OBJECTIVE To explore the effect and mechanism of berberine in ameliorating asthma in mice by regulating glycolysis via the hypoxia inducible factor-1α （HIF-1α）/pyruvate dehydrogenase kinase-1 （PDHK1） pathway.METHODS Mice were randomly divided into blank control group， model group， low- and high-dose berberine groups （100， 200 mg/kg， intragastric administration）， dimethyloxalylglycine （DMOG， HIF-1α agonist） group （2 mg， intranasal instillation）， and berberine+DMOG group （intragastric administration of 200 mg/kg berberine plus intranasal instillation of 2 mg DMOG）， with 12 mice in each group. Except for the blank control group， mice in the remaining groups were subjected to ovalbumin-induced sensitization and challenge to establish the asthma model. During the challenge period， mice were given corresponding drugs or normal saline once a day for 6 consecutive days. At 24 h after the last challenge， pulmonary function and airway reactivity of mice were determined； the content of ovalbumin-specific immunoglobulin E （OVA-sIgE） in serum was detected； inflammatory cells in bronchoalveolar lavage fluid （BALF） were counted； bronchial inflammation and goblet cell hyperplasia were histologically evaluated； the levels of inflammatory cytokines [interleukin-4 （IL-4）， IL-5， IL-13]， contents of glycolytic products [lactic acid， pyruvic acid， adenosine triphosphate （ATP）]， as well as mRNA and protein expressions related to the HIF-1α/PDHK1 pathway in lung tissue were measured.RESULTS Compared with the model group， the low- and high-dose berberine groups exhibited significantly elevated or increased dynamic lung compliance， peak expiratory flow， forced vital capacity （FVC）， forced expiratory volume in 0.1 second （FEV 0.1 ）， and FEV 0.1 /FVC （ P ＜0.05）， accompanied by significantly decreased airway resistance and enhanced pause value （ P ＜0.05）. Moreover， serum OVA-sIgE content， counts of white blood cell， neutrophil， lymphocyte， monocyte， eosinophil and basophil in BALF， scores for bronchial inflammation and goblet cell hyperplasia， levels of pulmonary inflammatory cytokines and contents of glycolytic products， as well as mRNA and protein expressions of HIF-1α， PDHK1， pyruvate kinase M2 and lactate dehydrogenase A were all significantly reduced （ P ＜0.05）. DMOG pretreatment obviously reversed the protective effects of high-dose berberine in asthmatic mice （ P ＜0.05）.CONCLUSIONS Berberine can inhibit the HIF-1α/PDHK1 pathway to decrease glycolytic level， so as to ameliorate airway inflammation and airway hyperresponsiveness in asthmatic mice.

Thoracic trauma has the characteristics of complexity, specificity, urgency and severity. Therefore, the treatment is particularly important. Thoracic Traumatology Group, Trauma Medicine Branch of Zhejiang Medical Association organized the writing of the thoracic trauma and further optimization consensus of Zhejiang thoracic surgery industry Treatment and diagnosis of rib and sternum trauma: A consensus statement by Zhejiang Association for Thoracic Surgery (version 2021), compiled the popular science book Emergency Treatment and Risk Avoidance Strategy of Thoracic Trauma and Illustration of Real Scene Treatment of Trauma, actively prepared to build the trauma database of Zhejiang Province, and participated in the construction of trauma group in the Yangtze River Delta. Although Zhejiang Province has carried out many related works in the diagnosis and treatment of chest trauma, it is still inconsistent with the development requirements of the times. Standardization of chest trauma treatment, popularization of relevant knowledge, management of trauma big data, grass-roots radiation promotion tour and further optimization of industry consensus are the requirements and objectives of this era.

OBJECTIVETo investigate the effect and mechanism of high dose Vitamin B3 on granulopoiesis in normal rat.

METHODSTwenty one healthy SD rats were randomly divided into three groups: the Vitamin B3 group (Vit B3 500 mg·kg⁻¹·d⁻¹, × 7 d), the rhG-CSF group (rhG-CSF 25 μg·kg⁻¹·d⁻¹, × 7 d) and the normal saline group (2 ml/d, × 7 d). The peripheral blood cell counts were analyzed by automatic blood cell counter before (day 0) treatment, the third day (day 3) and the seventh day (day 7) after administration of drugs, respectively. The concentration of serum nicotinamide adenine dinucleotide (NAD⁺) level was measured by enzymatic cycling assay before and after drugs treatment. The expressions of G-CSF, G-CSFR, SIRT1, C/EBPα, C/EBPβ, C/EBPε and NAMPT mRNA were detected by reverse transcription real-time fluorescent quantitative PCR.

RESULTSThe neutrophil counts increased significantly after 7 days of Vitamin B3 and rhG-CSF treatment compared with that of control group [(1.64 ± 0.19) × 10⁹/L, (1.88 ± 0.37)× 10⁹/L vs (0.86 ± 0.18) × 10⁹/L, P<0.01]; the level of serum NAD⁺ increased significantly [(0.96 ± 0.08) nmol/L, (0.65 ± 0.12) nmol/L vs (0.36 ± 0.15) nmol/L, P<0.01]; the expression of G-CSF, G-CSFR, SIRT1, C/EBPα, C/EBPε and NAMPT mRNA in bone marrow mononuclear cells were increased significantly compared with that of control group (P<0.01).

CONCLUSIONHigh dose of Vitamin B3 may play an important role in increasing absolute neutrophil count in healthy rat under steady state, and the mechanism may be dependent on NAMPT-NAD⁺-SIRT1 signaling pathways.

Animals ; Bone Marrow Cells ; Granulocyte Colony-Stimulating Factor ; Leukocyte Count ; Neutrophils ; drug effects ; Niacinamide ; pharmacology ; Rats ; Rats, Sprague-Dawley ; Recombinant Proteins