OBJECTIVE To design and synthesize mono-carbonyl curcumin analogues（MCACs） and investigate the activities of them against breast cancer. METHODS The analogues F1， F2， and F3 were obtained by aldol condensation reaction， and their antitumor activities（including the activities of human breast cancer cell MCF-7 and human lung cancer cell A549） were detected by MTT assay [evaluated with half inhibitory concentration（IC50）]. The results of MTT assay were compared with those of curcumin. Bioinformatics methods were used to collect the core targets of analogues F1， F2 and F3 acting on breast cancer， and then molecular docking verification was carried out. The cell experiments were conducted to investigate the effects of high， medium and low concentrations （16， 8， 4 μmol/L） of F1， F2 and F3 on the expression of the first core target protein as well as the effects of medium concentration of F1， F2 and F3 on the expression of cleaved-caspase-3. RESULTS Compared with curcumin， IC50 of analogues F1， F2 and F3 to A549 and MCF-7 cells（except for IC50 of analogue F2 to A549 cells） were decreased significantly（P＜ 0.05 or P＜0.01）； among them， IC50 of analogue F2 to MCF-7 cell was the lowest， being（9.67±1.27） μmol/L. Bioinformatics analysis showed that index of affinity of analogues F1， F2 and F3 with the first core target epidermal growth factor receptor （EGFR）， protein kinase B （AKT） and AKT were 5.909 2， 8.402 5 and 6.486 6， respectively； high concentration of F1 could significantly reduce the phosphorylation level of EGFR protein in MCF-7 cells（P＜0.01）， while low， medium， and high concentrations of F2 and high concentration of F3 could significantly reduce the phosphorylation level of AKT protein in MCF-7 cells（P＜0.05 or P＜0.01）. Medium concentration of F1， F2， and F3 could significantly increase the expression level of cleaved- caspase-3 protein in MCF-7 cells（P＜0.01）. CONCLUSIONS Designed and synthesized MCACs F1， F2 and F3 all have good anti- breast cancer activity， and F2 has better anti-breast cancer activity.

[摘 要] 目的：探究组蛋白去乙酰化酶（HDAC）抑制剂帕比司他对黑色素瘤生长和免疫性的影响及其机制。方法：常规培养黑色素瘤细胞B16F0，用不同浓度的帕比司他处理细胞，WB法检测帕比司他对B16F0细胞中HDAC表达的影响，CCK-8法、划痕愈合实验、Transwell实验和流式细胞术分别检测帕比司他对B16F0细胞增殖、迁移和侵袭能力，以及细胞凋亡和周期的影响。转录组学检测帕比司他对B16F0细胞基因表达的影响，用qPCR法加以验证。流式细胞术检测帕比司他对B16F0细胞表面MHC Ⅰ/Ⅱ类分子表达的影响，B16F0与骨髓来源树突状细胞（BMDC）共培养检测帕比司他对BMDC细胞表达CD11c、CD80和CD86的影响，B16F0细胞移植瘤实验检测帕比司他对移植瘤生长和裸鼠免疫功能的影响。结果：帕比司他促进B16F0细胞中组蛋白3（H3）和α-微管蛋白（α-TUB）蛋白乙酰化（P < 0.01或P < 0.001或P < 0.000 1），抑制B16F0细胞增殖、迁移和侵袭能力，促进其凋亡，并使细胞周期阻滞于G1期（P < 0.05或P < 0.001或P < 0.000 1），促进B16F0细胞表面表达MHC Ⅰ/Ⅱ类分子表达并促进共培养BMDC成熟（均P < 0.01）。转录组学检测结果显示，帕比司他促进B16F0细胞中E-cadherin和抗原提呈相关基因的表达，抑制N-cadherin、vimentin、c-Myc和CDK1的表达，qPCR法验证了这些结果。帕比司他抑制裸鼠移植瘤的生长并增强荷瘤裸鼠的免疫功能（P < 0.05, P < 0.000 1）。结论：帕比司他可抑制B16F0细胞的恶性生物学行为，促进其凋亡，调控其免疫性，增强荷瘤裸鼠的免疫功能。

OBJECTIVES: To analyze the early clinical outcomes of the Xcor^TM transcatheter aortic valve replacement (TAVR) system in treating severe aortic stenosis. This study has been registered at Chinese Clinical Trial Registry (ChiCTR2200065593). METHODS: This single-arm, prospective clinical trial enrolled patients with severe aortic stenosis treated with the Xcor^TM TAVR system at the Section of Heart Valve & Coronary Artery Surgery, Guangdong Provincial People's Hospital. Perioperative and follow-up parameters were compared to evaluate differences in hemodynamic outcomes. All-cause mortality, aortic regurgitation, paravalvular leakage, cerebrovascular events, and reoperation were analyzed. RESULTS: Thirty-two patients with severe aortic stenosis were included (20 males, 12 females), with (70.9±4.3) years old and a Society of Thoracic Surgeons (STS) score of 6.45% (6.07%, 7.28%). Notably, 87.5% of patients had New York Heart Association (NYHA) class≥Ⅲ. All patients underwent successful Xcor^TM bioprosthesis implantation, achieving an immediate technical success rate of 100.0% and device success rate of 96.9%. Mean aortic valve gradient decreased from (55.21±23.17) mmHg (1 mmHg=0.133 kPa) to (8.45±5.30) mmHg, peak aortic jet velocity decreased from (4.66±0.85) m/s to (1.99±0.48) m/s, aortic valve area increased from (0.66±0.21) cm² to (2.09±0.67) cm² (all P<0.01). Intraoperative ventricular fibrillation occurred in one patient, while one case exhibited moderate prosthetic valve regurgitation and paravalvular leakage post-procedure. At 12-month follow-up, sustained improvements were observed in cardiac function, left ventricular ejection fraction, hemodynamic parameters, and SF-12 quality-of-life scores (all P<0.01). All-cause mortality was 12.5% (4/32), with 13.8% (4/29) developing moderate paravalvular leakage. CONCLUSIONS The Xcor^TM TAVR system demonstrated favorable early outcomes in severe aortic stenosis patients, significantly improving symptoms and hemodynamics while exhibiting excellent performance in preventing malignant arrhythmias and coronary obstruction.
Humans ; Male ; Female ; Aortic Valve Stenosis/surgery* ; Transcatheter Aortic Valve Replacement/methods* ; Aged ; Follow-Up Studies ; Prospective Studies ; Treatment Outcome ; Aged, 80 and over ; Heart Valve Prosthesis ; Middle Aged

OBJECTIVE: To analyze the occurrence of arterial events and platelet parameters in patients with polycythemia vera (PV) and essential thrombocythemia (ET), and to explore the characteristics of platelet parameters in patients with PV and ET and their relationship with arterial complications. METHODS: The clinical and laboratory data of newly diagnosed PV and ET patients who visited the Department of Hematology, Beijing Anzhen Hospital, Capital Medical University from August 2017 to August 2022 were retrospectively analyzed. RESULTS: 86 MPN patients (46 males and 40 females) were enrolled, including 44 PV patients and 42 ET patients, with an median age of 61(23-83) years. The mutation rate of JAK2V617F gene, the number of megakaryocytes in bone marrow, the incidence of splenomegaly, and the levels of white blood cell count (WBC), hemoglobin (HGB), hematocrit (HCT), platelet distribution width (PDW), mean platelet volume (MPV), platelet-large cell ratio (P-LCR) in PV patients were significantly higher than those in ET patients (P < 0.05), while the levels of PLT and PCT were significantly lower than those in ET patients (P < 0.01). 22 cases (50%) of PV patients were complicated with arterial events, of which 12 had arterial stenosis in≥2 locations. Among arterial events, the PDW of PV patients with ischemic stroke was greater than that of PV patients without ischemic stroke (P =0.003), and the PDW of PV patients with arterial stenosis in≥2 locations was greater than that of PV patients with arterial stenosis in≤1 location (P =0.037). 23 cases (54.8%) of ET patients were complicated with arterial events, and 7 cases had arterial stenosis in≥2 locations. In arterial events, the PCT of ET patients complicated with ischemic stroke was greater than that of ET patients without ischemic stroke (P =0.037), and the PCT of ET patients with≥2 locations of arterial stenosis was greater than that of ET patients with≤1 location of arterial stenosis (P =0.049). The binary logistic regression analysis showed that elevated PDW and PCT were risk factors for ischemic stroke in PV and ET patients, respectively (P < 0.05). CONCLUSION The platelet parameters of PV and ET patients exhibit significantly different characteristics. Elevated PDW and PCT can predict a higher risk of ischemic stroke in PV and ET patients, respectively.
Humans ; Middle Aged ; Female ; Male ; Aged ; Retrospective Studies ; Adult ; Thrombocythemia, Essential/blood* ; Myeloproliferative Disorders/complications* ; Aged, 80 and over ; Polycythemia Vera/blood* ; Blood Platelets ; Platelet Count ; Young Adult ; Mean Platelet Volume

OBJECTIVE: To evaluate the safety and effectiveness of robot-assisted percutaneous coronary intervention (R-PCI) compared to traditional manual percutaneous coronary intervention (M-PCI). METHODS: This prospective, multicenter, randomized controlled, non-inferior clinical trial enrolled patients with coronary heart disease who met the inclusion criteria and had indications for elective percutaneous coronary intervention. Participants were randomly assigned to either the R-PCI group or the M-PCI group. Primary endpoints were clinical and technical success rates. Clinical success was defined as visually estimated residual post-percutaneous coronary intervention stenosis < 30% with no 30-day major adverse cardiac events. Technical success in the R-PCI group was defined as successful completion of percutaneous coronary intervention using the ETcath200 robot-assisted system, without conversion to M-PCI in the event of a guidewire or balloon/stent catheter that was unable to cross the vessel or was poorly supported by the catheter. Secondary endpoints included total procedure time, percutaneous coronary intervention procedure time, fluoroscopy time, contrast volume, operator radiation exposure, air kerma, and dose-area product. RESULTS: The trial enrolled 152 patients (R-PCI: 73 patients, M-PCI: 79 patients). Lesions were predominantly B2/C type (73.6%). Both groups achieved 100% clinical success rate. No major adverse cardiac events occurred during the 30-day follow-up. The R-PCI group had a technical success rate of 100%. The R-PCI group had longer total procedure and fluoroscopy times, but lower operator radiation exposure. The percutaneous coronary intervention procedure time, contrast volume, air kerma, and dose-area product were similar between the two groups. CONCLUSIONS For certain complex lesions, performing percutaneous coronary intervention using the ETcath200 robot-assisted system is safe and effective and does not result in conversion to M-PCI.

Objective:To investigate the clinical effect of free anterolateral thigh myocutaneous flap combined with oral repair membrane in the reconstruction of nasal mucosa defect after maxillary malignant tumor surgery. Methods:A total of 12 patients with maxillary gingival squamous cell carcinoma and maxillary sinus cancer who had been treated in Department of Oral and Maxillofacial Surgery, Beijing Anzhen Nanchong Hospital, Capital Medical University & Nanchong Central Hospital, were selected from November 2020 to November 2023. Free anterolateral thigh musculocutaneous flap transplantation combined with oral repair membrane were used in all patients. Meanwhile, maxillary soft and hard tissue defects and nasal mucosa defects left after tumor operation were repaired and reconstructed. The clinical effect was evaluated after 6-12 months follow-up. Results:Subtotal maxillary resection was performed in 1 case, total maxillary resection in 9 cases and extended maxillary resection in 2 cases. The musculocutaneous flaps of all patients survived, the facial appearance was basically symmetrical, no obvious depression deformity, the swallowing and speech function recovered well, the mouth and nasal cavity were closed completely, the food could be eaten through the mouth, and the lower nasal passage was not blocked. Conclusion:The free anterolateral thigh musculoflap combined with oral repair membrane can be used to repair and reconstruct maxillary malignant tumor complicated with extensive maxillary tissue and nasal mucosa defect after operation, and the appearance and function can be recovered well after operation, which is a choice for maxillary malignant tumor complicated with nasal mucosa defect.
Humans ; Myocutaneous Flap ; Plastic Surgery Procedures/methods* ; Maxillary Neoplasms/surgery* ; Carcinoma, Squamous Cell/surgery* ; Male ; Middle Aged ; Female ; Nasal Mucosa/surgery* ; Maxilla/surgery* ; Thigh/surgery* ; Maxillary Sinus Neoplasms/surgery*

The cardioprotective effects of histone deacetylase (HDAC) inhibitors (HDIs) are at odds with the deleterious effects of HDAC depletion. Here, we use HDAC3 as a prototype HDAC to address this contradiction. We show that adult-onset cardiac-specific depletion of HDAC3 in mice causes cardiac hypertrophy and contractile dysfunction on a high-fat diet (HFD), excluding developmental disruption as a major reason for the contradiction. Genetically abolishing HDAC3 enzymatic activity without affecting its protein level does not cause cardiac dysfunction on HFD. HDAC3 depletion causes robust downregulation of lipid oxidation/bioenergetic genes and upregulation of antioxidant/anti-apoptotic genes. In contrast, HDAC3 enzyme activity abolishment causes much milder changes in far fewer genes. The abnormal gene expression is cardiomyocyte-autonomous and can be rescued by an enzyme-dead HDAC3 mutant but not by an HDAC3 mutant (Δ33-70) that lacks interaction with the nuclear-envelope protein lamina-associated polypeptide 2β (LAP2β). Tethering LAP2β to the HDAC3 Δ33-70 mutant restored its ability to rescue gene expression. Finally, HDAC3 depletion, not loss of HDAC3 enzymatic activity, exacerbates cardiac contractile functions upon aortic constriction. These results suggest that the cardiac function of HDAC3 in adults is not attributable to its enzyme activity, which has implications for understanding the cardioprotective effects of HDIs.

OBJECTIVE: To investigate the association between long-term glycemic control and cerebral infarction risk in patients with diabetes through a large-scale cohort study. METHODS: This prospective, community-based cohort study included 12,054 patients with diabetes. From 2006 to 2012, 38,272 fasting blood glucose (FBG) measurements were obtained from these participants. FBG trajectory patterns were generated using latent mixture modelling. Cox proportional hazards models were applied to assess the subsequent risk of cerebral infarction associated with different FBG trajectory patterns. RESULTS: At baseline, the mean age of the participants was 55.2 years. Four distinct FBG trajectories were identified based on FBG concentrations and their changes over the 6-year follow-up period. After a median follow-up of 6.9 years, 786 cerebral infarction events were recorded. Different trajectory patterns were associated with significantly varied outcome risks (Log-Rank P < 0.001). Compared with the low-stability group, Hazard Ratio ( HR) adjusted for potential confounders were 1.37 for the moderate-increasing group, 1.23 for the elevated-decreasing group, and 2.08 for the elevated-stable group. CONCLUSION Sustained high FBG levels were found to play a critical role in the development of ischemic stroke among patients with diabetes. Controlling FBG levels may reduce the risk of cerebral infarction.
Humans ; Cerebral Infarction/blood* ; Middle Aged ; Male ; Female ; Blood Glucose/analysis* ; Fasting/blood* ; Aged ; Prospective Studies ; Risk Factors ; Diabetes Mellitus/blood* ; Adult ; Proportional Hazards Models

Critically ill patients are at high risk for hospital acquired infections, which can significantly increase the mortality rate and treatment costs for these patients. Therefore, in the process of treating the primary disease, strict prevention and control of new hospital infections is an essential component of the treatment for critically ill patients. The treatment of critically ill patients involves multiple steps and requires a concerted effort from various aspects such as theory, management, education, standards, and supervision to achieve effective prevention and control of hospital infections. However, there is currently a lack of unified understanding and standards for hospital infection prevention and control. To address this, in March 2024, a group of experts in critical care medicine, infectious diseases, and hospital infection from China discussed the current situation and issues of hospital infection control in the intensive care unit together. Based on a review of the latest evidence-based medical evidence from both domestic and international sources, 2024 Expert Consensus on Hospital Acquired Infection Control Principles in the Department of Critical Care Medicine was formed, aiming to provide a basis for the development of hospital infection prevention and control strategies in the field of critical care medicine.