Objective: To characterize perioperative dynamic changes in immune-cell phenotypes and inflammatory cytokines in patients undergoing CPB (cardiopulmonary bypass) cardiac surgery, and to explore their associations with postoperative outcomes. Methods: In this prospective cohort study, 120 adult patients who underwent elective cardiac surgery under CPB at West China Hospital from May 2022 to March 2023 were enrolled. Perioperative immune-cell phenotypes and concentrations of 40 inflammation-related cytokines were measured. The primary outcomes were the sequential organ failure assessment (SOFA) score at 24 h after surgery and ΔSOFA (the peak SOFA score within 48 h after surgery minus the preoperative SOFA score). Secondary outcomes included major adverse cardiovascular events (MACE), acute kidney injury (AKI), respiratory failure, severe liver injury, and infection. Results: The mean age of enrolled patients was 57±10 years. Of these, 52% (62/120) were male and 90% (108/120) underwent valve surgery. During the rewarming to the end of CPB, neutrophil counts rapidly increased (7.39×10 /L vs preoperative 3.07×10 /L, P<0.001), with significant upregulation of CD11b (7.30×10 /L vs preoperative 3.05×10 /L, P<0.001) and CD54 (7.15×10 /L vs preoperative 2.99×10 /L, P<0.001). Lymphocyte counts increased at the end of CPB (1.75×10 /L vs preoperative 1.12×10 /L, P<0.001) but decreased significantly at 24 h after surgery (0.59×10 /L vs preoperative 1.12×10 /L, P<0.001). Plasma analysis showed that multiple pro-inflammatory cytokines increased during CPB and remained elevated up to 24 h after surgery; five chemokines and the anti-inflammatory cytokine IL-10 peaked at the end of CPB. The SOFA score increased from 1 (1, 2) preoperatively to 7 (5, 10) at 24 h after surgery, with a ΔSOFA of 6 (4, 8). Within 30 days after surgery, 48 patients (40.0%) developed AKI, 17 (14.2%) developed infection, 4 (3.3%) developed severe liver injury, 3 (2.5%) developed respiratory failure, and 3 (2.5%) experienced MACE. During the 2-year follow-up, 8 patients (6.7%) experienced MACE and 5 (4.2%) died. Conclusion: Multi-organ dysfunction is common after cardiac surgery under CPB (median ΔSOFA, 6), accompanied by perioperative activation of multiple immune-cell subsets and upregulation of pro-inflammatory, anti-inflammatory, and chemotactic mediators. This study provides data-driven evidence and research clues for further investigation of the associations between CPB-related immune perturbations and postoperative organ dysfunction and clinical outcomes.

[Objective] To explore the relationship between neutrophil activation under cardiopulmonary bypass (CPB) and the incidence of cardiac surgery-associated acute kidney injury (CS-AKI). [Methods] This prospective cohort study enrolled adult patients who scheduled for cardiac surgery under CPB at West China Hospital between May 1, 2022 and March 31, 2023. The primary outcome was acute kidney injury (AKI). Blood samples (5 mL) were obtained from the central vein before surgery, at rewarming, at the end of CPB, and 24 hours after surgery. Neutrophils were labeled with CD11b, CD54 and other markers. To assess the effect of neutrophils activation on AKI, propensity score matching (PSM) was employed to equilibrate covariates between the groups. [Results] A total of 120 patients included into the study, and 17 (14.2%) developed AKI. Both CD11b⁺ and CD54⁺ neutrophils significantly increased during the rewarming phase and the increases were kept until 24 hours after surgery. During rewarming, the numbers of CD11b⁺ neutrophils were significantly higher in AKI compared to non-AKI (4.71×10⁹/L vs 3.31×10⁹/L, Z=-2.14, P<0.05). Similarly, the CD54⁺ neutrophils counts were also significantly higher in AKI than in non-AKI before surgery (2.75×10⁹/L vs 1.79×10⁹/L, Z=-2.99, P<0.05), during rewarming (3.12×10⁹/L vs 1.62×10⁹/L, Z=-4.34, P<0.05), and at the end of CPB (4.28×10⁹/L vs 2.14×10⁹/L, Z=-3.91, P<0.05). An analysis of 32 matched patients (16 in each group) revealed that CD11b⁺ and CD54⁺ neutrophil levels of AKI were 1.74 folds (4.83×10⁹/L vs 2.77×10⁹/L, Z=-2.72, P<0.05) and 2.34 folds (3.32×10⁹/L vs 1.42×10⁹/L, Z=-4.12, P<0.05), respectively, of non-AKI at rewarming phase. [Conclusion] Neutrophils are activated during CPB, and they can be identified by CD11b/CD54 markers. The activated neutrophils of AKI patients are approximately 2 folds of non-AKI during the rewarming phase, with disparity reached peak between groups during rewarming. These findings suggest the removal of 50% of activated neutrophils during the rewarming phase may be effective to reduce the risk of AKI.

Objective To develop and verify a gas chromatography method for the determination of β-propiolactone(BPL)residues in stock solution and semi-finished products of freeze-dried rabies vaccine for human use(Vero cells), so as to provide experimental basis for the vaccine quality control.Methods The gas chromatography conditions were as follows:The chromatographic column was Agilent DB-624 capillary column(30 m × 0. 250 mm × 1. 40 μm) with the injection port temperature of 180 ℃, the detector temperature of 250 ℃, the column oven temperature of 120 ℃, and the split ratio of 30∶1; The carrier gas was nitrogen at the flow rate of 1. 0 mL/min with the injection volume of 1 μL for automatic injection. The specificity, limit of detection(LOD), accuracy, reproducibility, linear range and robustness of the method were verified, and the method was used to detect the residual amount of BPL in two batches of stock solution and semi-finished products of freeze-dried rabies vaccines for human use(Vero cells).Results Using acetonitrile as the diluent and an isothermal injection program, the resolution of the mixture of BPL standard and vaccine stock solution was more than 1. 5, and the retention time of BPL peak was the same as that of standard solution. After injecting six portions of the BPL standard solution, the RSDs of the peak area, retention time and recovery rate were all less than 5%. BPL had a good linear relationship within the range of 10 to 200 μg/mL. The regression equation was y = 0. 241 6 x + 0. 024 7 with the correlation coefficient(r) of 0. 999 93. The LOD was 2 μg/mL. Under different column temperature conditions, the RSDs of the test results, peak area and retention time of the BPL standard solution were all less than 10. 0%. BPL was not detected in either the vaccine stock solution or the semi-finished products.Conclusion A gas chromatographic method for the determination of BPL residues in the stock solution and semi-finished products of freeze-dried human rabies vaccine(Vero cells) was developed with good specificity, accuracy, reproducibility and durability, and can be used for the determination of BPL residues in the vaccine stock solution and semi-finished products.

【Objective】 To analyze the clinical features of patients with infected pancreatic necrosis (IPN) complicated with fungal infection so as to identify possible risk factors for death. 【Methods】 We analyzed the clinical data of patients with IPN admitted to Xuanwu Hospital Capital Medical University from January 1, 2017 to December 31, 2021. According to the results of pancreatic necrotic tissue and drainage fluid culture, the patients were divided into the group with fungal infection and the group without fungal infection. The baseline data, clinical features and outcomes of the two groups were compared, and the risk factors for death in patients with fungal infection were analyzed. 【Results】 We included a total of 214 patients in the study, of whom 49 patients in the fungal infection group had wider necrotic involvement, lower hematopoietic volume, and higher blood glucose at admission. Patients with fungal infection had a higher proportion of multidrug-resistant bacteria (MDRB), and hospital and ICU stay as well as parenteral nutrition duration were also longer. In the group of patients with fungal infection, the proportion of patients undergoing surgery did not increase (P>0.05), but the proportion of patients with perioperative organ failure and death was higher (P<0.05). Candida albicans (44.8%) was the most common fungus detected, followed by Candida parapsilosis (28.6%) and Candida tropicalis (8.2%). Logistic regression analysis showed that MDRB infection (OR=1.37, 95% CI:1.02-1.83), fungemia (OR=1.53, 95% CI:1.06-2.23), hyperglycemia (OR=1.65, 95% CI:1.28-2.10), new organ failure (OR=1.65, 95% CI:1.19-2.29) and bleeding complications (OR=1.64, 95% CI:1.28-2.10) after surgery were risk factors for death in patients with fungal infection. 【Conclusion】 Fungal infection increases mortality in patients with IPN and the incidence of new organ failure after surgery. Attention to fungemia, MDRB infection, hyperglycemia, organ failure and postoperative bleeding can help reduce the risk of death.

BACKGROUND:Exosomes are vesicle-like structures secreted by cells into extracellular compartments in the form of cytosol,which contain a large amount of microRNAs with important intercellular communication roles.MicroRNAs in exosomes rely on exosome transport and are able to enter target cells to exert important biological regulatory effects.In common bone and joint diseases,abnormal or damaged bone metabolism releases a large number of exosomes,while some exosome-derived microRNAs also promote the progression of osteoarthritis.Therefore,exosome-derived microRNAs are closely related to the skeletal system and are important for the development as well as diagnosis and treatment of many osteoarticular diseases. OBJECTIVE:To review the research progress of exosome-derived microRNAs in bone metabolism and bone and joint diseases. METHODS:Using"exosomes,extracellular vesicle,microRNA,miRNA,bone,bone diseases,bone formation,bone regeneration,bone resorption,bone destruction"as Chinese and English search terms,articles were searched on CNKI,Metasys,and PubMed databases.Finally,86 articles were included for summarization. RESULTS AND CONCLUSION:Exosome-derived microRNAs can regulate bone metabolism by affecting bone formation and bone resorption,and are closely related to the development of bone and joint diseases such as fracture healing,osteoporosis,osteoarthritis,rheumatoid arthritis,osteonecrosis of the femoral head,and osteosarcoma.Exosome-derived microRNAs will be an effective means of diagnosis and treatment of certain bone and joint diseases in the future.However,the current research on exosome-derived microRNAs in osteoarthritic diseases is limited,and more explorations and researches are still needed to diagnose and treat osteoarthritic diseases using exosome-derived microRNAs.

Objective:To explore the clinical characteristics, pathological features, and diagnosis and treatment strategies of nasal chondromesenchymal hamartoma (NCMH) in infants and young children.Methods:A retrospective analysis was conducted on seven cases of NCMH infants and young children admitted to Beijing Children′s Hospital, Capital Medical University from April 2015 to January 2022. The cohort included 5 males and 2 females, aged from 6 days to 2 years and 3 months. General information, clinical symptoms, imaging findings, treatment plans, postoperative complications, recurrence and follow-up time were collected, summarized and analyzed. Additionally, immunohistochemical characteristics of the lesion were examined.Results:The clinical symptoms of 7 children included nasal congestion, runny nose, open mouth breathing, snoring during sleep, difficulty feeding, and strabismus. All patients underwent electronic nasopharyngoscopy examination, with 5 cases of tumors located in the right nasal cavity and 2 cases in the left nasal cavity. No case of bilateral nasal cavity disease was found. All 7 patients underwent complete imaging examinations, with 5 patients underwent MRI and CT examinations, 1 patient underwent CT examination only, and 1 patient underwent MRI examination only. The CT results showed that all tumors were broad-based, with uneven density, multiple calcifications and bone remodeling, and some exhibited multiple cystic components. The MRI results showed that the tumor showed low signal on T1 weighted imaging and high or slightly high signal on T2 weighted imaging. All patients were diagnosed through histopathological examination and immunohistochemistry, including 7 cases of Ki-67 and SMA (+), 5 cases of S-100 and Vimentin (+), and all EMA and GFAP were negative. All patients underwent endoscopic resection surgery through the nasal approach, with 3 cases using navigation technology. Five cases of tumors were completely removed, and two cases of tumors were mostly removed. No nasal packing was performed after surgery, and no postoperative nasal, ocular, or intracranial complication occurred in all patients. Follow up assessments conducted 6 to 84 months post-surgery revealed no instances of tumor recurrence in any of the patients.Conclusions:The clinical symptoms of children with NCHM mainly depend on the size and location of the tumor. Nasal endoscopic surgery is the main treatment method. In cases where critical structures like the skull base or orbit are implicated, staged surgical interventions may be warranted. Long-term follow-up is strongly advised to monitor for any potential recurrence or complications.

Cardiovascular disease (CVD) is currently one of the most severe diseases endangering human health, encompassing myocardial ischemia syndrome, myocardial fibrosis, atrial fibrillation, and other conditions. MicroRNAs (miRNAs/miR) are a class of small non-coding RNAs that can bind to specific sequences and subsequently regulate post-transcriptional processing, translation, or epigenetic modifications, thereby modulating gene expression. Studies have found that miR-223 is associated with the occurrence and development of CVD and represents a potential specific therapeutic target. This article summarizes the relevant research on miR-223 in CVD, focusing on myocardial ischemia syndrome, myocardial fibrosis, and atrial fibrillation, and discusses its application prospects and challenges as a specific therapeutic target, providing new ideas for the diagnosis and treatment of CVD.

Objective: To study the effect of stem cell factor (SCF) on the angiogenic ability of cocultured dental pulp stem cells (DPSCs) and human umbilical vein endothelial cells (HUVECs). Methods : This study has been reviewed and approved by the Ethics Committee. The experiment was split into the HUVECs, SCF+HUVECs, DPSCs+HUVECs, and SCF+DPSCs+HUVECs groups. A mixture of SCF and culture medium was used to prepare a mixed culture medium with an SCF concentration of 100 ng/mL. In vitro coculture of DPSCs and HUVECs was performed at a 1∶5 ratio. CCK-8 proliferation assay was used to observe the proliferative capacity of cells in each group on days 1, 3, 5, and 7. Wound healing and Transwell migration assays were used to detect the effect of SCF on cell migration under either direct or indirect coculture conditions, respectively. In vitro angiogenesis experiments were performed to detect the angiogenic capacity of the cells in each group. The vascular endothelial growth factor A (VEGFA) concentration in the cell culture supernatant was detected using ELISAs, and the protein expression levels of CD31, CD34, and VEGFA were detected using Western blot analysis. Results : Wound healing and Transwell migration experiments showed that SCF significantly promoted the migration of cocultured DPSCs and HUVECs (P<0.05). The in vitro angiogenesis experiment showed that the number of branches and the total length of branches of tubular structures in the SCF+DPSCs+HUVECs group were significantly greater than those of the other groups (P<0.05), and the expression levels of the vascular-related proteins CD31, CD34, and VEGFA in this group were greater (P<0.01). Conclusion SCF can enhance the migration and in vitro angiogenesis of cocultured DPSCs and HUVECs.

H 1-antihistamines are widely used in the treatment of various allergic diseases, but there are still many challenges in the safe and rational use of H 1-antihistamines in pediatrics, and there is a lack of guidance on the prescription review of H 1-antihistamines for children.In this paper, suggestions are put forward from the indications, dosage, route of administration, pathophysiological characteristics of children with individual difference and drug interactions, so as to provide reference for clinicians and pharmacists.

It is among the goals in metabolic engineering to construct microbial cell factories producing high-yield and high value-added target products, and an important solution is to design efficient synthetic pathway for the target products. However, due to the difference in metabolic capacity among microbial chassises, the available substrate and the yielded products are limited. Therefore, it is urgent to design related metabolic pathways to improve the production capacity. Existing metabolic engineering approaches to designing heterologous pathways are mainly based on biological experience, which are inefficient. Moreover, the yielded results are in no way comprehensive. However, systems biology provides new methods for heterologous pathway design, particularly the graph-based and constraint-based methods. Based on the databases containing rich metabolism information, they search for and uncover possible metabolic pathways with designated strategy (graph-based method) or algorithm (constraint-based method) and then screen out the optimal pathway to guide the modification of strains. In this paper, we reviewed the databases and algorithms for pathway design, and the applications in metabolic engineering and discussed the strengths and weaknesses of existing algorithms in practical application, hoping to provide a reference for the selection of optimal methods for the design of product synthesis pathway.
Algorithms ; Biosynthetic Pathways ; Metabolic Engineering ; Metabolic Networks and Pathways/genetics* ; Systems Biology