Tumor drug resistance is an important problem in the failure of chemotherapy and targeted drug therapy, which is a complex process involving chromatin remodeling. SWI/SNF is one of the most studied ATP-dependent chromatin remodeling complexes in tumorigenesis, which plays an important role in the coordination of chromatin structural stability, gene expression, and post-translation modification. However, its mechanism in tumor drug resistance has not been systematically combed. SWI/SNF can be divided into 3 types according to its subunit composition: BAF, PBAF, and ncBAF. These 3 subtypes all contain two mutually exclusive ATPase catalytic subunits (SMARCA2 or SMARCA4), core subunits (SMARCC1 and SMARCD1), and regulatory subunits (ARID1A, PBRM1, and ACTB, etc.), which can control gene expression by regulating chromatin structure. The change of SWI/SNF complex subunits is one of the important factors of tumor drug resistance and progress. SMARCA4 and ARID1A are the most widely studied subunits in tumor drug resistance. Low expression of SMARCA4 can lead to the deletion of the transcription inhibitor of the BCL2L1 gene in mantle cell lymphoma, which will result in transcription up-regulation and significant resistance to the combination therapy of ibrutinib and venetoclax. Low expression of SMARCA4 and high expression of SMARCA2 can activate the FGFR1-pERK1/2 signaling pathway in ovarian high-grade serous carcinoma cells, which induces the overexpression of anti-apoptosis gene BCL2 and results in carboplatin resistance. SMARCA4 deletion can up-regulate epithelial-mesenchymal transition (EMT) by activating YAP1 gene expression in triple-negative breast cancer. It can also reduce the expression of Ca²⁺ channel IP3R3 in ovarian and lung cancer, resulting in the transfer of Ca²⁺ needed to induce apoptosis from endoplasmic reticulum to mitochondria damage. Thus, these two tumors are resistant to cisplatin. It has been found that verteporfin can overcome the drug resistance induced by SMARCA4 deletion. However, this inhibitor has not been applied in clinical practice. Therefore, it is a promising research direction to develop SWI/SNF ATPase targeted drugs with high oral bioavailability to treat patients with tumor resistance induced by low expression or deletion of SMARCA4. ARID1A deletion can activate the expression of ANXA1 protein in HER2+ breast cancer cells or down-regulate the expression of progesterone receptor B protein in endometrial cancer cells. The drug resistance of these two tumor cells to trastuzumab or progesterone is induced by activating AKT pathway. ARID1A deletion in ovarian cancer can increase the expression of MRP2 protein and make it resistant to carboplatin and paclitaxel. ARID1A deletion also can up-regulate the phosphorylation levels of EGFR, ErbB2, and RAF1 oncogene proteins.The ErbB and VEGF pathway are activated and EMT is increased. As a result, lung adenocarcinoma is resistant to epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs). Although great progress has been made in the research on the mechanism of SWI/SNF complex inducing tumor drug resistance, most of the research is still at the protein level. It is necessary to comprehensively and deeply explore the detailed mechanism of drug resistance from gene, transcription, protein, and metabolite levels by using multi-omics techniques, which can provide sufficient theoretical basis for the diagnosis and treatment of poor tumor prognosis caused by mutation or abnormal expression of SWI/SNF subunits in clinical practice.

Objective With the widespread of transcatheter aortic valve replacement(TAVR)in patients with severe symptomatic aortic stenosis(AS),the life-cycle management has become a major determinant of prognosis.Methods A total of 408 AS patients who underwent successfully TAVR from June 2021 to August 2023 were consecutively enrolled in Hospital Valve Intervention Center.Patients were assigned to the Usual Care(UC)group between June 2021 and October 2022,while patients were assigned to the Heart Multi-parameter Monitoring(HMM)group between November 2022 and August 2023.The primary endpoint was defined as composite endpoint within 6 months post-TAVR,including all-cause death,cardiovascular death,stroke/transient ischemic attack,conduction block,myocardial infarction,heart failure rehospitalization,and major bleeding events.Secondary endpoints were the time interval(in hours)from event occurrence to medical consultation or advice and patient satisfaction.Statistical analysis was performed using Kaplan-Meier and multivariable Cox proportional hazards models.Results The incidence of primary endpoint in HMM group was significantly lower than that in UC group(8.9％vs.17.7％,P=0.016),the driving event was the rate of diagnosis and recognition of conduction block.The average time intervals from event occurrence to receiving medical advice were 3.02 h in HHM group vs.97.09 h in UC group(P＜0.001).Using cardiac monitoring devices and smart healthcare platforms provided significant improving in patients long-term management(HR 0.439,95％CI 0.244-0.790,P=0.006).Conclusions The utilization of cardiac monitoring devices and smart healthcare platforms effectively alerted clinical events and improved postoperative quality of life during long-term management post TAVR.

Objective To preliminarily evaluate the safety and effectiveness of a novel non-implantable atrial shunt device based on radiofrequency ablation for the treatment of chronic heart failure(CHF).Methods This was a prospective single-arm study.From January 2023 to December 2023,five eligible CHF patients were consecutively enrolled at Beijing Anzhen Hospital,Capital Medical University,and underwent inter-atrial shunt using Shenzhen Betterway atrial shunt device.Pulmonary capillary wedge pressure(PCWP),right atrial pressure(RAP),pulmonary artery pressure(PAP),total pulmonary resistance(TPR),pulmonary vascular resistance(PVR),and pulmonary/systemic blood flow ratio(Qp/Qs)were measured using right heart catheterization before and immediately after procedure.Patients were followed up for 90 days,and echocardiography,right heart catheterization,and cardiac functional indicators were evaluated.The primary endpoint was procedural success.Secondary endpoints included clinical success,echocardiographic changes,6-minute walk distance(6MWD)changes,New York Heart Association(NYHA)class changes,Kansas city cardiomyopathy questionnaire(KCCQ)score changes,and amino-terminal probrain natriuretic peptide(NT-proBNP)level changes at 90 days.The safety endpoint was major cardiovascular and cerebrovascular adverse events and device-related adverse events.Results All five patients successfully achieved left-to-right atrial shunt.Compared with baseline,PCWP decreased significantly immediately after procedure in all five patients,with a procedural success rate of 100％.There were no significant changes in RAP,PAP,TPR,and PVR before and immediately after procedure.After 90 days follow-up,four patients had persistent left-to-right atrial shunt,and PCWP was significantly lower than baseline,with a clinical success rate of 80％.Compared with baseline,LVEF increased,left ventricular end-diastolic diameter decreased,and tricuspid annular plane systolic excursion and right ventricular fractional area change were not impaired in all five patients at 90 days.KCCQ scores and 6MWT improved,NT-proBNP decreased,and NYHA class did not change significantly.There were no deaths,rehospitalizations for heart failure,stroke-related adverse events,or device-related adverse events during the follow-up.Conclusions The novel non-implantable atrial shunt catheter can safely and effectively improve hemodynamic,echocardiographic,and cardiac functional indicators in patients with heart failure.However,larger-scale clinical studies are still needed to validate its long-term clinical effectiveness.

Despite significant advancements in treatments for heart failure,the overall prognosis for patients remains poor.Hemodynamic abnormalities in heart failure manifest as elevated left atrial pressure and pulmonary congestion.Previous studies have shown that reducing left atrial pressure can improve symptoms and prognosis for heart failure patients,suggesting that left-sided heart overload may be a potential target for heart failure treatment.Atrial shunting procedures aim to create a stable and controlled left-to-right intracardiac shunt,restoring the decompensated left heart volume and pressure load in heart failure patients to a compensatory state,thereby improving heart failure symptoms and prognosis.Currently,this treatment is still in the clinical research stage globally.Existing data indicate that atrial shunting procedures can lower left atrial pressure at rest or during exercise in heart failure patients,improve pulmonary congestion,enhance patients'exercise tolerance,and clinical cardiac function.However,no studies have yet confirmed that it can improve clinical endpoints such as rehospitalization and mortality due to heart failure.Future research will focus on identifying heart failure patients who may benefit from atrial shunting,with assessments of heart failure etiology,right heart function,and reversibility of pulmonary vascular resistance,as well as heart failure classification based on ejection fraction,serving as potential key factors for patient selection.

Tricuspid regurgitation(TR)is a common heart valve disease traditionally treated with surgery,which is invasive and high-risk.Recently,transcatheter tricuspid valve intervention(TTVI)technology has achieved major breakthroughs.It is being promoted internationally and several expert consensus documents have been launched abroad.However,in China,there is still a lack of consensus documents in this regard.In order to promote the safe,standardized and healthy development of this technology,this expert consensus is specially compiled.This consensus will introduce anatomy,epidemiology,classification and pathogenesis of TR,the traditional treatment and TTVI,preoperative evaluation and clinical efficacy endpoints.We sort out ten core viewpoints so that readers can quickly grasp the essence of the consensus.

Transcatheter aortic valve replacement(TAVR)has reached maturity and has entered a stage of steady and stable development in China.From 2017 to 2023,the number of centers conducting TAVR in China has increased from less than 10 to over 600,and the annual implantation volume has increased from hundreds to over 10 000.The 2018 and 2021 editions of the"Expert Consensus on Clinical Pathway for Transcatheter Aortic Valve Replacement in China"played a crucial guiding role during the golden period of TAVR development in China.With significant progress in evidence-based practice,clinical experience,guideline updates,device development,and procedure technique improvements in the TAVR field,especially the important advances in technologies developed from China,protocol optimization based on Chinese clinical practices,it is necessary to update the previous clinical pathway consensus.The new version of the clinical pathway expert consensus has updated the standard procedures for preoperative clinical assessment,perioperative imaging evaluation,standardized procedural processes,comprehensive perioperative management,and postoperative rehabilitation follow-up for TAVR patients.This update aims to further promote the healthy and standardized development of TAVR technology in China and to steadily enhance the medical and scientific research capabilities with this therapeutic technology.

Humans ; Anemia, Aplastic ; Leukemia, Large Granular Lymphocytic/diagnosis* ; Immunophenotyping

Humans ; Transcatheter Aortic Valve Replacement ; Aortic Valve/surgery* ; Heart Valve Prosthesis Implantation ; Aortic Valve Stenosis/surgery* ; Treatment Outcome ; Heart Valve Prosthesis

OBJECTIVE: To observe the clinical efficacy of intercondylar fossa plasty in preventing intercondylar fossa impingement syndrome after high tibial osteotomy. METHODS: From August 2018 to August 2020, 84 patients with inverted knee osteoarthritis were treated by arthroscopy combined with high tibial osteotomy, and were divided into two groups with 42 cases in each group according to different surgical methods. In the intercondylar fossa plasty group, there were 13 males and 29 females, age ranged from 52 to 67 years old with an average of(58.27±4.32) years old, and arthroscopic intercondylar fossa plasty was performed first, and then high tibial osteotomy. In the arthroscopic cleansing group, 16 males and 26 females, age ranged from 50 to 71 years old with an average of (59.02±5.14) years old, underwent arthroscopic cleansing and then high tibial osteotomy. Postoperative treatment was evaluated using visual analogue scale(VAS), hospital for special surgery (HSS) score for the knee, and the occurrence of intercondylar percussa impingement. RESULTS: All 84 patients were followed up, the duration ranged from 12 to 18 months with an average of (14.1±1.6) months. The VAS and HSS score of knee joint at 6, 12 and 18 months after surgery were significantly improved compared with preoperative period, and there was no significant difference between the two groups (P>0.05), but the incidence of intercondylar fossa index and intercondylar fossa impact between the two groups was significantly compared 18 months after surgery (P<0.05). CONCLUSION Intercondylar fossa plasty can effectively prevent the incidence of intercondylar fossa impact after high tibial osteotomy, and has a more significant effect on postoperative knee pain and function improvement.
Male ; Female ; Humans ; Middle Aged ; Aged ; Tibia/surgery* ; Osteoarthritis, Knee/surgery* ; Knee Joint/surgery* ; Treatment Outcome ; Osteotomy/methods* ; Pain, Postoperative ; Retrospective Studies

OBJECTIVE: To explore the effective method of applying Chinese medicine manipulative repositioning Kirschner wire fixation for minimally invasive treatment of fractures of the neck of the fifth metacarpal. METHODS: From January 2018 to November 2021, 90 patients with closed fractures of the neck of the fifth metacarpal bone were treated minimally invasively with closed repositioning Kirschner wires, all fractures AO type was type A. All patients were divided into three groups according to the mode of internal fixation involving 30 cases in the crossed Kirschner's wire group, 30 cases in the transverse Kirschner's wire group, 30 patients in the intramedullary Kirschner's wire group. By comparison, gender, age, disease duration, and preoperative neck-stem angle were not significant. The postoperative fifth metacarpal neck-stem angles, postoperative fifth metacarpophalangeal joint flexion mobility and fifth metacarpophalangeal joint extension hyperextension angles were compared among three groups. The overall clinical efficacy was evaluated according to the patient outcomes of surgery-hand/arm(POS-Hand/Arm) scoring system. RESULTS: All patients had 12-month follow-up and achieved bony union without malunion. There was no significant difference in the 5th metacarpal neck-stem angle, the fifth metacarpophalangeal joint flexion angle and the fifth metacarpophalangeal joint extension hyperextension angles among three groups at 12 months after surgery(P>0.05). There was no significant difference in physical activity and symptom scores in POS-Hand/Arm scores at 12 months after surgery(P>0.05), psychological status and aesthetic score among three groups(P<0.05) and between cross and transverse Kirschner wire groups(P>0.05). The three POS-Hand/Arm total scores were statistically different(P<0.05), between the crossed and transverse(P>0.05), and the intramedullary group had the highest POS-Hand/Arm scores. CONCLUSION All three techniques of Kristener's wire fixation could achieve minimally invasive treatment, and patients have need for cosmetic and early activity, and the author recommend minimally invasive intramedullary fixation with manipulative repositioned Kristen wires as the preferred procedure.