Acute lung injury （ALI） is a clinically critical disease with limited treatment options and poor prognosis， with high morbidity and mortality. Pulmonary inflammation caused by trauma， infection， and other factors in vivo and in vitro can damage alveolar epithelial and vascular endothelial barriers， resulting in lung tissue congestion and edema and eventually leading to significant dyspnea and hypoxemia， It can further develop into acute respiratory distress syndrome. Oxidative stress is one of the pathogenesis of ALI. A large number of reactive oxygen species （ROS） can promote the aggregation of inflammatory cells， increase pulmonary capillary permeability， and even directly damage lung tissue. Therefore， regulating oxidative stress becomes one of the effective means to reduce the degree of lung injury. According to the theory of traditional Chinese medicine （TCM）， ALI is divided into the categories of "sudden wheezing" and "dyspnea due to wheezing". TCM treats the causes of dampness， heat， poison， and stasis by syndrome differentiation and treatment， regulates Qi and blood， and balances Yin and Yang to restore the physiological function of the lung. In recent years， a large number of studies have shown that TCM can regulate ROS through multiple targets and mechanisms and play a role in reducing lung inflammation and protecting alveolar epithelial cells and endothelial vessels， in which the nuclear factor E₂ associated factor 2 （Nrf2） antioxidant pathway plays an important role. Based on the generation and clearance of ROS， this article summarized the related mechanisms of TCM monomers， TCM pairs， and TCM compounds in regulating oxidative stress to prevent ALI， so as to provide theoretical reference for the research and development of new TCM for ALI and clinical treatment.

Background: In acute and chronic renal inflammatory diseases, the activation of inflammatory cells is involved in the defect of erythropoietin (EPO) production. Ras guanine nucleotide-releasing protein-4 (RasGRP4) promotes renal inflammatory injury in type 2 diabetes mellitus (T2DM). Our study aimed to investigate the role and mechanism of RasGRP4 in the production of renal EPO in diabetes. Methods: The degree of tissue injury was observed by pathological staining. Inflammatory cell infiltration was analyzed by immunohistochemical staining. Serum EPO levels were detected by enzyme-linked immunosorbent assay, and EPO production and renal interstitial fibrosis were analyzed by immunofluorescence. Quantitative real-time polymerase chain reaction and Western blotting were used to detect the expression of key inflammatory factors and the activation of signaling pathways. In vitro, the interaction between peripheral blood mononuclear cells (PBMCs) and C3H10T1/2 cells was investigated via cell coculture experiments. Results: RasGRP4 decreased the expression of hypoxia-inducible factor 2-alpha (HIF2A) via the ubiquitination–proteasome degradation pathway and promoted myofibroblastic transformation by activating critical inflammatory pathways, consequently reducing the production of EPO in T2DM mice. Conclusion RasGRP4 participates in the production of renal EPO in diabetic mice by affecting the secretion of proinflammatory cytokines in PBMCs, degrading HIF2A, and promoting the myofibroblastic transformation of C3H10T1/2 cells.

Background: In acute and chronic renal inflammatory diseases, the activation of inflammatory cells is involved in the defect of erythropoietin (EPO) production. Ras guanine nucleotide-releasing protein-4 (RasGRP4) promotes renal inflammatory injury in type 2 diabetes mellitus (T2DM). Our study aimed to investigate the role and mechanism of RasGRP4 in the production of renal EPO in diabetes. Methods: The degree of tissue injury was observed by pathological staining. Inflammatory cell infiltration was analyzed by immunohistochemical staining. Serum EPO levels were detected by enzyme-linked immunosorbent assay, and EPO production and renal interstitial fibrosis were analyzed by immunofluorescence. Quantitative real-time polymerase chain reaction and Western blotting were used to detect the expression of key inflammatory factors and the activation of signaling pathways. In vitro, the interaction between peripheral blood mononuclear cells (PBMCs) and C3H10T1/2 cells was investigated via cell coculture experiments. Results: RasGRP4 decreased the expression of hypoxia-inducible factor 2-alpha (HIF2A) via the ubiquitination–proteasome degradation pathway and promoted myofibroblastic transformation by activating critical inflammatory pathways, consequently reducing the production of EPO in T2DM mice. Conclusion RasGRP4 participates in the production of renal EPO in diabetic mice by affecting the secretion of proinflammatory cytokines in PBMCs, degrading HIF2A, and promoting the myofibroblastic transformation of C3H10T1/2 cells.

Background: In acute and chronic renal inflammatory diseases, the activation of inflammatory cells is involved in the defect of erythropoietin (EPO) production. Ras guanine nucleotide-releasing protein-4 (RasGRP4) promotes renal inflammatory injury in type 2 diabetes mellitus (T2DM). Our study aimed to investigate the role and mechanism of RasGRP4 in the production of renal EPO in diabetes. Methods: The degree of tissue injury was observed by pathological staining. Inflammatory cell infiltration was analyzed by immunohistochemical staining. Serum EPO levels were detected by enzyme-linked immunosorbent assay, and EPO production and renal interstitial fibrosis were analyzed by immunofluorescence. Quantitative real-time polymerase chain reaction and Western blotting were used to detect the expression of key inflammatory factors and the activation of signaling pathways. In vitro, the interaction between peripheral blood mononuclear cells (PBMCs) and C3H10T1/2 cells was investigated via cell coculture experiments. Results: RasGRP4 decreased the expression of hypoxia-inducible factor 2-alpha (HIF2A) via the ubiquitination–proteasome degradation pathway and promoted myofibroblastic transformation by activating critical inflammatory pathways, consequently reducing the production of EPO in T2DM mice. Conclusion RasGRP4 participates in the production of renal EPO in diabetic mice by affecting the secretion of proinflammatory cytokines in PBMCs, degrading HIF2A, and promoting the myofibroblastic transformation of C3H10T1/2 cells.

Background: In acute and chronic renal inflammatory diseases, the activation of inflammatory cells is involved in the defect of erythropoietin (EPO) production. Ras guanine nucleotide-releasing protein-4 (RasGRP4) promotes renal inflammatory injury in type 2 diabetes mellitus (T2DM). Our study aimed to investigate the role and mechanism of RasGRP4 in the production of renal EPO in diabetes. Methods: The degree of tissue injury was observed by pathological staining. Inflammatory cell infiltration was analyzed by immunohistochemical staining. Serum EPO levels were detected by enzyme-linked immunosorbent assay, and EPO production and renal interstitial fibrosis were analyzed by immunofluorescence. Quantitative real-time polymerase chain reaction and Western blotting were used to detect the expression of key inflammatory factors and the activation of signaling pathways. In vitro, the interaction between peripheral blood mononuclear cells (PBMCs) and C3H10T1/2 cells was investigated via cell coculture experiments. Results: RasGRP4 decreased the expression of hypoxia-inducible factor 2-alpha (HIF2A) via the ubiquitination–proteasome degradation pathway and promoted myofibroblastic transformation by activating critical inflammatory pathways, consequently reducing the production of EPO in T2DM mice. Conclusion RasGRP4 participates in the production of renal EPO in diabetic mice by affecting the secretion of proinflammatory cytokines in PBMCs, degrading HIF2A, and promoting the myofibroblastic transformation of C3H10T1/2 cells.

Objective:To investigate the influence of varied oxygen (O 2) concentration environments on the phenotypic transformation of pulmonary artery smooth muscle cells (PASMC) and the mechanism of pulmonary hypertension. Methods:Primary rat PASMC were isolated and cultured through the process of enzymatic digestion. Following identification, the stable passaged PASMC were subjected to a 6-hour incubation in sealed containers with normal O 2 content (group C) and relative O 2 content comprising 55% (group H55), 75% (group H75), and 95% (group H95). mRNA and protein expression of α-Actin (α-SMA), smooth muscle 22α (SM22α), osteopontin (OPN), and matrix metalloproteinase-2 (MMP-2) were measured using real-time quantitative PCR and western blot analysis. Results:The H55 group displayed no significant difference from the C group in terms of mRNA and relative protein expression levels for α-SMA, SM22α, OPN, and MMP-2 (all P>0.05). On the other hand, groups H75 and H95 exhibited a reduction in mRNA and relative protein expression of α-SMA and SM22α, along with an increase in mRNA and relative protein expression of OPN and MMP-2 when compared with both the C and H55 groups (all P<0.05). The H95 group showed a higher relative mRNA expression of MMP-2 as compared to the H75 group ( P<0.05). Conclusions:Oxygen concentration environments of 75% or higher can serve as the foundation for the pathogenesis of pulmonary hypertension, essentially by inducing a phenotypic transformation in PASMC towards adopting a robust secretory function. This induction is contingent upon the concentration of oxygen present.

Objective:To explore the clinical warning value of ischemic modified albumin (IMA) and IMA to human serum albumin (HSA) ratio (IMAR) in the development of pre-eclampsia (PE) and its severity.Methods:A total of 156 pregnant women with PE admitted to the Haidian District Maternal and Child Health Hospital of Beijing from April 2022 to March 2023 were collected as the PE group, and 156 healthy pregnant women with the same age and gestational age were matched as the control group. PE pregnant women were further divided into severe PE group (78 cases) and non-severe PE group (78 cases). Severe PE pregnant women were divided into emergency group (42 cases) and non-emergency group (36 cases) according to the disease progression time.All pregnant women were stratified according to their HSA levels (<30 g/L, 30-32 g/L, ≥32 g/L), and the peripheral blood IMA, HSA, and IMAR of pregnant women in different periods and subgroups were compared, and also the difference of IMA levels in umbilical artery blood. Bivariate correlation analysis was used to explore the correlation between severe PE and IMA or IMAR, and receiver operating characteristic (ROC) curves was used to analyze the diagnostic value of IMA, HSA, and IMAR for PE and severe PE.Results:(1) The IMA level and IMAR in peripheral serum of pregnant women in the PE group at diagnosis, and the IMA level in umbilical artery blood at delivery, and peripheral serum at 2 days after delivery were higher than those in the control group. The HSA level in peripheral serum was lower than that in the control group at diagnosis, and the differences were statistically significant (all P<0.001). (2) The IMA level and IMAR in the peripheral serum of pregnant women with severe PE were higher than those in the non-severe PE group at diagnosis, while the HSA level were lower than those in the non-severe PE group. The differences were statistically significant (all P<0.05). At diagnosis, the IMA level and IMAR in peripheral serum of pregnant women in the emergency group were higher than those in the non-emergency group, while the HSA level was lower than that in the non-emergency group. The differences were statistically significant (all P<0.05). When diagnosed, the peripheral serum IMA levels of pregnant women in the PE group were compared between subgroups with HSA<30 g/L, 30-32 g/L, ≥32 g/L, and there was no statistically significant difference ( F=0.366, P=0.694). However, the IMAR was compared between the three subgroups, and the difference was statistically significant ( F=28.544, P<0.001), which increased with the decrease of HSA levels. In the subgroup with HSA≥32 g/L, the peripheral serum IMA level and IMAR of pregnant women in the PE group were higher than those in the control group at diagnosis, and the differences were statistically significant (all P<0.001). (3) The severe PE manifestations positively correlated with peripheral serum IMAR at diagnosis include systolic blood pressure ( r=0.279), mean arterial pressure ( r=0.212), and urinary protein quantification ( r=0.277), while the severe PE manifestations negatively correlated include HSA levels ( r=-0.644) and newborn birth weight ( r=-0.305), all of which were significantly correlated ( P<0.05). (4) The area under curve (AUC) for IMAR diagnosis of PE was 0.875 (95% CI: 0.833-0.916), with the highest diagnostic efficiency at a cutoff value of 2.06, sensitivity of 72.5%, and specificity of 85.1%. The AUC for diagnosing severe PE was 0.871 (95% CI: 0.822-0.919), with the highest diagnostic efficacy at a cutoff value of 2.18, sensitivity of 72.3%, and specificity of 88.3%. The diagnostic efficacy of IMAR for PE and severe PE were higher than those of IMA and HSA levels. Conclusions:The level of IMA and IMAR in pregnant women with PE are higher than those in normal pregnant women. IMA and IMAR are correlated with the severity of PE, with IMAR changes occurring earlier and more significantly. IMAR could be considered as one of the evaluation indicators for the development of PE, or as a more sensitive PE severity warning indicator than HSA.

Objective:To investigate the correlation between the expression of cyclic RNA PIP5K1A (circPIP5K1A) and microRNA-124-3p (miR-124-3p) in the serum and the severity of the disease and infertility in patients with endometriosis (EM) .Methods:A total of 110 cases of EM patients admitted to Shanxi Provincial Children's Hospital (Shanxi Maternal and Child Health Hospital) from Jan. 2020 to Jan. 2022 were regarded as the research objects, and were diveded into infertility group (44 cases) and successful pregnancy group (66 cases) according to the pregnancy outcome. General data were collected and the levels of serum miR-124-3p and circPIP5K1A were compared between the two groups; Pearson correlation was applied to analyze the correlation between serum miR-124-3p and circPIP5K1A. The diagnostic value of miR-124-3p and circPIP5K1A levels in patients with stage III-V EM was evaluated by ROC curve; Logistic regression analysis was applied to analyze the factors influencing the occurrence of infertility.Results:The expression level of serum miR-124-3p in stage Ⅰ EM patients (1.06±0.21) was higher than that in stage Ⅱ (0.83±0.19), stage Ⅲ (0.65±0.12) and stage Ⅴ (0.44±0.08), and the serum miR-124-3p level decreased with the increase of r-AFS stage. The differences were statistically significant ( t=54.29, P<0.05). The expression level of circPIP5K1A (0.77±0.12) was lower than that of stage Ⅱ (0.90±0.15), stage Ⅲ (1.20±0.20) and stage Ⅴ (1.53±0.26), and increased with the increase of r-AFS stage, and the differences were statistically significant ( t=90.45, P<0.05). Pearson correlation analysis showed that the expression of circPIP5K1A and miR-124-3p in serum of EM patients was negatively correlated ( r=-0.424, P<0.05) ; the serum miR-124-3p level in infertility group was lower than that in successful pregnancy group, and the serum circPIP5K1A level in infertility group was higher than that in successful pregnancy group ( P<0.05). ROC curve results showed that the area under the curve (AUC) of serum miR-124-3p and circPIP5K1A levels in the diagnosis of stage III-V EM patients was 0.900 and 0.887 respectively. The corresponding sensitivity was 88.24%, 85.29%, and the specificity was 78.95%, 88.16%, respectively. The AUC of combined diagnosis was 0.937, the sensitivity was 82.35%, and the specificity was 90.79%. Multivariate Logistic regression analysis showed that miR-124-3p and circPIP5K1A were related factors affecting infertility ( P<0.05) . Conclusions:The expression of miR-124-3p in the serum of EM patients decreases, and the expression of circPIP5K1A increases. The combined detection of miR-124-3p and circPIP5K1A has certain diagnostic value for the patients with stage III-V EM, and they are closely related to the occurrence of infertility.

Objective:To analyze the clinical characteristics of children with systemic lupus erythematosus (SLE) combined with thrombotic microangiopathy (TMA), and clarify the clinical outcomes and related risk factors of pediatric patients through their treatment and follow-up.Methods:This was a single-center retrospective case-control study. Children diagnosed with SLE combined with TMA between January 2017 and January 2023 at Beijing Children′s Hospital, Capital Medical University, were selected as the TMA group, and SLE children without TMA were selected as the control group.According to the prognosis, children in the TMA group were further divided into the good prognosis group and the poor prognosis group.The data of the children were collected, including age, gender, SLE disease activity, clinical presentations at the time of diagnosis and at the time of thrombosis, laboratory examinations, treatment strategies, prognosis, and follow-up results.The chi-square test and Z-test were used for comparison of count data.The t-test was used for comparison of metrological pairing data.The Fisher′s exact test was used to compare the differences between the 2 groups in categorical variables.The univariate Logistic regression was used to analyze the risk factors of poor prognosis. Results:There were 29 cases in the TMA group, and the incidence of TMA accounted for 2.53% of SLE patients; 33 cases were in the control group.The age at diagnosis of TMA was 13 years and 5 months (ranging from 9 years, 1 month and 5 days to 17 years and 4 months).The common clinical manifestations in order of prevalence were renal involvement (28 cases, 96.55%), hematologic involvement (26 cases, 89.66%), serous effusion (17 cases, 58.62%), rash (13 cases, 44.82%), and neurologic involvement (12 cases, 41.38%).Pleurisy or pericarditis, renal involvement and neurological involvement occurred more often in the TMA group than in the control group (17 cases vs.3 cases, 28 cases vs.10 cases, 12 cases vs.3 cases), and the TMA group showed less facial rash and arthritis than the control group (13 cases vs.25 cases, 4 cases vs.17 cases), and the differences were statistically significant (all P<0.05).The Systemic Lupus Erythematosus Disease Activity Index score in the TMA group [(24.14±9.42) scores] was significantly higher than that in the control group [(10.18±9.42) scores], and the difference was statistically significant ( t=3.233, P<0.05).The hemoglobin level, platelet count, and complement C3 level of the children in the TMA group were significantly lower than those in the control group, whereas the double stranded DNA antibody, lactate dehydrogenase, D-dimer, urea, creatinine, ferritin level, and urine protein quantitation were significantly higher than those in the control group, and the differences were statistically significant (all P<0.05).In the TMA group, 5 cases had decreased ADAMTS13 activity, and 5 cases had significantly increased complement C5b9.A total of 15 cases (51.72%) in the TMA group underwent renal biopsy, and 13 of them had combined renal TMA.In the TMA group, 28 patients (96.6%) received hormone therapy, 17 patients received plasma exchange, and 12 patients were treated with immunosuppressants and biologics; 19 patients (65.5%) improved, and 10 patients (34.5%) gave up the treatment due to deterioration of the disease.The urea level and peripheral blood fragmented erythrocyte rate in the good prognosis group were significantly lower than those in the poor prognosis group [(13.18±4.39) mmol/L vs.(21.16±10.14) mmol/L, t=2.975, P=0.006; 8/17 (47.06%) vs.7/7 (100%), χ2=5.929, P=0.015].The univariate Logistic regression analysis showed that the fragmented erythrocyte, ADAMTS13 activity and urea were the independent risk factors for poor prognosis (all P<0.05). Conclusions:SLE patients with moderate-to-severe disease activity, especially children with hemolytic anemia, thrombocytopenia, and renal dysfunction as prominent manifestations, should be alert to the risk of TMA.Early diagnosis and treatment are crucial.

Objective To establish a dynamic model of lipopolysaccharide-induced acute lung injury in mice based on the NLRP3/Caspase-1/gasdermin D(GSDMD)pyroptosis pathway,and observe the result ing lung injury at different time points.We aimed to identify the optimal time for modelling according to the injury at different time points and the expression of pyroptosis pathway-related proteins,to lay the foundation for animal models for subsequent experiments.Methods Fifty-four 6～8 weeks old male SPF BALB/c mice were divided randomly into nine groups,including Con group and model groups at 1,3,6,12,18,24,48,and 72 h.Body weight and lung tissue were detected by general and pathological observations and semi-quantitative scoring,including lung index,lung water content,and wet and dry weight ratio.The white blood cell count and concentrations of tumor necrosis factor-α,interleukin(IL)-6,IL-1β,IL-18,and BCA protein were detected in bronchoalveolar lavage fluid(BALF).The classic pyroptosis pathway-related proteins NLRP3,pro-Caspase 1,Caspase 1,and GSDMD were detected by Western Blot.Results Body weight decreased in all experimental groups,with the most significant weight loss in the 24 and 48 h groups.Gross observation and pathological examination of lung tissue showed that the most severe lung injury occurred at 24～72 h,with significant differences between each group and the control group.The lung index,lung water content,and wet/dry weight ratio were also significantly increased at 24～72 h.White blood cells in BALF started to increase from 6 h after model initiation,48 h can reach a peak,72 h all keep increasing.IL-18 in BALF began to increase at 24 h and continued to increase at 72 h.The inflammatory factors tumor necrosis factor-α,IL-1β,IL-6 were highest at 6 h and significantly reduced at 48 h.Protein concentrations in BALF were significantly increased within 24,48,and 72 h compared with those in the control group.The pyroptosis pathway proteins NLRP3,pro-Caspase-1,Caspase-1,and GSDMD were significantly enhanced in each time series,and channel protein expression was significantly enhanced at 24～72 h compared with that in the Con group.Conclusions Comprehensive analysis of experimental indicators,inflammatory factors,and pathway proteins at different times showed that the mechanism of pyroptosis was closely related to the occurrence and progression of acute lung injury.Expression of the pyroptosis pathway was most obvious and lung injury was most serious at 24～48 h.This study provides a model reference and experimental basis for subsequent studies of the specific mechanism and intervention targets of acute lung injury.