The construction of National Regional Centers is a significant strategic deployment to promote the expansion of high-quality medical resources and a balanced regional layout.It introduces the performance of Peking University First Hospital in promoting the construction of National Regional Centre for women and children's hospital with the work mode of"geographical homogenization construction",summarizes effectiveness.It is believed that government support is the foundation,output hospital sinking is the key,and input hospital participation is the guarantee.

The construction of National Regional Centers is a significant strategic deployment to promote the expansion of high-quality medical resources and a balanced regional layout.It introduces the performance of Peking University First Hospital in promoting the construction of National Regional Centre for women and children's hospital with the work mode of"geographical homogenization construction",summarizes effectiveness.It is believed that government support is the foundation,output hospital sinking is the key,and input hospital participation is the guarantee.

The construction of National Regional Centers is a significant strategic deployment to promote the expansion of high-quality medical resources and a balanced regional layout.It introduces the performance of Peking University First Hospital in promoting the construction of National Regional Centre for women and children's hospital with the work mode of"geographical homogenization construction",summarizes effectiveness.It is believed that government support is the foundation,output hospital sinking is the key,and input hospital participation is the guarantee.

The construction of National Regional Centers is a significant strategic deployment to promote the expansion of high-quality medical resources and a balanced regional layout.It introduces the performance of Peking University First Hospital in promoting the construction of National Regional Centre for women and children's hospital with the work mode of"geographical homogenization construction",summarizes effectiveness.It is believed that government support is the foundation,output hospital sinking is the key,and input hospital participation is the guarantee.

The construction of National Regional Centers is a significant strategic deployment to promote the expansion of high-quality medical resources and a balanced regional layout.It introduces the performance of Peking University First Hospital in promoting the construction of National Regional Centre for women and children's hospital with the work mode of"geographical homogenization construction",summarizes effectiveness.It is believed that government support is the foundation,output hospital sinking is the key,and input hospital participation is the guarantee.

The construction of National Regional Centers is a significant strategic deployment to promote the expansion of high-quality medical resources and a balanced regional layout.It introduces the performance of Peking University First Hospital in promoting the construction of National Regional Centre for women and children's hospital with the work mode of"geographical homogenization construction",summarizes effectiveness.It is believed that government support is the foundation,output hospital sinking is the key,and input hospital participation is the guarantee.

The construction of National Regional Centers is a significant strategic deployment to promote the expansion of high-quality medical resources and a balanced regional layout.It introduces the performance of Peking University First Hospital in promoting the construction of National Regional Centre for women and children's hospital with the work mode of"geographical homogenization construction",summarizes effectiveness.It is believed that government support is the foundation,output hospital sinking is the key,and input hospital participation is the guarantee.

The construction of National Regional Centers is a significant strategic deployment to promote the expansion of high-quality medical resources and a balanced regional layout.It introduces the performance of Peking University First Hospital in promoting the construction of National Regional Centre for women and children's hospital with the work mode of"geographical homogenization construction",summarizes effectiveness.It is believed that government support is the foundation,output hospital sinking is the key,and input hospital participation is the guarantee.

OBJECTIVE: To explore the mechanisms of large-conductance calcium-activated potassium channel (BKCa) involved in inflammatory response in sepsis. METHODS: The serum levels of BKCa were measured by enzyme-linked immunosorbent assay (ELISA) in patients with sepsis (28 cases), patients with common infection (25 cases) and healthy people (25 cases). The relationship between levels of BKCa and acute physiology and chronic health evaluation II (APACHE II) were analyzed. Cultured RAW 264.7 cells were stimulated by lipopolysaccharide (LPS). In some experiments, a cell model of sepsis was constructed using Nigericin as the second stimulus signal. The mRNA and protein expressions of BKCa in RAW 264.7 cells stimulated with LPS (0, 50, 100, 1 000 μg/L) were measured by real-time fluorescence quantitative polymerase chain reaction (RT-qPCR) and Western blotting. RAW 264.7 cells were transfected with small interfering RNA of BKCa (siRNA-BKCa), and the levels of caspase-1 precursor (pro-caspase-1), interleukin-1β precursor (pro-IL-1β) in cell, and the levels of caspase-1 p20, IL-1β p17 of cell culture medium, and NOD-like receptor protein 3 (NLRP3), nuclear factor-κB (NF-κB) were measured by Western blotting. The apoptosis were detected by staining with propidium iodide (PI), the release rate of lactate dehydrogenase (LDH) were measured, and the expression of apoptotic protein Gasdermin D (GSDMD) was measured by Western blotting to evaluate the effect of silencing BKCa on cell pyrosis. RESULTS: The level of serum BKCa in patients with sepsis was significantly higher than that in patients with common infection and health peoples (ng/L: 165.2±25.9 vs. 102.5±25.9, 98.8±20.0, both P < 0.05). In addition, the level of serum BKCa in patients with sepsis was significantly positively correlated with APACHE II score (r = 0.453, P = 0.013). LPS could construct a sepsis cell model by which LPS could promote BKCa expression in mRNA and protein with a concentration-dependent manner. The mRNA and protein expressions of BKCa in the cells stimulated by 1 000 μg/L LPS were significantly higher than that in the blank group (0 μg/L) [BKCa mRNA (2^-ΔΔCt): 3.00±0.36 vs. 1.00±0.16, BKCa/β-actin: 1.30±0.16 vs. 0.37±0.09, both P < 0.05]. Compared with the control group, the ratios of caspase-1 p20/pro-caspase-1 and IL-1β p17/pro-IL-1β in the model group were significantly increased (caspase-1 p20/pro-caspase-1: 0.83±0.12 vs. 0.27±0.05, IL-1β p17/pro-IL-1β: 0.77±0.12 vs. 0.23±0.12, both P < 0.05), however, transfection of siRNA-BKCa induced the decrease both of them (caspase-1 p20/pro-capase-1: 0.23±0.12 vs. 0.83±0.12, IL-1β p17/pro-IL-1β: 0.13±0.05 vs. 0.77±0.12, both P < 0.05). Compared with the control group, the number of apoptotic cells, LDH release rate and GSDMD expression in the model group were significantly increased [LDH release rate: (30.60±8.40)% vs. (15.20±7.10)%, GSDMD-N/GSDMD-FL: 2.10±0.16 vs. 1.00±0.16, both P < 0.05], however, transfection of siRNA-BKCa induced the decrease both of them [LDH release rate: (15.60±7.30)% vs. (30.60±8.40)%, GSDMD-N/GSDMD-FL: 1.13±0.17 vs. 2.10±0.16, both P < 0.05]. The mRNA and protein expressions of NLRP3 in sepsis cells were significantly higher than those in the control group [NLRP3 mRNA (2^-ΔΔCt): 2.06±0.17 vs. 1.00±0.24, NLRP3/GAPDH: 0.46±0.05 vs. 0.15±0.04, both P < 0.05]. However, the expression of NLRP3 after siRNA-BKCa transfection was significantly lower than that in model group [NLRP3 mRNA (2^-ΔΔCt): 1.57±0.09 vs. 2.06±0.17, NLRP3/GAPDH: 0.19±0.02 vs. 0.46±0.05, both P < 0.05]. Compared with the control group, the NF-κB p65 nuclear transfer of sepsis cell were significantly increased (NF-κB p65/Histone: 0.73±0.12 vs. 0.23±0.09, P < 0.05). However, the NF-κB p65 expression in the nucleus were decreased after siRNA-BKCa transfection (NF-κB p65/Histone: 0.20±0.03 vs. 0.73±0.12, P < 0.05). CONCLUSIONS BKCa is involved in the pathogenesis of sepsis, and its possible mechanism is to activate NF-κB/NLRP3/caspase-1 signaling pathway to induce inflammatory factor production and cell death.
Humans ; Histones ; Caspase 1 ; Large-Conductance Calcium-Activated Potassium Channels ; Lipopolysaccharides ; NF-kappa B ; NLR Family, Pyrin Domain-Containing 3 Protein ; L-Lactate Dehydrogenase ; Sepsis ; RNA, Small Interfering ; Caspases

Objective:To compare and analyze the clinical characteristics between acute fatty liver of pregnancy (AFLP) and the hemolysis, elevated liver enzymes and low platelets (HELLP) syndrome.Methods:This is a retrospective cohort study. The clinical data of 13 cases with AFLP and 34 cases with HELLP syndrome were collected from three tertiary referral centers in Yunnan (the First Affiliated Hospital of Kunming Medical University, the Second Affiliated Hospital of Kunming Medical University, and Yan'an Hospital of Kunming City) from January 2016 to December 2021. The patients were diagnosed to AFLP and HELLP syndrome according to the Swansea criteria and the Tennessee classification system. The general characteristics, clinical features, laboratory results within 24 hours after admission, complications, maternal and neonatal outcomes were compared to analysis the differences between the two groups.Results:① Maternal characteristics: compared with HELLP syndrome group, AFLP group had lower body mass index (BMI) and blood pressure at admission (both P < 0.01). ②Clinical features: the most common symptoms in AFLP patients were skin jaundice, abdominal pain, nausea and vomiting, edema. The main manifestations of patients with HELLP syndrome were albuminuria, hypertension, edema, headache. Some patients had multiple symptoms concurrently. ③ Laboratory results: compared with HELLP syndrome group, the levels of platelet count (PLT), total bilirubin (TBil), direct bilirubin (DBil), γ-glutamyl transferase (γ-GGT), alkaline phosphatase (ALP), total bile acid (TBA), serum creatinine (SCr) and international standardized ratio (INR) in AFLP group were significantly increased within 24 hours after admission [PLT (×10 9/L): 107.69±51.13 vs.76.71±43.25, TBil (μmol/L): 121.60 (83.20, 170.00) vs.15.25 (7.22, 29.05), DBil (μmol/L): 86.50 (58.60, 104.00) vs. 4.30 (2.22, 10.10), γ-GGT (U/L): 87.00 (37.00, 127.00) vs. 41.00 (19.00, 64.42), ALP (U/L): 199.10 (109.00, 349.20) vs. 125.50 (90.50, 155.25), TBA (μmol/L): 51.50 (16.20, 117.40) vs. 4.15 (2.02, 6.95), SCr (μmol/L): 155.80 (129.00, 237.00) vs. 79.00 (65.43, 113.70), INR: 1.28 (1.17, 1.63) vs. 0.94 (0.88, 1.08), all P < 0.05], prothrombin time (PT) was significantly prolonged [seconds: 16.10 (14.50, 19.20) vs. 12.40 (11.43, 13.40), P < 0.05]. The level of blood glucose (GLU), fibrinogen (FIB) and the activity of antithrombin Ⅲ (ATⅢ) decreased significantly [GLU (mmol/L): 5.18±1.33 vs. 6.33±1.19, FIB (g/L): 1.96±1.46 vs. 3.81±1.58, ATⅢ (%): 40.61±25.84 vs. 66.39±24.11, all P < 0.05]; ④ Complications: compared with HELLP syndrome group, the incidence of patients with hypoglycemia [30.77% (4/13) vs. 0% (0/34)], acute liver failure [53.85% (7/13) vs. 5.88% (2/34)], acute renal insufficiency [69.23% (9/13) vs. 8.82% (3/34)], coagulopathy [76.92% (10/13) vs. 38.24% (13/34)], disseminated intravascular coagulation (DIC) [53.85% (7/13) vs. 5.88% (2/34)], and multiple organ dysfunction syndrome (MODS) [53.85% (7/13) vs. 5.88% (2/34)] were significantly higher in AFLP group (all P < 0.05). ⑤ Maternal and neonatal outcome: all patients delivered after admission. The total length of hospital and intensive care unit stay were significantly longer in the AFLP group than in the HELLP syndrome group [days: 17.00 (11.00, 25.00) vs. 9.00 (7.00, 12.00), 12.00 (4.00, 22.00) vs. 3.91 (0, 7.00), both P < 0.01]. Two AFLP patients died, including one due to intracranial venous thrombosis and one due to multiple organ failure and cardiopulmonary arrest. There were no deaths in the HELLP syndrome group. Conclusions:There are significant differences in maternal characteristics, laboratory results and complications between AFLP and HELLP syndrome. TBil, γ-GGT, SCr, FIB, INR and ATⅢ activity may help to distinguish the two diseases.