Effects of morphine withdrawal on the membrane properties of medium spiny neurons in the nucleus accumbens shell

Medium spiny neurons (MSNs) in the nucleus accumbens (NAc) undergo persistent alterations in their biological and physiological characteristics upon exposure to drugs of abuse. Previous studies demonstrated that the biochemical, morphological, and intrinsic physiological properties of MSNs are heterogeneous and provided new insights into the physiological and molecular roles of individual MSNs in addictive behaviors. However, it remains unclear whether MSNs in the NAc shell (NAcSh), an important region for mediating behavioral sensitization, are electrophysiologically heterogeneous and how such heterogeneity is relevant to neuroadaptation associated with drug addiction. Here, the membrane properties, i.e., the intrinsic excitability and spike adaptation, of MSNs in the NAcSh from saline- or morphine-treated rats were investigated in vitro by whole-cell recording. In saline-treated rats, three distinct cell types were identified by their membrane properties: type I neurons showed high levels of intrinsic excitability and rapid spike adaptation; type II neurons showed moderate levels of intrinsic excitability and relatively slow spike frequency adaptation; type III neurons showed low levels of intrinsic excitability and putative strong spike adaptation. MSNs in rats undergoing withdrawal from chronic morphine treatment (10–14 days after the last injection) also exhibited the typical firing behaviors of these three types of neurons. However, the membrane properties of the MSNs were differentially altered after withdrawal. There was an enhancement in intrinsic excitability in type II MSNs and a promotion of spike adaptation in type I MSNs. The apamin-sensitive afterhyperpolarization current (I_AHP) and the apamin-insensitive I_AHP of the NAcSh MSNs were attenuated after chronic morphine withdrawal. These findings suggest that individual MSNs in the NAcSh manifest unique electrophysiological properties, which might contribute to psychostimulant-induced neuroadaptation.     

Multimodality noninvasive cardiac imaging established the diagnosis of aneurysms of Vieussens’ arterial ring

Noninvasive cardiac imagines are rapidly evolving in recent years. In this patient with Vieussens’ arterial ring aneurysm, multimodality noninvasive cardiac imaging provided sufficient information for diagnosis and surgical decision making. This report no only provides unique information leading to better understanding on aneurysms of Vieussens’ arterial ring, but also highlights the important role of multimodality noninvasive cardiac imagines in the diagnosis and management of certain cardiac emergencies.     

朗格汉斯组织细胞增生症1例并文献复习

报告1例以皮肤损害就诊的朗格汉斯组织细胞增生症.患儿男,2岁半,因头面、躯干、下肢红斑、丘疹、脓疱一年半入院.皮肤组织病理检查:大量单个核细胞弥漫分布于真皮乳头层并向表皮侵入,单个核细胞体积较大,胞质淡染,核折叠成肾形,中央空泡化,可见线状沟,呈咖啡豆样外观.免疫组织化学法:CD1α及 S-100染色阳性.诊断为朗格汉斯组织细胞增生症.同时结合相关文献对朗格汉斯组织细胞增生症的临床表现、诊断和预后等进行分析.     

腹股沟疝前、后进路修补的随机对照研究

目的:比较前进路(常规疝手术)修补方法和后进路(腹膜前)修补方法治疗腹股沟疝病人的疗效、住院时间、总体费用、恢复工作时间、手术并发症等。方法:采用前瞻性随机对照方法,213例病人222侧疝(其中有9例同时患有双侧疝,男196例,女17例)随机分为前进路组(105例)和后进路组(108例)。前进路组采用常规修补,其中约1∕4病人(共27侧疝,Nyhus分型Ⅰ、Ⅲ型)用经典方法修补(Bassini术式21例和McVay术式6例)。3∕4病人(83侧疝,Nyhus分型Ⅱ、ⅢB、Ⅳ型)用假体的无张力修补(Lichtenstein术式21侧疝和Rutkow术式62侧疝);后进路组超过1∕3病人(38侧疝Nyhus分型Ⅰ、Ⅱ和ⅢA型)用不吸收缝线直接缝合修补,近2∕3病人(74侧疝,ⅢB、Ⅳ型)加用单层网片修补。结果:两组病人手术并发症的发生无明显差异。而平均住院时间、恢复日常生活时间前进路组要明显短于后进路组(P<0.01),在平均费用方面,后进路组明显少于前进路组(P<0.01),后术腹股沟区疼痛不适的发生率明显降低。结论:采用后进路方法进行腹股沟疝修补,可明显减少手术花费(不用人工假体或仅用单层平片),降低术后疼痛不适的发生率,改善疗效。因此,经后进路行腹股沟疝修补是一安全有效的方法,适合我国的国情,具有推广的价值。     

Stress sounds the alarmin: The role of the danger-associated molecular pattern HMGB1 in stress-induced neuroinflammatory priming

High mobility group box-1 (HMGB1) is an endogenous danger signal or alarmin that mediates activation of the innate immune response including chemotaxis and pro-inflammatory cytokine release. HMGB1 has been implicated in the pathophysiology of several neuroinflammatory conditions including ischemia, traumatic brain injury, seizure and chronic ethanol use. In the present review, the unique structural and functional properties of HMGB1 will be explored including its affinity for multiple pattern recognition receptors (TLR2/TLR4), redox sensitivity and adjuvant-like properties. In light of recent evidence suggesting that HMGB1 may also mediate stress-induced sensitization of neuroinflammatory responses, mechanisms of HMGB1 action in neuroinflammatory priming are explored. A model of neuroinflammatory priming is developed wherein glucocorticoids induce synthesis and release of HMGB1 from microglia, which signals through TLR2/TLR4, thereby priming the NLRP3 inflammasome. We propose that if GCs reach a critical threshold as during a fight/flight response, they may thus function as an alarmin by inducing HMGB1, thereby preparing an organism’s innate immune system (NLRP3 inflammasome priming) for subsequent immune challenges such as injury, trauma or infection, which are more likely to occur during a fight/flight response. In doing so, GCs may confer a significant survival advantage by enhancing the central innate immune and sickness response to immune challenges.     

Combined pulmonary fibrosis and emphysema (CPFE): an entity different from emphysema or pulmonary fibrosis alone

Chronic obstructive pulmonary disease (COPD) and idiopathic interstitial pneumonias (IIP), with different radiological, pathological, functional and prognostic characteristics, have been regarded as separate entities for a long time. However, there is an increasing recognition of the coexistence of emphysema and pulmonary fibrosis in individuals. The association was first described as a syndrome by Cottin in 2005, named “combined pulmonary fibrosis and emphysema (CPFE)”, which is characterized by exertional dyspnea, upper-lobe emphysema and lower-lobe fibrosis, preserved lung volume and severely diminished capacity of gas exchange. CPFE is frequently complicated by pulmonary hypertension, acute lung injury and lung cancer and prognosis of it is poor. Treatments for CPFE patients with severe pulmonary hypertension are less effective other than lung transplantation. However, CPFE has not yet attracted wide attention of clinicians and there is no research systematically contrasting the differences among CPFE, emphysema/COPD and IIP at the same time. The authors will review the existing knowledge of CPFE and compare them to either entity alone for the first time, with the purpose of improving the awareness of this syndrome and exploring novel effective therapeutic strategies in clinical practice.     

The Postoperative Immunosuppressive Phenotypes of Peripheral T Helper Cells Are Associated with Poor Prognosis of Breast Cancer Patients

Purpose: T helper cells play essential roles in anti-tumor immune response. However, the postoperative changes of peripheral T cell subsets and their clinical significance in breast cancer patients remain largely unknown.

Methods: We evaluated the perioperative changes of T lymphocyte subsets in invasive breast cancer (IBC) patients and breast fibroadenoma (BF) patients preoperatively (preop) and 6, 24, 72 hours postoperatively (POH6, POH24, and POH72). Proportions of CD3, CD4, CD8, T helper (Th) 1, Th2, Th17 cells, regulatory T cells (Treg), and CD4⁺/CD8⁺, Th1/Th2 ratio were detected by flow cytometry. Changes in T helper cell quantity were correlated to clinicopathological parameters. Furthermore, we explored the association between the perioperative variations of T cell subsets and disease-free survival (DFS) of IBC patients.

Results: In IBC patients, Th1 cells diminished while Tregs elevated in postoperative 72 hours in the peripheral blood. In contrast, no significant perioperative changes of T cell subsets were observed in BF patients. Postoperative lower Th1 cells at POH 72 of IBC patients were correlated with greater tumor burden, HER2 positive and Ki67 positive. The increased Tregs at POH 72 of IBC patients were correlated with larger tumor size and HER2 positive. Th1 cell decline and Treg increment were both associated with shorter DFS in IBC patients.

Conclusions: The variations of peripheral T helper cell subsets showed postoperative immunosuppression and were associated with poor prognosis in IBC patients.     

Fluorescent porous carbon nanocapsules for two-photon imaging,NIR/pH dual-responsive drug carrier,and photothermal therapy

An efficient nanomedical platform that can combine two-photon cell imaging, near infrared (NIR) light and pH dual responsive drug delivery, and photothermal treatment was successfully developed based on fluorescent porous carbon-nanocapsules (FPC-NCs, size ∼100 nm) with carbon dots (CDs) embedded in the shell. The stable, excitation wavelength (λ_ex)-tunable and upconverted fluorescence from the CDs embedded in the porous carbon shell enable the FPC-NCs to serve as an excellent confocal and two-photon imaging contrast agent under the excitation of laser with a broad range of wavelength from ultraviolet (UV) light (405 nm) to NIR light (900 nm). The FPC-NCs demonstrate a very high loading capacity (1335 mg g⁻¹) toward doxorubicin drug benefited from the hollow cavity structure, porous carbon shell, as well as the supramolecular π stacking and electrostatic interactions between the doxorubicin molecules and carbon shell. In addition, a responsive release of doxorubicin from the FPC-NCs can be activated by lowering the pH to acidic (from 7.4 to 5.0) due to the presence of pH-sensitive carboxyl groups on the FPC-NCs and amino groups on doxorubicin molecules. Furthermore, the FPC-NCs can absorb and effectively convert the NIR light to heat, thus, manifest the ability of NIR-responsive drug release and combined photothermal/chemo-therapy for high therapeutic efficacy.     

Trichophyton rubrum conidia modulate the expression and transport of Toll-like receptor 2 in HaCaT cell

Trichophyton rubrum (T. rubrum) represents the most important agent of dermatophytosis in humans. T. rubrum infection causes slight inflammation, and tends to be chronic and recurrent. It is suggested that T. rubrum can modulate the innate immune responses of host cells, which result in the failure of host cells to recognize T. rubrum and initiate effective immune responses. In this study we show how T. rubrum conidia modulate the expression and transport of Toll-like receptor 2 in HaCaT cell. Flow cytometric analysis showed that the surface and total expression of Toll-like receptor 2 were upregulated at the very early stage when keratinocytes were exposed to T. rubrum conidia regardless of the dose, and the upregulation of surface TLR2 was much more significant than that of total TLR2. Moreover, TLR2 expression was suppressed after upregulation in the initial stage of T. rubrum exposure, and the decrease of total TLR2 was earlier than that of surface TLR2. Our results suggest that in the early stage, TLR2 of keratinocytes were upregulated and transported to the cell surface. After then, the expression of TLR2 was suppressed by T. rubrum conidia.