Lipocalin-2 silencing suppresses inflammation and oxidative stress of acute respiratory distress syndrome by ferroptosis via inhibition of MAPK/ERK pathway in neonatal mice.

Neonatal acute respiratory distress syndrome (ARDS) has high morbidity and mortality rates worldwide, but there is a lack of pharmacologic treatment and clinical targeted therapies. In this study, we aimed to explore the effects of Lipocalin-2 (LCN2) on ferroptosis-mediated inflammation and oxidative stress in neonatal ARDS and the potential mechanism. In this study, we established an in vivo ARDS mouse model and an in vitro ARDS cell model by LPS (Lipopolysaccharide) stimulation. Lung tissue injury was evaluated by wet/dry ratios and histopathological examination. LCN2 expression was detected by qRT-PCR and Western blot. Inflammatory factors, oxidative stress and apoptosis were also detected. Ferroptosis was identified by detection of Fe2+ level and ferroptosis-associated protein expressions. Mitogen-activated protein kinases (MAPK)/extracellular signal-regulated kinase (ERK) pathway signaling was examined by Western blot analysis. The data revealed that LCN2 expression was significantly upregulated in neonatal mice with ARDS. Interference with LCN2 protected LPS-induced lung in neonatal mouse by reducing the radio of wet/dry and alleviating pathological damages. In addition, LCN2 silencing repressed LPS-induced inflammation, oxidative stress in vivo and in vitro, as well as apoptosis. Meanwhile, decreased level of Fe2+ and transferrin while increased levels of ferritin heavy chain 1 (FTH1) and glutathione peroxidase 4 (GPX4) were observed. The expression MAPK/ERK pathway was inhibited by depletion of LCN2. The present results suggest that LCN2 knockdown protected LPS-induced ARDS model via inhibition of ferroptosis-related inflammation and oxidative stress by inhibiting the MAPK/ERK pathway, thereby presenting a novel target for the treatment of ARDS.

Efficacy of acupuncture for primary insomnia: a randomized controlled clinical trial.

Objectives. To investigate the six-week influence of acupuncture on sleep quality and daytime functioning in primary insomnia. Methods. The study was a double-dummy, single-blinded, randomized, placebo-controlled clinical trial. A total of 180 patients with primary insomnia were randomly assigned to 3 groups: verum group underwent verum acupuncture plus placebo; estazolam group underwent estazolam plus sham acupuncture; sham group underwent sham acupuncture plus placebo. The outcome was measured by Pittsburgh Sleep Quality Index (PSQI), Epworth Sleepiness Scale (ESS), and the 36-item short-form health survey (SF-36). Results. The three groups showed significant improvement compared with the pretreatment baseline. Compared with the other two groups, the verum group reported improved sleep quality (SQ) and vitality (VT), decreased daytime dysfunction (DD) and sleepiness (ESS score). The differences were kept from the treatment period to the end of the trial. Discussion. Verum acupuncture appeared to be more effective in increasing sleep quality and daytime functioning than sham acupuncture and estazolam. Trial Registration. The trial is registeded with ClinicalTrials.gov ISRCTN12585433.

Efficacy of acupuncture for acute migraine attack: a multicenter single blinded, randomized controlled trial.

OBJECTIVE: We aim to investigate the efficacy of acupuncture for acute migraine attacks comparing with sham acupuncture. DESIGN: The study was designed as a multicenter, single-blinded, randomized controlled clinical trial. SETTING AND PATIENTS: From March 2007 to February 2009, 150 patients were randomly allocated to verum or sham acupuncture group in a ratio of 1:1. INTERVENTIONS: Every patient received a verum or sham acupuncture treatment when having a migraine attack and, medications were allowed if the pain failed to be relieved two hours after the acupuncture. OUTCOME MEASURES: The primary outcome was visual analog scale (VAS) scores for pain, ranging from 0 (no pain) to 10 (worst pain ever). RESULTS: The mean VAS scores 24 hours after treatment decreased from 5.7 ± 1.4 to 3.3 ± 2.5 in the verum acupuncture group, and from 5.4 ± 1.3 to 4.7 ± 2.4 in the sham acupuncture group. Significant differences existed between the two groups (P = 0.001). CONCLUSIONS: This trial suggested that verum acupuncture group was superior to sham acupuncture group on relieving pain and reducing the usage of acute medication.

Efficacy of acupuncture for migraine prophylaxis: a single-blinded, double-dummy, randomized controlled trial.

Insufficient clinical trial data were available to prove the efficacy of acupuncture for migraine prophylaxis. A multicenter, double-dummy, single-blinded, randomized controlled clinical trial was conducted at the outpatient departments of acupuncture at 5 hospitals in China to evaluate the effectiveness of acupuncture. A total of 140 patients with migraine without aura were recruited and assigned randomly to 2 different groups: the acupuncture group treated with verum acupuncture plus placebo and the control group treated with sham acupuncture plus flunarizine. Treated by acupuncture 3 times per week and drugs every night, patients from both groups were evaluated at week 0 (baseline), week 4, and week 16. The primary outcome was measured by the proportion of responders (defined as the proportion of patients with a reduction of migraine days by at least 50%). The secondary outcome measures included the number of migraine days, visual analogue scale (VAS, 0 to 10 cm) for pain, as well as the physical and mental component summary scores of the 36-item short-form health survey (SF-36). The patients in the acupuncture group had better responder rates and fewer migraine days compared with the control group (P<.05), whereas there were no significant differences between the 2 groups in VAS scores and SF-36 physical and mental component summary scores (P>.05). The results suggested that acupuncture was more effective than flunarizine in decreasing days of migraine attacks, whereas no significantly differences were found between acupuncture and flunarizine in reduction of pain intensity and improvement of the quality of life.

[Therapy for replenishing qi, nourishing yin and promoting blood circulation in patients with acute myocardial infarction undergoing percutaneous coronary intervention: a randomized controlled trial].

BACKGROUND: No-reflow phenomenon after reperfusion treatment of acute myocardial infarction (AMI) is becoming more recognized today. The effective treatment for no-reflow has not been reported. OBJECTIVE: To observe the effects of traditional Chinese medicine (TCM) therapy for replenishing qi, nourishing yin, and promoting blood circulation on AMI patients undergoing percutaneous coronary intervention (PCI). DESIGN, SETTING, PARTICIPANTS AND INTERVENTIONS: This study was conducted from January 2005 to March 2006 using a double-blinded, randomized method. Thirty-five AMI patients (Killip I-II) were first diagnosed as ST segment elevation AMI and obtained primary PCI. They were recruited from People's Hospital, Peking University. All patients' symptoms accorded with qi-yin deficiency syndrome and blood stasis syndrome. They were randomly and double blindly divided into control group (18 cases) and treatment group (17 cases). The patients in the control group received Western medicine treatment, and the patients in the treatment group were treated with Western medicine plus American ginseng and Salviae miltiorrhizae preparations. They were all treated for 3 months. MAIN OUTCOME MEASURES: Before and after 3-month treatment, the TCM symptoms were observed and scored. At the state of baseline and dobutamine stress, left ventricular ejection fraction (LVEF), wall motion score (WMS), WMS index and normal cardiac muscle percentage (NCMP), and the myocardial contrast echocardiography index k, which reflects myocardium microcirculation perfusion, were detected. RESULTS: After 3-month treatment, the TCM symptoms in the treatment group were improved as compared with the control group (X(2)=4.118, P=0.042). At the state of dobutamine stress, LVEF in the treatment group after treatment was higher than those in the control group (t=2.130, P=0.041) and before treatment (t=2.345, P=0.032). Although the number of the segments with increased k value was more than that in the control group, there was no significant difference. CONCLUSION: TCM therapy for replenishing qi, nourishing yin and promoting blood circulation can improve the clinical symptoms and quality of life of the AMI patients undergoing PCI, and is beneficial to myocardium microcirculation. Thus, it may be an alternative cardioprotective treatment strategy for successful myocardial microcirculation in AMI patients after reperfusion.

The design and protocol of acupuncture for migraine prophylaxis: a multicenter randomized controlled trial.

BACKGROUND: Many studies have already reported encouraging results in the prophylactic therapy of migraine by acupuncture, but there seems to be a lack of high quality randomized controlled trials from China. We design and perform a randomized controlled clinical trial to evaluate the efficacy of acupuncture compared with flunarizine in the prophylactic therapy of patients with migraine without aura in China. METHODS: This trial is a multicenter, prospective, randomized controlled clinical trial. The 140 migraine patients are randomly allocated to two different groups. The acupuncture groups (n = 70) is treated with acupuncture and placebo medicine; while the control group (n = 70) is treated with sham acupuncture and medicine (Flunarizine). Both Flunarizine and placebo are taken 10 mg once per night for the first 2 weeks and then 5 mg once per night for the next 2 weeks. Patients in both groups receive 12 sessions of verum/sham acupuncture in 4 weeks. DISCUSSION: The study design and the long term clinical practice of acupuncturists guarantee a high external validity for the results. The results of our trial will be helpful to supply the evidence on the efficacy of acupuncture for migraine prophylaxis in China.