Objective To investigate the protective effects of antioxidant taurine plus metoprolol on the blood pressure(BP)and blood vessel function of elderly spontaneously hypertensive rats(SHR).Methods SHRs were divided into three groups (6 rats,each):metoprolol group (100 mg · kg-1 · d-1,intragastric administration);taurine group (200 mg · kg-1 · d-1,intraperitoneal injection);taurine plus metoprolol group(metoprolol 100 mg· kg-1 · d-1,intragastric administration ± taurine 200 mg· kg-1 · d-1,intraperitoneal injection).The control group[6 Wistar-Kyoto(WKY) rats]was treated with the same volume of sterile normal saline on the same schedule in intragastric administration and intraperitoneal injection.Blood pressure variability(BPV),diurnal variation of BP,the level of glutathion peroxidase (GSH-Px),malonaldehyde (MDA) and the aorta GSTM1 enzyme expression were evaluated before and 14 days after treatment.Results The serum GSH-Px activities were higher in metoprolol group[(2 759.8 ± 117.6) kU/L],taurine group [(2 848.0 ± 280.2) kU/L] and taurine plus metoprolol group[(3 052.8±283.7)kU/L]than in control group[(2 368.0± 60.4) kU/L] (all P＜0.05).Fourteen days after treatment,MDA level was significantly lower in taurine group[(9.5±0.7)ng/L,P＜0.01]than in control group[(13.7±1.5)ng/L].However,there was no statistical difference in MDA level between metoprolol group/taurine plus metoprolol group and control group.Forty weeks after treatment with taurine,GSTM1 protein expression was increased,but it had no statistical difference.Conclusions The combined antioxidant taurine and metoprolol can effectively decrease BPV of elderly SHRs,in which the antioxidant effect might be associated with elevated GSTM1 protein expression.

Objective To investigate the relationship between hepatitis B surface antigen (HBsAg) levels and liver pathology at different phases of natural history in chronic hepatitis B (CHB) patients, and to establish a non-invasive liver fibrosis diagnostic model based on HBsAg quantification.Methods A total of 145 CHB patients were enrolled and underwent liver biopsy from January 2013 to January 2015, among which 73 patients were hepatitis B e antigen (HBeAg) positive.HBsAg levels and HBV DNA levels were compared between patients at different phases of natural history and between patients with different HBeAg statuses.Logistic analysis was used to analyze the risk factors associated with fibrosis in HBeAg-positive patients, and to evaluate the predictive value of non-invasive liver fibrosis diagnostic model based on HBsAg quantification.Analysis of variance was used for statistical analysis, and t test analysis was used for the comparison between two independent samples.Results The serum HBsAg levels at the immunologic tolerance phase, immunologic clearance phase, low copy phase and reactivation phase of CHB patients were (4.29±0.69), (3.56±0.61), (3.22±0.64), and (3.54±0.50) lg IU/mL, respectively (F=16.72, P<0.01), and the HBV DNA levels were (8.48±0.58), (6.69±1.44), (3.80±0.59), and (6.21±1.06) lg IU/mL, respectively (F=76.73, P<0.01).In HBeAg-positive CHB patients with liver inflammation stage (G)≤G1, G2, G3 and G4, the serum HBsAg levels were (4.44±0.65), (4.00±0.72), (3.74±0.62), and (3.28±0.50) lg IU/mL, respectively (F=9.198, P<0.01).In HBeAg-positive CHB patients with liver fibrosis stage (S)≤S1, S2, S3, and S4, the serum HBsAg levels were (4.55±0.54), (4.04±0.89), (3.59±0.63), and (3.34±0.50) lg IU/mL, respectively (F=10.66, P<0.01).Logistic analysis showed that age (OR=1.091, 95%CI: 1.013-1.175) and HBsAg level (OR=0.190, 95%CI: 0.066-0.542) were independent factors for predicting fibrosis stage.The area under receiver operating characteristic curve of the non-invasive fibrosis model based on age and HBsAg level was 0.849, which was higher than aspartate aminotransferase to platelet ratio index (0.749) and fibrosis index based on the 4 factors (0.763).Conclusions The serum HBsAg levels are significantly different among the different phases of natural history in CHB patients.The serum HBsAg levels decline with the progression of liver fibrosis in HBeAg-positive CHB patients.The non-invasive diagnostic model that based on HBsAg quantification could be used to evaluate the stage of liver fibrosis.

Objective: To investigate the effects of hesperetin on fine particulate matter (PM_2.5) induced apoptosis in H9c2 cells and related mechanisms. Methods: H9c2 cells were divided into 4 groups: control group (cells were cultured without intervention), PM_2.5 group (cells were treated with 800 µg/ml PM_2.5), hesperetin group (H group, cells were treated by 40 µmol/L hesperetin for 1 h at 37 ℃), and hesperetin+PM_2.5 group (H+PM_2.5 group, cells were pretreated with hesperetin before PM_2.5 treatment). Cells were cultured for corresponding interval. Apoptotic cells were detected by Annexin Ⅴ-FITC/PI apoptosis detection kit and Hoechst staining. The intracellular reactive oxygen species (ROS) levels were measured by DCFH-DA Fluorescence Probe and mitochondrial membrane potential (MMP) was detected with JC-1 staining, respectively in these groups. Apoptotic related protein and phosphorylated MAPK expression levels were determined by Western blot. Results: (1) Flow cytometry results showed that the apoptosis rate of PM_2.5 group ((48.94±3.20)%) was significantly higher than that of control group ((8.13±1.40)%, P<0.01), which was significantly reduced in H+PM_2.5 group ((34.80±2.21)%) (P=0.003 2 vs. PM_2.5 group, P<0.01 vs. control group). The number of Hoechst 33258 positive apoptotic cells was distinctly less in H+PM_2.5 group than in PM_2.5 group. (2) The ROS levels was significantly higher in PM_2.5 group ((49.69±5.05)%) than in control group (10.57±1.33)%, P<0.01), which was significantly reduced in H+PM_2.5 group ((35.08±3.90)%) (P=0.000 2 vs. PM_2.5 group, P<0.01 vs. control group). (3) Green fluorescence indicating the JC-1 monomer form, which represented MMP loss of H9c2 cells, was significantly higher in PM_2.5 group ((20.28±4.69)%) than in control group ((10.50±2.72)%, P<0.01), which was significantly decreased in H+PM_2.5 group ((13.41±2.89)%) (P<0.01 vs. PM_2.5 group, P=0.029 4 vs. control group). (4) The expression levels of Bcl-2 protein of H9c2 cells was lower in PM_2.5 group ((76.94±4.52)%) than in control group (100%, P=0.000 9), which was significantly upregulated in H+PM_2.5 group ((92.95±6.82)%) (P=0.027 5 vs. PM_2.5 group, P=0.15 vs. control group). The expression levels of cleaved caspase-3 protein of H9c2 cells was significantly higher in PM₂.5 group ((243.98±17.94)%) than in control group (100%, P=0.000 2), which was significantly downregulated in H+PM_2.5 group ((200.45±4.31)%) (P=0.015 vs. PM_2.5 group, P<0.01 vs. control group). (5) The expression levels of phosphorylated p38 MAPK protein of H9c2 cells was higher in PM_2.5 group ((118.90±4.78)%) than in control group(100%, P=0.002 7), which could be significantly downregulated in H+PM_2.5 group ((103.30±1.27)%) (P=0.01 vs. PM_2.5 group, P=0.05 vs. control group). The expression levels of phosphorylated ERK protein of H9c2 cells was higher in PM_2.5 group ((163.50±4.98)%) than in control group (100%, P<0.01), which was significantly downregulated in H+PM_2.5 group ((139.10±2.72)%) (P=0.001 6 vs. PM_2.5 group, P<0.01 vs. control group). Conclusions Hesperetin protects H9c2 cells from PM_2.5 stimulation through reducing oxidative stress and protecting mitochondrial function, regulating the expression of apoptotic associated proteins as well as MAPK signal pathway, thus inhibiting H9c2 cells apoptosis.

Objective:To investigate the value of growth differentiation factor-15 (GDF-15) and extravascular lung water index (EVLWI) in severity grading and prognosis prediction of patients with acute respiratory distress syndrome (ARDS).Methods:Patients with ARDS aged 18-75 years admitted to the department of respiratory intensive care unit (RICU) of Zhengzhou Central Hospital Affiliated to Zhengzhou University from January 2019 to February 2020 were enrolled. All patients were treated with conventional therapies such as mechanical ventilation, anti-infection, stabilization of water, electrolytes and acid-base environment, blood purification and nutritional support according to their conditions. Besides, the pulse-indicated continuous cardiac output (PiCCO) was performed after admission to the department, and EVLWI before treatment and at 24, 48 and 72 hours of treatment were recorded. Serum GDF-15 level was measured by enzyme linked immunosorbent assay (ELISA) during the same period. Patients were classified as mild, moderate, and severe degree according to the 2012 Berlin Definition of ARDS, and EVLWI and GDF-15 levels in patients with different disease levels before and after treatment were compared. In addition, the length of intensive care unit (ICU) stay, ICU mortality, and 28-day mortality of patients with different GDF-15 or EVLWI levels were analyzed comparatively, with the GDF-15 3 458 ng/L and EVLWI 15 mL/kg as the cut point.Results:A total of 82 patients with ARDS were enrolled, including 22 patients with mild ARDS, 28 patients with moderate ARDS, and 32 patients with severe ARDS. The GDF-15 and EVLWI levels in patients with moderate and severe ARDS at each time point before and after treatment were higher than those in patients with mild ARDS. Both GDF-15 and EVLWI levels in patients with severe ARDS were higher than those in the patients with moderate ARDS. The differences were statistically significant at all the time points except for the difference of GDF-15 levels at 24 hours after treatment (ng/L: 3 900.41±546.43 vs. 3 695.66±604.73, P > 0.05). [GDF-15 (ng/L): 3 786.11±441.45 vs. 3 106.83±605.09 before treatment, 3 895.48±558.96 vs. 3 333.29±559.66 at 48 hours, 3 397.33±539.56 vs. 3 047.53±499.57 at 72 hours; EVLWI (mL/kg): 19.06±1.91 vs. 14.31±1.50 before treatment, 18.56±2.23 vs. 13.26±1.69 at 24 hours, 17.23±1.76 vs. 12.45±1.36 at 48 hours, 15.47±1.81 vs. 11.13±2.19 at 72 hours, all P < 0.05]. According to the cut-off value, there were 23 patients with GDF-15 ≥ 3 458 ng/L and GDF-15 < 3 458 ng/L respectively and there were 23 patients with EVLWI ≥ 15 mL/kg and EVLWI < 15 mL/kg respectively. The length of ICU stay and 28-day mortality in patients with high GDF-15 were significantly higher than those in patients with low GDF-15 [length of ICU stay (days): 21.22±2.69 vs. 15.37±3.14, 28-day mortality: 56.5% vs. 21.7%, both P < 0.05]. The length of ICU stay and 28-day mortality in patients with high EVLWI were also significantly higher than those in patients with low EVLWI [length of ICU stay (days): 18.45±2.61 vs. 14.98±2.75, 28-day mortality: 47.8% vs. 17.4%, both P < 0.05]. Conclusion:To some extent, GDF-15 and EVLWI levels reflect the severity of patients with ARDS, and high GDF-15 and EVLWI levels are significantly associated with poor prognosis in patients with ARDS.

ObjectiveTo investigate the targets and mechanism of Baofeikang granules in the treatment of pulmonary fibrosis based on network pharmacology and verify the predicted mechanism based on animal experiment. MethodThe active ingredients and targets of Baofeikang granules were screened via the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform， and the targets of pulmonary fibrosis were searched in various disease databases. The common targets shared by Baofeikang granules and the disease were extracted for the establishment of the protein-protein interaction （PPI） network in STRING. Cytoscape 3.8.0 was used to analyze the network topology of the key targets and to establish the ''active ingredient-target'' network. Gene ontology （GO） and Kyoto Encyclopedia of Genes and Genomes （KEGG） enrichment analyses were performed on the core targets to explore their possible molecular mechanisms. The rats were assigned into four groups： normal group， model group， prednisone acetate group， and Baofeikang granules group. The rat model of interstitial lung fibrosis was established by tracheal instillation of bleomycin. After 21 days of gavage， the lung tissues of rats were stained with hemotoxylin and eosin （HE） for the observation of morphological changes， and phosphatidylinositol 3-kinase （PI3K） and protein kinase B （Akt） were detected via immunohistochemical （IHC） staining. ResultBased on network pharmacology， 18 key targets of Baofeikang granules were identified for the treatment of pulmonary interstitial fibrosis， including Akt1， mitogen-activated protein kinase （MAPK） 1， myelocytomatosis oncogene （MYC）， hypoxia-inducible factor-1α （HIF-1α）， cyclin-dependent kinase inhibitor 1A （CDKN1A）， epidermal growth factor receptor （EGFR）， and Runt-related transcription factor （RUNX2）. KEGG pathway enrichment predicted that Baofeikang granules exerted anti-fibrotic effect mainly through PI3K/Akt， tumor necrosis factor （TNF）， and interleukin-17 （IL-17） signaling pathways. The IHC results in animal experiment showed that the protein levels of PI3K and Akt were lower in the Baofeikang granules group than in the model group （P<0.05， P<0.01）. ConclusionBaofeikang granules has low toxicity， multiple targets， and multiple pathways in the treatment of pulmonary fibrosis. It may alleviate pulmonary fibrosis through regulating PI3K/Akt signaling pathway， so as to improve the lung function.

Blau syndrome is a rare genetic disorder characterized by the a mix of granulomatous arthritis, uveitis, and dermatitis. Patients typically manifest multisystem involvement, including ocular, skin, and skeletal abnormalities. Blau syndrome is extremely rare, with a global incidence of less than one in a million among children. In this multidisciplinary consultation, we present a case of a 21-year-old young female patient having multisystemic involvement since early childhood. She was presented with multiple joint swelling, skin lesions, increased eye discharge, and accompanied by hypertension and arterial abnormalities, and received a diagnosis of uveitis. The patient had been receiving steroid treatment since the age of 6 and has tried various medications, with some improvement in joint swelling and ocular symptoms. Through this rare disease multidisciplinary consultation, we aim to provide guidance in the molecular diagnosis of the patient, multisystem assessment, and the selection and formulation of treatment plans. Additionally, we hope that by reporting this case, clinical physicians can gain a better understanding of the diagnosis and comprehensive treatment strategies for Blau syndrome, thereby improving the management and treatment of rare diseases.