针灸防治癌因性疲乏临床实践指南研究

目的:探索针灸防治癌因性疲乏的临床应用方案,为制定临床实践指南提供依据.方法:通过计算机检索国家知识基础设施数据库(CNKI)、中国学术期刊数据库(CSPD)、中文科技期刊数据库(CCD)、中国生物文献、PubMed、EMBASE、Cochrane Library等数据库,全面收集针灸疗法治疗癌因性疲乏的现代文献证据;...     

子宫内膜消融术治疗良性病变所致子宫出血疗效的研究

目的探讨超声引导下子宫内膜消融术在良性疾病导致的异常子宫出血中的治疗效果。方法 应用自凝刀对114例患者在超声监护下行子宫内膜射频消融术,术后定期随访,观察疗效。结果自凝刀子宫内膜消融术治疗子宫出血平均（12.32±4.51）min,96例治愈,18例有效,总有效率100%,无严重并发症。结论超声引导下子宫内膜消融术治疗子宫异常出血是一种安全、疗效好、简单、快速的治疗方法。     

Specific cell targeting with APRPG conjugated PEG–PLGA nanoparticles for treating ovarian cancer

Good biocompatibility, specific tumor targeting, effective drug loading capacity and persistence in the circulation in vivo are imperative prerequisites for the antitumor efficiency of nanoparticles and their further clinical application. In this study, APRPG (Ala-Pro-Arg-Pro-Gly) peptide-modified poly (ethylene glycol)–poly (lactic acid) (PEG–PLA) nanoparticles (NP-APRPG) encapsulating inhibitors of angiogenesis (TNP-470) (TNP-470-NP-APRPG) were fabricated. TNP-470-NP-APRPG was designed to feature maleimide-PEG–PLA and mPEG–PLA as carrier materials, the APRPG peptide for targeting angiogenesis, PEG for prolonging circulation in vivo and PLA for loading TNP-470. TNP-470-NP-APRPG was confirmed to be approximately 130 nm in size with negative ζ-potential (−14.3 mV), narrow distribution (PDI = 0.27) and spherical morphology according to dynamic light scattering (DLS) and transmission electron microscopy (TEM) analyses. In addition, X-ray photoelectron spectra (XPS) analyses confirmed 7.73% APRPG grafting on the TNP-470-NP. In vitro, TNP-470-NP-APRPG exhibited effective inhibition of proliferation, migration and tube formation in human umbilical vein endothelial cells (HUVECs). Similar findings were observed for the retardation of tumor growth in SKOV3 ovarian cancer-bearing mice, suggesting the significant inhibition of angiogenesis and antitumor efficiency of TNP-470-NP-APRPG. Moreover, no obvious toxic drug responses were observed. Further evidence obtained from the immunohistochemical examination demonstrated that the tumor growth inhibition was closely correlated with the high rate of apoptosis among endothelial cells and the effective blockade of endothelial cell proliferation. These results demonstrate that NP-APRPG is a promising carrier for delivering TNP-470 to treat ovarian cancer and that this approach has the potential to achieve broad tumor coverage in the clinic.     

下腰痛患者后路手术并发症的防治

目的：分析下腰痛患者后路手术并发症出现的原因，探讨防治办法。方法：回顾分析我科自１９８８～１９９８年６月间采用后路手术治疗下腰痛，即腰椎间盘突出症和／或腰椎管狭窄症患者５７０例的临床资料。结果：３３例发生术后并发症，发生率５．７９％，早期（术后２周以内）并发症１８例，晚期并发症１５例，但无一例并发神经根损伤。结论：除了术中操作技能外，术前严格掌握手术适应证，术后及时观察、早期功能锻炼，都有利于并发症的防治。     

基于脑功能网络的抑郁症识别研究

传统基于脑电(EEG)的抑郁症研究将电极视为孤立节点,忽略了它们之间的关联性,难以发掘抑郁症患者异常大脑拓扑改变。为此,本文提出一种基于脑功能网络(BFN)的抑郁症识别框架,为避免容积导体效应,相位延迟指数用于构建BFN;以加权与二值化BFN信息互补为基础,选取"小世界"特性密切相关及最小生成树特定脑区BFN指标,采用递进式指标分析策略寻找抑郁症识别潜在标识物。本文以48名受试者静息态EEG数据用于验证方案,结果表明组间同步性在左颞、右顶枕、右额脑区明显改变;加权BFN最短路径长度和聚类系数,二值化BFN左颞和右额的叶子分数及右顶枕的直径与患者健康问卷9项(PHQ-9)之间具有相关性,且获得最高94.11%的识别率。此外,研究发现相对于健康对照者,抑郁症患者的信息处理能力明显下降。通过上述结论,期望本研究结果可为BFN构建与分析提供新的思路,为抑郁症识别潜在标识物的发掘提供新的方法。     

涎腺嗜酸细胞性脂肪腺瘤二例

报道2例罕见的发生于腮腺的涎腺嗜酸细胞性脂肪腺瘤。大体观察:2例均包膜完整,1例呈多结节状,1例呈哑铃状。镜下观察:2例肿瘤均被覆薄的纤维性包膜,由不同比例的脂肪组织和大小不等的嗜酸性细胞巢混合构成。免疫组织化学染色:2例嗜酸性细胞均表达人低分子量细胞角蛋白,部分表达细胞角蛋白(CK)7、CK5/6、CK19、p63、上皮细胞膜抗原(EMA),不表达S-100蛋白、Calponin、DOG1,Ki-67阳性指数约1%~2%。2例分别随访4和5个月,均未见复发。     

MiR-138 promotes induced pluripotent stem cell generation through the regulation of the p53 signaling

Induced pluripotent stem (iPS) cells, especially those reprogrammed from patient somatic cells, have a great potential usage in regenerative medicine. The expression of p53 has been proven as a key barrier limiting iPS cell generation, but how p53 is regulated during cell reprogramming remains unclear. In this study, we found that the ectopic expression of miR-138 significantly improved the efficiency of iPS cell generation via Oct4, Sox2, and Klf4, with or without c-Myc (named as OSKM or OSK, respectively), without sacrificing the pluripotent characteristics of the generated iPS cells. Exploration of the mechanism showed that miR-138 directly targeted the 3' untranslated region (UTR) of p53, significantly decreasing the expression of p53 and its downstream genes. Furthermore, the ectopic expression of p53 having a mutant 3'-UTR, which cannot be bound by miR-138, seriously impaired the effect of miR-138 on p53 signaling and OSKM-initiated somatic cell reprogramming. Combined with the fact that miR-138 is endogenously expressed in fibroblasts, iPS cells, and embryonic stem cells, our study demonstrated that regulation of the p53 signaling pathway and promotion of iPS cell generation represent an unrevealed important function of miR-138.     

Oral bioavailability of silymarin formulated as a novel 3-day delivery system based on porous silica nanoparticles

The purpose of this study was to develop porous silica nanoparticles (PSNs) as a carrier to improve oral bioavailability of poorly water-soluble drugs, using silymarin as a model. PSNs were synthesized by reverse microemulsion and ultrasonic corrosion methods. A 3-day release formulation consisting of a silymarin solid dispersion, a hydrophilic gel matrix and silymarin-loaded PSNs was prepared. In vitro release studies indicated that both the silymarin-loaded PSNs and the 3-day release formulation showed a typical sustained-release pattern over a long period, about 72 h. The in vivo studies revealed that the 3-day release formulation gave a significantly higher plasma concentration and larger area under the concentration-time curves than commercial tablets when orally administered to beagle dogs. This implies that the prepared 3-day release formulation significantly enhanced the oral bioavailability of silymarin, suggesting that PSNs can be used as promising drug carriers for oral sustained release systems. Thus providing a technically feasible approach for improving the oral bioavailability and long-term efficacy of poorly soluble drugs.     

Atom Transfer Radical Dispersion Polymerization of Styrene in the Presence of PEO‐based Macromonomer

Commercially available poly(ethylene oxide) macromonomers are successfully used as reactive stabilizers for atom transfer radical dispersion/precipitation polymerization of styrene. Polystyrene particles with PEO chains covalently anchored on the surfaces are obtained. Control over both the particle size and polymer chain growth is achieved using a two‐stage technique consisting of an initial free radical polymerization (FRP) for the nucleation followed by a reverse atom transfer radical polymerization (ATRP) for the controlled polymerization process. The limited monomer conversion at the FRP step ensures that the overall polymerization process is mainly controlled by the reverse ATRP step, resulting in the formation of particles containing well‐defined polymer chains.

     

GSK3326595 is a promising drug to prevent SARS-CoV-2 Omicron and other variants infection by inhibiting ACE2-R671 di-methylation

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) caused COVID-19 epidemic is worsening. Binding of the Spike1 protein of SARS-CoV-2 with the angiotensin-converting enzyme 2 (ACE2) receptor mediates entry of the virus into host cells. Many reports show that protein arginine methylation by protein arginine methyltransferases (PRMTs) is important for the functions of these proteins, but it remains unclear whether ACE2 is methylated by PRMTs. Here, we show that PRMT5 catalyses ACE2 symmetric dimethylation at residue R671 (meR671-ACE2). We indicate that PRMT5-mediated meR671-ACE2 promotes SARS-CoV-2 receptor-binding domain (RBD) binding with ACE2 probably by enhancing ACE2 N-glycosylation modification. We also reveal that the PRMT5-specific inhibitor GSK3326595 is able to dramatically reduce ACE2 binding with RBD. Moreover, we discovered that meR671-ACE2 plays an important role in ACE2 binding with Spike1 of the SARS-CoV-2 Omicron, Delta, and Beta variants; and we found that GSK3326595 strongly attenuates ACE2 interaction with Spike1 of the SARS-CoV-2 Omicron, Delta, and Beta variants. Finally, SARS-CoV-2 pseudovirus infection assays uncovered that PRMT5-mediated meR671-ACE2 is essential for SARS-CoV-2 infection in human cells, and pseudovirus infection experiments confirmed that GSK3326595 can strongly suppress SARS-CoV-2 infection of host cells. Our findings suggest that as a clinical phase II drug for several kinds of cancers, GSK3326595 is a promising candidate to decrease SARS-CoV-2 infection by inhibiting ACE2 methylation and ACE2-Spike1 interaction.