OBJECTIVES: To compare the efficacy of transcatheter tricuspid valve replacement (TTVR) using Lux-Valve and Lux-Valve Plus in patients with severe tricuspid regurgitation. METHODS: A total of 28 consecutive patients with severe tricuspid regurgitation who underwent TTVR with Lux-Valve (n=14) or Lux-Valve Plus (n=14) in the First Affiliated Hospital of the Air Force Medical University from August 2019 to November 2023 were enrolled. Transthoracic echocardiography was performed in all patients before and 6 months after the TTVR. The ultrasound indexes were compared before and 6 months after the TTVR in all patients and between Lux-Valve and Lux-Valve Plus groups. RESULTS: Compared with the Lux-Valve group, the Lux-Valve Plus group showed significantly reduced intraoperative bleeding and shorter postoperative hospital stays (both P<0.05). Six months after the TTVR, none of the patients exhibited more than a mild tricuspid valve regurgitation, and none of the patients had moderate or above perivalvular leakage except for one patient in the Lux-Valve Plus group who had a separation of the clamping member from the anterior tricuspid leaflet. The incidence of perivalvular leakage was significantly lower in the Lux-Valve Plus group (14.29%, 2/14) than in the Lux-Valve group (64.29%, 9/14, P<0.05). At 6 months after operation, the right chamber volume and right ventricle middle transverse diameter were reduced (both P<0.05); the peak blood flow velocity across the tricuspid valve, peak pressure gradient across the tricuspid valve, mean blood flow velocity of tricuspid valve, mean pressure gradient across the tricuspid valve and velocity time integral were increased in both groups (all P<0.05).Compared with the Lux-Valve group, the Lux-Valve Plus group showed higher left ventricular ejection fraction at 6 months postoperatively (P<0.05), while the rest of the indicators were not statistically different (all P>0.05). CONCLUSIONS The efficacy of using Lux-Valve and Lux-Valve Plus for TTVR in patients with severe tricuspid regurgitation is comparable. Six months after the TTVR, the right side of the heart has undergone reverse remodeling.While Lux-Valve Plus offers greater minimally invasive benefits, valve selection should consider device-specific characteristics and differences in individual patients.
Humans ; Tricuspid Valve Insufficiency/surgery* ; Male ; Female ; Heart Valve Prosthesis Implantation/methods* ; Middle Aged ; Aged ; Tricuspid Valve/surgery* ; Heart Valve Prosthesis ; Treatment Outcome ; Echocardiography ; Adult ; Cardiac Catheterization/methods*

OBJECTIVES: To investigate the application of transesophageal echocar-diography assessment for mitral valve in patients with atrial septal defects undergoing repair surgery. METHODS: The study group comprised of thirty-two adult patients with atrial septal defect who underwent thoracoscopic repair surgery at the First Affiliated Hospital of the Air Force Medical University from March to September 2022. Two-dimensional and real-time three-dimensional transesophageal ultrasonography of the mitral valve were performed after anesthesia. The parameters of the mitral valve structure at the late diastolic and late systolic stages were recorded, including anteroposterior and left-right annular diameters, anterior and posterior valves lengths, the vertical distance from the coaptation point of leaflet zone 2 during systole to the annular plane (mitral valve coaptation depth) and mitral valve coaptation length. Data from 32 patients with normal intracardiac structure and no mitral valve regurgitation (control group) were also collected and compared with those of the study group. Concurrent mitral valvoplasty was performed during the atrial septal defect repair surgery for 7 patients with significant mitral valve structural abnormalities and 2 patients with significantly increased mitral regurgitation after cardiac resuscitation. The study group was followed up with transthoracic echocardiography for 2 years postoperatively. RESULTS: In the study group, 26 (81.3%) patients had varying degrees of mitral valve morphological abnormalities. Among them, 10 (31.3%) patients had short mitral valve coaptation length or depth, 12 (37.5%) patients had closure point malposition, and 4 (12.5%) patients had different bulge of anterior and posterior leaflets. Compared with the control group, the study group had significantly smaller systolic and diastolic mitral left-right annular diameter, mitral posterior valves lengths, mitral coaptation length or depth (all P<0.05), a higher pulmonary systemic flow ratio (P<0.01), and a lower maximum blood flow velocity across the mitral valve (P<0.05). After 2 years of follow-up, among the 9 patients who underwent concurrent mitral valvoplasty, the mitral valve maintained no or little regurgitation, and the average mitral valve pressure difference was less than 5 mmHg (1 mmHg=0.133 kPa). Among the 23 patients without concurrent mitral valvoplasty, 2 patients had moderate regurgitation 1 year after surgery, with a pulmonary/systemic flow ratio larger than 2.8. CONCLUSIONS Patients with large atrial septal defects often have abnormal mitral valve structure. Therefore transesophageal echocardiography is recommended for mitral valve assessment during the surgery. If significant mitral valve structural abnormalities are detected, concurrent mitral valvoplasty is recommended.
Humans ; Heart Septal Defects, Atrial/diagnostic imaging* ; Echocardiography, Transesophageal/methods* ; Mitral Valve/surgery* ; Adult ; Female ; Male ; Middle Aged ; Mitral Valve Insufficiency/diagnostic imaging*

Mesenchymal stem cells (MSCs) have been widely used in the treatment of various autoimmune and inflammation-related diseases due to their potent immunomodulatory properties. Several studies have demonstrated that MSC-mediated immunomodulation is complex and bidirectional, with the in vivo microenvironment influencing the direction of this modulation. Indoleamine-2,3-dioxygenase (IDO), an immunosuppressive factor, has been identified as a key "switch" in the immunomodulatory role of MSCs. In this review, we explore how IDO functions as a critical regulator of MSC immunoregulatory plasticity. We delve into the mechanisms by which changes in IDO expression affect the function of various immune cells, summarize relevant research and clinical advances regarding the role of IDO expression in MSC-based therapies for various diseases, and discuss potential therapeutic strategies that target IDO to enhance the stability of MSC therapeutic effects. This provides a theoretical foundation for optimizing MSCs as safer and more effective clinical therapeutic agents.

Objective To preliminarily investigate the anti-tumor effects of phytosphingosine(PHS)and the involvement of inducing apoptosis of leukemia cells.Methods Cellular model of leukemia was established in leukemia cell lines K562 and SUP-B15.CCK-8 assay and EdU assay were used to measure the viability and DNA synthesis of K562 and SUP-B15 cells.RNA-seq was carried out to verify the differentially expressed genes(DEGs)after PHS treatment.Gene Ontology(GO)enrichment and Kyoto Encyclopedia of Genes and Genomes(KEGG)enrichment analyses were applied to analyze the involved functions and signaling pathways.Comparative Toxicogenomics Database(CTD)and Discovery Studio software were employed to predict the underlying targets of PHS and molecular docking.Cell apoptosis was detected by flow cytometry,mitochondrial membrane potential was evaluated by JC-1 probe,and protein expression of key molecules was validated by Western blotting.Results PHS inhibited the proliferation of K562 and SUP-B15 cells in a time-and dose-dependent manner.The half-maximal inhibitory concentration(IC50)of K562 cells was 17.67 and 12.52 pmol/L for 24 and 48 h,respectively,and the IC50 value of SUP-B15 cells was 17.58 and 14.86 μmol/L for 24 and 48 h,respectively.PHS treatment at a dose of 20 μmol/L for 48 h resulted in significant inhibition of DNA synthesis.GO enrichment analysis of the K562 cells showed that PHS might be involved in positive regulation of apoptotic process,plasma membrane and its integral components,and protein kinase binding and activity.Reverse predictive analysis showed that BCL-2 protein was the most likely target of PHS.PHS significantly increased the apoptotic rate of leukemia cells(P＜0.05)in a dose-dependent manner,reduced the mitochondrial membrane potential,and down-regulated BCL-2 level(P＜0.05)and up-regulated the levels of Cleaved caspase-3 and Cleaved caspase-9(P＜0.05).Conclusion PHS may inhibit the proliferation of leukemia cells by inducing mitochondria-dependent apoptosis,possibly through PHS and BCL-2 interaction.

Currently,human health due to corona virus disease 2019(COVID-19)pandemic has been seriously threatened.The coronavirus severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)spike(S)protein plays a crucial role in virus transmission and several S-based therapeutic approaches have been approved for the treatment of COVID-19.However,the efficacy is compromised by the SARS-CoV-2 evolvement and mutation.Here we report the SARS-CoV-2 S protein receptor-binding domain(RBD)inhibitor licorice-saponin A3(A3)could widely inhibit RBD of SARS-CoV-2 variants,including Beta,Delta,and Omicron BA.1,XBB and BQ1.1.Furthermore,A3 could potently inhibit SARS-CoV-2 Omicron virus in Vero E6 cells,with EC50 of 1.016 pM.The mechanism was related to binding with Y453 of RBD deter-mined by hydrogen-deuterium exchange mass spectrometry(HDX-MS)analysis combined with quan-tum mechanics/molecular mechanics(QM/MM)simulations.Interestingly,phosphoproteomics analysis and multi fluorescent immunohistochemistry(mIHC)respectively indicated that A3 also inhibits host inflammation by directly modulating the JNK and p38 mitogen-activated protein kinase(MAPK)path-ways and rebalancing the corresponding immune dysregulation.This work supports A3 as a promising broad-spectrum small molecule drug candidate for COVID-19.

Objective:To compare the efficacy of the horizontal plate plus raft screws above the acetabulum and fixation with screws only for acetabular fractures combined with dome impaction in the aged patients.Methods:A retrospective cohort study was conducted to analyze the clinical data of 20 aged patients with acetabular fractures combined with dome impaction, who were admitted to Tianjin hospital between May 2013 and January 2023, including 5 males and 15 females, aged 61-84 years [(72.2±7.3)years]. According to Letournel and Judet classification, 13 patients had anterior column fracture, 5 anterior column fracture combined with posterior transverse fracture and 2 two-column fracture. All the patients underwent open reduction and internal fixation through an anterior approach. Of them, 11 patients were treated with the fixation with the horizonal plate plus raft screws above the acetabulum (plate plus raft screw group) and 9 with the screws only (screw only group). The operative time, intraoperative blood loss, and intraoperative fluoroscopy times were compared between the two groups. The quality of fracture reduction was evaluated with the Matta′s radiographic criteria at 3 days after surgery and the function of the hip joint was assessed with Merle D′Aubigné and Postel scoring system at 3 months after surgery and at the last follow-up as well as the excellent and good rate at te last follow-up. The occurrence of postoperative complications was observed.Results:All the patients were followed up for 6-18 months [(13.1±3.1)months]. There were no significant differences in the operative time, intraoperative blood loss or intraoperative fluoroscopy times between the two groups ( P>0.05). According to the Matta′s radiographic criteria at 3 days after surgery, patients with anatomical reduction and satisfactory reduction accounted 6 and 5 in the plate plus raft screw group, compared to 5 and 4 respectively in the screw only group ( P>0.05). The values of Merle D′Aubigné and Postel score at 3 months after surgery and at the last follow-up were (14.0±2.4)points and (15.8±2.2)points in the plate plus raft screw group, which were higher than those in the screw only group [(11.0±2.6)points and (13.0±3.1)points] ( P<0.01). The values of Merle D′Aubigné and Postel score at the last follow-up of both groups were further enhanced from those at 3 months after surgery ( P<0.01). At the last follow-up, 3 patients were rated excellent, 6 good, 1 fair and 1 poor in the plate plus raft screw group, with an excellent and good rate of 81.8%, while in the screw only group, 3 were rated good, 2 fair and 4 poor, with an excellent and good rate of 33.3% ( P<0.05). One patient in the plate plus raft screw group and 5 in the screw only group had displacement of the dome impaction fragment combined with traumatic arthritis after surgery ( P<0.05). Conclusion:For acetabular fractures combined with dome impaction in the aged patients, the horizontal plate plus raft screw above the acetabulum can effectively improve the function restoration of the hip joint and reduce the occurrence of the displacement of the dome impaction fragment and traumatic arthritis after surgery compared to the fixation with screws only.

The rehabilitation compliance of stroke patients is generally low.Evaluating the rehabilitation motivation of patients is helpful to promote the rehabilitation management of patients,enhance the rehabilitation enthusiasm and compliance of patients,and improve the rehabilitation outcome.This paper reviews the existing stroke patients rehabilitation motivation assessment tools,and expounds the main contents,application status,characteristics and limitations of stroke patients rehabilitation motivation assessment tools,in order to provide references for the appropriate selection of clinical assessment tools,the rehabilitation management of stroke patients and the development of domestic localized stroke rehabilitation motivation assessment tools.

Objective:To explore the efficacy and safety of ibrutinib for the treatment of newly treated and relapsed refractory (R/R) lymphoplasmacytic lymphoma (LPL) /Waldenstr?m macroglobulinemia (WM) .Methods:Retrospectively collected clinical data of 98 cases of newly treated and R/R LPL/WM patients who received ibrutinib treatment at the Hematology & Blood Diseases Hospital of the Chinese Academy of Medical Sciences from March 2016 to June 2023, and analyzed their efficacy and safety.Results:A total of 98 LPL/WM patients were included, which consisted of 45 newly treated patients and 53 R/R patients. Of these, 74 were males (75.5%) and the cohort had a median age of 64 (42-87) years. Eighty-eight patients were eligible for efficacy evaluation with a median treatment time of 20.8 (2.1-55.0) months, a major remission rate (MRR) of 78.4%, and an overall response rate (ORR) of 85.2%. The MRR and ORR of the newly treated patients were 78.4% and 86.5%, respectively, whereas the MRR and ORR of the R/R patients were 78.4% and 84.3%, respectively. There were no statistically significant differences in MRR and ORR between the initial treatment and R/R patients (all P values >0.05) . The median follow-up period was 29.1 (2.9-50.3) months and the median overall survival time for newly treated and R/R patients was not reached. The median progression-free survival time was 23.5 (95% CI 10.5-36.5) months and 45.0 (95% CI 34.0-56.0) months, respectively, with no statistically significant differences (all P values >0.05) . There were 25 deceased patients and no deaths were related to ibrutinib treatment. The main adverse reactions of ibrutinib were thrombocytopenia (5.1%) , pneumonia (8.1%) , and hyperuricemia (21.4%) . The incidence of atrial fibrillation was 2.0%. Conclusion:Ibrutinib exhibits good efficacy and safety for newly treated and R/R LPL/WM patients.

Objective To investigate the effect of blood group serology and polymerase chain reaction with sequence-specific primers (PCR-SSP) on identification and genotyping of ambiguous ABO blood group. Methods Eighty suspicious ABO blood group samples were identified by serology and polymerase chain reaction with sequence-specific primers (PCR-SSP). The final blood group type and the strategy of the transfusion of each case were determined according to the results of serology and PCR-SSP. Results 40 cases were confirmed to be subtypes, and the remaining 40 cases were normal types with weakened antigens or missing antibodies due to other reasons. The results of molecular genetic blood group typing based on PCR-SSP were 41 cases of subtypes (There were 3 discrepancies between two methods: one was Ael identified by serological methods, while its gene type was O2O2; one was common type O, while its gene type was BO1; one was type A, while its gene type was AB.) and 39 cases of normal ones. Conclusion Genotyping technology combined with serological typing has an important significance in identification of ABO blood groups.
ABO Blood-Group System/genetics* ; Genotype ; Polymerase Chain Reaction ; Antibodies ; DNA Primers

Antibody‒drug conjugates (ADCs), which combine the advantages of monoclonal antibodies with precise targeting and payloads with efficient killing, show great clinical therapeutic value. The ADCs' payloads play a key role in determining the efficacy of ADC drugs and thus have attracted great attention in the field. An ideal ADC payload should possess sufficient toxicity, low immunogenicity, high stability, and modifiable functional groups. Common ADC payloads include tubulin inhibitors and DNA damaging agents, with tubulin inhibitors accounting for more than half of the ADC drugs in clinical development. However, due to clinical limitations of traditional ADC payloads, such as inadequate efficacy and the development of acquired drug resistance, novel highly efficient payloads with diverse targets and reduced side effects are being developed. This perspective summarizes the recent research advances of traditional and novel ADC payloads with main focuses on the structure-activity relationship studies, co-crystal structures, and designing strategies, and further discusses the future research directions of ADC payloads. This review also aims to provide valuable references and future directions for the development of novel ADC payloads that will have high efficacy, low toxicity, adequate stability, and abilities to overcome drug resistance.