Ischemia-reperfusion (I/R) injury following skin flap transplantation is a critical factor leading to flap necrosis and transplant failure. Antagonizing inflammatory responses and oxidative stress are regarded as crucial targets for mitigating reperfusion injury and enhancing flap survival. In this study, caffeic acid-vanadium metal polyphenol nanoparticles (CA-V NPs) were prepared for the treatment of skin flap ischemia and reperfusion. This study was conducted using a one-step method to prepare new types of CA-V NPs with uniform sizes and stable structures. In vitro, the CA-V NPs exhibited CAT-like and SOD-like activities and could effectively scavenge ROS, generate oxygen, and alleviate oxidative stress. In the H₂O₂-induced cellular oxidative stress model, CA-V NPs effectively reduced ROS levels and inhibited apoptosis through the XIAP/Caspase-3 pathway. In the cellular inflammation model induced by LPS combined with IFN-γ, CA-V NPs reprogrammed macrophage polarization toward the M2 phenotype and reduced inflammatory responses by reducing the expression of the chemokines CCL4 and CXCL2. In addition, animal experiments have shown that CA-V NPs can alleviate oxidative stress in skin flap tissues, inhibit apoptosis, promote angiogenesis, and ultimately improve the survival rate of skin flaps. CA-V NPs provide a new target and strategy for the treatment of flap I/R injury.

Klebsiella pneumoniae,as a clinically prevalent opportunistic pathogen,ranks as the second most com-monly detected pathogen in clinical isolates in China.The extensive clinical use of carbapenem antibiotics has led to a high global detection rate of carbapenem-resistant K.pneumoniae(CRKP).Characterized by complex resist-ance mechanisms and diverse evolutionary pathways,CRKP infections pose significant challenges in prevention and treatment,with high associated mortality rates,creating substantial obstacles for clinical anti-infective therapy.In recent years,the emergence and global spread of carbapenem-resistant hypervirulent K.pneumoniae(CR-hvKP)have escalated into a major public health threat.Notably,hypervirulent K.pneumoniae isolates carry-ing carbapenem resistance genes are rapidly disseminating worldwide,causing fatal infections even in immunocom-petent individuals.This article systematically reviews the latest research advances on the resistance mechanisms,evolutionary pathways,adaptive changes,and clinical management strategies of CR-hvKP,aiming to deepen un-derstanding of this"superbug"and provide a theoretical foundation for clinical prevention and control.

Objective:To investigate the essential determinants that are critical to initiating the assembly of outer membrane proteins by replacing the POTRA domains of the translocator protein FhaC and the insertase protein TtOmp85 of the Omp85 family. Methods:FhaC, TtOmp85 proteins and their recombinant chimeric proteins after replacing the POTRA domain were obtained by overexpression and purification in vitro. An in vitro reconstitution system was used to investigate the effects of the different domains on the transport efficiency of the substrate outer membrane protein FhaB and the membrane insertion efficiency of OmpA. Results:Replacing the POTRA domain of FhaC with that of TtOmp85 led to the loss of the transport function of FhaB. During the membrane insertion process of OmpA, the FhaC mutant containing the POTRA of TtOmp85 protein acquired the ability to assemble OmpA. Conclusion:The compositional differences in the POTRA domain of Omp85 family proteins determine their abilities to recognize their substrate proteins.

Objective To explore the current status and influencing factors of heart failure occurrence in patients with unstable angina pectoris (UAP), and to provide a scientific basis for developing individualized prevention and treatment strategies. Methods A total of 310 patients with UAP admitted to the Fifth People's Hospital from October 2021 to October 2024 were selected as study subjects. The current status of the patients' heart failure was statistically analyzed, and the patients were divided into heart failure group and non-heart failure group according to whether they had heart failure. Univariate and logistic multivariate regression analyses were used to analyze the risk factors for the occurrence of heart failure in patients with UAP. Results Among the 310 patients with UAP, 63 cases had heart failure, with an incidence rate of 20.32%. After logistic multivariate analysis, it was found that diabetes mellitus, hyperlipidemia, number of coronary artery lesions, homocysteine and plasma brain natriuretic peptide levels were risk factors of heart failure in patients with UAP, and hemoglobin level was a protective factor (OR: 2.010, 95%CI: 1.063-3.800; OR: 4.495, 95%CI: 2.228-9.067; OR: 2.408, 95%CI: 1.256-4.617; OR: 3.655, 95%CI: 1.812-7.372; OR: 4.693, 95%CI: 2.622-8.399; OR: 0.359, 95%CI: 0.205-0.628, P<0.05). Conclusion The coronary heart disease risk of heart failure is high in patients with UAP, and is affected by comorbidities, number of coronary artery lesions, homocysteine, and plasma brain natriuretic peptide levels. It is necessary to perform clinical screening and pay attention to such patients, and take active prevention and control interventions.

BACKGROUND: Valvular heart disease (VHD) has become increasingly common with the aging in China. This study aimed to evaluate regional differences in the clinical features, management strategies, and outcomes of patients with VHD across different regions in China. METHODS: Data were collected from the China-VHD Study. From April 2018 to June 2018, 12,347 patients who presented with moderate or severe native VHD with a median of 2 years of follow-up from 46 centers at certified tertiary hospitals across 31 provinces, autonomous regions, and municipalities in Chinese mainland were included in this study. According to the locations of the research centers, patients were divided into five regional groups: eastern, southern, western, northern, and central China. The clinical features of VHD patients were compared among the five geographical regions. The primary outcome was all-cause mortality or rehospitalization for heart failure. Kaplan-Meier survival analysis was used to compare the cumulative incidence rate. RESULTS: Among the enrolled patients (mean age, 61.96 years; 6877 [55.70%] male), multiple VHD was the most frequent type (4042, 32.74%), which was mainly found in eastern China, followed by isolated mitral regurgitation (3044, 24.65%), which was mainly found in northern China. The etiology of VHD varied significantly across different regions of China. The overall rate of valve interventions was 32.67% (4008/12,268), with the highest rate in southern China at 48.46% (205/423). In terms of procedure, the proportion of transcatheter valve intervention was relatively low compared to that of surgical treatment. Patients with VHD in western China had the highest incidence of all-cause mortality or rehospitalization for heart failure. Valve intervention significantly improved the outcome of patients with VHD in all five regions (all P  <0.05). CONCLUSIONS: This study revealed that patients with VHD in China are characterized by significant geographic disparities in clinical features, treatment, and clinical outcomes. Targeted efforts are needed to improve the management and prognosis of patients with VHD in China according to differences in geographical characteristics. REGISTRATION ClinicalTrials.gov , NCT03484806.
Aged ; Female ; Humans ; Male ; Middle Aged ; China/epidemiology* ; Heart Valve Diseases/therapy* ; Kaplan-Meier Estimate ; Tertiary Care Centers ; Treatment Outcome

Klebsiella pneumoniae,as a clinically prevalent opportunistic pathogen,ranks as the second most com-monly detected pathogen in clinical isolates in China.The extensive clinical use of carbapenem antibiotics has led to a high global detection rate of carbapenem-resistant K.pneumoniae(CRKP).Characterized by complex resist-ance mechanisms and diverse evolutionary pathways,CRKP infections pose significant challenges in prevention and treatment,with high associated mortality rates,creating substantial obstacles for clinical anti-infective therapy.In recent years,the emergence and global spread of carbapenem-resistant hypervirulent K.pneumoniae(CR-hvKP)have escalated into a major public health threat.Notably,hypervirulent K.pneumoniae isolates carry-ing carbapenem resistance genes are rapidly disseminating worldwide,causing fatal infections even in immunocom-petent individuals.This article systematically reviews the latest research advances on the resistance mechanisms,evolutionary pathways,adaptive changes,and clinical management strategies of CR-hvKP,aiming to deepen un-derstanding of this"superbug"and provide a theoretical foundation for clinical prevention and control.

Objective:To investigate the essential determinants that are critical to initiating the assembly of outer membrane proteins by replacing the POTRA domains of the translocator protein FhaC and the insertase protein TtOmp85 of the Omp85 family. Methods:FhaC, TtOmp85 proteins and their recombinant chimeric proteins after replacing the POTRA domain were obtained by overexpression and purification in vitro. An in vitro reconstitution system was used to investigate the effects of the different domains on the transport efficiency of the substrate outer membrane protein FhaB and the membrane insertion efficiency of OmpA. Results:Replacing the POTRA domain of FhaC with that of TtOmp85 led to the loss of the transport function of FhaB. During the membrane insertion process of OmpA, the FhaC mutant containing the POTRA of TtOmp85 protein acquired the ability to assemble OmpA. Conclusion:The compositional differences in the POTRA domain of Omp85 family proteins determine their abilities to recognize their substrate proteins.

Objective:To screen active antibacterial components from licorice extract using BamA and BamD, the core components of Escherichia coli ( E. coli) β-barrel assembly machinery (BAM), as targets in order to combat the increasingly serious problem of antibiotic resistance. Methods:Affinity ultrafiltration combined with high performance liquid chromatography-mass spectrometry (HPLC-MS) was used to screen the potential components interacting with BamA and BamD from licorice extract. Changes in the expression of bamA and bamD genes of E. coli after treatment with the compounds were detected by fluorescence quantitative PCR, and the effects of the compounds on the function of the BAM complex to integrate outer membrane proteins into the bacterial outer membrane were analyzed using an in vitro recombination system. The influence of the compounds on the integrity of bacterial membranes was evaluated through analyzing the accumulation of SDS within the bacterial cells. Results:Bioaffinity ultrafiltration combined with HPLC-MS screening revealed that 18β-glycyrrhetinic acid could interact with BamD. After 18β-glycyrrhetinic acid treatment, the expression of bamA gene increased by 1.5 times, and the expression of bamD gene increased by 2 times. However, the inhibitory effect of 18β-glycyrrhetinic acid on the membrane insertion function of the BAM complex was not observed in the in vitro recombinant system assay, and the cell membrane integrity assay experiments did not reveal any disruption of the E. coli cell membrane by 18β-glycyrrhetinic acid. Conclusions:Using BamA and BamD proteins as targets, a natural product screening method using affinity ultrafiltration combined with HPLC-MS is established. The screening result shows that 18β-glycyrrhetinic acid can interact with BamD and affect the expression of outer membrane proteins in E. coli. Therefore, the screening and experimental procedures established in this study are of good reference value for the screening of novel antimicrobial drugs from other sources targeting outer membrane proteins, and this study also suggests that the selection of the relevant target sites is crucial for the successful screening of the corresponding natural products.

Objective:To compare the efficacy of articaine infiltration anesthesia and lidocaine nerve block anesthesia in pulpotomy of deciduous mandibular second molars.Methods:Single blind crossover test was used for the pediatric patients who required bilateral de-ciduous mandibular second molar pulpotomy were given articaine infiltration anesthesia and lidocaine nerve block anesthesia respectively before the 2 times of operation.After the injection of anesthetic drugs and dental pulp treatment,the patients'responses to pain were e-valuated through sound,eye and body movements,and Wong-Baker facial pain rating scales.Quantitative comparisons were made.Student's t-test and chi-square test were performed for the collected data.Results:50 pediatric patients who met the inclusion criteria and successfully completed 2 treatments without any missed visits or adverse events.During the process of articaine infiltration anesthe-sia,the scores of the 3 indicators of pain severity,namely sound,eye and body movements,were lower than those of lidocaine nerve block anesthesia(P＜0.05).The analysis of facial pain rating scales also suggested that patients'pain and discomfort during the infiltra-tion anesthesia process with articaine were milder(P＜0.05).During the treatment of pulpotomy,both pain assessment methods showed no statistically significant difference in pain perception between the 2 anesthesia injections(P＞0.05).Conclusion:Articaine infiltra-tion anesthesia may effectively replace lidocaine nerve block anesthesia in pulp treatment of mandibular primary molars.

Pheochromocytomas and paragangliomas(PPGLs)cause symptoms by altering the circulation levels of catecholamines and peptide hormones.Currently,the diagnosis of PPGLs relies on diagnostic imaging and the detection of catecholamines.In this study,we used ultra-performance liquid chromatography(UPLC)/quadrupole time-of-flight mass spectrometry(Q-TOF MS)analysis to identify and measure the perioperative differential metabolites in the plasma of adrenal pheochromocytoma patients.We identified differentially expressed genes by comparing the transcriptomic data of pheochromocytoma with the normal adrenal medulla.Through conducting two steps of metabolomics analysis,we identified 111 differential metabolites between the healthy group and the patient group,among which 53 metabolites were validated.By integrating the information of differential metabolites and differentially expressed genes,we inferred that the cysteine-methionine,pyrimidine,and tyrosine metabolism pathways were the three main metabolic pathways altered by the neoplasm.The analysis of transcription levels revealed that the tyrosine and cysteine-methionine metabolism pathways were downregulated in pheochromocytoma,whereas the pyrimidine pathway showed no significant difference.Finally,we developed an optimized diagnostic model of two metabolites,L-dihydroorotic acid and vanylglycol.Our results for these metabolites suggest that they may serve as potential clinical biomarkers and can be used to supplement and improve the diagnosis of pheochromocytoma.