Refinement and standardisation of the management of clinical diagnostic and treatment operations is a key aspect of achieving high-quality development in hospitals.By analysing the management status quo of clinical diagnosis and treatment operations in hospitals,it combed the problems existing in this field.Based on the closed-loop management model,it proposed measures and recommendations to promote the continuous optimisation of the management of clinical diagnostic operations in hospitals.Hospitals should establish hospital-level operation catalog and conduct classified management,authorize operators and dynamically adjust them,carry out operation quality management,pay attention to information management of operation management,and combine operation management with physician performance management.

Objective:To establish venetoclax-resistant acute myeloid leukemia(AML)cell lines,assess the sensitivity of venetoclax-resistant cell lines to the BCL-2 protein family,and investigate their resistance mechanisms.Methods:CCK-8 method was used to screen AML cell lines(MV4-11,MOLM13,OCI-AML2)that were relatively sensitive to venetoclax.Low concentrations of venetoclax continuously induced drug-resistance development in the cell lines.Changes in cell viability and apoptosis rate before and after resistance development were measured using the CCK-8 method and flow cytometry.BH3 profiling assay was performed to anayze the transform of mitochondrion-dependent apoptosis pathway as well as the sensitivity of resistant cell lines to BCL-2 family proteins and small molecule inhibitors.Real-time fluorescence quantitative PCR(RT-qPCR)was utilized to examine changes in the expression levels of BCL-2 protein family members in both venetoclax-resistant cell lines and multidrug-resistant patients.Results:Venetoclax-resistant cell lines of MV4-11,MOLM13,and OCI-AML2 were successfully established,with IC50 values exceeding 10-fold.Under the same concentration of venetoclax,the apoptosis rate of resistant cells decreased significantly(P＜0.05).BH3 profiling assay revealed that the drug-resistant cell lines showed increased sensitivity to many pro-apoptotic proteins(such as BIM,BID and NOXA).RT-qPCR showed significantly upregulated MCL1 and downregulated NOXA1 were detected in drug-resistant cell lines.Expression changes in MCL1 and NOXA1 in venetoclax-resistant patients were consistent with our established drug-resistant cell line results.Conclusion:The venetoclax-resistant AML cell lines were successfully established through continuous induction with low concentrations of venetoclax.The venetoclax resistance resulted in alterations in the mitochondrial apoptosis pathway of the cells and an increased sensitivity of cells to pro-apoptotic proteins BIM,BID,and NOXA,which may be associated with the upregulation of MCL1 expression and downregulation of NOXA1 expression in the drug-resistant cells.

AIM:To investigate the role of NLR family CARD domain containing 3(NLRC3)in endothelial cells and evaluate its diagnostic value in coronary artery disease.METHODS:Twenty male ApoE-/-C57BL/6 mice,aged eight weeks,were randomly assigned into two groups:an experimental group and a control group,with each group com-prising ten mice.The experimental group was subjected to a high-fat diet for 8 weeks to induce atherosclerosis(AS),whereas the control group was maintained on a standard diet.The expression of NLRC3 in the aorta was evaluated using RT-qPCR and immunofluorescence techniques.Additionally,human umbilical vein endothelial cells(HUVECs)were ex-posed to interleukin-1β(IL-1β)to investigate the expression levels of NLRC3.Lentiviral vectors or plasmid vectors were employed to either overexpress or knock down NLRC3 in endothelial cells,and subsequently subjected to inflammation in-duced by IL-1β.The RT-qPCR and ELISA were employed to assess the impact of NLRC3 on inflammation in endothelial cells.Western blot and immunofluorescence techniques were utilized to investigate the modulation of the NF-κB signaling pathway in endothelial cells by NLRC3.Plasma NLRC3 levels in coronary artery disease patients and healthy controls were measured using ELISA,and its diagnostic potential was assessed through ROC curve analysis.RESULTS:In AS mice,distinct plaque lesions were observed in the aorta,accompanied by a significantly reduced expression of NLRC3 in the aortic arch relative to the control group.Expression of NLRC3 exhibited a significant down-regulation in IL-1β-stimu-lated HUVECs,demonstrating both time-dependent and dose-dependent effects(P<0.01).Overexpression of NLRC3 markedly suppressed the levels of IL-6,IL-8,monocyte chemoatbactant protein-1(MCP-1),p-p65,and p-IκBα in endo-thelial cells stimulated with IL-1β(P<0.01).Conversely,knockdown of NLRC3 resulted in elevated levels of IL-6,IL-8,MCP-1,p-p65 and p-IκBα in endothelial cells(P<0.01).Coronary artery disease patients had significantly lower plasma NLRC3 levels than controls,with an AUC of 0.851(95%CI:0.785～0.918,P<0.01).A diagnostic threshold of 1.605 μg/L yielded a sensitivity of 93.8%and a specificity of 71.3%.CONCLUSION:The NLRC3 may modulate endothelial inflammation and suppress AS progression through inhibition of the NF-κB signaling pathway,and it holds potential as a diagnostic biomarker for coronary artery disease.

Objective:To investigate the impact of immunosuppressive therapy on the severity of SARS-CoV-2 infection and cytokine levels in pediatric patients with kidney diseases.Methods:A retrospective analysis was conducted on the clinical data of 40 hospitalized pediatric patients who were diagnosed with SARS-CoV-2 infection at the 900th Hospital of PLA Joint Logistic Support Force from December 2022 to February 2023. Based on their immunosuppressive status prior to SARS-CoV-2 infection, these patients were categorized into immunosuppressive group and non-immunosuppressive group. Independent sample t-tests, Mann-Whitney U tests, and χ2 test were employed to compare the clinical baseline characteristics and laboratory data, the severity of SARS-CoV-2 infection, and the levels of cytokines between the 2 groups. Results:Among the 40 patients, 11 were in the immunosuppressive group (aged 13 (8, 14) years, 9 males and 2 females) and 29 in the non-immunosuppressive group (aged 2 (1, 4) years, 15 males and 14 females). In the immunosuppressive group, 2 were asymptomatic cases, 8 were mild cases, and 1 was moderate case, and there was no severe or critical cases. In the non-immunosuppressive group, 8 were mild cases, 5 were moderate, 15 were severe cases, 1 was critical case, and no asymptomatic cases. The underlying diseases in the immunosuppressive group included nephrotic syndrome (6 cases), IgA vasculitis nephritis (2 cases), lupus nephritis (1 case), post-renal transplantation (1 case), and renal failure (1 case), with a mean total immunosuppression score (TIS) of (3.6±1.4) points. In the non-immunosuppressive group, 2 patients had a history of epilepsy, and the remaining 27 cases had no underlying conditions, all with TIS scores of 0. Compared to the children in the non-immunosuppressive group, those in the immunosuppressive group were more likely to exhibit asymptomatic or mild infection, with lower risks of severe disease, cytokine storm, fever, and cough, but a higher risk of fatigue ( OR=1.22, 2.66, 0.48, 0.12, 0.12, 0.13, 1.22; 95% CI 0.93-1.62, 0.99-7.15, 0.33-0.70, 0.03-0.57, 0.03-0.57, 0.03-0.65, 0.93-1.62; all P<0.05). The levels of cytokine IL-6, interferon-α and interferon-γ in the immunosuppressive group were all lower than those in the non-immunosuppressive group ( Z=2.23, 2.51, 2.92, respectively; all P<0.05). Conclusion:Pediatric patients with kidney diseases receiving appropriate immunosuppressive therapy may mitigate the severity of SARS-CoV-2 infection by suppressing the expression of cytokines.

BACKGROUND: The protective effect of mesenchymal stem cells (MSCs) on cardiac ischemia-reperfusion (I/R) injury has been widely reported. Dental pulp-derived mesenchymal stem cells (DP-MSCs) have therapeutic effects on various diseases, including diabetes and cirrhosis. This study aimed to determine the therapeutic effects of DP-MSCs on I/R injury and elucidate the underlying mechanism. METHODS: Myocardial I/R injury model mice were treated with DP-MSCs or a miR-19a-3p mimic. The infarct volume, fibrotic area, pyroptosis, inflammation level, and cardiac function were measured. Cardiomyocytes exposed to hypoxia-reoxygenation were transfected with the miR-19a-3p mimic, miR-19a-3p inhibitor, or negative control. Pyroptosis and protein expression in the interferon regulatory factor 8/mitogen-activated protein kinase (IRF-8/MAPK) pathway were measured. RESULTS: DP-MSCs protected cardiac function in cardiac I/R-injured mice and inhibited cardiomyocyte pyroptosis. The upregulation of miR-19a-3p protected cardiac function, inhibited cardiomyocyte pyroptosis, and inhibited IRF-8/MAPK signaling in cardiac I/R-injured mice. DP-MSCs inhibited cardiomyocyte pyroptosis and the IRF-8/MAPK signaling by upregulating the miR-19a-3p levels in cardiomyocytes injured by I/R. CONCLUSION DP-MSCs protected cardiac function by inhibiting cardiomyocyte pyroptosis through miR-19a-3p under I/R conditions.
Animals ; MicroRNAs/metabolism* ; Pyroptosis/genetics* ; Mesenchymal Stem Cells/metabolism* ; Myocytes, Cardiac/cytology* ; Mice ; Male ; Mice, Inbred C57BL ; Dental Pulp/cytology* ; Myocardial Reperfusion Injury/therapy* ; MAP Kinase Signaling System/physiology*

Refinement and standardisation of the management of clinical diagnostic and treatment operations is a key aspect of achieving high-quality development in hospitals.By analysing the management status quo of clinical diagnosis and treatment operations in hospitals,it combed the problems existing in this field.Based on the closed-loop management model,it proposed measures and recommendations to promote the continuous optimisation of the management of clinical diagnostic operations in hospitals.Hospitals should establish hospital-level operation catalog and conduct classified management,authorize operators and dynamically adjust them,carry out operation quality management,pay attention to information management of operation management,and combine operation management with physician performance management.

AIM:To investigate the role of NLR family CARD domain containing 3(NLRC3)in endothelial cells and evaluate its diagnostic value in coronary artery disease.METHODS:Twenty male ApoE-/-C57BL/6 mice,aged eight weeks,were randomly assigned into two groups:an experimental group and a control group,with each group com-prising ten mice.The experimental group was subjected to a high-fat diet for 8 weeks to induce atherosclerosis(AS),whereas the control group was maintained on a standard diet.The expression of NLRC3 in the aorta was evaluated using RT-qPCR and immunofluorescence techniques.Additionally,human umbilical vein endothelial cells(HUVECs)were ex-posed to interleukin-1β(IL-1β)to investigate the expression levels of NLRC3.Lentiviral vectors or plasmid vectors were employed to either overexpress or knock down NLRC3 in endothelial cells,and subsequently subjected to inflammation in-duced by IL-1β.The RT-qPCR and ELISA were employed to assess the impact of NLRC3 on inflammation in endothelial cells.Western blot and immunofluorescence techniques were utilized to investigate the modulation of the NF-κB signaling pathway in endothelial cells by NLRC3.Plasma NLRC3 levels in coronary artery disease patients and healthy controls were measured using ELISA,and its diagnostic potential was assessed through ROC curve analysis.RESULTS:In AS mice,distinct plaque lesions were observed in the aorta,accompanied by a significantly reduced expression of NLRC3 in the aortic arch relative to the control group.Expression of NLRC3 exhibited a significant down-regulation in IL-1β-stimu-lated HUVECs,demonstrating both time-dependent and dose-dependent effects(P<0.01).Overexpression of NLRC3 markedly suppressed the levels of IL-6,IL-8,monocyte chemoatbactant protein-1(MCP-1),p-p65,and p-IκBα in endo-thelial cells stimulated with IL-1β(P<0.01).Conversely,knockdown of NLRC3 resulted in elevated levels of IL-6,IL-8,MCP-1,p-p65 and p-IκBα in endothelial cells(P<0.01).Coronary artery disease patients had significantly lower plasma NLRC3 levels than controls,with an AUC of 0.851(95%CI:0.785～0.918,P<0.01).A diagnostic threshold of 1.605 μg/L yielded a sensitivity of 93.8%and a specificity of 71.3%.CONCLUSION:The NLRC3 may modulate endothelial inflammation and suppress AS progression through inhibition of the NF-κB signaling pathway,and it holds potential as a diagnostic biomarker for coronary artery disease.

Objective:To investigate the impact of immunosuppressive therapy on the severity of SARS-CoV-2 infection and cytokine levels in pediatric patients with kidney diseases.Methods:A retrospective analysis was conducted on the clinical data of 40 hospitalized pediatric patients who were diagnosed with SARS-CoV-2 infection at the 900th Hospital of PLA Joint Logistic Support Force from December 2022 to February 2023. Based on their immunosuppressive status prior to SARS-CoV-2 infection, these patients were categorized into immunosuppressive group and non-immunosuppressive group. Independent sample t-tests, Mann-Whitney U tests, and χ2 test were employed to compare the clinical baseline characteristics and laboratory data, the severity of SARS-CoV-2 infection, and the levels of cytokines between the 2 groups. Results:Among the 40 patients, 11 were in the immunosuppressive group (aged 13 (8, 14) years, 9 males and 2 females) and 29 in the non-immunosuppressive group (aged 2 (1, 4) years, 15 males and 14 females). In the immunosuppressive group, 2 were asymptomatic cases, 8 were mild cases, and 1 was moderate case, and there was no severe or critical cases. In the non-immunosuppressive group, 8 were mild cases, 5 were moderate, 15 were severe cases, 1 was critical case, and no asymptomatic cases. The underlying diseases in the immunosuppressive group included nephrotic syndrome (6 cases), IgA vasculitis nephritis (2 cases), lupus nephritis (1 case), post-renal transplantation (1 case), and renal failure (1 case), with a mean total immunosuppression score (TIS) of (3.6±1.4) points. In the non-immunosuppressive group, 2 patients had a history of epilepsy, and the remaining 27 cases had no underlying conditions, all with TIS scores of 0. Compared to the children in the non-immunosuppressive group, those in the immunosuppressive group were more likely to exhibit asymptomatic or mild infection, with lower risks of severe disease, cytokine storm, fever, and cough, but a higher risk of fatigue ( OR=1.22, 2.66, 0.48, 0.12, 0.12, 0.13, 1.22; 95% CI 0.93-1.62, 0.99-7.15, 0.33-0.70, 0.03-0.57, 0.03-0.57, 0.03-0.65, 0.93-1.62; all P<0.05). The levels of cytokine IL-6, interferon-α and interferon-γ in the immunosuppressive group were all lower than those in the non-immunosuppressive group ( Z=2.23, 2.51, 2.92, respectively; all P<0.05). Conclusion:Pediatric patients with kidney diseases receiving appropriate immunosuppressive therapy may mitigate the severity of SARS-CoV-2 infection by suppressing the expression of cytokines.

Objective:To analyze the related factors of treatment failure in children with acute lymphoblastic leukemia (ALL)in real-world.Methods:The clinical data of 1414 newly diagnosed children with ALL admitted to five hospital in Fujian province from April 2011 to December 2020 were retrospectively analyzed.Treatment failure was defined as relapse,non-relapse death,and secondary tumor.Results:Following-up for median time 49.7 (0.1-136. 9)months,there were 269 cases (19.0％)treatment failure,including 140 cases (52.0％)relapse,and 129 cases (48.0％)non-relapse death.Cox univariate and multivariate analysis showed that white WBC≥50 ×109/L at newly diagnosis,acute T-cell lymphoblastic leukemia (T-ALL),BCR-ABL1,KMT2A-rearrangement and poor early treatment response were independent risk factor for treatment failure (all HR>1.000,P<0.05).The 5-year OS of 140 relapsed ALL patients was only 23.8％,with a significantly worse prognosis for very early relapse (relapse time within 18 months of diagnosis).Among 129 patients died from non-relapse death,71 cases (26.4％)were died from treatment-related complications,56 cases (20.8％)died from treatment abandonment,and 2 cases (0.7％)died from disease progression.Among them,treatment-related death were significantly correlated with chemotherapy intensity,while treatment abandonment were mainly related to economic factors.Conclusion:The treatment failure of children with ALL in our province is still relatively high,with relapse being the main cause of treatment failure,while treatment related death and treatment abandonment caused by economic factors are the main causes of non-relapse related death.

Objective:This study aimed to assess left atrial function in adults across various age groups using 4-dimensional automated left atrial quantification(4D Auto LAQ)technology.The study also aimed to compare the differences in two-dimensional(2D)and four-dimensional(4D)strains of the left atrium among different age groups, with the goal of enhancing the clinical utility of 4D Auto LAQ.Methods:A total of 409 healthy volunteers were recruited for the research.Two-dimensional and four-dimensional images were obtained using a GE Vivid E95 ultrasound system with a 4Vc four-dimensional probe.The study examined variations in 2D and 4D ultrasound parameters across various age groups.Furthermore, the relationship between left atrial reservoir strain(LASr), Left atrial conduit strain(LAScd), left atrial contraction strain(LASct), and age was explored.Results:The study involved 409 volunteers, with 217 males and 192 females, who were categorized into three age groups: young(18-45 years, n=56), middle-aged(46-65 years, n=202), and elderly(>65 years, n=151).Conventional ultrasound measurements indicated changes in left atrial anterior-posterior diameter with age progression: (31.70±3.65)mm for the young group, (34.02±3.91)mm for the middle-aged group, and(35.2±4.37)mm for the elderly group( P<0.01).The 2D and 4D left atrial parameters across the age groups were as follows: LASr(2D)(%): 37.48±7.51, 30.95±8.23, 26.9±7.56( P<0.01); LA VImax(ml/m 2): 23.54±5.79, 26.33±7.6, 28.99±8.15( P<0.01); LASr(%): 31.2±17.07, 22.5±8.59, 19.49±7.47( P<0.01).Both 2D and 4D left atrial parameters exhibited significant associations with age.Specifically, the correlations between LASr(2D)(%), LAScd(2D)(%), LASr(%), LAScd(%), and age were -0.429, 0.580, -0.354, 0.298, respectively( P<0.01). Conclusions:The 4D Auto LAQ technology is efficient in assessing left atrial function across various age groups, with age playing a significant role in influencing left atrial parameters.When compared to other ultrasound parameters, both 2D and 4D left atrial strain parameters have the ability to detect differences at an early stage, making them suitable for the early screening, evaluation, and monitoring of age-related left atrial dysfunction, especially in the elderly population.