阻塞型睡眠呼吸暂停低通气综合征患者海马MRS参数与认知功能的相关性

目的 探讨阻塞型睡眠呼吸暂停低通气综合征（OSAHS）患者海马MRS成像参数与认知功能之间的相关性。方法 对31例OSAHS患者（OSAHS组）及28名健康志愿者（对照组）行单体素MRS检查,检测双侧海马NAA、Cho和Cr峰值,计算NAA/Cr、Cho/Cr、NAA/Cho;采用蒙特利尔认知评估量表（MoCA）和简易智能状态量表（MMSE）评估认知功能,分析双侧海马NAA/Cr、Cho/Cr、NAA/Cho与MoCA、MMSE评分间的相关性。结果 OSAHS组双侧海马Cho/Cr较对照组增高,NAA/Cho较对照组减低（P均<0.05）,NAA/Cr差异无统计学意义（P均>0.05）。OSAHS患者双侧海马Cho/Cr与MoCA、MMSE评分呈负相关（P均<0.05）,NAA/Cho与MMSE评分呈正相关（P均<0.05）。结论 OSAHS患者双侧海马MRS参数与认知功能相关,可作为OSAHS患者认知功能损害的神经影像学标记。     

新型冠状病毒的研究现状与进展

目的:分析新型冠状病毒研究的主题和进展,以期为新型冠状病毒研究的开展提供帮助.方法:检索主要中英文数据库、国家卫生健康委员会和中华医学会等网站,纳入新型冠状病毒的期刊文献、指南和共识.用VOSviewer 1.6.13软件对纳入研究的关键词进行提取,并生成聚类分析知识图谱.结果:最终纳入165篇中文研究,91篇英文研究.中文新型冠状病毒研究的主题主要为新型冠状病毒疫情下医护人员的防护和护理人员的管理、新型冠状病毒肺炎的防控和诊疗、中医药对新型冠状病毒肺炎的疗效.英文新型冠状病毒研究的主题包括新型冠状病毒的检测及其基因组序列分析、新型冠状病毒肺炎的流行病学和临床特征、新型冠状病毒的基本再生数预测、瑞德西韦对新型冠状病毒肺炎的疗效.指南和共识主要关注的是新型冠状病毒肺炎的防控和诊疗.结论:新型冠状病毒肺炎的防控和诊疗是目前研究的热点,需要更多研究以提供新型冠状病毒疫情下特殊患者的管理和诊疗方案,中医药在新型冠状病毒肺炎患者康复过程中的疗效有待发掘.     

儿童新型冠状病毒肺炎诊疗方案汇总分析

目的:分析儿童新型冠状病毒肺炎(COVID-19)的诊断和治疗方案,为儿童COVID-19的诊疗提供参考.方法:检索主要中英文数据库、国家卫生健康委员会和中华医学会等网站,纳入提供了儿童COVID-19诊疗方案的研究.利用Excel 2016制定数据提取表,提取基本信息、诊断标准和治疗方案,并进行汇总分析.结果:COVID-19疑似病例和确诊病例的诊断方法较为明确,且各研究提供的方法较为一致.治疗方法包括一般治疗、抗病毒治疗、抗菌药物治疗、糖皮质激素治疗、免疫球蛋白治疗、呼吸支持、器官功能支持、血液净化和中医治疗等方面.一些药物的疗效不确定,仅为尝试使用.许多治疗方法的适应证、用法、用量尚不清楚.结论:目前的治疗方案存在一定的不足,未来应不断修改和完善儿童COVID-19的诊疗方案,制定更为严谨的循证指南.     

Linear PVA–DTPA–Gd conjugate for magnetic resonance imaging

In this study, we report the preparation and characterization of the PVA–DTPA–Gd conjugate as a potential MRI contrast agent (CA). The r₁ value and the r₂/r₁ ratio were about 5.6 mM⁻¹ s⁻¹ and 1.31, respectively. In vitro toxicity studies not only demonstrated that the polymeric system possessed good biocompatibility, but also proved that the conjugate could be an attractive candidate for CA.

In this study, we report the preparation and characterization of the PVA–DTPA–Gd conjugate as a potential MRI contrast agent (CA).

Magnetic resonance imaging (MRI) is the most frequently used tool for the detection and diagnosis of cancer in clinical settings, due to its high-resolution, noninvasive monitoring manner and excellent tissue penetration depth.^1–3 However, it is still hard to differentiate tumors from healthy tissues by MRI, due to its unsatisfactory detection sensitivity.⁴ Many paramagnetic contrast agents (CAs) have been demonstrated and applied to enhance the image contrast and to ultimately highlight the pathological areas. The positive CAs, so-called T₁-weighted CAs, generate bright signals,^5,6 whereas, the negative CAs with dark signals are called T₂-weighted CAs.⁷ Gd³⁺-based T₁ CAs are famous positive CAs with great safety, which have been widely applied clinically. Unfortunately, some Gd³⁺-based T₁ CAs may trigger the development of nephrogenic systemic fibrosis with renal failure.⁸ Thus, the signal intensity, which is related to the concentration of CAs in the region of interest, should be improved to decrease its injected doses. Many studies have been focused on the development of various Gd-based T₁-weighted contrast agents with high r₁ value and low r₂/r₁ ratio; both parameters are used to characterize the performance of MRI.¹² High relaxivity and low r₂/r₁ ratio could be achieved by a high payload of active magnetic centers according to the SBM theory.^9–11 Forming covalent conjugations with macromolecules is an effective way to control the tumbling motion and ensure optimal water residency times.¹³ Various polymers, such as polyethylene glycol (PEG), poly(N-2-hydroxypropyl methacrylamide) (PHPMA), poly(lactic-co-glycolic acid (PLGA) and chitosan have emerged as promising carriers for delivering the Gd chelates. Typically, Lim et al. conjugated gadolinium chelates to a serial of polyamidoamine dendrimers, and the resultant CAs exhibited high r₁ value and long circulation in the blood.¹⁴ Telechelic PEG-polymers end-capped with diphenylalanine motifs containing a DOTA–Gd complex bound on a lysine side chain at the centre of the peptide moiety were synthesized with relaxivity of around 11 mM⁻¹ s⁻¹ (B₀ = 3.0 T).¹⁵ A dendronized heparin–gadolinium polymer CAs was reported and its r₁ value was 16.3 mM⁻¹ s⁻¹ (B₀ = 3.0 T).¹⁶ Guo et al. conjugated Gd–DOTA onto a biodegradable poly[N-(1,3-di-hydroxypropyl)methacrylamide] copolymer backbone through a GSH-sensitive cleavable disulfide bond to produce novel Gd-CAs; its relaxivity was 10.24 mM⁻¹ s⁻¹ (B₀ = 3.0 T).¹⁷ In another report, multiple chelated Gd(iii) ions were attached to the hydrazide modified dextran–poly(glycidyl methacrylate), and the prepared MRI CAs exhibited a satisfactory r₁ value of 44.4 mM⁻¹ s⁻¹ (B₀ = 3.0 T).¹⁸ As a kind of synthetic polymer, polyvinyl alcohol (PVA) is an interesting commercial polymer with the highest annual production of over 1.2 billion kg.¹⁹ PVA is non-toxic, biodegradable, biocompatible and low-cost, making it a promising potential component of sustainable and degradable commodity plastics.^20–23 A few studies on PVA-based CAs have been published and the majority of them involved complicated methods that are not conducive to the large-scale production of CAs, with increased security risks and cost. For example, Cilliers et al. reported the synthesis and characterization of PVA embolic particles modified with DTPA–Gd, with the help of dangerous n-butyl lithium.²⁴ Tachibana et al. fabricated poly(vinyl alcohol)–gadolinium CA via two complex and costly steps. (i) PVA was stirred with carbonyl diimidazole, then 1,3-propanediamine was added to the mixture and the product was obtained by freeze-drying. (ii) The aminated PVA was reacted with DOTA–NHS–ester to form the PVA–DOTA.²⁵In order to simplify the reaction process of PVA-based CAs, a novel preparation strategy for PVA–DTPA–Gd conjugate was proposed and realized in this study. As Scheme 1 shows, PVA–DTPA was synthesized by grafting DTPA onto PVA via the reaction between the anhydrides of DTAP and –OH groups in PVA. The biodegradable PVA–DTPA–Gd conjugate was successfully constructed by the chelating reaction between DTPA and Gd³⁺. By varying the feed ratio, the loaded content of DTPA could be facilely and securely regulated. The macromolecular contrast agents could efficiently retard rotational motion, increase rotational correlation time and prevent rapid renal clearance.Open in a separate windowScheme 1The synthesis of the PVA–DTPA–Gd conjugate.A series of characterizations was applied to confirm the successful preparation of the polymer. Firstly, the free PVA, PVA–DTPA and PVA–DTPA–Gd were all characterized by FT-IR, and the results are given in Fig. S1.^† Compared with the spectrum of PVA, a pair of new vibration peaks appeared in the spectrum of PVA–DTPA–Gd at 1724 and 1639 cm⁻¹, which could be ascribed to the stretching vibration absorption peak of C O in the ester bond and free carboxyl.²⁶ Furthermore, a stretching vibration absorption peak of C–N appeared at 1225 cm⁻¹.²⁷ All the characteristic peaks demonstrated the successful synthesis of PVA–DTPA. For PVA–DTPA–Gd, the peak at 1639 cm⁻¹ disappeared and a new vibration peak appeared at 1591 cm⁻¹, suggesting that the coordination interaction between the C O group in the PVA–DTPA and metal Gd³⁺ ions may take place.²⁸ Additionally, a weak peak at 520 cm⁻¹ was found in the PVA–DTPA–Gd conjugate, which could be assigned to the stretching vibration of the Gd–O bond.²⁸The polymer composition was also studied by ¹H NMR spectroscopy, and the NMR spectra of the PVA and PVA–DTPA are shown in Fig. S2.^† The spectra show a broad singlet signal observed at 4.70 ppm, which corresponds to the chemical shifts of protons in the –OH group from the PVA repeating units (Fig. S2a^†). The broad singlet signal at δ = 3.86 ppm could be attributed to the methane proton from the –CH–(OH) group. The spectrum also showed a characteristic signal of methylene protons from the main polymer chain of the PVA backbone at δ = 1.40–1.90 ppm.²⁹ In Fig. S2b,^† the resonance signals corresponding to methylene protons (–N–(CH₂)₂–N–) and –CH₂COOH from the DTPA group were located at δ = 3.78 and 3.02 ppm, respectively (marked as k and l),^30,31 suggesting that the DTPA group was successfully bonded to the PVA.The thermal stability curves of the PVA and PVA–DTPA–Gd conjugate are presented in Fig. S3.^† The low-temperature weight loss from 25 °C to 200 °C in both samples corresponds to the evaporation of the physically adsorbed water.³² The PVA showed a dramatic mass loss of ∼60% from around 250 °C to 350 °C, which was due to the oxidation of –OH groups in the polymer.³³ The slow mass loss that occurred between 350 °C and 500 °C could be assigned to the combustion of the polymer. The weight loss of the PVA–DTPA–Gd conjugate also included two parts. The smooth and sharp weight losses were observed when the temperature ranged from 100 °C to 260 °C and 260 °C to 500 °C, respectively. By assuming that pure Gd₂O₃ with a weight percentage of 12.8% in PVA–DTPA–Gd conjugate, was the main product of the TGA measurement, it could be estimated that the Gd³⁺ content in the initial PVA–DTPA–Gd conjugate was about 11.2%, and the rest could be the PVA–DTPA.³⁴The molecular weight and polydispersity index of PVA and the PVA–DTPA–Gd conjugate were determined via GPC (Fig. S4^†). The results clearly indicated that the obtained curves are monomodal and symmetrical with a relatively narrow molecular weight distribution for both samples.³⁵ Tailing peaks were observed at neither the lower nor higher molecular weight sides, indicating the complete and successful synthesis of the target polymer.³⁶ The main molecular characteristics are listed in Fig. S4.^† The M_w and Đ values of PVA were determined to be 5.73 × 10⁴ g mol⁻¹ and 1.139, respectively, and the M_w and Đ values of the PVA–DTPA–Gd were 6.36 × 10⁴ g mol⁻¹ and 1.223, respectively. Previous studies demonstrated that the longitudinal relaxivities were molecular weight dependent: the higher the molecular weight, the greater the longitudinal relaxivity.³⁷ It was also found that the molecular weights of the polymer samples were greater than 5 × 10⁴ g mol⁻¹, which may result in the high r₁ value of CAs.The morphology of the PVA–DTPA–Gd conjugate was analyzed by TEM (Fig. S5^†). It was found that the PVA–DTPA–Gd exhibited an irregular size and looked like flakes, and the size was almost hundreds of nanometers. Furthermore, the EDX analysis of the PVA–DTPA–Gd shown in Fig. S5b^† successfully demonstrated the distribution of Gd, O, N and C elements in the polymer conjugate. The result further implied that the Gd³⁺ ions were fully confined within the polymer during the process of coordination, and the two components of Gd³⁺ and PVA–DTPA were strongly coupled together in the conjugate. Furthermore, the signal of the Cu element was also found in Fig. S5b,^† which might have been due to the copper mesh for testing. Additionally, it can be clearly observed that the PVA–DTPA–Gd conjugate had an irregular spherical structure with the diameter varying from 120 to 150 nm (Fig. S6^†). The particle sizes obtained from TEM were smaller as compared to those obtained from DLS, which may be ascribed to the DLS samples being thoroughly dissolved in water, while the TEM samples were initially dispersed in buffer and then dried before measurements. Therefore, the DLS data represented the real hydrodynamic diameters.In Fig. S7a.^† The C, O, N and Gd elements are clearly shown in the XPS survey spectrum of the PVA–DTPA–Gd conjugate, also indicating that the Gd³⁺ ions were successfully intercalated into the polymer. Fig. S7b–d^† shows the C 1s, O 1s and Gd 4d XPS spectra, respectively. The deconvoluted C 1s XPS spectra showed six peaks with energies of 284.4 eV, 284.8 eV, 285.2 eV, 285.6 eV, 287.5 eV and 288.4 eV, which could be assigned to the C atoms coming from C–C, C–O, C–O–C, C–N, O–C O and COOH, respectively.^38,39 Furthermore, two distinct peaks could be identified in the high-resolution O 1s spectrum (Fig. S7c^†): the peak located at 532.3 eV for the C–O groups and the peak at 533.6 eV from the C O group.³⁹ In order to confirm that Gd³⁺ was successfully seeded in the PVA–DTPA–Gd polymer, high-resolution XPS spectra of Gd 4d were obtained (Fig. S7d^†). Two strong binding peaks were observed; the binding energy of 142.8 eV could correspond to the Gd 4d_5/2 energy level, and 153.6 eV could correspond to the Gd 4d_3/2 energy level.⁴⁰ The appearance of the Gd 4d binding peaks indicated the presence of the Gd³⁺ oxidation state in the PVA–DTPA–Gd. Regarding the aforementioned results, the existence of Gd–N and Gd–O bonds demonstrated the successful formation of the PVA–DTPA–Gd conjugate.The stability of the PVA–DTPA–Gd was also tested, and the results are listed in Fig. S8.^† In Fig. S8a,^† the amount of Gd³⁺ released by the PVA–DTPA–Gd conjugate was carefully determined by UV-Vis. A calibration curve was obtained according to the functional relation between the Gd³⁺ concentration and absorption intensity. It was found that the absorption curves showed similar shapes, even under different concentrations (Fig. S8a^† inset). The maximum absorption wavelength was located at around 656 nm. The intensity of the UV absorption peak increased along with the increasing of the concentration of PVA–DTPA–Gd and a good linear correlation was established between them with a correlation coefficient of R² = 0.997. Thus, the amount of Gd³⁺ at each time interval could be calculated according to this linear equation. Fig. S7b^† shows the release kinetics curve and the related UV spectrum is exhibited in the inset. Remarkably, it was found that the negligible Gd³⁺ was released in 75 h, indicating that the PVA–DTPA–Gd conjugate has excellent stability.The cellular toxicity of CAs is an important aspect in biological applications. In this work, the cytotoxicity of the free DTPA–Gd and PVA–DTPA–Gd conjugate on a normal HUVEC cell line was evaluated via MTT assay. The viability of the cells was tested after incubation with free DTPA–Gd and the PVA–DTPA–Gd conjugate for 48 h, and both of the concentrations of the tested targets were selected in the range of 10 to 100 μg Gd³⁺ mL⁻¹. According to Fig. 1, the viability of the HUVEC cells was still higher than 90% after incubation with the PVA–DTPA–Gd conjugate and free DTPA–Gd, respectively, even at a concentration of 100 μg Gd³⁺ mL⁻¹ for a long incubation time (48 h). These results indicate that both the free DTPA–Gd and the PVA–DTPA–Gd conjugate demonstrate no serious toxic effects at high doses. In addition, it was found that the cytotoxicity of PVA–DTPA–Gd was lower than that of the free DTPA–Gd, demonstrating that the conjugated Gd ions are not easily released due to the excellent binding strength of DTPA to Gd³⁺ ions and the minimized cell interaction with Gd³⁺. Therefore, the nephrotoxicity risk induced by the conjugate is potentially lower than that of free DTPA–Gd at the same Gd dosages.⁴¹Open in a separate windowFig. 1Cytotoxicity studies of PVA–DTPA–Gd in HUVEC cells after incubation for 48 h.Hemolysis is the destruction of the erythrocytes (red blood cells, RBCs) in the blood, while hemocompatibility is a necessary component of safety. Due to the interactions of the cell-polymer with the cell membrane, the membrane integrity is often measured as a proxy for hemocompatibility. When the cell membrane integrity of the RBCs is destroyed, hemoglobin is released and thus, the results can be used in quantitative analysis. The materials can then be defined as non-hemolytic (0–2% of hemolysis), slightly hemolytic (2–5%), and hemolytic (5–100%).⁴⁰ As such, the blood compatibility of the PVA–DTPA–Gd conjugate was determined and the results are given in Fig. 2 and Fig. S9;^† no hemolysis was observed, even at 1100 μg mL⁻¹ of the experimental agents. When the concentration of the conjugate was 730 μg mL⁻¹, the hemolysis was about 2.53 ± 0.31%, meaning that the conjugate is non-hemolytic. When the concentration of the conjugate increased to 1100 μg mL⁻¹, the conjugate showed 4.67 ± 0.28% hemolysis, which is slightly hemolytic. These results indicate that that the prepared conjugate has no destructive effect on red blood cells, and it has good blood compatibility. This may be due to the fact that the acidic groups contained in the polymer hindered its interaction with red blood cells.Open in a separate windowFig. 2The hemolysis rate of PVA–DTPA–Gd.To evaluate the capability of the as-prepared PVA–DTPA–Gd conjugate in MRI application, longitudinal proton relaxation times (T₁) and spin–spin relaxation times (T₂) of the conjugate were determined. Based on this, the r₁ and r₂ relaxivity was calculated to be 5.6 and 7.3 mM⁻¹ s⁻¹ (Fig. 3a and b), respectively, by the linear fit of Gd³⁺ concentration vs. 1/T₁ and 1/T₂. Additionally, the r₂/r₁ ratio, another important parameter for characterizing contrast agents, was about 1.31, indicating that this conjugate is a kind of standard T₁ CAs. Based on this, the r₁ value of the PVA–DTPA–Gd conjugate was about 1.24 times higher than that of the DTPA–Gd (r₁ = 4.5 mM⁻¹ s⁻¹). The r₂/r₁ ratio was lower than that of the corresponding small-molecule contrast agent, and the improved relaxivity can be explained by the complexation leading to slower molecular tumbling, thus reducing the relaxation time of water.^42,43 These results successfully demonstrated the excellent contrast effect of the conjugate prepared in this work. The T₁-weighted MR images of the PVA–DTPA–Gd conjugate and free DTPA–Gd solutions are exhibited in Fig. 3c and S9,^† respectively. It is clear that the brightness of the MR images was enhanced with the increase in the concentration of Gd³⁺, as shown in Fig. 3c. It was also found from the black and white images that the conjugate exhibited better MRI efficiency as compared to the free DTPA–Gd (Fig. S10^†). These results have demonstrated the great potential of the polymer conjugate as an effective contrast agent for T₁-weighted MRI.Open in a separate windowFig. 3(a) T₁, (b) T₂-relaxation rate and (c) T₁-weighted MRI images of PVA–DTPA–Gd.     

内源性硫化氢的中枢心血管效应与KATP通道开放机制有关

背景：硫化氢具有舒张离体血管平滑肌、促进下丘脑促肾上腺皮质激素释放激素和细胞膜超极化的作用。中枢内硫化氢是否参与心血管活动的调节目前尚未得到充分的研究。 目的：观察中枢内源性硫化氢的心血管效应及其机制。 设计、时间及地点：随机对照动物实验，于2007-10/2008-10在解放军第一医院检验科完成。 材料：清洁级雄性SD大鼠40只，体质量200~250 g；S-腺苷蛋氨酸，KATP通道阻断剂格列苯脲为Sigma公司产品。 方法：40只大鼠随机被分为6组：①对照组6只，注射人工脑脊液。②S-腺苷蛋氨酸低剂量组6只注射S-腺苷蛋氨酸5 μmol、中剂量组5只注射S-腺苷蛋氨酸10 μmol、高剂量组7只注射S-腺苷蛋氨酸20 μmol。③预先注射人工脑脊液8只或格列苯脲格列苯脲8只，40 min后注射10 μmol S-腺苷蛋氨酸。将大鼠固定于立体定位仪，进行侧脑室注射。 主要观察指标：①侧脑室注射不同剂量S-腺苷蛋氨酸后对血压及心率的影响。②侧脑室注射KATP通道阻断剂格列苯脲对侧脑室注射S-腺苷蛋氨酸中枢心血管效应的影响。 结果：侧脑室注射S-腺苷蛋氨酸能够显著降低麻醉大鼠的血压，减慢大鼠的心率。侧脑室注射人工脑脊液不影响麻醉大鼠的血压和心率。格列苯脲预处理能显著减弱侧脑室 10 μmol S-腺苷蛋氨酸产生的降低血压效应，与人工脑脊液预处理组比较差异有显著性意义(P < 0.05)，格列苯脲+ S-腺苷蛋氨酸组和对照组比较差异无显著性意义(P > 0.05)。 结论：侧脑室注射S-腺苷蛋氨酸增加内源性硫化氢产生的中枢性降低血压、减慢心率的作用可能与KATP通道开放有关。     

中医象思维的相关理论探讨

在探讨中医象思维的内涵与挖掘的过程中,疏理象思维的中医原创思维的基础上,对象思维概念进行中医哲学的诠释和解读,抽提象思维的表述方式和中医象思维范式的特点,以中医原创思维理念为指导,依据"以象为素,以素为候,以候为证,据证言病,病证结合,法依证出,方证相应"的中医诊疗模式,探讨象思维医学的科学性。     

布氏杆菌病性脊柱炎13例临床分析

目的 探讨布氏杆菌病性脊柱炎临床特点。方法 回顾性分析甘肃省人民医院2015-2022年收治的13例布氏杆菌病性脊柱炎患者的临床资料、治疗及预后。结果 13例均出现腰背部不适,其中间断发热8例。13例红细胞沉降率、白介素-6均升高,虎红平板凝集试验、试管凝集试验均阳性,其中血培养阳性2例,磁共振成像均有不同程度受累。结论 布氏杆菌病性脊柱炎与脊柱结核、化脓性脊柱炎、脊柱肿瘤等疾病临床表现类似,极易误诊。对于发热、腰腿痛、肢体麻木患者,应详细询问流行病学史,完善血清学相关检查、脊柱磁共振成像,早诊断早治疗。     

初诊原发性甲减患者静息态脑功能的初步研究

目的利用静息态分数低频振幅(fractional amplitude of low-frequency fluctuations,fALFF)技术探讨初诊原发性甲状腺功能减退症(甲减)患者脑损害的神经病理生理机制。材料与方法对25名初诊未治疗的甲减患者(甲减组)和19名健康对照(健康对照组)行认知心理量表评定和头颅MRI扫描,用两样本t检验比较全脑fALFF值的组间差异,并与临床变量及认知心理评分行Pearson相关分析。结果甲减组蒙特利尔认知评估量表评分减低(P=0.009),汉密顿抑郁量表-24和汉密顿焦虑量表评分增高(P=0.013;P=0.041),其左侧枕下回、舌回和右侧梭状回、枕上回、脑岛、中央后回的fALFF值减低(GRF校正,体素水平P<0.005,团块水平P<0.05),其中左侧枕下回、舌回和右侧梭状回的fALFF值与认知评分呈正相关(r=0.514,P=0.009;r=0.468,P=0.018;r=0.400,P=0.048)。当体素水平阈值降至P<0.001时,左侧舌回fALFF仍显著减低,且与认知评分呈正相关(r=0.547,P=0.005),另外,甲减组甲状腺素与抑郁评分呈负相关(r=-0.363,P=0.005)。结论甲减患者存在认知功能受损、抑郁及焦虑状态。静息状态下,多个与认知功能及情绪密切相关脑区的自发性神经元活动减低,可能是甲减患者认知功能受损及情绪异常的重要神经病理生理机制。     

固本增骨方对去卵巢大鼠血清BGP、TRACP-5b及骨质量的影响＊

目的 观察固本增骨方对去卵巢大鼠血清BGP、TRACP-5b及骨质量的影响，探讨固本增骨方防治绝经后骨质疏松症的作用机制。方法 卵巢切除法建立大鼠骨质疏松模型，随机分为模型对照组、戊酸雌二醇组、固本增骨方高、中、低浓度组，选取同龄大鼠作为空白对照组。用药干预12w后，腹腔麻醉，采用双能X线骨密度测量仪计算大鼠全身骨密度；ELISA法检测大鼠血清骨生成代谢指标BGP及骨吸收代谢指标TRACP-5b；解剖分离左侧股骨标本，置于AG-X系列台式电子万能试验机，计算骨生物力学性能指标；激光共聚焦显微镜扫描各组股骨组织游离[Ca²⁺]i浓度。结果 与空白对照组相比，模型组大鼠全身骨密度值显著下降，股骨最大载荷和弹性模量明显降低，差异有统计学意义（P < 0.05）。与空白对照组比较，模型组大鼠BGP、TRAP-5b含量明显升高（P < 0.05）；给予药物干预后，与模型组相比，戊酸雌二醇组和固本增骨方各组BGP、TRAP-5b含量均明显下降（P < 0.05）；且固本增骨方高浓度组优于低浓度组（P < 0.05）；与模型组对比，戊酸雌二醇组和固本增骨方不同浓度组可显著增加全身骨密度值，明显提高股骨最大载荷和弹性模量、[Ca²⁺]i浓度，差异有统计学意义（P < 0.05）。固本增骨方高浓度组与低浓度组比较有统计学差异（P < 0.05），呈量效依赖关系。固本增骨方各组与戊酸雌二醇组比较差异无统计学意义（P > 0.05）。结论 固本增骨方可降低去卵巢大鼠模型血清BGP、TRAP-5b含量，改善全身骨密度，提升骨生物力学性能，增加骨组织中游离[Ca²⁺]i浓度，从而发挥对绝经后骨质疏松症的防治作用。