Objective To analyze the characteristics of real-world adverse drug events(ADEs)of trabectedin based on the FDA Adverse Event Reporting System(FAERS)database in order to provide references for clinical drug safety management.Methods A total of 1 349 trabectedin-related reports were extracted from the FAERS database from Q1 2007 to Q4 2024.Using the MedDRA coding classification system for system organ class(SOC)and preferred term(PT),signal detection was performed through 4 proportional imbalance methods,including reporting odds ratio(ROR)and proportional reporting ratio(PRR).Subgroup analyses by gender,age,and temporal trends were also conducted.Results Hematological and lymphatic system disorders and hepatobiliary system disorders were the primary SOCs involved.High-frequency PTs included neutropenia(123 cases)and anemia(117 cases).Eight potential ADEs that have not been listed in the drug product instruction were identified.The median onset time of ADEs was 21 d,showing an early failure pattern,with differences observed by gender(females more prone to hematological toxicity)and age(elderly more susceptible to febrile neutropenia).Conclusion Trabectedin requires close attention to hematological toxicity,hepatotoxicity,and newly identified multi-system potential risks.Clinically,monitoring should be strengthened based on time windows and population characteristics to optimize drug regimens.Countermeasure It is recommended to strengthen the full cycle monitoring of anti-tumor drugs,standardize the reporting of adverse reactions,and establish a multi-departmental collaborative research platform.

In recent years, studies have demonstrated that exosomes can replace mesenchymal stem cell for chronic wound repair. However, exosomes have some problems such as poor targeting, low availability and low yield, which collectively limit their therapeutic efficacy in chronic wound treatment. Maximizing the therapeutic benefits of exosomes is the primary challenge that needs to be overcome when used for chronic wound repair. Studies have shown that the treatment potential of exosomes can be further developed by pretreatment and engineering modification of exosomes. This article reviewed the research progress of exosome pretreatment and engineering modification in chronic wound repair, and provided reference for subsequent research and clinical application.

As a physiologic pacing technique,conduction system pacing(CSP)can capture the intrinsic conduction system and rebuilt cardiac electrical synchronization.CSP including His bundle pacing(HBP)and left bundle branch pacing(LBBP),which played novel and important roles in patients with heart failure with reduced ejection fraction(HFrEF)resulted from intraventricular or interventricular asynchrony.This review aims to demonstrate the current status and prospects CSP for cardiac resynchronization therapy in patients with HFrEF.

Objective:To investigate protective effect and mechanism of Tim-3 on sepsis-induced acute lung injury(ALI)by pro-moting mitophagy of alveolar macrophages and inhibiting activation of NLRP3 inflammasome.Methods:LPS-stimulated mouse alveo-lar macrophage(MH-S)model and sepsis-induced ALI mouse model were constructed.Tim-3 siRNA interference technique was used to knock down Tim-3 expression in MH-S cells,and anti-Tim-3 antibody mice were injected intraperitoneally to block Tim-3 function.Western blot was used to detect protein expressions of NLRP3,ASC,cleaved-caspase-1 and mitophagy-related proteins(LC3B,P62,PINK1 and Parkin)in MH-S cells and lung tissue of mice with sepsis-induced ALI.Laser confocal fluorescence staining was used to measure ROS level and mitochondrial membrane potential of MH-S cells.Pathological examination of lung tissue was performed in mice with sepsis-induced ALI in each group,and degree of lung tissue injury was evaluated by Smith scoring system.Bronchoalveolar lavage fluid(BALF)and lung tissue were collected from mice with ALI induced by sepsis in each group.BCA protein quantification method was used to determine protein concentration in BALF.MPO activity in lung tissue was detected by colorimetry.MDA content in lung tissue was detected by TBA method.LC3B protein expression in lung tissue was detected by immunohistochemistry.Results:In mouse alveolar macrophages,Tim-3 knockdown could promote expressions of NLRP3,ASC,cleaved-caspase-1 and P62 proteins,increase ROS release,inhibit PINK1/Parkin pathway activation and LC3B protein expression,and reduce mitochondrial membrane potential.In mice with sepsis-induced ALI,Tim-3 functional blockade could promote expressions of NLRP3,ASC,cleaved-caspase-1 and P62 proteins in lung tissue,aggravate lung pathological injury and pulmonary edema,increase MPO activity and MDA content in lung tissue,and reduce positive rate of LC3B protein.Conclusion:Tim-3 plays a protective role in sepsis-induced ALI by promoting mitophagy in alveolar macrophages and inhibiting NLRP3 inflammasome activation via PINK1/Parkin.

As a physiologic pacing technique,conduction system pacing(CSP)can capture the intrinsic conduction system and rebuilt cardiac electrical synchronization.CSP including His bundle pacing(HBP)and left bundle branch pacing(LBBP),which played novel and important roles in patients with heart failure with reduced ejection fraction(HFrEF)resulted from intraventricular or interventricular asynchrony.This review aims to demonstrate the current status and prospects CSP for cardiac resynchronization therapy in patients with HFrEF.

Objective:To investigate protective effect and mechanism of Tim-3 on sepsis-induced acute lung injury(ALI)by pro-moting mitophagy of alveolar macrophages and inhibiting activation of NLRP3 inflammasome.Methods:LPS-stimulated mouse alveo-lar macrophage(MH-S)model and sepsis-induced ALI mouse model were constructed.Tim-3 siRNA interference technique was used to knock down Tim-3 expression in MH-S cells,and anti-Tim-3 antibody mice were injected intraperitoneally to block Tim-3 function.Western blot was used to detect protein expressions of NLRP3,ASC,cleaved-caspase-1 and mitophagy-related proteins(LC3B,P62,PINK1 and Parkin)in MH-S cells and lung tissue of mice with sepsis-induced ALI.Laser confocal fluorescence staining was used to measure ROS level and mitochondrial membrane potential of MH-S cells.Pathological examination of lung tissue was performed in mice with sepsis-induced ALI in each group,and degree of lung tissue injury was evaluated by Smith scoring system.Bronchoalveolar lavage fluid(BALF)and lung tissue were collected from mice with ALI induced by sepsis in each group.BCA protein quantification method was used to determine protein concentration in BALF.MPO activity in lung tissue was detected by colorimetry.MDA content in lung tissue was detected by TBA method.LC3B protein expression in lung tissue was detected by immunohistochemistry.Results:In mouse alveolar macrophages,Tim-3 knockdown could promote expressions of NLRP3,ASC,cleaved-caspase-1 and P62 proteins,increase ROS release,inhibit PINK1/Parkin pathway activation and LC3B protein expression,and reduce mitochondrial membrane potential.In mice with sepsis-induced ALI,Tim-3 functional blockade could promote expressions of NLRP3,ASC,cleaved-caspase-1 and P62 proteins in lung tissue,aggravate lung pathological injury and pulmonary edema,increase MPO activity and MDA content in lung tissue,and reduce positive rate of LC3B protein.Conclusion:Tim-3 plays a protective role in sepsis-induced ALI by promoting mitophagy in alveolar macrophages and inhibiting NLRP3 inflammasome activation via PINK1/Parkin.

In recent years, studies have shown that exosomes can replace mesenchymal stem cell for chronic wound repair. However, exosomes have some problems such as poor targeting, low availability and low yield, so it has limited effect in the treatment of chronic wound. Maximizing the therapeutic benefits of exosomes is the primary challenge that needs to be overcome when used for chronic wound repair. Studies have shown that the treatment potential of exosomes can be further developed by pretreatment and engineering modification of exosomes. This article reviewed the research progress of exosome pretreatment and engineering modification in chronic wound repair, and provided reference for subsequent research and clinical application.

In recent years, studies have shown that exosomes can replace mesenchymal stem cell for chronic wound repair. However, exosomes have some problems such as poor targeting, low availability and low yield, so it has limited effect in the treatment of chronic wound. Maximizing the therapeutic benefits of exosomes is the primary challenge that needs to be overcome when used for chronic wound repair. Studies have shown that the treatment potential of exosomes can be further developed by pretreatment and engineering modification of exosomes. This article reviewed the research progress of exosome pretreatment and engineering modification in chronic wound repair, and provided reference for subsequent research and clinical application.

In recent years, the number of interventions for valvular heart disease has been increasing day by day, and it has become a hot topic in the field of cardiovascular surgery. Given the aging global population and trends in the prevalence of valvular disease and the broadening of indications for transcatheter aortic valve replacement (TAVR), a breakthrough of 130 000 TAVR procedures is expected by 2026. In the new technology development period, the development potential and technical advantages of heart valve interventional therapy should be faced squarely. This paper focuses on key issues such as comparison of outcomes after TAVR versus surgical aortic valve replacement (SAVR), prosthetic valve endocarditis after TAVR, and broadening of indications for TAVR, as well as recommendations on how surgeons face the era of TAVR. We hope that this article will help and attract the attention of cardiac surgeons.

Objective:To explore the clinical characteristics and predictors of severe acute pancreatitis complicated with acute respiratory distress syndrome (SAP-ARDS).Methods:Clinical data of consecutive 313 SAP patients hospitalized from January 2000 to January 2020 in Peking Union Medical College Hospital, were retrospectively analyzed, including 258 cases with ARDS (ARDS group) and 55 cases without ARDS (non-ARDS group). According to the severity of ARDS, ARDS group were further divided into mild ARDS group (165 cases) and moderate to severe ARDS group (93 cases). Clinical symptoms, laboratory examination and imaging results, ICU admission time and clinical outcome, as well as the local and systemic complications, acute physiology and chronic health evaluation (APACHEⅡ) within 24 h after admission, bedside index for severity in acute pancreatitis (BISAP), CT severity index (CTSI), sequential organ failure assessment (SOFA) and quick sequenctial organ failure assessment(qSOFA) score were recorded. Univariate and multivariate logistic regression were performed to analyze independent risk factors of SAP complicated with moderate to severe ARDS. Receiver operating characteristics curves (ROC) was drawn to calculate area under the ROC curve (area under curve, AUC) and evaluate the performance of WBC and hsCRP in predicting SAP complicated with moderate to severe ARDS, and assess the performance of APACHEⅡ, BISAP, CTSI, SOFA and qSOFA scores in predicting SAP-ARDS endotracheal intubation.Results:The ICU length of stay and mortality rate of SAP-ARDS patients were significantly higher than those without ARDS [(8.3±11.6 day vs 5.7±7.7 day, 12.4% vs 3.6%, all P value <0.05)]. Univariate analysis showed that elevated WBC ( OR 4.52, 95% CI 1.64-12.4) and hsCRP ( OR 3.69, 95% CI 1.29-10.48) on admission were independent risk factors for moderate to severe ARDS with SAP. The AUC of WBC and hsCRP for predicting SAP with moderate to severe ARDS at admission were 0.651(95% CI 0.532-0.770) and 0.615 (95% CI 0.500-0.730), respectively. The predicted cut-off values (Cut-off values) were 17.5×10 9/L and 159 mg/L, respectively, and the sensitivity was 53.1% and 78.1%, the specificity was 78.1% and 48.4% respectively. The area under the ROC curve for APACHEⅡ, BISAP, CTSI, SOFA, and qSOFA score 24 h after admission in the early prediction of endotracheal intubation were 0.739 (95% CI 0.626-0.840), 0.705 (95% CI 0.602-0.809), 0.753 (95% CI 0.650-0.849 ), 0.737 (95% CI 0.615-0.836) and 0.663 (95% CI 0.570-0.794), and the optimum Cut-off values were 14 points, 3 points, 5 points, 7 points, 2 points, and the sensitivity and specificity for these predictors were 58.8% and 81.4%, 79.4% and 60.0%, 73.5% and 67.1%, 38.2% and 98.6%, 45.5% and 83.3%, respectively. Conclusions::Elevated blood WBC and hsCRP on admission were independent risk factors for moderate to severe ARDS in SAP. APACHEⅡ≥14, BISAP≥3, CTSI≥5, SOFA≥7, or qSOFA≥2 within the 24 h admission indictaed that the risk of SAP patients to receive endotracheal intubation was high.