To improve the status of management in respiratory failure in China,the project of Study on Pathogenesis and Treatment of Respiratory Failure was designed and conducted by three medical centers(Beijing Institute of Respiratory Medicine-Beijing Chaoyang Hospital,Affiliated to Capital Medical University,Zhongshang Hospital-Fudan University,Guangzhou Institute of Respiratory Medicine-First Guangzhou Medical College)for more than ten years.This project was focused on pathogenesis and treatment strategies of respiratory failure and achieved the following important innovations:(1)Pulmonary Infection Control Window(PIC Window)was firstly proposed and used to determine the time switching point of sequential invasive-noninvasive ventilation;(2)The largest sample size of early use of noninvasive positive pressure ventilation(NPPV)for acute exacerbated COPD(AECOPD)on general ward provided the evidence-based data for expanding the indication of NPPV from treating respiratory failure to alleviating respiratory muscle fatigue;(3)Three new types of masks with intellectual property for NPPV were developed;(4)Designing of intrinsic expiratory end positive pressure(PEEPi)lung model with property of expiratory flow limitation confirmed that PEEPi was the most important factor that increased inspiratory difficulty;(5)The systematic measurement was established for diaphragm strength and endurance;(6)Aquaporin 1(AQP1)was firstly proved the key channel of fluid transportation in the lung;(7)A multicenter prospective cohort study provided objective data that depression had causal effect on COPD exacerbation and hospitalization;(8)Two guidelines for NPPV and mechanical ventilation of AECOPD were initiated by this group.This project has been widely used in clinical practice and promoted the research and treatment of respiratory failure in China.

Adult ; Clavicle ; injuries ; Female ; Fractures, Bone ; surgery ; Humans ; Male ; Scapula ; injuries ; Shoulder Joint ; surgery ; Young Adult

Objective: To study the effect of continuous static pressure on the endoplasmic reticulum of human periodontal ligament cells (hPDLCs) and the mechanism of osteogenic differentiation. Methods: hPDLCs cultured in vitro were subjected to 1 g/cm 2 of continuous compressive pressure (CCP) by custom-made, round, glass panes for 0, 2, 4, and 6 h, respectively. Alkaline phosphatase staining was used to detect osteogenic differentiation, and real-time quantitative PCR was used to detect the expression of protein kinase receptor-like ER kinase (PERK), eukaryotic translation initiation factor 2α (eIF2α), and transcription activation factor 4 (ATF-4). The 0 h loading group was the control group. Results: After CCP treatment, the alkaline phosphatase staining of hPDLCs was blue-violet and significantly stronger than that of cells in the control group. The expression levels of PERK and ATF4 in the hPDLCs after CCP treatment were higher than those of cells in the control group (P < 0.05) and increased over time (P < 0.05). The expression of eIF2α was lower in the experimental groups than in the control group (P < 0.05) and decreased over time (P < 0.05). Conclusion Mechanical stimulation can activate ERS in hPDLCs, leading to enhanced PERK-eIF2α-ATF4 signaling and inducing osteogenic differentiation.

Objective: This study aimed to explore the root length of maxillary and mandibular anterior teeth and central incisor crown-root morphology in patients with high-angle skeletal Class Ⅱ open bite, aiming to provide a reference for clinical treatment. . Methods: This study was reviewed and approved by the Ethics Committee, and informed consent was obtained from the patients. CBCT images of eighty-one untreated patients (40 anterior open bite patients and 41 normal overbite patients) with high-angle skeletal Class Ⅱ malocclusion were selected before treatment. Dolphin software was used to study the root length of maxillary and mandibular anterior teeth and central incisor crown-root morphology, and the differences between the two groups were analyzed. Results: There was no statistical significance in the root length of maxillary lateral incisor and canine between the open bite group and the normal overbite group, significant differences were found in the root length of maxillary central incisor （11.12 ± 1.37） mm、mandibular central incisor（10.15 ± 1.09）mm, mandibular lateral incisor（11.27 ± 1.15）mm and mandibular canine（12.81 ± 1.48）mm between the open bite group and the normal overbite group（P<0.05）. On the other hand, the two groups were significantly different in crown-root morphology of the maxillary central incisor (1.10° ± 3.62° vs. 4.53° ± 2.30°, P<0.01) but not in the mandibular central incisor. Conclusion The root length of the maxillary central incisor, mandibular central incisor, mandibular lateral incisor, mandibular canine in high-angle Class Ⅱ open bite patients is shorter than that in high-angle Class Ⅱ normal overbite patients, and the long axis of the crown of the maxillary central incisor in high-angle Class Ⅱ open bite patients obviously deviates toward the labial side relative to the long axis of the root. The crown-root angle is smaller, which is beneficial to torque control or adduction movement of the anterior teeth in high-angle Class Ⅱ open bite patients.

Objective: To explore the effect of hypoxia inducible factor 1α (HIF-1α) gene silencing in rat bone marrow mesenchymal stem cells (BMMSCs) under mechanical distraction on the expression of bone sialoprotein (BSP) and osterix and to provide a new idea for repairing bone defects with BMMSCs. Methods : The shRNA sequence was designed according to the rat HIF-1α gene, and the pGMLV-SC1RNAi lentiviral vector was cloned after PCR amplification. After screening positive clones and identifying competent transformed cells by sequencing, 293T cells were packaged and titered, rat BMMSCs were transfected and cultured in vitro. Clones with stably silenced HIF-1α expression were screened by inverted fluorescence microscopy. The RNAi response experiment was divided into four groups: the blank control group, the HIF-1α shRNA group, the negative control group, and the response group. Western blot was used to detect the expression of HIF-1α protein in the four groups to verify the response of the target genes and exclude off-target effects. A Flexcell FX-5000T cell stress loading system was used to intervene in the mechanical stretch of the cells. qRT-PCR and Western blot were used to detect the expression of BSP and osterix in the blank control group, HIF-1α shRNA group, and negative control group. Results: The HIF-1α shRNA lentiviral vector was successfully constructed. The results of the RNAi response showed no significant difference in the expression of HIF-1α between the response and the blank control group (P > 0.05). The recombinant lentivirus could effectively silence HIF-1α in BMMSCs. After mechanical distraction of the BMMSCs, compared with the blank and negative control groups, the HIF-1α shRNA group showed significantly increased mRNA and protein expression of the bone-related factors BSP and osterix (P < 0.05); there was no significant difference in the mRNA and protein expression of BSP or osterix between the blank and negative control groups (P > 0.05). Conclusion Silencing HIF-1α in BMMSCs under mechanical distraction can promote the expression of BSP and osterix.

Since the outbreak of 2019-nCoV, the epidemic has developed rapidly and the situation is grim. LANCET figured out that the 2019-nCoV is closely related to "cytokine storm". "Cytokine storm" is an excessive immune response of the body to external stimuli such as viruses and bacteria. As the virus attacking the body, it stimulates the secretion of a large number of inflammatory factors: interleukin(IL), interferon(IFN), C-X-C motif chemokine(CXCL) and so on, which lead to cytokine cascade reaction. With the exudation of inflammatory factors, cytokines increase abnormally in tissues and organs, interfering with the immune system, causing excessive immune response of the body, resulting in diffuse damage of lung cells, pulmonary fibrosis, and multiple organ damage, even death. Arachidonic acid(AA) metabolic pathway is principally used to synthesize inflammatory cytokines, such as monocyte chemotactic protein 1(MCP-1), tumor necrosis factor(TNF), IL, IFN, etc., which is closely related to the occurrence, development and regression of inflammation. Therefore, the inhibition of AA metabolism pathway is benefit for inhibiting the release of inflammatory factors in the body and alleviating the "cytokine storm". Based on the pharmacophore models of the targets on AA metabolic pathway, the traditional Chinese medicine database 2009(TCMD 2009) was screened. The potential herbs were ranked by the number of hit molecules, which were scored by pharmacophore fit value. In the end, we obtained the potential active prescriptions on "cytokine storm" according to the potential herbs in the "National novel coronavirus pneumonia diagnosis and treatment plan(trial version sixth)". The results showed that the hit components with the inhibitory effect on AA were magnolignan Ⅰ, lonicerin and physcion-8-O-β-D-glucopy-ranoside, which mostly extracted from Magnoliae Officinalis Cortex, Zingiberis Rhizoma Recens, Lonicerae Japonicae Flos, Rhei Radix et Rhizoma, Salviae Miltiorrhizae Radix et Rhizoma, Scutellariae Radix, Gardeniae Fructus, Ginseng Radix et Rhizoma, Arctii Fructus, Dryopteridis Crassirhizomatis Rhizoma, Paeoniaeradix Rubra, Dioscoreae Rhizoma. Finally the anti-2019-nCoV prescriptions were analyzed to obtain the potential active prescriptions on AA metabolic pathway, Huoxiang Zhengqi Capsules, Jinhua Qinggan Granules, Lianhua Qingwen Capsules, Qingfei Paidu Decoction, Xuebijing Injection, Reduning Injection and Tanreqing Injection were found that may prevent 2019-nCoV via regulate cytokines. This study intends to provide reference for clinical use of traditional Chinese medicine to resist new coronavirus.
Arachidonic Acid/metabolism* ; Betacoronavirus ; COVID-19 ; Coronavirus Infections/immunology* ; Cytokines/immunology* ; Drugs, Chinese Herbal/pharmacology* ; Humans ; Medicine, Chinese Traditional ; Metabolic Networks and Pathways ; Pandemics ; Pneumonia, Viral/immunology* ; SARS-CoV-2 ; COVID-19 Drug Treatment

ObjectiveTo explore the protective effect and mechanism of Zingiberis Rhizoma Recens alcohol extract on lipopolysaccharide （LPS）-induced acute lung injury in mice. MethodBalb/c mice were randomly divided into normal group， model group， dexamethasone group， and low- and high-dose Zingiberis Rhizoma Recens groups. Mice in the normal group were instilled with normal saline through the nose， and the other groups were instilled with normal saline containing LPS （50 μg）. After 30 minutes of modeling， the dexamethasone group was gavaged with 5 mg·kg^-1 of dexamethasone acetate solution， the low- and high-dose Zingiberis Rhizoma Recens groups were gavaged with different doses of （7， 14 g·kg^-1） of Zingiberis Rhizoma Recens alcohol extract， and the normal group and the model group were gavaged with the same volume of water. After 24 hours of modeling， the total number of white blood cells in bronchoalceolar lavage fluid （BALF） was detected by cell counter， and the levels of the inflammatory factors including tumor necrosis factor （TNF）-α， interleukin （IL）-1β， IL-6， and superoxide dismutase （SOD）， and myeloperoxidase （MPO） was detected by enzyme-linked immunosorbent assay （ELISA）. Haematoxylin-eosin （HE） staining method was used to observe the pathological changes of lung tissue in each group， and the Western blot was used to detect the protein expression of nuclear transcription factor （NF）-κB p65， phosphorylation （p）-NF-κB p65， and Toll-like receptor 4 （TLR4） in lung tissue. ResultCompared with the normal group， the white blood cell count in BALF and the levels of TNF-α， IL-1β， IL-6， and MPO in the model group was increased （P<0.01）， and the level of SOD was decreased （P<0.05）. Pathological damage of lung tissue was obvious， and the protein expression of NF-κB p65， p-NF-κB p65， and TLR4 in lung tissue was increased （P<0.01）. Compared with the model group， the white blood cell count in BALF and the levels of TNF-α， IL-1β， IL-6， and MPO in the treatment group was decreased （P<0.05，P<0.01）， and the level of SOD was increased （P<0.05，P<0.01）. Pathological damage of lung tissue was alleviated， and the protein expression of NF-κB p65， p-NF-κB p65， and TLR4 in lung tissue was decreased （P<0.01）. ConclusionZingiberis Rhizoma Recens alcohol extract may play a protective role in LPS-induced acute lung injury in mice by inhibiting the TLR4/NF-κB signaling pathway.