Trim14-IκBα Signaling Regulates Chronic Inflammatory Pain in Rats and Osteoarthritis Patients.

Chronic inflammatory pain is the highest priority for people with osteoarthritis when seeking medical attention. Despite the availability of NSAIDs and glucocorticoids, central sensitization and peripheral sensitization make pain increasingly difficult to control. Previous studies have identified the ubiquitination system as an important role in the chronic inflammatory pain. Our study displayed that the E3 ubiquitin ligase tripartite motif-containing 14 (Trim14) was abnormally elevated in the serum of patients with osteoarthritis and pain, and the degree of pain was positively correlated with the degree of Trim14 elevation. Furthermore, CFA-induced inflammatory pain rat model showed that Trim14 was significantly increased in the L3-5 spinal dorsal horn (SDH) and dorsal root ganglion (DRG), and in turn the inhibitor of nuclear factor Kappa-B isoform α (IκBα) was decreased after Trim14 elevation. After intrathecal injection of Trim14 siRNA to inhibit Trim14 expression, IκBα expression was reversed and increased, and the pain behaviors and anxiety behaviors of rats were significantly relieved. Overall, these findings suggested that Trim14 may contribute to chronic inflammatory pain by degrading IκBα, and that Trim14 may become a novel therapeutic target for chronic inflammatory pain.

TET1-TRPV4 Signaling Contributes to Bone Cancer Pain in Rats.

Bone cancer pain (BCP) is excruciating for cancer patients, with limited clinical treatment options and significant side effects, due to the complex and unclear pathogenesis of bone cancer pain. Peripheral sensitization in dorsal root ganglion (DRG) neurons is a recognized cellular mechanism for bone cancer pain. The pathological mechanism of chronic pain is increasingly being affected by epigenetic mechanisms. In this study, we unbiasedly showed that the DNA hydroxymethylase ten-eleven translocation 1 (TET1) expression was significantly increased in the L4-6 DRG of BCP rats and ten-eleven translocation 2 (TET2) expression did not change significantly. Notably, TET1 inhibition by intrathecal injection of Bobcat339 (a TET1 inhibitor) effectively relieved mechanical hyperalgesia in BCP rats. Peripheral sensitization in chronic pain relies on the activation and overexpression of ion channels on neurons. Here, we demonstrated that TRPV4, one of the transient receptor potential ion channel family members, was significantly elevated in the L4-6 DRG of BCP rats. In addition, TRPV4 inhibition by intrathecal injection of HC067047 (a TRPV4 inhibitor) also significantly attenuated mechanical hyperalgesia in BCP rats. Interestingly, we found that TET1 inhibition downregulated TRPV4 expression in the L4-6 DRG of BCP rats. As a result, these findings suggested that TET1 may contribute to bone cancer pain by upregulating TRPV4 expression in the L4-6 DRG of BCP rats and that TET1 or TRPV4 may become therapeutic targets for bone cancer pain.

Increased ten-eleven translocation methylcytosine dioxygenase one in dorsal root ganglion contributes to inflammatory pain in CFA rats.

DNA hydroxylation catalyzed by Tet dioxygenases occurs abundantly in neurons in mammals. However, effects of ten-eleven translocation methylcytosine dioxygenase 1 (TET1) expression and hydroxymethylation status on neuron injury remain unclear. This study was designed to explore the effects of TET1 and TET2 expression in the inflammatory pain of rats induced by complete Freund's adjuvant (CFA). Mechanical paw withdrawal threshold (PWT) and thermal withdrawal latency (TWL) were detected to assess pain behavior. The expression of TET1 and TET2 were measured in the dorsal root ganglion (DRG) with western blotting analysis. Immunofluorescence staining is employed to detect the expression and co-location of TRPV1 with TET1. Intrathecal administration of Bobcat339 was used to inhibit TET1 function in dorsal root ganglion. The paw withdrawal threshold and thermal withdrawal latency of rats were significantly reduced after CFA Injection. Western blot results showed that the expression of TET1 was significantly increased at 3 days after CFA injection, but TET2 had no statistical difference. Immunofluorescence results showed that TET1 was co-localized with TRPV1. Intrathecal administration of Bobcat339 improved mechanical and thermal pain threshold in CFA rats. Our findings highlight the role of TET1 in chronic inflammatory pain model. The expression of TET1 was increased in CFA rats, and suppression of TET1 will ameliorate inflammatory pain.

Radical 1,4-Aryl Migration Enabled Remote Cross-Electrophile Coupling of α-Amino-ß-Bromo Acid Esters with Aryl Bromides.

We report an unprecedented, efficient nickel-catalysed radical relay for the remote cross-electrophile coupling of ß-bromo-α-benzylamino acid esters with aryl bromides via 1,4-aryl migration/arylation cascades. ß-Bromo-α-benzylamino acid esters are considered as unique molecular scaffolds allowing for aryl migration reactions, which are conceptually novel variants for the radical Truce-Smiles rearrangement. This reaction enables the formation of two new C(sp3 )-C(sp2 ) bonds using a bench-stable Ni/bipyridine/Zn system featuring a broad substrate scope and excellent diastereoselectivity, which provides an effective platform for the remote aryl group migration and arylation of amino acid esters via redox-neutral C(sp3 )-C(sp2 ) bond cleavage. Mechanistically, this cascade reaction is accomplished by combining two powerful catalytic cycles consisting of a cross-electrophile coupling and radical 1,4-aryl migration through the generation of C(sp3 )-centred radical intermediates from the homolysis of C(sp3 )-Br bonds and the switching of the transient alkyl radical into a robust α-aminoalkyl radical.

Intelligent prediction of RBC demand in trauma patients using decision tree methods.

BACKGROUND: The vital signs of trauma patients are complex and changeable, and the prediction of blood transfusion demand mainly depends on doctors' experience and trauma scoring system; therefore, it cannot be accurately predicted. In this study, a machine learning decision tree algorithm [classification and regression tree (CRT) and eXtreme gradient boosting (XGBoost)] was proposed for the demand prediction of traumatic blood transfusion to provide technical support for doctors. METHODS: A total of 1371 trauma patients who were diverted to the Emergency Department of the First Medical Center of Chinese PLA General Hospital from January 2014 to January 2018 were collected from an emergency trauma database. The vital signs, laboratory examination parameters and blood transfusion volume were used as variables, and the non-invasive parameters and all (non-invasive + invasive) parameters were used to construct an intelligent prediction model for red blood cell (RBC) demand by logistic regression (LR), CRT and XGBoost. The prediction accuracy of the model was compared with the area under the curve (AUC). RESULTS: For non-invasive parameters, the LR method was the best, with an AUC of 0.72 [95% confidence interval (CI) 0.657-0.775], which was higher than the CRT (AUC 0.69, 95% CI 0.633-0.751) and the XGBoost (AUC 0.71, 95% CI 0.654-0.756, P < 0.05). The trauma location and shock index are important prediction parameters. For all the prediction parameters, XGBoost was the best, with an AUC of 0.94 (95% CI 0.893-0.981), which was higher than the LR (AUC 0.80, 95% CI 0.744-0.850) and the CRT (AUC 0.82, 95% CI 0.779-0.853, P < 0.05). Haematocrit (Hct) is an important prediction parameter. CONCLUSIONS: The classification performance of the intelligent prediction model of red blood cell transfusion in trauma patients constructed by the decision tree algorithm is not inferior to that of the traditional LR method. It can be used as a technical support to assist doctors to make rapid and accurate blood transfusion decisions in emergency rescue environment, so as to improve the success rate of patient treatment.

The effect of catalytic copper pretreatments on CVD graphene growth at different stages.

The controllable synthesis of high-quality and large-area graphene by chemical vapor deposition (CVD) remains a challenge nowadays. The massive grain boundaries in graphene grown on polycrystalline Cu by CVD significantly reduce its carrier mobility, limiting its application in high-performance electronic devices. Here, we confirm that the synergetic pretreatment of Cu with electropolishing and surface oxidation is a more efficient way to further suppress the graphene nucleation density (GND) and to accelerate the growth rate of the graphene domain by CVD. With increasing the growth time, we found that the increasing amount of GND and growth rate of the graphene domain were both decreasing during the whole CVD process when the Cu surface was not oxidized. By contrast, they kept growing over time when the Cu surface was pre-oxidized, which suggested that the change trends of the effects on the GND and growth rate between the Cu surface morphology and oxygen were opposite in the CVD process. In addition, not only the domain shape, but the number of graphene domain layers were impacted as well, and a large number of irregular ellipse graphene wafers with dendritic multilayer emerged when the Cu surface was oxidized.

[A Predictive Model for Hemoglobin Change before and after Collection of Apheresis Autologous Red Blood Cells in Patients].

OBJECTIVE: To analyze the affecting factors of hemoglobin changes in apheresis red blood cells (RBCs), and to establish a predictive model for the evaluation of apheresis. METHODS: The clinical data of 130 patients undergoing selective surgery for apheresis autologous RBCs from January 2017 to December 2018 were collected. The change of hemoglobin and its affecting factors before and after apheresis were analyzed. The predictive model of the hemoglobin change was established by machine learning algorithm and compared with the theoretical predictive model. RESULTS: The average Hb level in the 300 ml autologous RBC group decreased by 22.61±8.85 g/L, and the average Hb in 400 ml group decreased by 29.08±7.25 g/L. The change of Hb was mainly affected by Hb level before apheresis and peripheral circulation blood volume (P＜0.05). Sex, age, and the interval time between blood collection and operation not significantly influenced Hb change (P＞0.05). The initially established predictive model by the machine learning (MAE 6.27) is superior to the theoretical predictive model (MAE 8.11). CONCLUSION: The predictive model established by the machine learning can provide a reference for more accurate evaluation of apheresis autologous red blood cells.

[New discussion on the connotation of Star Twelve Points].

With the discussion on the origins and the evolution of Star Twelve Points, combined with ancient astronomical stellar map, it is realized that the three-dimensional spatial diagram of Star Twelve Points can be approximately regarded as a Big Dipper map from the side view. Under the direction of image thinking, the function of Big Dipper was compared with the function of Star Twelve Points. Furthermore, according to "the opening-closing-pivoting" theory in The Inner Canon of Huangdi and the theory of "qi cycle in round" proposed by HUANG Yuan-yu, the mechanisms of Star Twelve Points on adjusting functional activities of qi and the movement of viscera-meridian-qi-blood is elaborated, providing a new idea for acupuncture clinical treatment of miscellaneous diseases.

Ultrasound features predicting the 3-week outcome of Pavlik harness treatment for developmental hip dysplasia.

BACKGROUND: The treatment protocol for children with developmental dysplasia of the hip (DDH) is routinely adjusted by assessing the hip reduction after 3 weeks of Pavlik harness treatment. However, there is a high risk of failure and complications in the treatment adjustment. The aim of this study was to explore the value of ultrasound features in predicting the treatment outcome of Pavlik harness after 3 weeks in DDH children. METHODS: A total of 215 DDH children were recruited and the demographics and the changes of ultrasound features [α and ß angle and femoral head coverage (FHC)] during the Pavlik harness treatment were recorded. The children were divided into the success group and the failure group according to the reduction outcome after 3 weeks. Univariate and multivariate analyses were performed to analyze the independent predictors for the treatment outcome. Repeated-measures analysis of variance was used to compare the changes of ultrasound features between the two groups during the treatment. Receiver operating characteristic (ROC) curves were plotted to analyze the predictive accuracy of the ultrasound features. RESULTS: Graf type III (P=0.036), bilateral dislocation (P=0.031), and age at diagnosis (P=0.021) were associated with an increased risk of Pavlik harness failure in the multivariate analysis. The changes in α and ß angle and FHC were generally greater in the success group than in the failure group. The α angle and FHC were larger in the success group, while the ß angle was larger in the failure group (P<0.05). Each ultrasound parameter (α and ß angle and FHC) alone could not accurately predict the treatment outcome within 3 weeks. However, the combined ultrasonic features at the second week could accurately predict the outcome of Pavlik harness treatment after the third week. The combination of the ultrasound features at the first week and the influencing factors (Graf classification, age at diagnosis, and side of pathology) could accurately predict the outcome at the first week [area under curve (AUC) =0.931, sensitivity =82.14%, specificity =97.86%]. CONCLUSIONS: The combined model of ultrasonic features at the second week could accurately predict the reduction outcome of Pavlik harness after the third week. The combined model including independent predictors and ultrasonic features could accurately predict the reduction outcome at the first week.

Cis-2-dodecenoic Acid Mediates Its Synergistic Effect with Triazoles by Interfering with Efflux Pumps in Fluconazole-resistant Candida albicans.

OBJECTIVE: To evaluate the synergy of the Burkholderia signaling molecule cis-2-dodecenoic acid (BDSF) and fluconazole (FLU) or itraconazole (ITRA) against two azole-resistant C. albicans clinical isolates in vitro and in vivo. METHODS: Minimum inhibitory concentrations (MICs) of antibiotics against two azole-resistant C. albicans were measured by the checkerboard technique, E-test, and time-kill assay. In vivo antifungal synergy testing was performed on mice. Analysis of the relative gene expression levels of the strains was conducted by quantitative reverse-transcription polymerase chain reaction (qRT-PCR). RESULTS: BDSF showed highly synergistic effects in combination with FLU or ITRA with a fractional inhibitory concentration index of ⪕ 0.08. BDSF was not cytotoxic to normal human foreskin fibroblast cells at concentrations of up to 300 µg/mL. The qRT-PCR results showed that the combination of BDSF and FLU/ITRA significantly inhibits the expression of the efflux pump genes CDR1 and MDR1 via suppression of the transcription factors TAC1 and MRR1, respectively, when compared with FLU or ITRA alone. No dramatic difference in the mRNA expression levels of ERG1, ERG11, and UPC2 was found, which indicates that the drug combinations do not significantly interfere with UPC2-mediated ergosterol levels. In vivo experiments revealed that combination therapy can be an effective therapeutic approach to treat candidiasis. CONCLUSION: The synergistic effects of BDSF and azoles may be useful as an alternative approach to control azole-resistant Candida infections.

Copper-catalyzed radical cascades of para-quinone methides with AIBN and H2O via α-cyanoalkylation by C-C bond cleavage: new access to benzofuran-2(3H)-ones.

We describe the first one-pot construction of a benzofuran-2(3H)-one scaffold via a radical cascade reaction of para-quinone methides with azodiisobutyronitrile and water. In the presence of CuI (20 mol%), this cascade proceeds smoothly through 1,6-conjugate addition/aromatization, α-cyanoalkylation by unstrained and non-polar C(aryl)-C(t-butyl) bond cleavage, and downstream cyano-insertion/cyclization/hydrolysis, which leads to cyano-containing benzofuran-2(3H)-ones with an excellent functional-group compatibility.

A Multicenter, Randomized, Controlled Trial of Electroacupuncture for Perimenopause Women with Mild-Moderate Depression.

OBJECTIVE: Up to 62% of perimenopausal women have depression symptoms. However, there is no efficacy treatment. The aim of this study is to compare the clinical efficacy and safety of EA therapy and escitalopram on perimenopause women with mild-moderate depressive symptom. METHOD: A multicenter, randomized, positive-controlled clinical trial was conducted at 6 hospitals in China. 242 perimenopause women with mild-moderate depressive symptom were recruited and randomly assigned to receive 36 sessions of EA treatment or escitalopram treatment. The primary outcome measure was the 17-item Hamilton Depression Rating Scale (HAMD-17). The secondary outcome measures include menopause-specific quality of life (MENQOL) and serum sexual hormones which include estrogen, follicle-stimulating hormone, and luteinizing hormone. RESULTS: 221 (91.3%) completed the study, including 116 in the EA group and 105 in the escitalopram group. The baseline levels of demographic and outcome measurements were similar in the two groups. In the intervention period, there was no difference between two groups. However, in the follow-up, both HAMD-17 and MENQOL were significantly decreased, and at week 24 the mean differences were -2.23 and -8.97, respectively. There were no significant differences in the change of serum sexual hormones between the two groups. No serious adverse events occurred. CONCLUSION: EA treatment is effective and safe in relieving depression symptom and improving the quality of life in the perimenopausal depression. Further research is needed to understand long-term efficacy and explore the mechanism of this intervention. This study is registered with ClinicalTrials.gov NCT02423694.

[Regularity of Clinical Application of Lianquan (CV 23) in Chinese Ancient Times According to Literature of Traditional Chinese Medicine].

OBJECTIVE: To summarize the regularity of application of Lianquan (CV 23) in clinical practice in Chinese ancient times through analysis of ancient traditional Chinese medical (TCM) literature. METHODS: A total of 60 books involving CV 23 from the 1 156 ancient TCM books listed in the fifth edition of Encyclopedia of Traditional Chinese Medicine were collected by using CV 23 as the main keyword and "Sheben" "Benchi", and "Jieben" (the other names of CV 23 in TCM)as the supplementary keywords and analyzed systematically. A database was then constructed from the collected data, including the related types of disorders or symptoms, acupoint recipes, and methods of needling and moxibustion, contraindications, etc. RESULTS: A total of 196 articles related to the application of CV 23 from 60 ancient classical books were collected in accordance with the inclusive criteria. Among them, 155 articles are referred to the indications of CV 23, 35 to types of disorders such as asthma, cough, tongue swelling with difficulty in speaking, protracted tongue, acute contraction of tongue root, vomiting, spasm syndrome, stroke, aphtha, problems of mouth and teeth, throat problems, etc. of the internal medicine, surgery, pediatrics, and five-sense organs; 64 items are referred to the application of single CV 23, 91 to CV 23-included recipes containing 111 adjunct acupoints, and 78 to stimulation of CV 23 with acupuncture needle, moxibustion, pricking blood, and fire needle. Moreover, of the 111 adjunct acupoints, the most commonly used are Shaoshang (LU 11), Tiantu (CV 22), Hegu (LI 4), Yuye (EX-HN 13), Zhongchong (PC 9), etc. CONCLUSION: Lianquan (CV 23) is mainly used for glossopharyngeal problems chiefly by syndrome-meridian differentiation. The supplement of complementary acupoints or five-shu points in combination with CV 23 has a synergistic effect. Moxibustion (3 moxa- cones in general) is often employed, and the needling depth is usually about 7.5 mm. The common contraindication of CV 23 is severe tongue swelling.

[Preliminary research on multi-neurotransmitters' change regulation in 120 depression patients' brains].

In view of the effective traditional Chinese medicine (TCM) in the treatment of clinical depression, the mechanism is not clear, this study attempts to research the cause of depression in a complex situation to lay the foundation for the next step of TCM curative effect evaluation. Based on the brain wave of 120 depression patients and 40 ordinary person, the change regulation of acetylcholine, dopamine, norepinephrine, depression neurotransmitters and excited neurotransmitters in the whole and various encephalic regions' multi-neurotransmitters of depression patients-serotonin are analysed by search of encephalo-telex (SET) system, which lays the foundation for the diagnosis of depression. The result showed that: contrased with the normal person group, the mean value of the six neurotransmitters in depression patients group are: (1) in the whole encephalic region of depression patients group the dopamine fall (P < 0.05), and in the double centralregions, right temporal region and right parietal region distinct fall (P < 0.01); (2) in the right temporal region of depression patients group the serotonin rise (P < 0.05); (3) in the right central region, left parietal region of depression patients group the acetylcholine fall (P < 0.05), left rear temporal region fall obviously (P < 0.01). The correlation research between antagonizing pairs of neurotransmitters and neurotransmitters: (1) the three antagonizing pairs of neurotransmitters-serotonin and dopamine, acetylcholine and norepinephrine, depression neurotransmitters and excited neurotransmitters, in ordinary person group and depression patients group are characterizeed by middle or strong negative correlation. Serotonin and dopamine, which are characterized by weak negative correlation in the right rear temporal region of ordinary person group, are characterized by strong negative correlation in the other encephalic regions and the whole encephalic (ordinary person group except the right rear temporal region: the range of [r] is [0.82, 0.92], P < 0.01)/(depression patients group:the range of [r] is [0.88, 0.94], P < 0.01); acetylcholine and norepinephrine, in the whole and various encephalic region are characterized by middle negative correlation(ordinary person group:the range of [r] is [0.39, 0.76], P < 0.01 or P < 0.05)/(depression patients group: the range of [Ir] is [0.56, 0.64], P < 0.01); depression neurotransmitters and excited neurotransmitters are characterized by middle strong negative correlation (ordinary person group: the range of [r] is [0.57, 0.80], P < 0.01)/(depression patients group: the range of [r] is [0.68, 0.78], P < 0.01). (2) The two neurotransmitters which are not antagonizing pairs of neurotransmitters, serotonin and excited neurotransmitters, or acetylcholine and depression neurotra-nsmitters, or dopamine and depression neurotransmitters in the various encephalic regions are characterized by weak negative correlation. Serotonin and excited neurotransmitters are characterizeed by weak negative correlation (ordinary person group: in the right central region, left parietal region, double front temporal regions, right rear temporal region, the range of [r] is [0.25, 0.50], P < 0.01 or P < 0.05)/(depression patients group: in the whole encephalic regions, double parietal regions, double occipital regions, right front temporal region, left central region, left frontal region, the range of [r] is [0.18, 0.37], P < 0.01 or P < 0.05); acetylcholine and depression, neurotransmitters are characterized by weak negative correlation (ordinary person group: in the double frontal regions, left parietal region, left front temporal region, right rear temporal region, the range of [r] is [0.31, 0.46], P < 0.01 or P < 0.05)/(depression patients group: in double rear temporal regions, right front temporal region, double occipital regions, left central region, the range of [r] is [0.20, 0.32] , P < 0.01 or P < 0.05); do-pamine and depression neurotransmitters are characterized by weak middle negative correlation (ordinary person group: in left parietal region, right central region, left frontal region, left occipital region, double front temporal regions, the range of [r] is [0.33, 0.68], P < 0.01 or P < 0.05)/(depression patients group: in the whole region and other various regions except the left frontal region, right central region, the range of Irl is [0.21, 0.34], P < 0.01 or P < 0.05). Dopamine and acetylcholine or norepinephrine and serotonin are characterized by weak positive correlation in all encephalic regions. Dopamine and acetylcholine are characterized by weak positive correlation (ordinary person group: in left frontal region, right parietal region, left front temporal region and left rear temporal region, the range of [r] is [0.37, 0.46], P < 0.01)/(depression patients group: in the whole region and the orther various regions except the double central regions, the range of [r] is [0.23, 0.5], P < 0.01 or P < 0.05); norepinephrine and serotonin are characterized by weak positive correlation (ordinary person group: in double front temporal regions, double rear temporal regions, right frontal region and left parietal region, the range of [r] is [0.34, 0.48], P < 0.01 or P < 0.05)/(depression patients group: in the whole and various regions, the range of [r] is [0.18, 0.42], P < 0.01). The main differences between the depression patients group and ordinary person group are: (1) In the whole regin, left frontal region and right central region of depression patients group, the six neurotransmitters all fall normally (P < 0.05). (2) The percent of dopamine falling or including dopamine falling, or including dopamine falling and serotonin rising in depression patients group increases. The percent of dopamine falling or including dopamine falling in the whole region, right frontal region, right central region increases (P < 0.01), such as dopamine decreasing, serotonin increasing dopamine decreasing, serotonin increasing acetylcholine decreasing dopamine decreasing, dopamine decreasing norepinephrine increasing depression neurotransmitters decreasing, serotonin increasing acetylcholine decreasing dopamine decreasing neurotransmitters increasing and so on. (3) The percent of acetylcholine falling, or including acetylcholine falling, or including acetylcholine falling and neurotransmitters (beta)-receptor)rising in depression patients group increases. The percent of acetylcholine falling, or including acetylcholine falling in the right temporal region, double central regions increases (P < 0.05 or P < 0.01), such as acetylcholine decreasing, acetylcholine decreasing neurotransmitters increaseng, acetylcholine decreasing neurotransmitters increasing depression neurotransmitters decreasing, serotonin increasing acetylcholine decreasing dopamine decreasing neurotransmitters increasing and so on. It's showed in research that depression patients' brain are characterized by multi-neurotransmitters abnormal, the synchronous change of multi-neurotransmitters has some certain regularities, which are not the simple linear relation. It's conformed that the three antagonizing pairs, neurotransmitters-serotonin and dopamine, acetylcholine and norepinephrine, depression eurotransmitters and excited neurotransmitters of ordinary person group and depression patients group, are both characterized by strong antagonizing relation, that the two neurotransmitters which are not antagonizing pairs of neurotransmitters are characterized by weak positive correlation or negative correlation, prompt maybe has the indirect causal relationship. And the change of six neurotransmitters in depression patients' various encephalic regions is rather complex. It's conformed preliminarily that the right frontal region and right central region are characterized by dopamine decreasing, acetylcholine decreasing, serotonin increasing dopamine decreasing, serotonin increasing acetylcholine decreasing dopamine decreasing, dopamine decreasing norepinephrine increasing excited neurotransmitters decreasing, serotonin increasing acetylcholine decreasing dopamine decreasing neurotransmitters increasing, acetylchoine decreasing neurotransmitters increasing, acetylcholine decreasing neurotransmitters increasing excited neurotransmitters decreasing and so on. Contrasted with the ordinary person group, the depression patients group have the notable difference.

Leukemia inhibitory factor in the neuroimmune communication pathways in allergic asthma.

In the pathogenesis of asthma, central sensitization is suggested to be an important neural mechanism, and neurotrophins and cytokines are likely to be the major mediators in the neuroimmune communication pathways of asthma. However, their impact on the central nervous system in allergic asthma remains unclear. We hypothesize that central neurogenic inflammation develops in the pathogenesis of allergic asthma, and nerve growth factor (NGF) and leukemia inhibitory factor (LIF) are important mediators in its development. An asthma model of rats was established by sensitization and challenged with ovalbumin (OVA). For further confirmation of the role of LIF in neurogenic inflammation, a subgroup was pretreated with intraperitoneally (i.p.) LIF antibody before OVA challenge. The levels of LIF and NGF were measured with reverse transcription and polymerase chain reaction (RT-PCR), in situ hybridization (ISH) and immunohistochemistry stain in lung tissue, airway-specific dorsal root ganglia (DRG, C7-T5) and brain stem of asthmatic rats, anti-LIF pretreated rats and controls. A significantly increased number of LIF- and NGF-immunoreactive cells were detected in lung tissue, DRG and the brain stem of asthmatic rats. In the asthma group a significantly increase level of mRNA encoding LIF and NGF in lung tissue was detected, but not in DRG and the brain stem. Pretreatment with LIF antibody decreased the level of LIF and NGF in all tissues. LIF is an important mediator in the crosstalk between nerve and immune systems. Our study demonstrate that the increased level of LIF and NGF in DRG and brain stem may be not based on result from de novo synthesis, but rather on result from retrograde nerve transport or passage across the blood-brain-barrier.

Effects of acupuncture treatment on depression insomnia: a study protocol of a multicenter randomized controlled trial.

BACKGROUND: More than 70% of patients with depression who see their doctors experience insomnia. Insomnia treatment is a very important link for depression treatment. Furthermore, antidepression treatment is also important for depression insomnia. In acupuncture, LU-7 (Lie Que) and KID-6 (Zhao Hai), which are two of the eight confluence points in meridian theory, are used as main points. An embedded needle technique is used, alternately, at two groups of points to consolidate the treatment effect. These two groups of points are BL-15 (Xin Shu) with BL-23 (Shen Shu) and BL-19 (Dan Shu) with N-HN-54 (An Mian). The effectiveness of these optimized acupuncture formulas is well proven in the practice by our senior acupuncturists in Guangdong Provincial Hospital of TCM. This study has been designed to examine whether this set of optimized clinical formulas is able to increase the clinical efficacy of depression insomnia treatment. METHODS/DESIGN: In this randomized controlled multicenter trial, all the eligible participants are diagnosed with depression insomnia. All participants are randomly assigned to one of two groups in a ratio of 1:1 and receive either conventional acupuncture treatment or optimized acupuncture treatment. Patients are evaluated using the Pittsburgh Sleep Quality Index(PSQI)and the Hamilton rating scale(HAMD) for depression. The use of antidepression and hypnotics drugs is also considered. Results are obtained at the start of treatment, 1 and 2 months after treatment has begun, and at the end of treatment. The entire duration of the study will be approximately 36 months. DISCUSSION: A high quality of trial methodologies is utilized in the study, and the results may provide better evidence for the effectiveness of acupuncture as a treatment for depression insomnia. The optimized acupuncture formula has potential benefits in increasing the efficacy of treating depression insomnia. TRIAL REGISTRATION: The trial was registered in Chinese Clinical Trial Register (ChiCR-TRC-00000481) on 12 August 2009.

A new quorum-sensing inhibitor attenuates virulence and decreases antibiotic resistance in Pseudomonas aeruginosa.

Quorum sensing (QS) has been a novel target for the treatment of infectious diseases. Here structural analogs of Pseudomonas aeruginosa autoinducer N-acyl homoserine lactone (AHL) were investigated for QS inhibitor (QSI) activity and a novel QSI was discovered, N-decanoyl-L-homoserine benzyl ester (C2). Virulence assays showed that C2 down-regulated total protease and elastase activities, as well as the production of rhamnolipid, that are controlled by QS in P. aeruginosa wild-type strain PAO1 without affecting growth. C2 was also shown to inhibit swarming motility of PAO1. Using a microdilution checkerboard method, we identified synergistic interactions between C2 and several antibiotics, tobramycin, gentamycin, cefepime, and meropenem. Data from real-time RT-PCR suggested that C2 inhibited the expression of lasR (29.67%), lasI (21.57%), rhlR (28.20%), and rhlI (29.03%).

[Randomized controlled study on rehabilitation of hemiplegia in cerebral infarction at the early stage with acupuncture and moxibustion based on meridian harmonization and zang-organ regulation].

OBJECTIVE: To explore the better therapeutic method for the treatment of hemiplegia in cerebral infarction. METHODS: One hundred and fifty cases were randomized into a meridian-harmonization group (group A), a zang-organ regulation group (group B) and a meridian-harmonization and zang-organ regulation group (group C), 50 cases in each one. On the basis of conventional treatment, in group A, the acupoints were selected along meridians, such as Hegu (LI 4), Taichong (LR 3), Jianyu (LI 15), Waiguan (TE 5), Huantiao (GB 30) and Yanglingquan (GB 34)ect. In group B, the acupoints were selected in light of abdominal acupuncture such as Zhongwan (CV 12), Xiawan (CV 10), Qihai (CV 6), Guanyuan (CV 4), Shangqu (KI 17, healthy side) and Daheng (SP 15)etc. In group C, the acupoints in group A and group B were selected in combination. Before and after treatment, all the patients received the test of Barthel Index (BI) to assess the disability level and the simple Fugl-Meyer Motor Scale (FMMS) for the evaluation of motor function. RESULTS: After treatment, all the three groups presented the significant improvement of BI, the down-regulation of disability rate and up-regulation of FMMS score, indicating significant differences in statistics as compared with those before treatment (P < 0.05, P < 0.01). In group C, the results of BI improvement, the down-regulation of disability rate and the improvement of limb motor function were all superior to those in either group A or group B (P < 0.05, P < 0.01). CONCLUSION: Acupuncture in light of meridian-harmonization and zang-organ regulation is the better approach for the early-stage rehabilitation of hemiplegia in cerebral infarction and its efficacy is superior to that of either simple meridian harmonization therapy or zang-organ regulation therapy.

[Effect of transection or pretreatment of the infraorbital nerve with snake venom on the analgesia induced by electroacupuncture of "Sibai" (ST 2) acupoint in visceral pain rats].

OBJECTIVE: To observe the role of large-diameter fibers of infraorbital nerve (ION) in "Sibai" (ST 2)-electroacupuncture (EA) induced analgesia in visceral pain (VP) rats. METHODS: A total of 36 SD rats were randomized into control, VP, EA, ION transaction, snake venom (SV) and saline groups, with 6 rats in each group. EA(2 Hz/20 Hz) was applied to bilateral "Sibai" (ST 2) for 20 min. VP model was established by intraperitoneal injection of 0.6% acetic acid (10 mL/kg). Bilateral ION were transacted or pretreated by regional application of snake venom to selectively destroy A fibers,respectively. Behavior reactions were assessed by counting abdominal muscular contractions. Meanwhile, c-fos expression in the nucleus of the solitary tract (NTS) and paratrigeminal nucleus (PTN) was displayed by immunohistochemistry. RESULTS: In comparison with control group, the numbers of abdominal muscular contraction,and c-fos immuno-reaction (IR) positive neurons in both NTS and PTN increased significantly in VP group (P < 0.001); while in comparison with VP group, the numbers of the abdominal contraction, and c-fos IR-positive neurons of both NTS and PTN in EA and SV and saline groups decreased considerably (P < 0.05, P < 0.01). No significant differences were found between ION transaction and VP groups in the abdominal contraction number, and c-fos IR-positive neurons in both NTS and PTN areas,and among EA and SV and saline groups in the numbers of abdominal contraction and c-fos IR-positive neurons of both NTS and PTN (P > 0.05). CONCLUSION: The large-diameter (A) fibers of ION are not the major afferent fibers affecting EA-ST 2 induced analgesia in visceral pain rats; and somatic sensory afferents from orofacial areas and visceral pain input converge in the NTS and PTN, which may be the basis of the EA analgesia in the present study.