Novel multidisciplinary cooperation model for obstetric medical quality control: A quasi-experimental study.

OBJECTIVE: To explore the impact of a novel multidisciplinary cooperation model in obstetric medical quality control. METHODS: This quasi-experimental study analyzed the quality indicators of full-term pregnant women who underwent vaginal trial labor in Zibo Maternal and Child Health Hospital between July 2021 and June 2022. The pregnant women were divided into two groups based on implementation of novel multidisciplinary cooperation: multidisciplinary and non-multidisciplinary. We compared the rate of labor analgesia, postpartum hemorrhage in vaginal delivery, transfer to cesarean section, and the 5-min Apgar score ≤7 in full-term neonates. RESULTS: A total of 3751 pregnant women were enrolled into the study, of whom 2004 were included in the non-multidisciplinary group and 1747 in the multidisciplinary group. The analgesic rate of delivery of the multidisciplinary group was higher than that of the non-multidisciplinary group (P = 0.000). We established that the rate of postpartum bleeding (P = 0.040), transfer cesarean section (P = 0.003) and the incidence of Apgar score ≤7 in 5 min of full-term neonates (P = 0.038) of the multidisciplinary group was lower than that of the non-multidisciplinary group. There was no significant difference in the mean ages (29.40 ± 3.99 vs. 29.90 ± 4.27 years; P = 0.126), mean delivery gestational ages (39.65 ± 0.87 vs. 39.64 ± 1.06; P = 0.221), mean gravidity values (1.93 ± 1.09 vs. 2.00 ± 1.18; P = 0.586) and mean parity (1.40 ± 0.56 vs. 1.42 ± 0.59; P = 0.635) of the women in the two groups. CONCLUSION: Multidisciplinary cooperation in delivery management can significantly improve some quality indicators. We established the analgesic rate of delivery can be increased and the rate of postpartum bleeding, transfer cesarean section and the incidence of Apgar score ≤7 in 5 min of full-term neonates can be decreased with the implementation of novel multidisciplinary cooperation.

SIRT6 is an epigenetic repressor of thoracic aortic aneurysms via inhibiting inflammation and senescence.

Thoracic aortic aneurysms (TAAs) develop asymptomatically and are characterized by dilatation of the aorta. This is considered a life-threating vascular disease due to the risk of aortic rupture and without effective treatments. The current understanding of the pathogenesis of TAA is still limited, especially for sporadic TAAs without known genetic mutation. Sirtuin 6 (SIRT6) expression was significantly decreased in the tunica media of sporadic human TAA tissues. Genetic knockout of Sirt6 in mouse vascular smooth muscle cells accelerated TAA formation and rupture, reduced survival, and increased vascular inflammation and senescence after angiotensin II infusion. Transcriptome analysis identified interleukin (IL)-1ß as a pivotal target of SIRT6, and increased IL-1ß levels correlated with vascular inflammation and senescence in human and mouse TAA samples. Chromatin immunoprecipitation revealed that SIRT6 bound to the Il1b promoter to repress expression partly by reducing the H3K9 and H3K56 acetylation. Genetic knockout of Il1b or pharmacological inhibition of IL-1ß signaling with the receptor antagonist anakinra rescued Sirt6 deficiency mediated aggravation of vascular inflammation, senescence, TAA formation and survival in mice. The findings reveal that SIRT6 protects against TAA by epigenetically inhibiting vascular inflammation and senescence, providing insight into potential epigenetic strategies for TAA treatment.

Mic60 is essential to maintain mitochondrial integrity and to prevent encephalomyopathy.

Mitochondrial encephalomyopathies (ME) are frequently associated with mutations of mitochondrial DNA, but the pathogenesis of a subset of ME (sME) remains elusive. Here we report that haploinsufficiency of a mitochondrial inner membrane protein, Mic60, causes progressive neurological abnormalities with insulted mitochondrial structure and neuronal loss in mice. In addition, haploinsufficiency of Mic60 reduces mitochondrial membrane potential and cellular ATP production, increases reactive oxygen species, and alters mitochondrial oxidative phosphorylation complexes in neurons in an age-dependent manner. Moreover, haploinsufficiency of Mic60 compromises brain glucose intake and oxygen consumption in mice, resembling human ME syndrome. We further discover that MIC60 protein expression declined significantly in human sME, implying that insufficient MIC60 may contribute for pathogenesis of human ME. Notably, systemic administration of antioxidant N-acetylcysteine largely reverses mitochondrial dysfunctions and metabolic disorders in haplo-insufficient Mic60 mice, also restores neurological abnormal symptom. These results reveal Mic60 is required in the maintenance of mitochondrial integrity and function, and likely a potential therapeutics target for mitochondrial encephalomyopathies.

[Observation of preventive effect of intervention strategy based on Caprini risk evaluation model on venous thromboembolism after total knee arthroplasty].

OBJECTIVE: To observe preventive effect of Caprini based thrombosis risk evaluation model on venous thromboembolism (VTE) after total knee replacement (TKA). METHODS: Totally 257 TKA patients were admitted from May 2017 to December 2021 were selected. They were divided into conventional intervention strategies (121 patients in control group) and intervention strategies based on Caprini thrombosis risk evaluation model (136 patients in observation group), based on whether Caprini thrombosis risk evaluation model was introduced in May 2019. In normal gourp, there were 79 males and 42 females aged from 50 to 78 years old with an average of (63.10±11.86) years old;body mass index (BMI) ranged from 19 to 32 with an average of (25.21±4.95) kg/m2;55 patients on the left side and 66 on the right side. In observation group, there were 81 males and 55 females aged from 50 to 78 years old with an average of (64.35±10.54) years old;BMI ranged from 19 to 32 with an average of (24.43±5.18) kg/m2;87 patients on the left side and 49 on the right side. The incidence of VTE, visual analogue scale (VAS), Hospital for Special Surgery (HSS) score, affected limb swelling, mean velocity(Vm), peak velocity (PV), D-dimer (D-D), prothrombin time(PT), and incidence of complications were analyzed and compared. RESULTS: The incidence of VTE in observation group was 1.47%(2/136), and 9.09%(11/121) in control group, and there was statistically difference between two groups (χ2=6.976, P=0.008). At 7 days after operation, VAS, HSS score and the difference in circumference of the affected limb in observation group were significantly better than those in control group, and had statistically differences (P<0.05). Blood flow Vm and PV levels between two groups were significantly increased (P<0.001), and blood flow Vm and PV levels in observation group were significantly higher than those in control group on the 7th day after operation, and had differences (P<0.001). The serum D-D level in observation group was significantly lower than that of in control group on the 7th day after operation, and PT level was significantly higher than that of in control group, and had difference(P<0.05). There was no difference in total incidence of complications between two groups (χ2=4.488, P=0.034). CONCLUSION: Intervention strategy based on caprini thrombus risk evluation model could effectively reduce incidence of VTE and complications in TKA patients, improve swelling, hemodynamics and coagulation function of the affected limbs, and contribute to recovery of knee joint function.

The Involvement of CaV1.2 in Estrogenic Modulation of Morphine Antinociception in Rats Under Uterine Cervix Pain.

BACKGROUND: Morphine is one of the preferred drugs for the clinical treatment of pain. Both clinical and preclinical studies have reported sexual dimorphism in morphine analgesia. Different circulating levels of estrogen could be involved in sex differences in response to morphine analgesia. In our previous research, we found that capsaicin injection into the cervix of rats caused acute visceral pain that could be relieved by morphine. The role of estrogen in morphine analgesia in rats under uterine cervix pain and its underlying mechanisms remain to be explored. OBJECTIVES: The present study aims to investigate the effect of estrogen on morphine analgesia and its underlying mechanism in rats under uterine cervix pain. STUDY DESIGN: Controlled animal study. SETTING: University laboratory. METHODS: First, we compared the analgesic effect of morphine in ovariectomized rats with uterine cervix pain with or without estrogen replacement. Then, the changes in the expression of opioid receptors and L-type voltage-gated calcium channels (L-type-VGCC, LTCC) at the spinal level were detected by real-time quantitative polymerase chain reaction. Finally, we investigated the effect of the manipulation of spinal LTCC (L-type CaV1.2 calcium channel, L-type CaV1.3 calcium channel) on the estrogen-mediated inhibition of morphine analgesia. RESULTS: Our study shows that morphine antinociception is  diminished in rats with uterine cervix pain that are treated with estrogen. Estrogen treatment increases the expression of spinal CaV1.2 and CaV1.3, while only anti-CaV1.2 treatment impaired estrogenic suppression of morphine antinociception. LIMITATIONS: More underlying mechanisms of the role of spinal CaV1.2 in modulating estrogen-mediated inhibition of morphine analgesia need to be explored in future research. CONCLUSIONS: This is the first evidence that spinal CaV1.2 is involved in estrogenic modulation of morphine antinociception in rats under uterine cervix pain. Our results will provide new ideas and references for estrogen-related differential prescription of opioids.

Comparison of the in-vivo effect of two tranexamic acid doses on fibrinolysis parameters in adults undergoing valvular cardiac surgery with cardiopulmonary bypass - a pilot investigation.

BACKGROUND: The blood saving efficacy of TXA in cardiac surgery has been proved in several studies, but TXA dosing regimens were varied in those studies. Therefore, we performed this study to investigate if there is a dose dependent in-vivo effect of TXA on fibrinolysis parameters by measurement of fibrinolysis markers in adults undergoing cardiac surgery with CPB. METHODS: A double-blind, randomized, controlled prospective trial was conducted from February 11, 2017 to May 05, 2017. Thirty patients undergoing cardiac valve surgery were identified and randomly divided into a placebo group, low-dose group and high-dose group by 1: 1: 1. Fibrinolysis parameters were measured by plasma levels of D-Dimers, plasminogen activator inhibitor-1 (PAI-1), thrombin activatable fibrinolysis inhibitor (TAFI), plasmin-antiplasmin complex (PAP), tissue plasminogen activator (tPA) and thrombomodulin (TM). Those proteins were measured at five different sample times: preoperatively before the TXA injection (T1), 5 min after the TXA bolus (T2), 5 min after the initiation of CPB (T3), 5 min before the end of CPB (T4) and 5 min after the protamine administration (T5). A Thrombelastography (TEG) and standard coagulation test were also performed. RESULTS: Compared with the control group, the level of the D-Dimers decreased in the low-dose and high-dose groups when the patients arrived at the ICU and on the first postoperative morning. Over time, the concentrations of PAI-1, TAFI, and TM, but not PAP and tPA, showed significant differences between the three groups (P <  0.05). Compared with the placebo group, the plasma concentrations of PAI-1 and TAFI decreased significantly at the T3 and T4 (P <  0.05); TAFI concentrations also decreased at the T5 in low-dose group (P < 0.05). Compared with the low-dose group, the concentration of TM increased significantly at the T4 in high-dose group. CONCLUSIONS: The in-vivo effect of low dose TXA is equivalent to high dose TXA on fibrinolysis parameters in adults with a low bleeding risk undergoing valvular cardiac surgery with cardiopulmonary bypass, and a low dose TXA regimen might be equivalent to high dose TXA for those patients. TRIAL REGISTRATION: ChiCTR-IPR-17010303 , Principal investigator: Zhen-feng ZHOU, Date of registration: January 1, 2017.

BC@DNA-Mn3(PO4)2 Nanozyme for Real-Time Detection of Superoxide from Living Cells.

Electrochemical in situ sensing of small signal molecules released from living cells has an increasing significance in early diagnosis, pathological analyses, and drug discovery. Here, a living cell-fixed sensing platform was built using the BC@DNA-Mn3(PO4)2 nanozyme, in which a highly biocompatible bacterial cellulose riveted with very tiny Mn3(PO4)2; it not only delivers high catalytic activity toward superoxide anions but possesses excellent biocompatibility for cell adsorption and growth. Additionally, the experimental results suggested that fixing the living cells on the surface of the sensing platform facilitates tiny Mn3(PO4)2 activity centers to capture and detect O2•- very quickly and simultaneously has great potential in miniaturization, cost reduction, and real-time monitoring.

Estrogen modulation of visceral pain.

It is commonly accepted that females and males differ in their experience of pain. Gender differences have been found in the prevalence and severity of pain in both clinical and animal studies. Sex-related hormones are found to be involved in pain transmission and have critical effects on visceral pain sensitivity. Studies have pointed out the idea that serum estrogen is closely related to visceral nociceptive sensitivity. This review aims to summarize the literature relating to the role of estrogen in modulating visceral pain with emphasis on deciphering the potential central and peripheral mechanisms.

Constructing high effective nano-Mn3(PO4)2-chitosan in situ electrochemical detection interface for superoxide anions released from living cell.

Monitoring superoxide anions in living cells have attracted much academic and biomedical interest due to their important role in metabolic processes. Herein, we confined ultra-small nano-Mn3(PO4)2 in chitosan and designed a unique puffy woven sphere consisted by nanowires. Further constructed an effective in situ detection chip using the as-synthesized nano-Mn3(PO4)2-chitosan for electrochemical sensing of superoxide anions from murine breast tumor cells (4T1). The excellent biocompatibility of chitosan and large size of the Mn3(PO4)2-chitosan spheres greatly reduced the damage and toxicity of the detection interface to the living cells, while the ultra-small nano-Mn3(PO4)2 in chitosan could effectively catalyze the superoxide anions released from cells. The nano-Mn3(PO4)2-chitosan-based sensor exhibited high sensitivity (1.6 µA µM-1), low detection limit (9.4 nM at S/N = 3) and good selectivity for O2•-. After cell culture on the surface of nano-Mn3(PO4)2-chitosan based electrode. As a miniature analytical and sensing platform, results further suggest that the prepared chip offers a more sensitive detective superoxide anions (O2•-) released from 4T1 cell lines than traditional electron paramagnetic resonance (EPR) analysis.

Effects of Intranasal Cellulose Powder on Asthma Control in Children With Mild-to-Moderate Perennial Allergic Rhinitis: A Randomized, Placebo-Controlled Trial.

BACKGROUND: Perennial allergic rhinitis (PAR) often coexists in asthmatic patients. Intranasal cellulose powder (ICP) was reportedly effective in ameliorating PAR. OBJECTIVE: We investigated whether ICP is equally effective compared with intranasal corticosteroids in improving asthma control as well as nasal symptoms among children with PAR and allergic asthma (AA). METHODS: Between July 2015 and September 2016, we did a single-center, randomized, placebo-controlled trial. Asthmatic children aged 6 to 11 years with mild-to-moderate PAR were randomly assigned to formoterol/budesonide inhalation (4·5 µg/80 µg, twice daily) plus intranasal budesonide 64 µg twice daily (group A), ICP 250 µg thrice daily (group B), or intranasal placebo 250 µg thrice daily (group C) for 8 weeks. The primary outcome was change in asthma control test for children (C-ACT) score from baseline to week 8 posttreatment. Changes in spirometry, peak expiratory flow (PEF), fractional exhaled nitric oxide (FeNO), and visual analog scale (VAS) for nasal and ocular symptoms were detected as secondary outcomes. RESULTS: We included 121 patients (38 in group A, 41 in group B, and 42 in group C) in full-analysis set. C-ACT score was markedly higher at week 8 compared with baseline (mean difference: 5.11, 6.05, and 4.85 points in groups A, B, and C, respectively; P < .05). There were interactions between baseline and treatment in C-ACT scores ( P < .05). Group B demonstrated greater improvement in C-ACT score than group C among children with baseline C-ACT score of 6 to 18. 95% confidence intervals of group A at baseline overlapped with those of groups B and C. The treatment achieved reduced VAS symptoms in groups A and B but not in group C. Incidence of adverse events was comparable. No serious adverse event was reported. CONCLUSIONS: ICP could be recommended for children with PAR and AA who have poorer asthma control.

Sirt6 regulates efficiency of mouse somatic reprogramming and maintenance of pluripotency.

BACKGROUND: Mouse somatic cells can be reprogrammed into induced pluripotent stem cells (iPSCs) by defined factors known to regulate pluripotency, including Oct4, Sox2, Klf4, and c-Myc. It has been reported that Sirtuin 6 (Sirt6), a member of the sirtuin family of NAD+-dependent protein deacetylases, is involved in embryonic stem cell differentiation. However, whether and how Sirt6 influences epigenetic reprogramming remains unknown. METHODS: Mouse embryonic fibroblasts isolated from transgenic Oct4-GFP reporter mice with or without Sirt6 were used for reprogramming by Yamanaka factors. Alkaline phosphatase-positive and OCT4-GFP-positive colony were counted to calculate reprogramming efficiency. OP9 feeder cell co-culture system was used to measure the hematopoietic differentiation from mouse ES and iPS cells. RNA sequencing was measured to identify the differential expressed genes due to loss of Sirt6 in somatic and pluripotent cells. RESULTS: In this study, we provide evidence that Sirt6 is involved in mouse somatic reprogramming. We found that loss of function of Sirt6 could significantly decrease reprogramming efficiency. Furthermore, we showed that Sirt6-null iPS-like cell line has intrinsically a differentiation defect even though the establishment of normal self-renewal. Particularly, by performing transcriptome analysis, we observed that several pluripotent transcriptional factors increase in knockout cell line, which explains the underlying loss of pluripotency in Sirt6-null iPS-like cell line. CONCLUSIONS: Taken together, we have identified a new regulatory role of Sirt6 in reprogramming and maintenance of pluripotency.

Intraoperative tranexamic acid is associated with postoperative stroke in patients undergoing cardiac surgery.

BACKGROUND: Stroke is a devastating and potentially preventable complication of cardiac surgery. Tranexamic acid (TXA) is a commonly antifibrinolytic agent in cardiac surgeries with cardiopulmonary bypass (CPB), however, there is concern that it might increase incidence of stroke after cardiac surgery. In this retrospective study, we investigated whether TXA usage could increase postoperative stroke in cardiac surgery. METHODS: A retrospective study was conducted from January 1, 2010, to December 31, 2015, in 2,016 patients undergoing cardiac surgery, 664 patients received intravenous TXA infusion and 1,352 patients did not receive any antifibrinolytic agent. Univariate and propensity-weighted multivariate regression analysis were applied for data analysis. RESULTS: Intraoperative TXA administration was associated with postoperative stroke (1.7% vs. 0.5%; adjusted OR, 4.11; 95% CI, 1.33 to 12.71; p = 0.014) and coma (adjusted OR, 2.77; 95% CI, 1.06 to 7.26; p = 0.038) in cardiac surgery. As subtype analysis was performed, TXA administration was still associated with postoperative stroke (1.7% vs. 0.3%; adjusted OR, 5.78; 95% CI, 1.34 to 27.89; p = 0.018) in patients undergoing valve surgery or multi-valve surgery only, but was not associated with postoperative stroke (1.7% vs. 1.3%; adjusted OR, 5.21; 95% CI, 0.27 to 101.17; p = 0.276) in patients undergoing CABG surgery only. However, TXA administration was not associated with postoperative mortality (adjusted OR, 1.31; 95% CI, 0.56 to 3.71; p = 0.451), seizure (adjusted OR, 1.13; 95% CI, 0.42 to 3.04; p = 0.816), continuous renal replacement therapy (adjusted OR, 1.36; 95% CI, 0.56 to 3.28; p = 0.495) and resternotomy for postoperative bleeding (adjusted OR, 1.55; 95% CI, 0.55 to 4.30; p = 0.405). No difference was found in postoperative ventilation time (adjusted B, -1.45; SE, 2.33; p = 0.535), length of intensive care unit stay (adjusted B, -0.12; SE, 0.25; p = 0.633) and length of hospital stay (adjusted B, 0.48; SE, 0.58; p = 0.408). CONCLUSIONS: Based on the 5-year experience of TXA administration in cardiac surgery with CPB, we found that postoperative stroke was associated with intraoperative TXA administration in patients undergoing cardiac surgery, especially in those undergoing valve surgeries only. This study may suggest that TXA should be administrated according to clear indications after evaluating the bleeding risk in patients undergoing cardiac surgery, especially in those with high stroke risk.

EphrinB-EphB Signaling Induces Hyperalgesia through ERK5/CREB Pathway in Rats.

BACKGROUND: There are numerous studies implicating that EphB receptors and ephrinB ligands play important roles in modulating the transduction of spinal nociceptive information. EphrinB-EphB signaling may contribute to hyperalgesia via various kinds of downstream molecules, the mechanisms of which have not been completely understood. OBJECTIVE: The aim of the present study was to identify whether ephrinB-EphB signaling could contribute to hyperalgesia through ERK5/CREB pathway. STUDY DESIGN: Controlled animal study. SETTING: University laboratory. METHODS: This study attempted to detect the changes of pain behaviors and the protein level of p-ERK5 and p-CREB by activating EphB receptors in the spinal cord of rats. To further confirm our hypothesis, we designed LV-siRNA for knockdown of spinal ERK5. When ERK5 was inhibited, we recorded the changes of spinal p-CREB expression and the pain behaviors of rats after activating EphB receptors. We also confirmed this conclusion in rat CCI model. Statistical analyses were performed using GraphPad Prism 5. RESULTS: Intrathecal injection of ephrinB2-Fc in rats evoked thermal hyperalgesia and mechanical allodynia, along with activation of ERK5 and CREB in the spinal cord. Knockdown of ERK5 inhibited ephrinB2-Fc-induced CREB activation and hyperalgesia. Blocking EphB receptors prevented CCI-induced neuropathic pain and spinal ERK5/CREB activation. LIMITATIONS: More underlying mechanisms that underlie the relationship between ephrinB-EphB signaling and ERK5/CREB pathway will need to be explored in future studies. CONCLUSIONS: Our study suggests that ERK5/CREB pathway plays important roles in the transduction of nociceptive information associated with ephrinB-EphB signaling. This study provides further understanding of the downstream mechanisms of ephrinB-EphB signaling and helps to explore new targets for treating pathological pain.

Research progress of the role and mechanism of extracellular signal-regulated protein kinase 5 (ERK5) pathway in pathological pain.

Extracellular signal-regulated protein kinase 5 (ERK5), also known as big mitogen-activated protein kinase 1 (MAPK1), is an important member of ERK family, which is a subfamily of the large MAPK family. ERK5 is expressed in many tissues, including the dorsal root ganglion (DRG) neurons and the spinal cord. In this review, we focus on elaborating ERK5-associated pathway in pathological pain, in which the ERK5/CREB (cyclic adenosine monophosphate (cAMP)-response element-binding protein) pathway plays a crucial role in the transduction of pain signal and contributes to pain hypersensitivity. ERK5 activation in the spinal dorsal horn occurs mainly in microglia. The activation of ERK5 can be mediated by N-methyl-D-aspartate (NMDA) receptors. We also elaborate the relationship between ERK5 activation and nerve growth factor-tyrosine kinase A (NGF-TrkA), and the connection between ERK5 activation and brain-derived neurotrophic factor (BDNF) in pathological pain in detail.

[Body acupuncture combined with auricular acupressure for menstrual headache: a randomized controlled clinical trial].

OBJECTIVE: To observe the therapeutic effect of body acupuncture combined with auricular acupressure for treatment of menstrual headache of hyperactivity of "liver fire". METHODS: A total of 85 menstrual headache patients with hyperactivity of "liver-fire" were randomly divided into control group (n = 42) and treatment group (n = 43). Patients of the control group were treated by oral administration of Flunarizine Hydrochloride Capsules (Sibelium, 5 mg/time, twice daily) for 5 days beginning at the headache attack in the first menstrual cycle, and for two weeks (except weekends) in the second and third menstrual cycles. Patients of the treatment group were treated by manual acupuncture stimulation of body acupoints Baihui (GV 20), Fengchi (GB 20), Sanyinjiao (SP 6), Taichong (LR 3), Xiaxi (GB 43), Taiyang (EX-HN 5), Hanyan (GB 4), Xuanlu (GB 5) and Shuaigu (GB 8) beginning from the headache attack, and otopoint-pellet pressure of otopoints unilateral Endocrine, Ovaries, Shenmen, Cortex, Liver, Spleen and Kidney (beginning 5 days before menstrual onset) and bilateral Shenmen, Nie, Liver, Gallbladder, Subcortex and Jiaogan during headache attack. Clinical symptom scores were assessed according to the "Guiding Principles for Clinical Research on New Chinese Herbal Drugs" issued by the Chinese Ministry of Health. RESULTS: After the treatment, of the 42 and 43 cases in the control and treatment groups, 9 (21.43%) and 20 (46.51%) were cured, 12 (28.57%) and 14 (32.56%) had a marked improvement, 13 (30.95%) and 7 (16.28%) were effective, 8 (19.05%) and 2 (4.65%) invalid, with the effective rates being 80.95% and 95.35% , respectively. The curative effect of the treatment group was significantly better than that of the control group (P<0.05). The symptom score and VAS score after the treatment and 3 months post-treatment in the treatment group were significantly lower than those of the control group (P<0.01). The headache scores and VAS scores were significantly reduced following the treatment and 3 months after the treatment in both control and treatment groups (P<0.01). After the treatment for 2-3 therapeutic courses, the headache attack duration during menstruation was markedly and gradually shortened in both groups (P<0.01), and therapeutic effect of the treatment group was significantly better than that of the control group (P<0.01). CONCLUSION: Body acupuncture combined with auricular acupressure treatment can effectively relieve menstrual headache in menstrual women with hyperactivity of "liver fire".

Suppression of Mic60 compromises mitochondrial transcription and oxidative phosphorylation.

Precise regulation of mtDNA transcription and oxidative phosphorylation (OXPHOS) is crucial for human health. As a component of mitochondrial contact site and cristae organizing system (MICOS), Mic60 plays a central role in mitochondrial morphology. However, it remains unclear whether Mic60 affects mitochondrial transcription. Here, we report that Mic60 interacts with mitochondrial transcription factors TFAM and TFB2M. Furthermore, we found that Mic60 knockdown compromises mitochondrial transcription and OXPHOS activities. Importantly, Mic60 deficiency decreased TFAM binding and mitochondrial RNA polymerase (POLRMT) recruitment to the mtDNA promoters. In addition, through mtDNA immunoprecipitation (mIP)-chromatin conformation capture (3C) assays, we found that Mic60 interacted with mtDNA and was involved in the architecture of mtDNA D-loop region. Taken together, our findings reveal a previously unrecognized important role of Mic60 in mtDNA transcription.

Respiratory syncytial virus induces leukotriene C4 synthase expression in bronchial epithelial cells.

BACKGROUND AND OBJECTIVE: Respiratory syncytial virus (RSV) results in acute wheezing in infants and is frequently associated with recurrent wheezing. Although RSV-induced wheezing clinically resembles that of asthma, corticosteroids are not equivalently effective in RSV-associated wheezing. The study sought to determine the mechanisms of RSV-induced wheezing by establishing an in vitro model of RSV-infected human bronchial epithelial cells (16-HBEC). METHODS: Leukotriene C4 synthase (LTC4 S) messenger RNA (mRNA) expression in 16-HBEC was detected using fluorescence quantitative polymerase chain reaction, and the relative level of LTC4 S mRNA was expressed as quotient cycle threshold (qCt) based on the threshold cycle number value compared with that of ß-actin. Cysteinyl leukotrienes (CysLT) in culture supernatant were measured by enzyme-linked immunosorbent assay. RSV-infected 16-HBEC was incubated with gradient concentration of budesonide (BUD) to assess its effects on LTC4 S expression and CysLT secretion. RESULTS: RSV infection resulted in increased LTC4 S mRNA expression between 48 and 96 h post-infection. High level of CysLT was detected in the supernatant of RSV-infected 16-HBEC. BUD at concentrations of 10(-10) to 10(-5) mol/L did not significantly alter LTC4 S mRNA expression. CONCLUSIONS: RSV infection upregulated LTC4 S expression in HBEC leading to increased CysLT secretion. Such induction was not attenuated by BUD, suggesting that CysLT might contribute to the pathogenesis of RSV-induced wheezing.

Effects of nebulized high-dose budesonide on moderate-to-severe acute exacerbation of asthma in children: a randomized, double-blind, placebo-controlled study.

BACKGROUND AND OBJECTIVE: The efficacy of inhaled corticosteroids (ICS) in asthma exacerbation are yet to be clarified. The aim of this study was to investigate the efficacy of nebulized ICS in children with moderate-to-severe acute exacerbation of asthma in an emergency room setting in order to elucidate the potential use of ICS as the first-line therapy in the management of acute exacerbation of asthma. METHODS: This was a prospective, randomized, double-blind, placebo-controlled study. Paediatric patients with moderate-to-severe acute exacerbation of asthma in emergency room were randomized to receive nebulized salbutamol and ipratropium bromide, with the addition of nebulized high-dose budesonide (BUD group, n = 60) or normal saline (control group, n = 58), three doses in the first hour. RESULTS: The improvement in forced expiratory volume in 1 s was similar in both groups at 0 h after three doses of nebulization, but there was significantly further improvement at 1 and 2 h in the BUD group (0.095 ± 0.062 L and 0.100 ± 0.120 L, respectively) compared with the control group (0.059 ± 0.082 L and 0.021 ± 0.128 L, respectively), P = 0.013 and 0.001, respectively. Complete remission rate was significantly higher (84.7% vs 46.3%, P = 0.004) and need for oral corticosteroids was significantly lower (16.9% vs 46.3%, P = 0.011) in BUD group than in control group. CONCLUSION: On the basis of nebulized short-acting bronchodilators, addition of nebulized high-dose budesonide resulted in clinical improvement in children with moderate-to-severe acute exacerbation of asthma, suggesting that nebulized high-dose ICS can be used as first-line therapy for non-life-threatening acute exacerbation of asthma in children.

[Effect of mild moxibustion on macrophage number and collagen expression of raw surface tissue in chronic refractory skin ulcer rats].

OBJECTIVE: To observe the effect of mild moxibustion on the number of macrophages and contents of collagen I and III in the raw surface tissue in chronic skin ulcer rats so as to study its mechanism underlying promoting scar formation. METHODS: Eighty male SD rats were randomly divided into normal (n = 8), model (n = 24), TDP (n = 24) and moxibustion (n = 24) groups. Chronic refractory skin ulcer was established by making an open wound at the back and local intramuscular injection of hydrocortisone sodium succinate. For rats of the TDP and moxibustion groups, TDP irradiation or mild moxibustion was applied to the raw surface, bilateral "Shenshu" (BL 23) and "Zusanli" (ST 36) for 15 min, once daily for 7, 10 and 14 days, respectively. The number of macrophages in the raw surface tissue was counted under light microscope after H. E. staining and col- lagen I and III expressions of the raw surface tissue were detected by immunohistochemistry. RESULTS: In comparison with the normal group, the numbers of macrophages in the raw surface tissue were increased significantly in the model group on day 7, 10 and 14 (P < 0.05); while compared with the model group, the numbers of macrophages were increased further obviously in the moxibustion group on day 7 and 10 and in the TDP group on day 10 after the treatment (P < 0.05). Compared with the model group, the numbers of macrophages in both TDP and moxibustion groups were down-regulated obviously (P < 0. 05). In regard to collagen I and III expression of the raw surface tissue, compared with the normal group, the collagen I protein expression level was down-regulated markedly in the model group on the 7th day (P < 0.01); whereas in comparison with the model group, the expression levels of collagen I and III were increased considerably in the TDP and moxibustion groups on day 7 and 14 after the treatment (P < 0.05, P < 0.01). The ratios of collagen I/III expression were remarkably higher in the model group than in the normal group on day 7 and 14 (P < 0.05), and significantly lower in the TDP group on day 7 and 14 and in the moxibustion group on day 14 than in the model group (P < 0.05, P < 0.01). The effects of moxibustion were obviously superior to those of TDP in up-regulating macrophage number on day 10, up-regulating collagen I and III expressions on day 14, and down-regulating macrophage number on day 14 after the treatment (P < 0.05, P < 0.01). No significant differences were found between the TDP and moxibustion groups in up-regulating macrophage number, and collagen I and III protein expressions, and in down-regulating the ratios of collagen I/III expression on day 7 after the treatment (P > 0.05). CONCLUSION: Mild moxibustion can regulate the number of macrophages and strengthen the expression of collagen proteins in the raw surface tissue in the chronic skin ulcer rats, which may contribute to its effect in promoting wound healing and reducing scar formation.

Mitofilin regulates cytochrome c release during apoptosis by controlling mitochondrial cristae remodeling.

Mitochondria amplify caspase-dependent apoptosis by releasing proapoptotic proteins, especially cytochrome c. This process is accompanied by mitochondrial cristae remodeling. Our studies demonstrated that mitofilin, a mitochondrial inner membrane protein, acted as a cristae controller to regulate cytochrome c release during apoptosis. Knockdown of mitofilin in HeLa cells with RNAi led to fragmentation of the mitochondrial network and disorganization of the cristae. Mitofilin-deficient cells showed cytochrome c redistribution between mitochondrial cristae and the intermembrane space (IMS) upon intrinsic apoptotic stimuli. In vitro cytochrome c release experiments further confirmed that, compared with the control group, tBid treatment led to an increase in cytochrome c release from mitofilin-deficient mitochondria. Furthermore, the cells with mitofilin knockdown were more prone to apoptosis by accelerating cytochrome c release upon the intrinsic apoptotic stimuli than controls. Moreover, mitofilin deficiency did not interfere with the activation of proapoptotic member Bax upon intrinsic apoptotic stimuli. Thus, mitofilin distinctly functions in cristae remodeling and controls cytochrome c release during apoptosis.