督脉刺法治疗脑血管性痴呆的临床研究

目的观察督脉刺法治疗血管性痴呆的临床疗效。方法将85例血管性痴呆患者随机分为2组:治疗组用针刺加哈伯因治疗,对照组仅用哈伯因治疗,治疗前后用简易智能量表(MMSE)、日常生活能力量表(ADL)进行评分。结果2组治疗后MMSE积分、ADL积分均明显提高,且治疗组提高程度优于对照组。结论督脉刺法能显著改善血管性痴呆患者的认知功能及日常生活能力,临床疗效显著。     

Hepatitis C virus F protein inhibits cell apoptosis by activation of intracellular NF-κB pathway

Aim:  To observe the influence of HCV F protein on apoptosis of HepG2 cells, and explore the association between F protein and NF-κB signal pathway.
Methods:  HCV 1b F gene containing HepG2-F cells and HCV 1b C gene containing HepG2-C cells were treated with 100 IU/mL TNF-α, and analyzed by flow cytometry, Western blotting, and dual luciferase reporter assay. Empty plasmid pcDNA3.1⁺ containing HepG2-3.1 cells were used as control.
Results:  (i) With the treatment of TNF-α for 18 h, the apoptosis rates (AR) of HepG2-F and HepG2-3.1 cells were 0.41% (± 0.11%) and 37.43% (± 2.03%) respectively, while that of HepG2-C was 4.07% (± 0.18%). At 36 h after TNF-α treatment, the AR of HepG2-F and HepG2-3.1 cells were 10.03% (± 0.41%) and 44.63% (± 3.37%), and that of HepG2-C was 14.95% (± 0.85%). (ii) After the treatment of TNF-α for 0.5–18 h, the p65 contents in the whole cells of HepG2-F and HepG2-3.1 showed no significant difference ( P  = 0.34, t  = 1.08), while the p65 contents in the nucleus of HepG2-F and HepG2-3.1 cells were 3.8–1.9 times and 1.8–1.0 times higher than that in the non-treated cells ( P  = 0.013, t  = 4.25). (iii) The relative luciferase unit (RLU) of the HepG2 cells, co-transfected with pcDNA3.1-F and pNF-κB-luc, and then treated with TNF-α (100 IU/mL) for 18 h, showed a pcDNA3.1-F dose-dependent increase.
Conclusion:  HCV F protein can over-activate NF-κB signal pathway, which makes HepG2-F cells able to resist TNF-α induced apoptosis.     

Pericardial effusion with cardiac tamponade as a cardiac manifestation of duchenne muscular dystrophy

Duchenne muscular dystrophy (DMD) is the most common hereditary neuromuscular disease in children. It is an X‐linked hereditary dystrophinopathy due to the absence of dystrophin. Its onset is often in early childhood and presents with proximal distribution of weakness and a progressive course. Cardiac involvement in DMD is common, and its onset is usually after the age of 10 years. The most common cardiac manifestations are a dilated cardiomyopathy and cardiac arrhythmia. However, pericardial effusion with cardiac tamponade is a very rare cardiac complication of DMD. We report a boy with DMD who initially presented with progressive dyspnea and an enlarged cardiac silhouette on chest radiography who subsequently developed a large pericardial effusion with cardiac tamponade. Early recognition of pericardial effusion with cardiac tamponade is important for institution appropriate therapy. Muscle Nerve, 2009     

Robust monolithic polymer(resorcinol-formaldehyde) reinforced alumina aerogel composites with mutually interpenetrating networks

Monolithic polymer(resorcinol-formaldehyde) reinforced alumina (RF/Al₂O₃) aerogel composites were prepared using a sol–gel method and supercritical fluid CO₂ drying. The formation mechanism, chemical compositions, pore structures, morphologies, thermal and mechanical performances of RF/Al₂O₃ aerogel composites with different RF/Al molar ratios were investigated. The results show that the two networks of organic resorcinol-formaldehyde and inorganic alumina are completely independent of one another. The as-synthesized RF/Al₂O₃ aerogels consist of spherical organic carbon particles and fibrous alumina, which possess low bulk density (0.077–0.112 g cm⁻³), low shrinkage (1.55–2.76%), low thermal conductivity (0.024–0.028 W m⁻¹ K⁻¹), and high specific surface area (453.26–722.75 m² g⁻¹). Especially, the sample prepared with molar ratio RF/Al = 1 shows the best network structure with the higher compressive strength (1.83 MPa) and Young''s modulus (122.57 MPa). The resulting robust RF/Al₂O₃ aerogel composites could be potentially used as thermal insulators, catalysts and adsorbents.

Monolithic polymer(resorcinol-formaldehyde) reinforced alumina (RF/Al₂O₃) aerogel composites were prepared using a sol–gel method and supercritical fluid CO₂ drying.     

Retracted Article: Elevation of USP4 antagonizes oxygen glucose deprivation/reoxygenation-evoked microglia activation and neuroinflammation-mediated neurotoxicity via the TRAF6-NF-κB signaling

An ischemic stroke is a devastating neurological disease with the typical occurrence of brain ischemia/reperfusion (I/R) injury, and it has high mortality and disability globally. Microglia activation after a stroke results in the release of pro-inflammatory cytokines that can further aggravate brain damage. A recent study confirmed the potential role of ubiquitin-specific peptidase 4 (USP4) in the injury process. Nevertheless, the role and mechanism of USP4 during an ischemic stroke remain elusive. In this research, we simulated an I/R injury by oxygen glucose deprivation/reoxygenation (OGD/R) in vitro and confirmed the obvious down-regulation of USP4 in microglia under OGD/R conditions. Moreover, USP4 elevation antagonized the OGD/R-induced microglia proliferation and activation by suppressing the NO levels and the expression of the microglial marker IBA-1. Additionally, the overexpression of USP4 suppressed the release of microglia activation-induced pro-inflammatory cytokines, including IL-1β, IL-6, and TNF-α. Intriguingly, incubation with the conditioned medium from the microglia under OGD/R conditions induced neurotoxicity by inhibiting cell viability and increasing the LDH release, apoptosis, and caspase-3 activity, which were reversed following USP4 overexpression. Mechanism analysis corroborated that USP4 up-regulation repressed the OGD/R-induced activation of TRAF6-NF-κB signaling. Notably, restoring the TRAF6 signaling ameliorated the suppressive effects of USP4 elevation on microglia activation, inflammation, and the subsequent neuron injury. These findings suggest that USP4 may alleviate ischemic stroke by restraining microglia-mediated neuro-inflammation and neurotoxicity via the TRAF6-NF-κB pathway, due to which it is a promising therapeutic agent against strokes.

An ischemic stroke is a devastating neurological disease with the typical occurrence of brain ischemia/reperfusion (I/R) injury, and it has high mortality and disability globally.     

Enhanced catalytic degradation of amoxicillin with TiO2–Fe3O4 composites via a submerged magnetic separation membrane photocatalytic reactor (SMSMPR)

A novel photo-Fenton catalytic system for the removal of organic pollutants was presented, including the use of photo-Fenton process and a submerged magnetic separation membrane photocatalytic reactor (SMSMPR). We synthesized TiO₂–Fe₃O₄ composites as the photocatalyst and made full use of the magnetism of the photocatalyst to realize the recollection of the catalyst from the medium, which is critical to the commercialization of photocatalytic technology for wastewater treatment. The photo-Fenton performance of TiO₂–Fe₃O₄ is evaluated with amoxicillin trihydrate (AMX) as a target pollutant. The results indicate that the TiO₂–Fe₃O₄/H₂O₂ oxidation system shows efficient degradation of AMX. Fe₃O₄ could not only enhance the heterogeneous Fenton degradation of organic compounds but also allow the photocatalyst to be magnetically separated from treated water. After four reaction cycles, the TiO₂–Fe₃O₄ composites still exhibit 85.2% removal efficiency of AMX and show excellent recovery properties. Accordingly, the SMSMPR with the TiO₂–Fe₃O₄ composite is a promising way for removing organic pollutants.

With a TiO₂–Fe₃O₄ composite as the catalyst, amoxicillin was degraded via a photo-Fenton process using a submerged magnetic separation membrane photocatalytic reactor.     

Synthesis of 1,4,5,6-tetrahydropyridazines and pyridazines via transition-metal-free (4 + 2) cycloaddition of alkoxyallenes with 1,2-diaza-1,3-dienes

We developed an economical and practical protocol for the synthesis of 1,4,5,6-tetrahydropyridazines. A diverse range of alkoxyallenes and 1,2-diaza-1,3-dienes undergo (4 + 2) cycloaddition to generate the desired products in excellent yields. The high efficiency, wide substrate scope and good functional group tolerance of this process, coupled with operational simplicity, render the method synthetically attractive. The utility of the cycloaddition is also demonstrated by the preparation of various pyridazines from 1,4,5,6-tetrahydropyridazines.

We developed an economical and practical protocol for the synthesis of 1,4,5,6-tetrahydropyridazines and pyridazines via cyclization of alkoxyallenes and 1,2-diaza-1,3-dienes.

For several years, we have been developing the methodologies of cumulative dienes¹ for the synthesis of heterocyclic compounds.² In the past few decades, allenes have attracted significant attention in organic synthesis.³ By virtue of their reactive and cumulative double bonds, allenes are widely used as valuable C3-feedstocks.⁴ Functional groups at the double bonds of allene moieties strongly influence the reactivities, and thus allow site- and regioselective transformations. For example allenoates, bearing electron-withdrawing substituents (carboxylic ester groups) at the allene moieties, lead to preferred reactions with nucleophiles attacked on the central carbon, and have been thoroughly studied.⁵ Nevertheless, investigations of alkoxyallenes are still limited.⁶ As special enol ethers, alkoxyallenes were frequently employed as strong nucleophiles via deprotonations and metalations.⁷ Moreover, the electronic bias imposed by the alkoxyl groups makes them unique dienophiles; the electron-deficient or electron-rich double bonds could engage in cycloadditions.Recently, Goeke⁸ and Luo⁹et al. developed (4 + 2) annulation of alkoxyallenes with cyclopentadienes and β,γ-unsaturated α-keto esters, respectively (Scheme 1). These established methods employed expensive heavy metals (Au, In), which maybe resulting in the contamination of medicinal products. Accordingly, there is a clear demand for the development of transition-metal-free protocols with high efficiency, operational simplicity, atom economy and general applicability.Open in a separate windowScheme 1Transition-metal-catalyzed (4 + 2) cycloadditions of alkoxyallenes.In 2015, Favi et al. developed (4 + 2) cycloaddition of alkoxyallene with α-halohydrazones (precursors of 1,2-diaza-1,3-dienes), but in which only methoxyallene could be employed as the dienophile (Scheme 2a).¹⁰ The approach allows access to 1,4,5,6-tetrahydropyridazines, which are versatile building blocks and prevalent in a large number of pharmacologically active molecules.¹¹ However, the cyclization suffered from moderate conversion and narrow substrates scope, required long reaction time (up to 7 days) and high stoichiometric ratio of reactants (methoxyallene/Na₂CO₃/α-halohydrazone = 7 : 5 : 1).Open in a separate windowScheme 2(4 + 2) cycloadditions of alkoxyallenes with 1,2-diaza-1,3-dienes.Currently, there is an increased drive to find new ways to maximize synthetic efficiency and minimize waste in chemical and pharmaceutical industries.¹² As part of our group''s continuous interest in cumulene chemistry and transition-metal-free synthesis,¹³ the (4 + 2) annulation of alkoxyallene with 1,2-diaza-1,3-dienes was thus systematically reinvestigated, and in this context, we demonstrate that the cyclization can proceed with a broad range of substrates, producing a wide variety of 1,4,5,6-tetrahydropyridazines in high efficiency. Besides, it was found that these adducts could further convert into pyridazines (Scheme 2b).The investigations began with assaying the (4 + 2) cycloaddition between benzyloxyallene 1a and α-halohydrazone 2a, as shown in

Biological and clinical implications of nicastrin expression in invasive breast cancer

Nicastrin is an essential component of the gamma secretase (GS) enzyme complex, required for its synthesis and recognition of substrates for proteolytic cleavage. The purpose of this study was to investigate whether nicastrin has prognostic value or potential as a therapeutic target in breast cancer (BC). The suitability of nicastrin as a target in BC was assessed using BC tissue microarrays (TMAs) (n = 1050), and its biological role in vitro was evaluated in BC cell lines following gene silencing. Nicastrin blocking antibodies were developed and evaluated for their suitability as potential clinical therapeutics. TMA and cell line analysis confirmed that nicastrin expression was upregulated in BC compared to normal breast cells. In TMA patient samples, high nicastrin expression was observed in 47.5% of cases and correlated with ER?? expression, patient age, and tumor grade. In pre-defined subset analysis, high nicastrin expression predicted for worse BC specific survival in the ER?? ?ve cohort. In vitro gene silencing of nicastrin resulted in disruption of the GS complex and a decrease in notch1 cleavage. This was sufficient to increase E-cadherin expression and its co-localization with p120 catenin at cell?Ccell junctions in MCF7 cells. Nicastrin silencing in invasive MDA-MB-231 cells resulted in loss of vimentin expression and a marked reduction in both cell motility and invasion; which was concomitant with the de novo formation of cell?Ccell junctions characterized by the colocalization of p120 catenin and F-actin. These data indicate that nicastrin can function to maintain epithelial to mesenchymal transition during BC progression. Anti-nicastrin polyclonal and monoclonal antibodies were able to decrease notch1 and vimentin expression and reduced the invasive capacity of BC cells in vitro. This supports our hypothesis that a nicastrin blocking antibody could be used to limit metastatic dissemination in invasive BC.     

The role of topoisomerase IIα in predicting sensitivity to anthracyclines in breast cancer patients: a meta-analysis of published literatures

Topoisomerase IIα is not only a proliferation marker of tumor cells, but is also a target for anthracycline-based chemotherapy. Both in vitro and in vivo studies have shown that there is a relationship between topo IIα and chemosensitivity to anthracyclines, but the predictive role of topo IIα in breast cancer patients is still controversial. A meta-analysis based on published studies was performed to obtain an accurate assessment of the association between topo IIα and sensitivity to anthracycline-based chemotherapy. A total of 13 eligible studies, including 2,633 cases and 2,118 controls were identified. Topo IIα was associated with sensitivity to anthracyclines in locally advanced breast cancer patients who received neoadjuvant chemotherapy [five studies, including three using fluorescence in situ hybridization (FISH) and two using immunohistochemistry (IHC): relative risk (RR) = 1.93, 95% confidence interval (95% CI): 1.27–2.94, P = 0.002; two using FISH and three using IHC: RR = 1.98, 95% CI: 1.37–2.86, P < 0.001]. This association existed among three studies using FISH (RR = 2.03, 95% CI: 1.14–3.61, P = 0.017), but did not exist among three studies using IHC (P > 0.05). In early-stage breast cancer patients who received anthracycline-based adjuvant chemotherapy compared with non-taxane-based polychemotherapy, amplification [hazard ratio (HR) = 0.64, 95% CI: 0.49–0.83, P = 0.001; HR = 0.59, 95% CI: 0.35–1.01, P = 0.056] or deletion (HR = 0.82, 95% CI: 0.67–1.00, P = 0.051; HR = 0.58, 95% CI: 0.35–0.97, P = 0.036) of topo IIα was significantly associated with better recurrence-free survival and overall survival. In summary, the present meta-analysis suggests that topo IIα is a predictive factor for breast cancer patients who receive anthracycline-based chemotherapy. Larger and well-designed prospective studies are required to further evaluate the predictive role of topo IIα in clinical practice.