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Objective: To investigate the effect of Fuhe decoction on the behavior and levels of monoamine neurotransmitters in different brain regions in a depression rat model induced by chronic unpredictable mild stimulation (CUMS) combined with social isolation. Methods: Fifty male SD rats were randomly divided into a blank group, model group, fluoxetine group, Chaiqinwendan decoction group, and Fuhe decoction group. Chronic unpredictable mild stimulation combined with a social isolation method was used to replicate the depression rat model. After 42 days of administration, a tail suspension test and high-performance liquid electrochemical detection (HPLC-ECD) were used to detect the behavioral changes and changes in the content of monoamine neurotransmitters norepinephrine (NE), dopamine (DA), 5-hydroxytrytamine (5-HT), and metabolites in different brain regions of rats in each group before and after treatment. Results: Compared with the model group, the epinephrine (E) content in the Fuhe decoction group was highly significantly increased (P

Stroke is a major cause of death and disability in China, and no therapies have proven effective to prevent it. Popular belief holds that the lunar cycle affects human physiology, behavior, and health. The aim of our study is to determine whether the lunar cycle impacts the incidence of stroke subtypes [intracerebral hemorrhage (ICH), transient ischemic attack (TIA) and ischemic stroke (IS)]. We retrospectively extracted the discharge registry data of all patients with first-ever acute stroke hospitalized in the affiliated hospital of Beijing University of Traditional Chinese Medicine during 2002-2015. The onset times of stroke were assigned to four primary lunar phases based on NASA definitions. Chi-square tests and multiple logistic regression analyses were used to estimate the association between the lunar cycle and stroke incidence with adjustment for age, sex and season. A total of 5,965 patients with stroke (4,909 admissions for ischemic stroke IS, 754 admissions for ICH, and 302 admissions for TIA) were evaluated in our study. Subgroup analysis indicated that the admission rates of different sexes for IS tended to have opposite variation during the four moon phases. More female patients were admitted during the new moon than in the first and third quarters, while fewer male patients were admitted during the new moon than in the first and third quarters (χ2 = 15.589, P = .001). Multiple logistic regression analyses revealed that men were more likely to be admitted for IS in the first quarter than during the new moon (odds ratio [OR] = 1.252, 95% confidence interval [CI] = 1.076-1.456) (P = .004), and a corresponding trend was also identified for the third quarter (OR = 1.235, 95% CI = 1.062-1.437) (P = .006). No significant gender differences were shown in ICH or TIA. No sex difference is obvious during the full moon. Moon phases seem to affect both genders, but in very different ways. It seems that the new moon is a protective factor for male ischemic stroke patients and a risk factor for female ones. Woman tends to be more vulnerable than ever at the new moon, so deserves more attention and care. The mechanisms underlying this observation are worth studying further.

Objective: Findings on the effect of the lunar cycle on mental illness are conflicting. We investigated the association between the lunar cycle and a number of psychiatric presentations of schizophrenia and determined which subtypes were susceptible to lunar phases.Methods: We evaluated 13,067 patients admitted to Zhumadian Psychiatric Hospital between January 1, 2012, and December 31, 2017 (73 lunar cycles). Patients were retrospectively assigned to lunar phase based on their admission date: new moon +/- 1 day, first quarter +/- 1 day, full moon +/- 1 day, and third quarter +/- 1 day. The International Statistical Classification of Diseases, 10th revision (ICD-10), was used for diagnosis. We used a Chi-squared goodness of fit test to evaluate the distribution of admissions across the lunar phase and R*C Chi-squared tests to compare age, sex, birth season, and clinical subtype distributions by phase. We used multiple logistic regression to further identify the relationship between clinical subtype and lunar phase.Results: Psychiatric admissions for schizophrenia varied significantly across the lunar cycle (χ2 = 36.400, p .05).Conclusions: Psychiatric admissions for schizophrenia show lunar periodicities. People with schizophrenia tend to be stable in the new moon, but their condition is easily aggravated during the first quarter and full moon. Patients with paranoid schizophrenia are more susceptible to deterioration at the full moon, so merit more attention and care from communities, families, and hospitals.

Neuropathic pain is one of the most common and notorious neurological diseases. The changes in cerebral structures after nerve injury and the corresponding contributions to neuropathic pain are not well understood. Here we found that the majority of glutamatergic neurons in the area 2 of midcingulate cortex (MCC Cg2Glu) were inhibited by painful stimulation in male mice. Optogenetic manipulation revealed that these neurons were tonically involved in the inhibitory modulation of multimodal nociception. We further identified the projections to GABAergic neurons in the zona incerta (ZIGABA) mediated the pain inhibitory role. However, MCC Cg2Glubecame hypoactive after nerve injury. Although a brief activation of the MCC Cg2Gluto ZIGABAcircuit was able to relieve the aversiveness associated with spontaneous ongoing pain, consecutive activation of the circuit was required to alleviate neuropathic allodynia. In contrast, glutamatergic neurons in the area 1 of MCC played opposite roles in pain modulation. They became hyperactive after nerve injury and only consecutive inhibition of their activity relieved allodynia. These results demonstrate that MCC Cg2Gluconstitute a component of intrinsic pain inhibitory circuitry and their hypoactivity underlies neuropathic pain. We propose that selective and persistent activation of the MCC Cg2Gluto ZIGABAcircuit may serve as a potential therapeutic strategy for this disease.SIGNIFICANCE STATEMENTGlutamatergic neurons in the area 2 of midcingulate cortex (MCC Cg2Glu) are tonically involved in the intrinsic pain inhibition via projecting to GABAergic neurons in the zona incerta. They are hypoactive after nerve injury. Selective activation of the circuit compensates the reduction of its analgesic strength and relieves neuropathic pain. Therefore, MCC Cg2Gluand the related analgesic circuit may serve as therapeutic targets for neuropathic pain. In contrast, MCC Cg1Gluhave an opposite role in pain modulation and become hyperactive after nerve injury. The present study provides novel evidence for the concept that neuropathic pain is associated with the dysfunction of endogenous pain modulatory system and new perspective on the treatment of neuropathic pain.

Global myocardial work (MW) analysis by pressure-strain loops (PSL) allows the non-invasive assessment of left ventricular (LV) function. We aimed to investigate the relationship between LV global MW and the degree of coronary artery stenosis in suspected coronary artery disease (CAD) patients with normal LV ejection fraction and regional wall motion. A total of 164 suspected CAD patients were divided into four groups according to coronary artery angiography. The results showed that global work efficiency (GWE) as the most significant predictor in all MW parameters had the optimal cut-off value of 94.5% for detecting moderate stenosis, and the sensitivity and specificity was 89.7% and 85.8%, respectively. A cut-off value of 94.0% for GWE was the most significant predictor of severe stenosis, and the sensitivity and specificity was 81.4% and 76.1%, respectively. In conclusion, LV global MW is a sensitive tool in detecting the degree of coronary artery stenosis and a potential valuable method to provide early diagnosis for CAD patients.

Pain sensitization after partial infraorbital nerve transection (p-IONX) in mice not only presents in orofacial region, but also spreads to distant body parts. The roles of toll-like receptor 4 (TLR4) in orofacial pain and the spreading process are still unclear. Here, we found that mice with deficient TLR4 because of Tr4 gene point mutation (C3H/HeJ) or spontaneous deletion (C57BL/10ScNJ) developed tactile allodynia and thermal hyperalgesia in the vibrissal pad in a parallel way to their respective wild types (C3HeB/FeJ or C57BL/6J) after p-IONX. However, allodynia in the hind paw was absent in mice with TLR4 deficiency. Pharmacological antagonism of TLR4 with LPS-RS, administered either intracisternally or intrathecally, abrogated allodynia in the hind paw without affecting the hypersensitivity in the vibrissal pad and hyperalgesia in the hind paw. Although TNF-α expression was upregulated in both the medulla and lumbar cord, the expression of TLR4 downstream molecule MyD88 increased only in the lumbar cord after p-IONX in wild types. By contrast, hind paw hypersensitivity after partial sciatic nerve ligation was significantly attenuated by TLR4 deletion. The hypersensitivity, which did not spread to the vibrissal pad, was accompanied with upregulation of MyD88 in the lumbar cord rather than in the medulla. These results suggest that TLR4 participates in the spread of allodynia component of orofacial pain to distant body sites, but not trigeminal neuropathic pain or the spread of its hyperalgesia component. This study suggests that TLR4 may serve as a potential target for the management of widespread allodynia associated with orofacial pain.

Background Over the past decades there have been outbreaks of mumps in many countries, even in populations that were vaccinated. Some studies suggest that the incidence of mumps is related to meteorological changes, but the results of these studies vary in different regions. To date there is no reported study on correlations between mumps incidence and meteorological parameters in Beijing, China. Methods A time series analysis incorporating selected weather factors and the number of mumps cases from 1990 to 2012 in Beijing was performed. First, correlations between meteorological variables and the number of mumps cases were assessed. A seasonal autoregressive integrated moving average model with explanatory variables (SARIMAX) was then constructed to predict mumps cases. Results Mean temperature, rainfall, relative humidity, vapor pressure, and wind speed were significantly associated with mumps incidence. After constructing the SARIMAX model, mean temperature at lag 0 (β = 0.016, p

Clinical studies show that chronic pain can spread to adjacent or even distant body regions in some patients. However, little is known about how this happens. In this study, we found that partial infraorbital nerve transection (p-IONX) in MRL/MPJ mice induced not only marked and long-lasting orofacial thermal hyperalgesia but also thermal hyperalgesia from day 3 postoperatively (PO) and tactile allodynia from day 7 PO in bilateral hind paws. Pain sensitization in the hind paw was negatively correlated with facial thermal hyperalgesia at early but not late stage after p-IONX. After a rapid activation of c-Fos, excitability and excitatory synaptic neurotransmission in lumbar dorsal horn neurons were elevated from day 3 and day 7 PO, respectively. In addition, microglial activation after p-IONX transmitted caudally from the Vc in the medulla to lumber dorsal horn in a time-dependent manner. Inhibition of microglial activation by minocycline at early but not late stage after p-IONX postponed and attenuated pain sensitization in the hind paw. These results indicate that neuropathic pain after p-IONX in MRL/MPJ mice spreads from the orofacial region to distant somatic regions and that a rostral-caudal transmission of central sensitization in the spinal cord is involved in the spreading process of pain hypersensitivity.

This retrospective cohort study attempts to investigate pregnancy complications and adverse pregnancy outcomes in women of advanced maternal age (AMA). Data were extracted from electronic medical records system at West China Second University Hospital of Sichuan University from January 2013 to July 2016. The study cohort consisted 8 subgroups of women on 4 different age levels (20–29 years, 30–34 years, 35–39 years and ≥40 years) and 2 different parities (primiparity and multiparity). In the study period, 38811 women gave birth at our hospital, a randomized block was used to include 2800 women of singleton pregnancy >28 gestational weeks, with 350 patients in each subgroup. Maternal complications and fetal outcomes were collected and defined according to relevant guidelines. Confounding factors representing maternal demographic characteristics were identified from previous studies and analysed in multivariate analysis. There was an increasing trend for the risks of adverse pregnancy outcomes with increasing age, especially in AMA groups. Our study showed that AMA, primiparity, maternal overweight or obesity, lower educational level and residence in rural area increased pregnancy complications and adverse fetal outcomes. Increased professional care as well as public concern is warranted.

Background It is known that histamine participates in pain modulation. However, the effect of central histamine on neuropathic pain is not fully understood. Here, we report a critical time window for the analgesic effect of central histamine in the partial sciatic nerve ligation model of neuropathic pain. Methods Neuropathic pain was induced by partial sciatic nerve ligation (PSL) in rats, wild-type (C57BL/6J) mice and HDC−/− (histidine decarboxylase gene knockout) and IL-1R−/− (interleukin-1 receptor gene knockout) mice. Histidine, a precursor of histamine that can increase the central histamine levels, was administered intraperitoneally (i.p.). Histidine decarboxylase (HDC) enzyme inhibitor α-fluoromethylhistidine was administered intracerebroventricularly (i.c.v.). Histamine H1 receptor antagonist mepyramine and H2 receptor antagonist cimetidine were given intrathecally (i.t.) and intracisternally (i.c.). Withdrawal thresholds to tactile and heat stimuli were measured with a set of von Frey hairs and infrared laser, respectively. Immunohistochemistry and Western blot were carried out to evaluate the morphology of microglia and IL-1β production, respectively. Results Histidine (100 mg/kg, i.p.) administered throughout days 0–3, 0–7, or 0–14 postoperatively (PO) alleviated mechanical allodynia and thermal hyperalgesia in the hindpaw following PSL in rats. Intrathecal histamine reversed PSL-induced thermal hyperalgesia in a dose-dependent manner and intracisternal histamine alleviated both mechanical allodynia and thermal hyperalgesia. Moreover, α-fluoromethylhistidine (i.c.v.) abrogated the analgesic effect of histidine. However, histidine treatment initiated later than the first postoperative day (treatment periods included days 2–3, 4–7, and 8–14 PO) did not show an analgesic effect. In addition, histidine treatment initiated immediately, but not 3 days after PSL, inhibited microglial activation and IL-1β upregulation in the lumbar spinal cord, in parallel with its effects on behavioral hypersensitivity. Moreover, the inhibitory effects on pain hypersensitivity and spinal microglial activation were absent in HDC−/− mice and IL-1R−/− mice. H1 receptor antagonist mepyramine (200 ng/rat i.t. or i.c.), but not H2 receptor antagonist cimetidine (200, 500 ng/rat i.t. or 500 ng/rat i.c.), blocked the effects of histidine on pain behavior and spinal microglia. Conclusions These results demonstrate that central histamine is analgesic within a critical time window in the PSL model of neuropathic pain via histamine H1 receptors. This effect may partly relate to the inhibition of microglial activation and IL-1β production in the spinal cord following nerve injury. Electronic supplementary material The online version of this article (doi:10.1186/s12974-016-0637-0) contains supplementary material, which is available to authorized users.

Background and Methods: Pregabalin alleviates stimulus-evoked neuropathic pain (NeuP) in some pain patients and rodents in models of painful neuropathies. But it is not known if pregabalin can also alleviate spontaneous NeuP. Sciatic and saphenous neurectomy in rats elicits spontaneous self-mutilation of the denervated hindpaw, a behavior that models spontaneous NeuP. We tested if pregabalin (20 or 30 mg/kg/day; twice daily, per os) for 7 days before denervation, or 42 days thereafter, can suppress this behavior. Results: Compared with the vehicle, pregabalin administered in both treatment regimens markedly and significantly delayed autotomy onset and suppressed its levels for weeks after treatment cessation. Conclusions: At doses known to effectively suppress stimulus-evoked pain in rats, pregabalin can prevent development of spontaneous NeuP and suppress it postoperatively.