Objective: To compare and analyze the antibacterial effects of platelets against five common clinical pathogenic bacteria including MRSA, SE, SA, E. coli, and CRKP, and to preliminarily explore the role of DCD sensitivity in the observed variations of antibacterial effects. Methods: The same number of platelets were used to establish co-culture systems of platelets and platelet lysates with the five pathogenic bacteria. The antibacterial effects of platelets and platelet lysates on the five pathogenic bacteria were evaluated by observing the turbidity of the bacterial solution, measuring the OD value of the bacterial solution and counting the colonies. The supernatant protein of platelets co-cultured with MRSA was collected for quantitative proteomics analysis to explore the important antibacterial proteins of platelets. The content of DCD in the supernatant after co-culture of platelets and platelet lysates with the five pathogenic bacteria was detected by ELISA to preliminarily analyze the reasons for the different antibacterial effects of platelets on the five pathogenic bacteria. Results: Compared with the control group of MRSA, SA, and SE, the turbidity of the bacterial solution decreased after co-culture of platelets and platelet lysates with MRSA, SA, and SE for 12 h, and the OD value and colony count were significantly reduced (P<0.05). The turbidity of the bacterial solution did not change significantly after co-culture of platelets and platelet lysates with E. coli for 24 h, but the OD value decreased (P<0.05), and the colony count decreased to 10 CFU/mL but the difference was not statistically significant (P>0.05). Compared with the control group of CRKP, the turbidity, OD value, and colony count of the bacterial solution did not change significantly after co-culture of platelets and platelet lysates with CRKP (P>0.05). Proteomics results showed that after co-culture with MRSA, important proteins related to platelet activation, including collagen, fibrinogen, von Willebrand factor, integrin αIIbβ3, platelet glycoprotein V and IV were significantly up-regulated. ELISA results showed that after co-culture with the five pathogenic bacteria, platelets could secrete a large amount of DCD, with the content around 3 μg/mL. Conclusion: The antibacterial effect of platelets on Gram-positive bacteria MRSA, SA, and SE is better than that on Gram-negative bacteria E. coli and CRKP, and platelets have the best antibacterial effect on MRSA. The differences in antibacterial effects of platelets on the five pathogenic bacteria may be related to the sensitivity of DCD antibacterial peptides to the five pathogenic bacteria.

Objective To investigate the common molecular features of immunothrombosis, thus enhancing the comprehension of thrombosis triggered by immune and inflammatory responses and offering crucial insights for identifying potential diagnostic and therapeutic targets. Methods Differential gene expression analysis and functional enrichment analysis were conducted on datasets of systemic lupus erythematosus (SLE) and venous thromboembolism (VTE). The intersection of differentially expressed genes in SLE and VTE with those of neutrophil extracellular traps (NET) yielded cross-talk genes (CG) for SLE-NET and VTE-NET interaction. Further analysis included functional enrichment and protein-protein interaction (PPI) network assessments of these CG to identify hub genes. Venn diagrams and receiver operating characteristic (ROC) curve analysis were employed to pinpoint the most effective shared diagnostic CG, which were validated using a graft-versus-host disease (GVHD) dataset. Results Differential expression genes in SLE and VTE were associated with distinct biological processes, whereas SLE-NET-CG and VTE-NET-CG were implicated in pathways related to leukocyte migration, inflammatory response, and immune response. Through PPI network analysis, several hub genes were identified, with matrix metalloproteinase 9 (MMP9) and S100 calcium-binding protein A12 (S100A12) emerging as the best shared diagnostic CG for SLE (AUC: 0.936 and 0.832) and VTE (AUC: 0.719 and 0.759). Notably, MMP9 exhibited good diagnostic performance in the GVHD dataset (AUC: 0.696). Conclusion This study unveils the common molecular features of SLE, VTE, and NET, emphasizing MMP9 and S100A12 as the optimal shared diagnostic CG, thus providing valuable evidence for the diagnosis and therapeutic strategies related to immunothrombosis. Additionally, the expression of MMP9 in GVHD highlights its critical role in the risk of VTE associated with immune system disorders.
Humans ; Computational Biology/methods* ; Lupus Erythematosus, Systemic/immunology* ; Protein Interaction Maps/genetics* ; Venous Thromboembolism/therapy* ; Matrix Metalloproteinase 9/genetics* ; Extracellular Traps/metabolism* ; Gene Regulatory Networks ; Thrombosis/immunology* ; Graft vs Host Disease/genetics* ; Gene Expression Profiling

Fanconi anemia (FA) is an inheritable disorder that presents with bone marrow failure, developmental anomalies, and an increased susceptibility to cancer. The etiology of this condition stems from a genetic mutation that disrupts the proper repair of interstrand DNA cross-links (ICLs). The resultant dysregulation of the DNA damage response mechanism can induce genomic instability, thereby elevating the mutation rates and the likelihood of developing cancer. The FA pathway assumes a pivotal role in safeguarding genome stability through its involvement in the repair of DNA cross-links and the maintenance of overall genomic integrity. A mutation in the germ line of any of the genes responsible for encoding the FA protein results in the development of FA. The prevalence of aberrant FA gene expression in somatic cancer, coupled with the identification of a connection between FA pathway activation and resistance to chemotherapy, has solidified the correlation between the FA pathway and cancer. Consequently, targeted therapies that exploit FA pathway gene abnormalities are being progressively developed and implemented. This review critically examines the involvement of the FA protein in the repair of ICLs, the regulation of the FA signaling network, and its implications in cancer pathogenesis and prognosis. Additionally, it explores the potential utility of small-molecule inhibitors that target the FA pathway.

The persistent，difficult-to-treat，and recurrent abdominal pain，diarrhea，and mucinous bloody stools that characterize ulcerative colitis （UC） are indicative of an inflammatory bowel disorder. The cause of the sickness remains uncertain，and the outcome of modern medical treatment is not encouraging. The incidence of UC has been steadily increasing over time，making it essential to discover novel treatments in clinical practice. For centuries，traditional Chinese medicine （TCM） has been a successful method for preventing and curing this malady. In the original text of Shanghanlun， ZHANG Zhongjing repeatedly discussed symptoms similar to UC，such as diarrhea，chronic dysentery，intestinal wind，and visceral toxins. The effective formulas proposed in Shanghanlun have laid the groundwork for the later use of TCM for treatment of UC. Research in recent times has revealed the distinct benefits of TCM in both relieving the symptoms and improving the quality of life of UC patients. Banxia Xiexintang，a compound of this type，has been found to be effective in network pharmacology，molecular docking，clinical observation，and animal experiments，and its therapeutic effects have been considerable in the treatment of UC. Extensive experiments have revealed a strong correlation between the effectiveness of Banxia Xiexintang in treating UC and factors such as inflammatory cytokines，intestinal microbiota，immune responses，related signaling pathways， and pyroptosis. This article presents a comprehensive examination of Banxia Xiexintang for treatment of UC，encompassing its theoretical basis，drug composition，and mechanism of action. This paper is expected to provide more theoretical support for clinical application of Banxia Xiexintang.

Objective:To investigate the effects of extracorporeal carbon dioxide removal (ECCO 2R) combined with continuous renal replacement therapy (CRRT) on respiratory efficiency and diaphragm function in patients with acute respiratory distress syndrome (ARDS) received mechanical ventilation. Methods:A prospective randomized controlled study was conducted. Sixty patients with mild to moderate ARDS admitted to the department of respiratory and critical care medicine of Henan Provincial People's Hospital from January 2019 to January 2021 were enrolled, and they were divided into observation group and control group according to the random number table method, with 30 cases in each group. All patients received antibiotics, anti-inflammatory, and mechanical ventilation therapy. On this basis, the observation group received ECCO 2R and CRRT, while the control group received bedside CRRT. Baseline data including gender, age, etiology, acute physiology and chronic health evaluationⅡ(APACHEⅡ), etc., were recorded. Arterial blood gas analysis [including arterial partial pressure of oxygen (PaO 2), arterial partial pressure of carbon dioxide (PaCO 2), and oxygenation index (PaO 2/FiO 2)] was performed at 12 hours and 24 hours during the treatment, and respiratory mechanics parameters [including tidal volume, respiratory rate, maximum expiratory pressure (MEP), and maximum inspiratory pressure (MIP)] were recorded, and rapid shallow breathing index (RSBI) was calculated. The levels of glutathione peroxidase (GSH-Px), malondialdehyde (MDA), and superoxide dismutase (SOD) in serum were detected by enzyme-linked immunosorbent assay (ELISA). Diaphragm thickness and diaphragm activity were measured by ultrasonography at 24 hours during the treatment. Results:There were no significantly differences in age, gender, etiology, and APACHEⅡ score between the two groups, indicating that the baseline data of the two groups were balanced and comparable. Compared with the 12 hours after treatment, the PaO 2 and PaO 2/FiO 2 in the observation group significantly increased, PaCO 2 significantly decreased, RSBI significantly decreased, MEP and MIP significantly increased, and serum GSH-Px and MDA significantly decreased, while SOD significantly increased at 24 hours during the treatment. In the control group, only PaCO 2 significantly decreased. Compared with the control group, the PaCO 2 significantly decreased in the observation group at 12 hours and 24 hours [mmHg (1 mmHg≈0.133 kPa): 55.05±7.57 vs. 59.49±6.95, 52.77±7.88 vs. 58.25±6.92, both P < 0.05], but no significantly differences in PaO 2 and PaO 2/FiO 2. Compared with the control group, the observation group showed significant decreases in RSBI at 12 hours and 24 hours (times·min -1·L -1: 85.92±8.83 vs. 90.38±3.78, 75.73±3.86 vs. 90.05±3.66, both P < 0.05), significant increases in MEP and MIP [MEP (mmH 2O, 1 mmH 2O≈0.01 kPa): 86.64±5.99 vs. 83.88±4.18, 93.70±5.59 vs. 85.04±3.73; MIP (mmH 2O): 44.19±6.66 vs. 41.17±3.13, 57.52±5.28 vs. 42.34±5.39, all P < 0.05], and significant decreases in serum GSH-Px and MDA [GSH-Px (mg/L): 78.52±8.72 vs. 82.10±3.37, 57.11±4.67 vs. 81.17±5.13; MDA (μmol/L): 7.84±1.97 vs. 8.71±0.83, 3.67±0.78 vs. 8.41±1.09, all P < 0.05], as well as a significant increase in SOD (U/L: 681.85±49.24 vs. 659.40±26.47, 782.32±40.56 vs. 676.65±51.97, both P < 0.05). Compared with the control group, the observation group showed significant increases in diaphragm thickness and diaphragm activity at 24 hours of treatment [diaphragm thickness (cm): 1.93±0.28 vs. 1.40±0.24, diaphragmatic thickening fraction: (0.22±0.04)% vs. (0.19±0.02)%, quiet breathing diaphragm displacement (cm): 1.42±0.13 vs. 1.36±0.06, deep breathing diaphragm displacement (cm): 5.11±0.75 vs. 2.64±0.59, all P < 0.05]. Conclusion:ECCO 2R combined with CRRT can reduce work of breathing and oxidative stress levels in ARDS patients receiving non-invasive ventilation, and protect diaphragm function.

Objective To explore the therapeutic effects of estrogen-intervened endothelial progenitor cells( EPCs) transplantation on diabetic ischemic stroke rats. Methods PKH26-labeled diabetic EPCs and estrogen-intervened diabetic EPCs were injected into rats via the tail vein 24 h after cerebral ischemia. Cerebral ischemic volume, behavioral changes, ischemic site vascularization and homing of EPCs were measured 3 d after EPCs injection. Results Compared with diabetic ischemic rats, estrogen-intervened EPCs transplantation had reduced infarct volumes, improved behavioral scores and ischemic site revascularization and promoted homing of EPCs to sites of injury(P<0.05). Conclusion Estrogen-intervened EPCs transplantation had a better therapeutic effect on diabetic ischemic stroke by promoting EPCs homing to injury site and EPCs-medicated neovascularization .

Objective:To analyse the clinical characteristics and antiviral therapy in immunosuppressed hospitalized patients with influenza.Methods:The clinical data of 273 patients with positive influenza A or B virus nucleic acid admitted in Peking University People’s Hospital from November 2015 to March 2022 were retrospectively analyzed. Among them, 123 were immunosuppressed and 150 were non-immunosuppressed. The clinical characteristics and antiviral therapy in immunosuppressed patients with influenza were analyzed. SPSS 22.0 software was used to analyze the data.Results:Chemotherapy for malignancies was the most common cause of immunosuppression (61.8%, 76/123), followed by haemopoietic stem cell transplantation (24.4%, 30/123). The common symptoms were fever (93.5%, 115/123) and cough (41.5%, 51/123). The proportions of co-infections (22.8%, 28/123) and complications (43.9%, 54/123) in immunosuppressed hospitalized patients were higher than those in non-immunosuppressed patients ( χ2=9.365 and 7.496, both P<0.01). Compared with single drug therapy, combination of antiviral drugs did not shorten the fever time, negative conversion time of virus nucleic acid and the length of hospital stay, and reduce the death ( U/ χ2=312.5, 356.0, 749.5 and 0.185, all P>0.05). Compared to patients without corticosteroids use, the use of corticosteroids did not increase mortality in immunosuppressed patients ( χ2=2.508, P=0.113). Conclusions:Classical symptoms may be absent in immunosuppressed patients with influenza, and early detection of influenza virus is still an important means of early diagnosis. Co-infections and complications are more common in immunosuppressed influenza patients. Immunosuppressed influenza patients did not benefit from the combination of antiviral therapy.

OBJECTIVE To analyze the implementation of insulin centralized volume-based procurement policy （hereinafter referred to as “centralized procurement”） in our hospital and its effect on the use of insulin products in clinical. METHODS The manufacturer， specifications， usage， sales amount and agreed purchase volume of insulin products in our hospital before （July 4， 2021 to January 3， 2022） and after （July 4， 2022 to January 3， 2023） the centralized procurement were collected. The defined daily dose （DDD） method was used to calculate defined daily doses （DDDs）， defined daily cost （DDC）， the progress of procurement completion and actual cost saving. RESULTS After the centralized procurement， the number of insulin products had increased from 20 to 29 in our hospital； except for the Insulin degludec/aspart injection in our hospital’s original insulin catalog that had not been centrally purchased， all other existing varieties had been included in centralized procurement catalog. The use of Insulin aspart 30 injection produced by Novo Nordisk （China） Pharmaceutical Co.， Ltd. always ranked the first place in the list of usage and DDDs before and after the centralized procurement. The sales amount of Insulin glargine injection produced by Ganli Pharmaceutical Co.， Ltd. and Tonghua Dongbao Pharmaceutical Co.， Ltd. increased significantly due to the significant increase in usage. The centralized procurement of Degu insulin injection from Novo Nordisk （China） Pharmaceutical Co.， Ltd. had achieved a relatively high completion rate in our hospital’s original insulin catalog， while the completion rate for new varieties was low. After the centralized procurement， our hospital actually saved a total of 1 388 582.66 yuan in expenses. CONCLUSIONS After the centralized procurement， the selection and usage of insulin varieties in our hospital are reasonable， which saves patients’ insulin treatment costs， and reduces economic pressure on patients and society.

Objective To propose the blood detection strategies for human immunodeficiency virus (HIV) among blood donors, and provide reference for the detection, early diagnosis and transmission blocking of HIV. Methods A total of 117 987 blood samples from blood donors were screened using the third- and fourth-generation ELISA HIV detection reagents. Western blot analysis was used to verify the reactive results of the third-generation reagent alone, or both the third-generation and fourth-generation reagents. HIV nucleic acid test was carried out for those with negative test results of the third- and fourth-generation reagents. For those with positive results of the fourth-generation reagent only, nucleic acid test followed by a confirmatory test by Western blot analysis was carried out. Results 117 987 blood samples from blood donors were tested by different reagents. Among them, 55 were tested positive by both the third- and fourth-generation HIV detection reagents at the same time, accounting for 0.047% and 54 cases were confirmed HIV-positive by Western blot analysis, and 1 case was indeterminate, then turned positive during follow-up testing. 26 cases were positive by the third-generation reagent test alone, among which 24 cases were negative and 2 were indeterminate by Western blot analysis. The band types were p24 and gp160 respectively detected by Western blot analysis, and were confirmed to be HIV negative in follow-up testing. 31 cases were positive by the fourth-generation HIV reagent alone, among which 29 were negative by nucleic acid test, and 2 were positive according to the nucleic acid test.Western blot analysis was used to verify that the two cases were negative. However, after 2~4 weeks, the results turned positive when the blood sample was retested by Western blot analysis during the follow-up of these two cases. All the specimens that were tested negative by both the third- and fourth-generation HIV reagents were validated negative by HIV nucleic acid test. Conclusion A combined strategy with both third- and fourth-generation HIV detection reagents can play a complementary role in blood screening among blood donors. The application of complementary tests, such as nucleic acid test and Western blot analysis, can further improve the safety of blood supply, thus contributing to the early diagnosis, prevention, transmission and treatment of blood donors potentially infected by HIV.
Humans ; HIV Infections/diagnosis* ; HIV Antibodies ; Blood Donors ; HIV-1 ; Blotting, Western ; Nucleic Acids

Objective To explore the effect and mechanism of estrogen on endothelial progenitor cells（EPCs）function in diabetic rats. Methods EPCs were isolated from bone marrow of rats and characterized by fluorescence microscopy and flow cytometry. Rat diabetic model was established via streptozotocin induction. The bone marrow was taken to culture EPCs. EPCs of diabetes were incubated with Estrogen 10 nmol/L for 24h. The functions and proliferation of EPCs in vitro were detected. The levels of MnSOD and NO in EPCs and TSP-1 in supernatant were assayed. Results Compared with control group, EPCs proliferation, adhesion and angiogenesis functions were impaired in diabetic rats. The level of MnSOD and NO in diabetic EPCs were significantly decreased, while TSP-1 protein level in the supernatant increased. The above changes can be reversed with estrogen incubation. Conclusion Estrogen improved the EPCs migration and tubule formation in diabetic rats. The mechanism may be related to the reduction of oxidative stress and downregulation of TSP-1 expression in diabetic EPCs.