[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.

ObjectiveTo provide more basic information of comparative medicine for the study of biological changes and pathogenesis of COVID-19 by systematical sorting and analyzing the transcriptome data.MethodsFollowing a retrieval strategy, using COVID-19 and SARS-CoV-2 as key words, transcriptome datasets related to COVID-19 from January 2020 to May 2023 were collected from GEO, ArrayExpress and GEN Transcriptome databases. The composition, distribution, and research application of COVID-19 transcriptome data resources were analyzed. Data distribution was visually displayed and correlation analysis was performed. The research applications and limitations of existing COVID-19 transcriptome data were analyzed from the perspectives of clinical medicine and comparative medicine, focusing on clinical-related molecular mechanisms, biomarkers and related immune responses, treatment intervention strategies, etc. The research value and application prospects were discussed.Results A total of 975 sets of COVID-19 transcriptome data were included. Among three databases, datasets from humans accounted for the highest proportion, namely 71.9%, 77.9%, and 90%, respectively. Species other than humans, such as mice, were the main sources of data, with the respiratory and nervous systems having the highest distribution of data. Twenty-seven datasets were associated with clinical significance. Analysis revealed that respiratory tract injury and other related molecular mechanisms were obtained through transcriptome data mining. Biomarkers such as cfDNA could be used as therapeutic targets. The severity of COVID-19 infection was associated with cell changes and disorders represented by M1 macrophages. Comparative medical analysis showed that mice, hamsters, and other animals were susceptible to SARS-CoV-2. Rhesus monkeys and cynomolgus monkeys exhibited infection characteristics highly similar to human. Apart from respiratory symptoms, hamsters also exhibited digestive system symptoms. SARS-CoV-2 can replicate in the respiratory organs of various susceptible animals, the intestines of ferrets and the ears of minks, resulting in interstitial pneumonia, diffuse lung injury and other pathological changes of varying degrees. Based on the differences in immune responses, hamsters can be used for neutralizing antibody reaction research.Conclusion Currently there is a wealth of COVID-19 transcriptome data, but there is a lack of comparative transcriptome research. Transcriptomics can be combined with comparative medicine to further explore the differences in comparative medicine of COVID-19.

OBJECTIVE To investigate the protective effect and mechanism of cryptotanshinone （CTS） on heart and kidney function in rats with cardiorenal syndrome （CRS） by regulating phosphoinositide kinase-3 （PI3K）/protein kinase B （Akt）/ mammalian target of rapamycin （mTOR） signaling pathway. METHODS CRS model of rats was induced by left anterior descending coronary artery ligation combined with acute renal ischemia-reperfusion injury. Model rats were randomly divided into CRS model group （CRS group）， low-dose CTS group （CTS-L）， high-dose CTS group （CTS-H group）， high-dose CTS+PI3K activator 740Y-P group （CTS-H+740Y-P group）， with 12 rats in each group. Another 12 rats were selected as the normal control group （Normal group） and were carried out surgery without modeling. CTS-L group and CTS-H group were respectively given CTS 30 and 60 mg/kg intragastrically， once a day， for consecutive 14 d. Besides the intervention of CTS 60 mg/kg intragastrically， CTS-H+740Y-P group was given 10 mg/kg 740Y-P intraperitoneally， once a day， for 14 consecutive days. After the last medication， the levels of cardiac function [left ventricular ejection fraction （LVEF）， left ventricular end-systolic diameter （LVESD）， left ventricular end-diastolic diameter （LVEDD）， left ventricular fraction shortening （LVFS）] and renal function [24 h urinary protein， blood urea nitrogen （BUN）， serum creatinine （Scr）， brain natriuretic peptide （BNP）] were detected in rats. The pathological changes and fibrosis of the heart and kidney in rats were observed； the expressions of PI3K/Akt/mTOR signaling pathway in heart and renal tissue were all detected. RESULTS Compared with Normal group， the levels of LVEF and LVFS in rats were all decreased significantly in CRS group （P＜0.05）； the levels of LVESD， LVEDD， 24 h urinary protein， serum levels of BUN， Scr and BNP， collagen area and the phosphorylation of PI3K， Akt and mTOR protein in heart and renal tissue were all increased significantly （P＜0.05）. The morphology of myocardial cells was enlarged and disordered； the structure ofrenal tubules was disordered， epithelial cells were wrinkled， and there was infiltration of inflammatory cells. Compared with CRS group， the above indexes of rats were reversed significantly in CTS-L group and CTS-H group （P＜0.05）； heart and kidney function had been restored， and pathological damage and fibrosis had been reduced. PI3K activator 740Y-P weakened the protective effect of CTS on cardiac and renal function in CRS rats. CONCLUSIONS CTS can protect heart and kidney function in CRS rats， the mechanism of which may be associated with inhibiting the PI3K/Akt/mTOR signaling pathway.

Objective:To analyze the clinical characteristics and outcomes of patients with invasive fungal sinusitis (invasive fungal rhinosinusitis, IFR) after allogeneic hematopoietic stem cell transplantation (allo-HSCT) and explored the risk factors for IFR after allo-HSCT.Methods:Nineteen patients with IFR after allo-HSCT at Peking University People’s Hospital from January 2012 to December 2021 were selected as the study group, and 95 patients without IFR after allo-HSCT during this period were randomly selected as the control group (1:5 ratio) .Results:Nineteen patients, including 10 males and 9 females, had IFR after allo-HSCT. The median age was 36 (10–59) years. The median IFR onset time was 68 (9–880) days after allo-HSCT. There were seven patients with acute myeloid leukemia, five with acute lymphoblastic leukemia, two with myelodysplastic syndrome, two with chronic myeloid leukemia, one with acute mixed-cell leukemia, one with multiple myeloma, and one with T-lymphoblastic lymph node tumor. There were 13 confirmed cases and 6 clinically diagnosed cases. The responsible fungus was Mucor in two cases, Rhizopus in four, Aspergillus in four, and Candida in three. Five patients received combined treatment comprising amphotericin B and posaconazole, one patient received combined treatment comprising voriconazole and posaconazole, nine patients received voriconazole, and four patients received amphotericin B. In addition to antifungal treatment, 10 patients underwent surgery. After antifungal treatment and surgery, 15 patients achieved a response, including 13 patients with a complete response and 2 patients with a partial response. Multivariate analysis revealed that neutropenia before transplantation ( P=0.021) , hemorrhagic cystitis after transplantation ( P=0.012) , delayed platelet engraftment ( P=0.008) , and lower transplant mononuclear cell count ( P=0.012) were independent risk factors for IFR after allo-HSCT. The 5-year overall survival rates in the IFR and control groups after transplantation were 29.00%±0.12% and 91.00%±0.03%, respectively ( P<0.01) . Conclusion:Although IFR is rare, it is associated with poor outcomes in patients undergoing allo-HSCT. The combination of antifungal treatment and surgery might be effective.

Objectives:To determine the effect of glucose-6-phosphate-dehydrogenase (G6PD) deficiency on patients’ complications and prognosis following allogeneic stem cell hematopoietic transplantation (allo-HSCT) .Methods:7 patients with G6PD deficiency (study group) who underwent allo-HSCT at Peking University People's Hospital from March 2015 to January 2021 were selected as the study group, and thirty-five patients who underwent allo-HSCT during the same period but did not have G6PD deficiency were randomly selected as the control group in a 1∶5 ratio. Gender, age, underlying diseases, and donors were balanced between the two groups. Collect clinical data from two patient groups and perform a retrospective nested case-control study.Results:The study group consisted of six male patients and one female patient, with a median age of 37 (range, 2-45) years old. The underlying hematologic diseases included acute myeloid leukemia ( n=3), acute lymphocytic leukemia ( n=2), and severe aplastic anemia ( n=2). All 7 G6PD deficiency patients achieved engraftment of neutrophils within 28 days of allo-HSCT, while the engraftment rate of neutrophils was 94.5% in the control group. The median days of platelet engraftment were 21 (6–64) d and 14 (7–70) d ( P=0.113). The incidence rates of secondary poor graft function in the study group and control group were 42.9% (3/7) and 8.6% (3/35), respectively ( P=0.036). The CMV infection rates were 71.4% (5/7) and 31.4% (11/35), respectively ( P=0.049). The incidence rates of hemorrhagic cystitis were 57.1% (4/7) and 8.6% (3/35), respectively ( P=0.005), while the bacterial infection rates were 100% (7/7) and 77.1% (27/35), respectively ( P=0.070). The infection rates of EBV were 14.3% (1/7) and 14.3% (5/35), respectively ( P=1.000), while the incidence of fungal infection was 14.3% (1/7) and 25.7% (9/35), respectively ( P=0.497). The rates of post-transplant lymphoproliferative disease (PTLD) were 0% and 5.7%, respectively ( P=0.387) . Conclusions:The findings of this study indicate that blood disease patients with G6PD deficiency can tolerate conventional allo-HSCT pretreatment regimens, and granulocytes and platelets can be implanted successfully. However, after transplantation, patients should exercise caution to avoid viral infection, complications of hemorrhagic cystitis, and secondary poor graft function.

Objective In this study,inbred BALB/c mice infected with the pneumonia virus of mice(PVM)were used to establish an animal model of viral pneumonia,and the changes in the pro-inflammatory alarmin molecule,high mobility group box 1 protein(HMGB1),during PVM infection were observed,as well as the in vivo intervention effects of the HMGB1 inhibitor,glycyrrhizic acid(GA),on PVM-induced lung injury.Methods Three-week-old female BALB/c mice were randomly divided into three groups,each consisting of 6 mice.One group,uninfected by PVM,served as the control group(Control).The other two groups were inoculated intranasally with PVM at a dose of 1×104 50％tissue culture infective dose(TCID50)/25 μL,and subsequently treated with GA saline solution(GA group)or plain saline solution(normal saline,NS group)via gavage for 15 consecutive days.During this period,changes in body weight and appearance were monitored in each group.At the end of the experiment,lung tissue samples were collected from all groups.The distribution of PVM and HMGB1 proteins in the lung tissues was analyzed using hematoxylin-eosin staining and immunohistochemistry.The expression levels of HMGB1 and its Toll-like receptor 4(TLR-4),advanced glycosylation end-product-specific receptor(AGER),and inflammatory cytokines such as interleukin(IL)-1β,IL-2,and tumor necrosis factor-α(TNF-α)in lung tissues of mice were measured using real time fluorescence quantitative PCR.Results Compared with the Control group,the NS group showed a significant weight loss after 6 days(P＜0.05).Histopathological tests revealed pronounced inflammatory lesions in their lungs.Immunohistochemistry results showed that HMGB1 was released from the nucleus to the cytoplasm,and real time fluorescence quantitative PCR results indicated that the expression levels of HMGB1,IL-1β,and IL-2 were significantly upregulated(P＜0.05).In the GA group,there was no significant change in the clinical symptoms or body weight.However,compared with the NS group,the pathological damages of lung tissues in the GA group were significantly reduced,and the expression levels of HMGB1,IL-1 β,IL-2,and interferon-γ(IFN-γ)in lung tissues were also significantly decreased(P＜0.05),although the expression level of AGER was significantly increased(P＜0.05).Conclusion PVM infection can cause significant inflammatory pathological lung damages in mice,and GA can effectively alleviate the damages.Its therapeutic effect may be related to the activation of HMGB1 signaling pathway.

Objective This study analyzes the omics data resources in human-infecting coronavirus animal models collected from various public databases,focusing on data distribution,dataset quantity,data types,species,strains,and research content.It aims to enhance our understanding of biological characteristics and pathogenic mechanisms of coronaviruses,thereby providing a solid foundation for devising effective therapeutic strategies and preventive measures.Methods Query strategies,including specific virus names,time ranges,and inclusion and exclusion criteria,were defined to retrieve data from major public omics databases such as GEO and ArrayExpress.Secondary filtering was performed based on different field types to obtain a more accurate data list.An omics data text database was established for bibliometric analysis.Co-occurrence networks were constructed for the analysis of the correlation strengths between different research themes,technical methods,and involved species.The cell types,organs,and biological pathways involved in studies were examined to further elucidate the pathogenic interplay between pathogens and hosts.Results About twenty public databases containing coronavirus-related omics data were identified,with a primary focus on novel coronavirus infection.Commonly used species include humans,mice,hamsters,and monkeys,while the commonly used virus strains are Wuhan-Hu-1 and USA-WA1/2020.Lung tissues are primarily used in animal models such as mice,macaques,and ferrets,while airway epithelial cells and Calu-3 cells are predominantly employed in human-related studies.Expression profiling data indicate that gene pathways involved in inflammation,cytokine response,complement pathway,cell damage,proliferation,and differentiation are significantly upregulated after infection.Proteomics studies reveal significant changes in phosphoproteome,ubiquitinome,and total proteome of patient samples at different infection stages.Specific protein categories,including viral receptors and proteases,transcription factors,cytokines,proteins associated with coagulation system,angiogenesis-related proteins,and fibrosis markers,show alterations after coronavirus infection.In addition,metabolomics data suggest that phosphocholine,phosphoethanolamine,arachidonic acid,and oleic acid could serve as potential metabolic markers.Epigenomics research indicates m6A methylation plays a role in SARS-CoV-2 replication,infection,and transmission,affecting host cell-virus interactions.Among these,N,S,and non-structural proteins 2 and 3 exhibit the most significant ubiquitination.Trends in microbiomics research suggest that microbial communities in the gut and wastewater are emerging as new research focuses.Conclusion The data types of coronavirus omics are diverse,with a wide variety of models and cell types used.The selection of species and technical methods for modelling varies based on the characteristics of different viruses.Multi-omics data from animal models of coronavirus infection can reveal key interactions between hosts and pathogens,identifying biomarkers and potential therapeutic targets,and provide valuable information for a deeper understanding of biological characteristics and infection mechanisms of coronaviruses.

OBJECTIVE To provide a reference for establishing an automatic checking mode and improving the checking efficiency of the unit dose dispensing system of oral drugs in hospital. METHODS The automatic checking process reengineering team was established in our hospital. ECRSI method was adopted to sort out the verification process and mode of drug bags for the unit dose formula of our hospital through five principles of eliminating， combining， rearranging， simplifying and increasing， and the hardware series problem and the problem of excessive system false-positive proportion were optimized. The drug bags for the unit dose formula were randomly selected from 10 wards， the efficiency and external error rates of manual check and automatic checking mode before and after optimization were compared， and the false-positive reporting failure in automatic checking mode was also compared before and after optimization. RESULTS After the establishment of the automatic checking mode of the unit dose formula for oral drugs， the average checking time of drug bags was significantly shorter than that of manual checking mode in the other 8 wards except for cardiovascular and renal departments （P＜0.05）. After the optimization of the automatic checking mode， the average checking time of drug bags in all wards was significantly shorter than that in manual checking mode （P＜0.05）. Compared with before optimization of the automatic checking mode， the average checking time of drug bags was shortened by 0.43 s， and the average checking time of drug bags in half of the wards was shortened significantly （P＜0.05）. At the same time， the false-positive proportion decreased from 96.83% before optimization to 92.76% after optimization （P＜0.05）. The external error rate dropped from 0.039‰ in manual checking mode to 0.019‰ before optimization and 0.015‰ after optimization （P＜0.05）. CONCLUSIONS Based on ECRSI method， the automatic checking mode for the unit dose dispensing system of oral drugs can effectively reduce the average checking time of drug bags， reduce external error and improve the work efficiency of pharmacists.

BACKGROUND: Dysfunction of the gap junction channel protein connexin 43 (Cx43) contributes to myocardial ischemia/reperfusion (I/R)-induced ventricular arrhythmias. Cx43 can be regulated by small ubiquitin-like modifier (SUMO) modification. Protein inhibitor of activated STAT Y (PIASy) is an E3 SUMO ligase for its target proteins. However, whether Cx43 is a target protein of PIASy and whether Cx43 SUMOylation plays a role in I/R-induced arrhythmias are largely unknown. METHODS: Male Sprague-Dawley rats were infected with PIASy short hairpin ribonucleic acid (shRNA) using recombinant adeno-associated virus subtype 9 (rAAV9). Two weeks later, the rats were subjected to 45 min of left coronary artery occlusion followed by 2 h reperfusion. Electrocardiogram was recorded to assess arrhythmias. Rat ventricular tissues were collected for molecular biological measurements. RESULTS: Following 45 min of ischemia, QRS duration and QTc intervals statistically significantly increased, but these values decreased after transfecting PIASy shRNA. PIASy downregulation ameliorated ventricular arrhythmias induced by myocardial I/R, as evidenced by the decreased incidence of ventricular tachycardia and ventricular fibrillation, and reduced arrythmia score. In addition, myocardial I/R statistically significantly induced PIASy expression and Cx43 SUMOylation, accompanied by reduced Cx43 phosphorylation and plakophilin 2 (PKP2) expression. Moreover, PIASy downregulation remarkably reduced Cx43 SUMOylation, accompanied by increased Cx43 phosphorylation and PKP2 expression after I/R. CONCLUSION PIASy downregulation inhibited Cx43 SUMOylation and increased PKP2 expression, thereby improving ventricular arrhythmias in ischemic/reperfused rats heart.
Rats ; Male ; Animals ; Myocardial Reperfusion Injury/metabolism* ; Connexin 43/genetics* ; Sumoylation ; Down-Regulation ; Rats, Sprague-Dawley ; Arrhythmias, Cardiac/drug therapy* ; Myocardial Ischemia/metabolism* ; RNA, Small Interfering/metabolism*

Background::Given that seizures may be triggered by vaccination, this study aimed to evaluate the risk and correlative factors of seizures in patients with epilepsy (PWE) after being vaccinated against coronavirus disease 2019 (COVID-19).Methods::This study retrospectively enrolled PWE who were vaccinated against COVID-19 in the epilepsy centers of 11 hospitals in China. We divided the PWE into two groups as follows: (1) patients who developed seizures within 14 days of vaccination were assigned to the SAV (with seizures after vaccination) group; (2) patients who were seizure-free within 14 days of vaccination were assigned to the SFAV (seizure-free after vaccination) group. To identify potential risk factors for seizure reccurence, the binary logistic regression analysis was performed. Besides, 67 PWE who had not been vaccinated were also included for elucidating the effects of vaccination on seizures recurrence, and binary logistic regression analysis was performed to determine whether vaccination would affect the recurrence rate of PWE who had drug reduction or withdrawal.Results::The study included a total of 407 patients; of which, 48 (11.8%) developed seizures within 14 days after vaccination (SAV group), whereas 359 (88.2%) remained seizure-free (SFAV group). The binary logistic regression analysis revealed that duration of seizure freedom ( P < 0.001) and withdrawal from anti-seizure medications (ASMs) or reduction in their dosage during the peri-vaccination period were significantly associated with the recurrence of seizures (odds ratio= 7.384, 95% confidence interval = 1.732–31.488, P = 0.007). In addition, 32 of 33 patients (97.0%) who were seizure-free for more than three months before vaccination and had a normal electroencephalogram before vaccination did not have any seizures within 14 days of vaccination. A total of 92 (22.6%) patients experienced non-epileptic adverse reactions after vaccination. Binary logistic regression analysis results showed that vaccine did not significantly affect the recurrence rate of PWE who had the behavior of ASMs dose reduction or withdrawal ( P = 0.143). Conclusions::PWE need protection from the COVID-19 vaccine. PWE who are seizure-free for >3 months before vaccination should be vaccinated. Whether the remaining PWE should be vaccinated depends on the local prevalence of COVID-19. Finally, PWE should avoid discontinuing ASMs or reducing their dosage during the peri-vaccination period.