BACKGROUND: The available evidence regarding the benefits of percutaneous coronary intervention (PCI) on patients receiving dialysis with coronary artery disease (CAD) is limited and inconsistent. This study aimed to evaluate the association between PCI and clinical outcomes as compared with medical therapy alone in patients undergoing dialysis with CAD in China. METHODS: This multicenter, retrospective study was conducted in 30 tertiary medical centers across 12 provinces in China from January 2015 to June 2021 to include patients on dialysis with CAD. The primary outcome was major adverse cardiovascular events (MACE), defined as a composite of cardiovascular death, non-fatal myocardial infarction, and non-fatal stroke. Secondary outcomes included all-cause death, the individual components of MACE, and Bleeding Academic Research Consortium criteria types 2, 3, or 5 bleeding. Multivariable Cox proportional hazard models were used to assess the association between PCI and outcomes. Inverse probability of treatment weighting (IPTW) and propensity score matching (PSM) were performed to account for potential between-group differences. RESULTS: Of the 1146 patients on dialysis with significant CAD, 821 (71.6%) underwent PCI. After a median follow-up of 23.0 months, PCI was associated with a 43.0% significantly lower risk for MACE (33.9% [ n  = 278] vs . 43.7% [ n  = 142]; adjusted hazards ratio 0.57, 95% confidence interval 0.45-0.71), along with a slightly increased risk for bleeding outcomes that did not reach statistical significance (11.1% vs . 8.3%; adjusted hazards ratio 1.31, 95% confidence interval, 0.82-2.11). Furthermore, PCI was associated with a significant reduction in all-cause and cardiovascular mortalities. Subgroup analysis did not modify the association of PCI with patient outcomes. These primary findings were consistent across IPTW, PSM, and competing risk analyses. CONCLUSION This study indicated that PCI in patients on dialysis with CAD was significantly associated with lower MACE and mortality when comparing with those with medical therapy alone, albeit with a slightly increased risk for bleeding events that did not reach statistical significance.
Humans ; Percutaneous Coronary Intervention/methods* ; Male ; Female ; Coronary Artery Disease/drug therapy* ; Retrospective Studies ; Renal Dialysis/methods* ; Middle Aged ; Aged ; China ; Proportional Hazards Models ; Treatment Outcome

HDAC7, a member of class IIa HDACs, plays a pivotal regulatory role in tumor, immune, fibrosis, and angiogenesis, rendering it a potential therapeutic target. Nevertheless, due to the high similarity in the enzyme active sites of class IIa HDACs, inhibitors encounter challenges in discerning differences among them. Furthermore, the substitution of key residue in the active pocket of class IIa HDACs renders them pseudo-enzymes, leading to a limited impact of enzymatic inhibitors on their function. In this study, proteolysis targeting chimera (PROTAC) technology was employed to develop HDAC7 drugs. We developed an exceedingly selective HDAC7 PROTAC degrader B14 which showcased superior inhibitory effects on cell proliferation compared to TMP269 in various diffuse large B cell lymphoma (DLBCL) and acute myeloid leukemia (AML) cells. Subsequent investigations unveiled that B14 disrupts BCL6 forming a transcriptional inhibition complex by degrading HDAC7, thereby exerting proliferative inhibition in DLBCL. Our study broadened the understanding of the non-enzymatic functions of HDAC7 and underscored the importance of HDAC7 in the treatment of hematologic malignancies, particularly in DLBCL and AML.

T-cell acute lymphoblastic leukemia (T-ALL) is a highly aggressive hematologic malignancy with a poor prognosis, despite advancements in treatment. Many patients struggle with relapse or refractory disease. Investigating the role of the super-enhancer (SE) regulated gene ubiquitin-specific protease 20 (USP20) in T-ALL could enhance targeted therapies and improve clinical outcomes. Analysis of histone H3 lysine 27 acetylation (H3K27ac) chromatin immunoprecipitation sequencing (ChIP-seq) data from six T-ALL cell lines and seven pediatric samples identified USP20 as an SE-regulated driver gene. Utilizing the Cancer Cell Line Encyclopedia (CCLE) and BloodSpot databases, it was found that USP20 is specifically highly expressed in T-ALL. Knocking down USP20 with short hairpin RNA (shRNA) increased apoptosis and inhibited proliferation in T-ALL cells. In vivo studies showed that USP20 knockdown reduced tumor growth and improved survival. The USP20 inhibitor GSK2643943A demonstrated similar anti-tumor effects. Mass spectrometry, RNA-Seq, and immunoprecipitation revealed that USP20 interacted with hypoxia-inducible factor 1 subunit alpha (HIF1A) and stabilized it by deubiquitination. Cleavage under targets and tagmentation (CUT&Tag) results indicated that USP20 co-localized with HIF1A, jointly modulating target genes in T-ALL. This study identifies USP20 as a therapeutic target in T-ALL and suggests GSK2643943A as a potential treatment strategy.

OBJECTIVE: miR-34c-3p is down-regulated in nasopharyngeal carcinoma (NPC). The biological role of miR-34c-3p in NPC and its underlying mechanisms are unknown and were explored in this study. METHODS: Flow cytometry and immunohistochemical staining were employed to detect cluster of differentiation 86 (CD86) and cluster of differentiation 206 (CD206) expression; quantitative real-time polymerase chain reaction (qRT-PCR) and western blotting were employed to examine mRNA expression and protein levels; cell counting kit-8 (CCK8) and transwell assays were employed to assess cell proliferation, migration, and invasion; and hematoxylin-eosin (HE) staining was employed to assess pathological changes in tumor tissues. RESULTS: Our results revealed that the miR-34c-3p mimic markedly inhibited M2 polarization of macrophages by targeting SLC7A11, and M2 macrophages transfected with the miR-34c-3p mimic inhibited the proliferation, migration, and invasion of NPC cells. The in vivo experiments further confirmed that miR-34c-3p mimics blocked tumor growth and reduced inflammatory infiltration in tumor tissues. CONCLUSION This study provides novel insights into the pathogenesis of NPC and a new treatment strategy.
MicroRNAs/metabolism* ; Nasopharyngeal Carcinoma/genetics* ; Humans ; Animals ; Nasopharyngeal Neoplasms/genetics* ; Macrophages/physiology* ; Cell Line, Tumor ; Mice ; Cell Proliferation ; Mice, Inbred BALB C ; Cell Movement ; Male ; Gene Expression Regulation, Neoplastic ; Mice, Nude ; Female

Objective To investigate the clinical effect of total hip replacement(THA)in the treatment of traumatic arthritis secondary to acetabular fracture.Methods From October 2019 to June 2022,15 patients with secondary traumatic arthritis of acetabulum fracture were treated with THA.There were 8 males and 7 females,aged from 40 to 76 years old with an average of(59.20±9.46)years old.Prosthesis loosening,dislocation of hip joint,range of motion of hip joint,nerve injury and other conditions were recorded before and after surgery.Harris score,visual analogue scale(VAS)and imaging were used to e-valuate hip joint function and surgical effect.Results Follow-up time ranged 6 to 39 months with an average of(18.33±9.27)months.All the 15 patients successfully completed the operation,no nerve and blood vessel injury during the operation,post-operative wound healing was stage Ⅰ,no infection,one case of acetabular side prosthesis loosening at half a year after opera-tion,and recovered well after revision surgery,one case of hip dislocation was cured after open reduction treatment,no adverse consequences.Harris score at the last postoperative follow-up was(88.60±4.01)points,compared with the preoperative(47.20±1 1.77)points,the difference was statistically significant(P＜0.05),and VAS at the lateat postoperative follow-up was 1(1)points,compared with the preoperative 8(2)points,the difference was statistically significant(P＜0.05).At the last follow-up,the pain symptoms were relieved or disappeared,and the joint function was satisfactory.The imaging data of the latest fol-low-up showed joint was well pseudoradiated,no abnormal ossification occurred,and the prosthesis was not loose.Conclusion THA is effective in the treatment of traumatic arthritis secondary to acetabular fracture and can effectively improve the quality of life of patients.Preoperative comprehensive evaluation and bone defect evaluation of patients,and intraoperative manage-ment of acetabulum,femur,internal fixation and bone defect are key factors for the success of surgery.

Objective To study the correlation between traditional Chinese medicine(TCM)constitution and pathogenic factors in patients with ankylosing spondylitis(AS).Methods One hundred patients of AS and their family members who had medical consultation in the Fifth Hospital of Xi'an(i.e.,Shaanxi Hospital of Integrated Traditional Chinese and Western Medicine)in August 2019 and September 2020 were selected as the study subjects.The guidelines of Classification and Determination of Traditional Chinese Medicine Constitution issued by the China Association of Chinese Medicine were adopted to determine the traditional Chinese medicine(TCM)constitution types of the study subjects.The sociodemographic information,living habits,clinical symptoms,and TCM constitution types of the AS patients and their family members were collected by means of questionnaires and clinical investigations,and then the pathogenic factors of the patients with AS were investigated.The binomial Logistic regression model was used to analyze the correlation between TCM constitution types and pathogenic factors in patients with AS.Results(1)Among the 100 AS patients,the majority of them had the biased constitutions,and the biased constitutions with the occurrence frequency in descending order were yang deficiency constitution,qi deficiency constitution,and damp-heat constitution,which accounted for 33.00%,14.00%,and 18.00%,respectively.(2)The prevalence rates of AS in the first-,second-,and third-degree relatives of AS patients were 56.25%,40.00%and 25.00%,respectively.For the positive rates of human leukocyte antigen B27(HLA-B27)in AS patients and their family members,HLA-B27 in AS patients was all positive,while the positive rates of HLA-B27 in the first-,second-,and third-degree relatives of AS patients were 44.31%,30.67%and 15.63%,respectively.(3)The results of regression analysis showed that the disease duration of AS patients was significantly correlated with qi deficiency constitution,the grading of sacroiliac arthritis was correlated with qi stagnation constitution,and age was correlated with blood stasis constitution(P＜0.05 or P＜0.01).The results indicated that disease duration and age were the important factors affecting the constitution types of AS patients,and disease duration was closely related to qi deficiency while age was closely related to blood stasis.Conclusion AS is a highly hereditary autoimmune disease,and its onset is associated with HLA-B27.Yang deficiency is the basic constitution type of AS,and damp-heat constitution is the main constitution type in the progression of AS(especially in the active stage of the disease).The prolongation of the disease will exacerbate the illness condition of AS and then the manifestations of qi deficiency will be more obvious.

Efficient bacterial drug susceptibility test can help precise guidance on using antimicrobial and improve the efficiency of development of antibiotics.Traditional antimicrobial susceptibility testing(AST)methods are simple,reliable and specific,but suffer from drawbacks of time-consuming.The CCK8 reagent can be reduced by the dehydrogenase in the bacterial cells to form a water-soluble orange-yellow formazan,and the concentration of viable bacteria is proportional to the absorbance of formazan at 450 nm(OD450 nm).In this work,based on the principle of CCK8 colorimetry,the antibiotic loaded composite fiber membrane was used as the culture matrix for AST.Simple,rapid and high-throughput AST was realized by the difference in OD450 nm,which reflected the differences in viable bacteria quantity during bacterial growth.The total detection time was less than 8 h.The potential application of the method was evaluated using S.aureus,P.aeruginosa in wound simulation fluid and E.coli in artificial urine as simulated actual samples.The results of this method were in consistent with the disk diffusion test.This method provided a new idea for AST,which was helpful for the guidance of clinical medication and the development of antibiotics.

BACKGROUND: In China, lung cancer remains the cancer with the highest incidence and mortality rate. Among early-stage lung adenocarcinomas (LUAD), the micropapillary (MPP) component is prevalent and typically exhibits high aggressiveness, significantly correlating with early metastasis, lymphatic infiltration, and reduced five-year survival rates. Therefore, the study is to explore the similarities and differences between MPP and non-micropapillary (non-MPP) components in malignant pulmonary nodules characterized by GGOs in early-stage LUAD, identify unique mutational features of the MPP component and analyze the relationship between the ZNF469 gene, a member of the zinc-finger protein family, and the prognosis of early-stage LUAD, as well as its correlation with immune infiltration. METHODS: A total of 31 malignant pulmonary nodules of LUAD were collected and dissected into paired MPP and non-MPP components using microdissection. Whole-exome sequencing (WES) was performed on the components of early-stage malignant pulmonary nodules. Mutational signatures analysis was conducted using R packages such as maftools, Nonnegative Matrix Factorization (NMF), and Sigminer to unveil the genomic mutational characteristics unique to MPP components in invasive LUAD compared to other tumor tissues. Furthermore, we explored the expression of the ZNF469 gene in LUAD using The Cancer Genome Atlas (TCGA) database to investigate its potential association with the prognosis. We also investigated gene interaction networks and signaling pathways related to ZNF469 in LUAD using the GeneMANIA database and conducted Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis. Lastly, we analyzed the correlation between ZNF469 gene expression and levels of immune cell infiltration in LUAD using the TIMER and TISIDB databases. RESULTS: MPP components exhibited a higher number of genomic variations, particularly the 13th COSMIC (Catalogue of Somatic Mutations in Cancer) mutational signature characterized by the activity of the cytidine deaminase APOBEC family, which was unique to MPP components compared to non-MPP components in tumor tissues. This suggests the potential involvement of APOBEC in the progression of MPP components in early-stage LUAD. Additionally, MPP samples with high similarity to APOBEC signature displayed a higher tumor mutational burden (TMB), indicating that these patients may be more likely to benefit from immunotherapy. The expression of ZNF469 was significantly upregulated in LUAD compared to normal tissue, and was associated with poor prognosis in LUAD patients (P<0.05). Gene interaction network analysis and GO/KEGG enrichment analysis revealed that COL6A1, COL1A1, COL1A2, TGFB2, MMP2, COL8A2 and C2CD4C interacted with ZNF469 and were mainly involved in encoding collagen proteins and participating in the constitution of extracellular matrix. ZNF469 expression was positively correlated with immune cell infiltration in LUAD (P<0.05). CONCLUSIONS The study has unveiled distinctive mutational signatures in the MPP components of early-stage invasive LUAD in the Asian population. Furthermore, we have identified that the elevated expression of mutated ZNF469 impacts the prognosis and immune infiltration in LUAD, suggesting its potential as a diagnostic and prognostic biomarker in LUAD.
Humans ; Lung Neoplasms/genetics* ; Adenocarcinoma of Lung/genetics* ; China ; Prognosis ; Transcription Factors

Objective To campare biomechanical effects of different postural compression techniques on three-dimensional model of lumbar disc herniation(LDH)by finite element analysis.Methods Lumbar CT image of a 48-year-old female patient with LDH(heighted 163 cm,weighted 53 kg)was collected.Mimics 20.0,Geomagic Studio,Solidwords and other software were used to establish three-dimensional finite element model of LDH on L4,5 segments.Compression techniques under horizon-tal position,30° forward bending and 10° backward extension were simulated respectively.After applying the pressure,the ef-fects of compression techniques under different positions on stress,strain and displacement of various tissues of intervertebral disc and nerve root were observed.Results L4,5 segment finite element model was successfully established,and the model was validated.When compression manipulation was performed on the horizontal position,30° flexion and 10° extension,the annular stress were 0.732,5.929,1.286 MPa,the nucleus pulposus stress were 0.190,1.527,0.295 MPa,and the annular strain were 0.097,0.922 and 0.424,the strain sizes of nucleus pulposus were 0.153,1.222 and 0.282,respectively.The overall displace-ment distance of intervertebral disc on Y direction were-3.707,-18.990,-4.171 mm,and displacement distance of nerve root on Y direction were+7.836,+5.341,+3.859 mm,respectively.The relative displacement distances of nerve root and interverte-bral disc on Y direction were 11.543,24.331 and 8.030 mm,respectively.Conclusion Compression manipulation could make herniated intervertebral disc produce contraction and retraction trend,by increasing the distance between herniated interverte-bral disc and nerve root,to reduce symptoms of nerve compression,to achieve purpose of treatment for patients with LDH,in which the compression manipulation is more effective when the forward flexion is 30°.