisomucronulatol，formononetin，calycosin，luteolin，quercetin，kaempferol，β-sitosterol，and baicalein screened by network pharmacology were the main active components of Gupi Xiaoji decoction. Go enrichment analysis showed that multiple biological processes were involved， including responses to oxidative stress and metal ions，ubiquitin-like protein ligase binding，and phosphatase binding. KEGG pathway enrichment analysis showed MAPK pathway，nuclear factor（NF）-κB pathway，p53 pathway， and hypoxia-inducible factor-1（HIF-1） pathway were involved. Molecular docking showed that the targets had good binding with the components. In vitro experiments displayed that compared with the blank plasma group，the VX-765 group showed weakened GSDMD-N fluorescence signal，reduced release of LDH，IL-1β，and IL-18，and declining expression of Caspase-1 and GSDMD-N（P<0.01）， and the medicated plasma group showed increased GSDMD-N fluorescence signal， increased release of LDH，IL-1β，and IL-18，and up-regulated expression of Caspase-1 and GSDMD-N（P<0.01）. ConclusionGupi Xiaoji Decoction can induce the pyroptosis of HepG2.2.15 cells by regulating Caspase-1 through multiple targets and multiple pathways.