Mechanism of tonifying kidney and activating blood therapy for premature ovarian failure:a review / 中国中药杂志

Healthy birth and child development are the prerequisite for improving the overall quality of the population. However, premature ovarian failure(POF) threatens the reproductive health of women. The incidence of this disease has been on the rise, and it tends to occur in the young. The causes are complex, involving genetics, autoimmune, infectious and iatrogenic factors, but most of the causes remain unclear. At the moment, hormone replacement therapy and assisted reproductive technology are the main clinical approaches. According to traditional Chinese medicine(TCM), kidney deficiency and blood stasis are one of the major causes of POF, and TCM with the effects of tonifying kidney and activating blood has a definite effect. Through clinical trials, TCM prescriptions for POF have excellent therapeutic effect as a result of multi-target regulation and slight toxicity. In particular, they have no obvious side effects. A large number of studies have shown that the kidney-tonifying and blood-activating TCM can regulate the neuroendocrine function of hypothalamic-pituitary-ovarian axis, improve ovarian hemodynamics and microcirculation, reduce the apoptosis of granulosa cells, alleviate oxidative stress injury, and modulate immunologic balance. The mechanism is that it regulates the phosphatidylinositol 3-kinase(PI3K)/protein kinase B(Akt), vascular endothelial growth factor(VEGF), transforming growth factor(TGF)-β/Smads, nuclear factor E2-related factor 2(Nrf2)/antioxidant response element(ARE), and nuclear factor-kappa B(NF-κB) signaling pathways. This article summarized the pathological mechanisms of tonifying kidney and activating blood TCM in the prevention and treatment of POF and explored the biological basis of its multi-pathway and multi-target characteristics in the treatment of this disease. As a result, this study is expected to serve as a reference for the treatment of POF with the tonifying kidney and activating blood therapy.

Research progress on the biological effects of HIF-1α on follicle development and ovulation / 生理学报

Hypoxia inducible factor-1α (HIF-1α), as a hypoxia inducible factor, affects women's reproductive function by regulating the development and excretion of follicles. HIF-1α induces glycolysis and autophagy in the granule cells by promoting oocyte development, regulating the secretion of related angiogenic factors, and improving follicle maturity. In addition, HIF-1α promotes the process of luteinization of follicular vesicles, maintains luteal function, and finally completes physiological luteal atrophy through cumulative oxidative stress. Dysfunction of HIF-1α will cause a series of pathological consequences, such as angiogenesis defect, energy metabolism abnormality, excessive oxidative stress and dysregulated autophagy and apoptosis, resulting in ovulation problem and infertility. This article summarizes the previous studies on the regulation of follicle development and excretion and maintenance of luteal function and structural atrophy by HIF-1α. We also describe the effective intervention mechanism of related drugs or bioactive ingredients on follicular dysplasia and ovulation disorders through HIF-1α, in order to provide a systematic and in-depth insights for solving ovulation disorder infertility.

Anterior Cingulate Cortex Mediates Hyperalgesia and Anxiety Induced by Chronic Pancreatitis in Rats / 神经科学通报·英文版

Central sensitization is essential in maintaining chronic pain induced by chronic pancreatitis (CP), but cortical modulation of painful CP remains elusive. Here, we examined the role of the anterior cingulate cortex (ACC) in the pathogenesis of abdominal hyperalgesia in a rat model of CP induced by intraductal administration of trinitrobenzene sulfonic acid (TNBS). TNBS treatment resulted in long-term abdominal hyperalgesia and anxiety in rats. Morphological data indicated that painful CP induced a significant increase in FOS-expressing neurons in the nucleus tractus solitarii (NTS) and ACC, and some FOS-expressing neurons in the NTS projected to the ACC. In addition, a larger portion of ascending fibers from the NTS innervated pyramidal neurons, the neural subpopulation primarily expressing FOS under the condition of painful CP, rather than GABAergic neurons within the ACC. CP rats showed increased expression of vesicular glutamate transporter 1, and increased membrane trafficking and phosphorylation of the N-methyl-D-aspartate receptor (NMDAR) subunit NR2B and the α-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid receptor (AMPAR) subunit GluR1 within the ACC. Microinjection of NMDAR and AMPAR antagonists into the ACC to block excitatory synaptic transmission significantly attenuated abdominal hyperalgesia in CP rats, which was similar to the analgesic effect of endomorphins injected into the ACC. Specifically inhibiting the excitability of ACC pyramidal cells via chemogenetics reduced both hyperalgesia and comorbid anxiety, whereas activating these neurons via optogenetics failed to aggravate hyperalgesia and anxiety in CP rats. Taken together, these findings provide neurocircuit, biochemical, and behavioral evidence for involvement of the ACC in hyperalgesia and anxiety in CP rats, as well as novel insights into the cortical modulation of painful CP, and highlights the ACC as a potential target for neuromodulatory interventions in the treatment of painful CP.

Advances in morphological and functional studies on the paraventricular thalamic nucleus / 解剖学报

Paraventricular thalamic nucleus (PVT) is an essential component of the midline thalamus, which has been regarded as a transmit relay nucleus and an integrated center in multiple behaviors including wakefulness, food intake, addiction, reward and fear memory. PVT is predominantly populated with glutaminergic excitatory neurons expressing vesicular glutamate transporter-2 (VGluT2) but without GABAergic inhibitory neurons. Therefore, based on the paradox of its multiplexed roles in different behaviors and its comparatively simplex excitatory nature, more specific subclassification of excitatory PVT neurons is required in studies in this field. In the present review, morphological and electrophysiological characteristics, efferent and afferent connections, and morphological and functional distinctions in anterior subregion and posterior subregion of PVT are summarized. In addition, neural connections and neurochemical properties are used as subclassification criteria in PVT neurons. This review might explain the integrated role of PVT in different behaviors, which would be helpful for further studies on the PVT.

Establishment of Acquired Aplastic Anemia SD Rat Model / 中国实验血液学杂志

OBJECTIVE@#To establish a stable and rapidly rat model acquired aplastic anemia.@*METHODS@#The SD rats were exposed to Csγ-ray at 3.5 and 4.0 Gy ( 91 cGy/min), and intraperitoneally injected with CTX at 35 mg/( kg·d) and CHL at 45 mg/( kg·d) in d 4, 6 and 8 after irradiation; the WBC, platelet and reticulocyte counts in peripheral blood, the smears and nucleated cells counts of bone marrow were observed.@*RESULTS@#The levels of peripheral blood 3-lineage cells of SD rats treated with Csγ-irradiation combined with cyclophosphamide and chloramphenicol were significantly reduced, among which white blood cells, platelets and reticulocytes decreased rapidly, and the number of bone marrow nucleated cells decreased significantly; bone marrow pathological sections showed severe reduction of hematopoietic cells, and the non-hematopoietic cells such as fat cells increased, and a serve or lightly reduction of bone marrow cells were found.@*CONCLUSION@#The rat model established by Csγ-ray irradiation combined with cyclophosphamide and chloramphenicol meets the clinical characteristics of aplastic anemia, and this study provides a stable rat model for the study of new therapeutic drugs for acquired aplastic anemia.

Protective Effect and Mechanisms of Geraniin on D-galactosamine-induced Liver Injury in Mice / 中国实验方剂学杂志

Objective:To explore the hepatoprotective effect and its mechanism of the geraniin on mice with acute liver injury induced by D-galactosamine (D-GalN). Method:A total of 60 Kunming mice were randomly divided into normal group, model group, Silymarin group (positive group 180 mg·kg-1), and low, medium and high-dose geraniin groups (50, 100, 200 mg·kg-1). All the mice were given with saline or corresponding dose of drugs (10 mL·kg-1) by gavage once a day for 10 d. After 2 h of the last administration, except the normal group, the mice of other groups were injected intraperitoneally with D-GalN (500 mg·kg-1) to induce the acute liver injury. After 16 h, the eye balls of mice were removed to take blood, and all mice were put to death to collect samples of liver. Activity or content of alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase (ALP), total bilirubin (TBIL), malondialdehyde (MDA), total superoxide dismutase (T-SOD) and glutathione peroxidase (GSH-Px) in liver were determined by biochemical method. The serum levels of tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β), γ-interferon (IFN-γ) and interleukin-6 (IL-6) were detected by enzyme-linked immunosorbent assay (ELISA), and expressions of Toll-like receptor-4(TLR-4) and nuclear factor(NF)-κB proteins were detected by Western blot. Liver histopathological changes were observed by hematoxylin-eosin (HE) staining. Result:Compared with the normal group, the serum levels of ALT, AST, ALP, TBIL and liver MDA in the model group were significantly increased (PPPPPPα, IL-1β, IL-6, IFN-γ and the expressions of TLR-4 and NF-κB proteins in serum (PPConclusion:Geraniin has an obvious protective effective on acute liver injuries induced by D-GalN in mice. Its mechanism may be correlated with oxidative stress, inflammation and TLR-4/NF-κB signaling pathway.

Effect of Jin-3-needling therapy on plasma corticosteroid, adrenocorticotrophic hormone and platelet 5-HT levels in patients with generalized anxiety disorder / 中国结合医学杂志

<p><b>OBJECTIVE</b>To observe the therapeutic efficacy of Jin-3-needling therapy (J3N) on generalized anxiety disorder (GAD) through clinical global impression scale (CGI), and to explore the mechanism by measuring the plasma levels of corticosteroid (CS), adrenocorticotrophic hormone (ACTH), and platelet 5-hydroxytryptamine (5-HT) before and after treatment.</p><p><b>METHODS</b>Eighty-six GAD patients with the diagnosis agreeing with the inclusion criteria were assigned, according to the sequence of visiting time, to three groups. The 29 patients in the Western medicine group were treated mainly with fluoxetine or paroxetine, Alprazolam might be given additionally in severe conditions if necessary; the 29 patients in the needling group received J3N therapy with Sishenzhen, Dingshenzhen, Neiguan (PC6), Shenmen (HT7) and Sanyinjiao (SP6) as the chief acupoints selected; and the 28 patients in the combined treatment group were treated with both drugs and needling in the same way as applied in the above two groups. The therapeutic course for all was 6 weeks. Conditions of patients were evaluated before and after treatment with CGI, and levels of CS, ACTH as well as 5-HT were measured by high performance liquid chromatography-electrochemistry.</p><p><b>RESULTS</b>By CGI scoring, the scores of severity index and the general index were not different significantly in the three groups, but the efficacy index proved to be the highest in the needling group, the second in the combined trentment group, and the lowest in the drug group. Plasma level of ACTH and platelet content of 5-HT were lowered in all the three groups after treatment, showing statistical significance (P<0.05), but no significant change was found in CS level (P>0.05).</p><p><b>CONCLUSION</b>The therapeutic efficacy of J3N in treating GAD is equivalent to, but with the efficacy index significantly higher than, that of conventional treatment. Moreover, when combined with drugs, needling might effectively prevent the side effect of the routinely used Western drugs. The regulatory action of needling on platelet 5-HT and plasma ACTH is probably one of the acting pathways for J3N treatment on GAD.</p>