Projections from anteromedial thalamus nucleus to the midcingulate cortex mediate pain and anxiety-like behaviors in mice.

Prior research has demonstrated the involvement of the midcingulate cortex (MCC) and its downstream pathway in pain regulation. However, the mechanism via which pain information is conveyed to the MCC remains unclear. The present study utilized immunohistochemistry, chemogenetics, optogenetics, and behavior detection methods to explore the involvement of MCC, anteromedial thalamus nucleus (AM), and AM-MCC pathway in pain and emotional regulation. Chemogenetics or optogenetics methods were employed to activate/inhibit MCCCaMKIIα, AMCaMKIIα, AMCaMKIIα-MCC pathway. This manipulation evokes/relieves mechanical and partial heat hyperalgesia, as well as anxiety-like behaviors. In the complete Freund,s adjuvant (CFA) inflammatory pain model, chemogenetic inhibition of the AMCaMKIIα-MCCCaMKIIα pathway contributed to pain relief. Notably, this study presented the first evidence implicating the AM in the regulation of nociception and negative emotions. Additionally, it was observed that the MCC primarily receives projections from the AM, highlighting the crucial role of this pathway in the transmission of pain and emotional information.

[Mechanism of tonifying kidney and activating blood therapy for premature ovarian failure:a review].

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)-ß/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.

Association between testosterone levels and bone mineral density in females aged 40-60 years from NHANES 2011-2016.

Growing evidence indicates that testosterone is a conspicuous marker for assessing male bone mineral density (BMD). However, research regarding testosterone levels and BMD is sparse and controversial for females. Hence, we aimed to investigate the association between testosterone levels and BMD among adult females aged 40-60 years in the United States. In this cross-sectional study, all participants were part of the National Health and Nutrition Examination Survey (2011-2016). A weighted general linear model was used to estimate the association between testosterone levels and lumbar BMD. Age, race, income level, education level, body mass index (BMI), blood urea nitrogen (BUN) level, serum uric acid (UA) level, serum calcium (Ca) level, serum phosphorus (P) level, the use of oral contraceptive pills, the use of hormone replacement therapy (HRT), smoking status, drinking status, and the use of corticosteroids were adjusted using a weighted multiple regression model. Subgroup analyses were performed using the same regression model. We included 2198 female participants in the study, and testosterone levels were positively associated with lumbar BMD after adjusting for all the covariates (ß = 1.12, 95% CI 0.31, 1.93). In subgroup analyses, the associations in the fourth quartile of testosterone levels were stronger for the participants aged 40-50 years old (quartile 4, ß = 42.92, 95% CI 7.53, 78.30 vs. quartile 1) and 50 to 60-year-old (quartile 4, ß = 32.41, 95% CI 0.14, 64.69 vs. quartile 1). Similar results were found in other subgroups, including subgroups for race (Non-Hispanic Black, Other), income level (income ≤ 1.3, income > 3.5), education level (college or higher), BMI > 25 kg/m2, BUN levels ≤ 20 mg/dL, UA levels ≤ 6 mg/dL, Ca levels ≤ 10.1 mg/dL, P levels ≤ 5 mg/dL, drinking status, never smoker, never taking birth control pills, and HRT user. There was no interaction among the covariates in the association between lumbar BMD and testosterone levels (P for interaction > 0.05). In US adult females aged 40-60 years, the testosterone level was a positive predictor of the lumbar BMD after adjusting for covariates.

Efficacy of Bushen Culuan decoction on ovarian follicle and follicular granulosa cells in mice with premature ovarian insufficiency induced by tripterygium wilfordii polyglycoside.

OBJECTIVE: To investigate the protective efficacy of Bushen Culuan decoction (BCD) on ovarian follicle and follicular granulosa cells in mice with premature ovarian insufficiency (POI) induced by tripterygium wilfordii polyglycoside, and to study the potential mechanism underlying the action. METHODS: Eighty female Balb/c mice were randomly divided into 4 groups (n = 20 each): blank group, model group, Bushen Culuan decoction intervening group (BCD group) and estradiol valerate intervening group (EV group). In the first 14 model establishing d, mice in model group, BCD group and EV group were under Tripterygium wilfordii polyglycoside (TWP) gavage to establish POI models. In the 14-day therapeutic stage, mice in BCD group were taken BCD 18.35 mg·kg-1d-1, mice in EV group were taken EV solution 0.15 mg·kg-1d-1, while mice in blank group and model group were taken normal saline. When the mice accomplished therapy, whole blood was collected for serum hormone including follicle stimulating hormone (FSH), luteal hormone (LH), estradiol (E2), antimullerian hormone (AMH) levels and vascular endothelial growth factor (VEGF), bone morphogenetic protein-7 (BMP-7) measurement. Ovarian tissues were harvested for morphologic observation, follicle counting, ovarian follicular graulosa cell apoptosis test and testing BMP-7 and caspase-3 expressions. RESULTS: The body weights of the mice kept growing stably in the process expect in TWP intervening stage. Compared with model group, BCD group had significantly higher ovarian index, serum E2, AMH, VEGF, BMP-7 levels and significantly lower FSH level (P < 0.05). Meanwhile the VEGF level in BCD group was higher than in EV group (P < 0.05). Compared with model group, the histopathological damage and GCs apoptosis were mitigated; developing follicle counting, BMP-7 expression were up-regulated, and caspase-3 expression was downregulated in BCD groups (P < 0.05). CONCLUSION: BCD treatment could attenuate pathological process in POI ovaries, suppress GC apoptosis, probably through promoting BMP-7 expression and following inhibiting caspase-3 activation.

Projecting neurons in spinal dorsal horn send collateral projections to dorsal midline/intralaminar thalamic complex and parabrachial nucleus.

Itch is an annoying sensation that always triggers scratching behavior, yet little is known about its transmission pathway in the central nervous system. Parabrachial nucleus (PBN), an essential transmission nucleus in the brainstem, has been proved to be the first relay station in itch sensation. Meanwhile, dorsal midline/intralaminar thalamic complex (dMITC) is proved to be activated with nociceptive stimuli. However, whether the PBN-projecting neurons in spinal dorsal horn (SDH) send collateral projections to dMITC, and whether these projections involve in itch remain unknown. In the present study, a double retrograde tracing method was applied when the tetramethylrhodamine-dextran (TMR) was injected into the dMITC and Fluoro-gold (FG) was injected into the PBN, respectively. Immunofluorescent staining for NeuN, substance P receptor (SPR), substance P (SP), or FOS induced by itch or pain stimulations with TMR and FG were conducted to provide morphological evidence. The results revealed that TMR/FG double-labeled neurons could be predominately observed in superficial laminae and lateral spinal nucleus (LSN) of SDH; Meanwhile, most of the collateral projection neurons expressed SPR and some of them expressed FOS in acute itch model induced by histamine. The present results implicated that some of the SPR-expressing neurons in SDH send collateral projections to the dMITC and PBN in itch transmission, which might be involved in itch related complex affective/emotional processing to the higher brain centers.

Effect of Jin-3-needling therapy on plasma corticosteroid, adrenocorticotrophic hormone and platelet 5-HT levels in patients with generalized anxiety disorder.

OBJECTIVE: 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. METHODS: 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. RESULTS: 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). CONCLUSION: 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.