低氧刺激鼻息肉黏膜上皮细胞炎性因子变化的初探

目的:研究低氧刺激慢性鼻窦炎伴鼻息肉（CRSwNP）与正常鼻黏膜上皮细胞炎性因子的变化与异同,探讨其在CRSwNP发病机制中的作用。方法:选择2015年6月至2018年1月在吉林大学中日联谊医院就诊的68例CRSwNP患者,其中男性36例,女性32例,年龄（45.2±12.5）岁（ xˉ±s,下同）,患者的...     

Graves病患者血清性激素与干扰素γ、白细胞介素4水平及相关性研究

目的观察Graves病(GD)患者治疗前后血清性激素及干扰素γ(IFN-γ)、白细胞介素4(IL-4)的动态变化,探讨GD患者Ⅰ型辅助性T细胞(Th1)/Ⅱ型辅助性T细胞(Th2)细胞因子平衡的偏离方向,及性激素对Th1/Th2平衡的影响。方法选取初发未治的Graves病患者80例为治疗组,经抗甲状腺药物治疗12周后均临床缓解,治疗前后分别应用应用放免法(RIA)检测血清雌二醇(E2)、睾酮(T)、黄体生成素(LH)、卵泡刺激素(FSH)水平,应用酶联免疫吸附测定(ELISA)法检测血清IFN-γ、IL-4水平;健康体检者50例作为正常对照组。结果女性GD患者治疗前血清E2、LH、FSH水平均较正常对照组明显升高(均P<0.01),治疗后均接近正常对照组;治疗前血清IL-4水平较正常对照组明显升高(P<0.001),血清IFN-γ水平较正常对照组降低(P<0.01);治疗后IL-4水平下降,而IFN-γ水平升高,均接近正常对照组;经多元逐步回归分析,血清E2水平是影响IL-4及IFN-γ水平的独立因素,分别呈正相关和负相关;IL-4与IFN-γ水平是相互的独立因素,呈负相关。结论初发未治的GD患者存在性激素水平的变化及Th1/Th2细胞因子失衡,治疗前可能以Th2免疫反应为主,治疗后向Th1免疫反应漂移,雌激素可能在Th1/Th2平衡方面起着重要作用。     

颈动脉与冠状动脉粥样硬化的病理对比分析

目的探讨颈动脉粥样硬化与冠状动脉粥样硬化病变之间的关系。方法应用图象分析对17例尸检患者的272段颈动脉和冠状动脉血管进行测量,比较内容包括动脉壁厚比值腔面积/截面积比值和狭窄血管支数比值。结果颈动脉和冠状动脉粥样硬化病变血管支数的比值呈正相关(r=0.79,P<0.01),其余比值无相关性。结论颈动脉粥样硬化病变的存在可以预示冠状动脉有病变,但二者病变的严重程度无明确的相关性。     

硬化萎缩性苔藓的病因学研究进展

硬化萎缩性苔藓（LSA）病因尚不清楚,大量研究表明免疫因素、遗传因素、疏螺旋体属的感染、性激素水平及其受体的减少和氧化应激损伤均与该病的发生发展有着密切的关系。     

应变率成像对正常儿童左心室心肌形变能力的定量研究

目的 定量研究我国正常儿童左心室心肌应变率参数及其随年龄变化的特点。方法 正常儿童92名,按年龄分为4组,应用GEVivid7超声仪及Q-analyze软件分别对各组儿童左心室侧壁、下壁、前壁、后壁及前、后室间隔心肌各节段进行应变率定量分析。结果 前3组（1～9岁）儿童左心室心肌应变率在各节段的分布不一致,差异有统计学意义;10～14岁组左心室心肌各节段收缩期和舒张早期应变率差异无统计学意义,呈均衡分布。结论 正常儿童左心室心肌各节段收缩期、舒张早期应变率随年龄增长逐渐趋向一致,10岁后分布模式与成人相似。     

A Novel Herbal Extract Blend Product Prevents Particulate Matters-Induced Inflammation by Improving Gut Microbiota and Maintaining the Integrity of the Intestinal Barrier

Air pollutants of PM2.5 can alter the composition of gut microbiota and lead to inflammation in the lung and gastrointestinal tract. The aim of this study was to evaluate the protective effect of a novel herbal extract blend, FC, composed of Lonicera japonica extract, Momordica grosvenori extract, and broccoli seed extract, on PM2.5-induced inflammation in the respiratory and intestinal tract. A549 cells and THP-1 cells, as well as C57BL/6 mice, were stimulated with PM2.5 to establish in vitro and in vivo exposure models. The models were treated with or without FC. The expression of inflammatory cytokines and tight junction proteins were studied. Proteomic analysis was performed to elucidate mechanisms. Mouse feces were collected for gut microbiota analysis. FC was shown to modulate the upregulation of pro-inflammatory cytokines mRNA expression in A549 and THP-1 cells and downregulated tight junction proteins mRNA expression in A549 cells due to PM2.5 stimulation. In animal models, the decreased expression of the anti-inflammatory factor il-10, tight junction protein ZO-1, and the elevated expression of COX-2 induced by PM2.5 were improved by FC intervention, which may be associated with zo-1 and cox-2 signaling pathways. In addition, FC was shown to improve the gut microbiota by increasing the abundance of beneficial bacteria.     

Resistance of Xanthomonas oryzae pv. oryzae to Lytic Phage X2 by Spontaneous Mutation of Lipopolysaccharide Synthesis-Related Glycosyltransferase

Phage therapy is a promising biocontrol management on plant diseases caused by bacterial pathogens due to its specificity, efficiency and environmental friendliness. The emergence of natural phage-resistant bacteria hinders the application of phage therapy. Xanthomonas oryzae pv. oryzae (Xoo) is the causal agent of the devastating bacterial leaf blight disease of rice. Here, we obtained a spontaneous mutant C2R of an Xoo strain C2 showing strong resistance to the lytic phage X2. Analysis of the C2R genome found that the CDS2289 gene encoding glycosyltransferase acquired a frameshift mutation at the 180th nucleotide site, which also leads to a premature stop mutation at the 142nd amino acid. This mutation confers the inhibition of phage adsorption through the changes in lipopolysaccharide production and structure and bacterial surface morphology. Interestingly, glycosyltransferase-deficient C2R and an insertional mutant k2289 also showed reduced virulence, suggesting the trade-off costs of phage resistance. In summary, this study highlights the role of glycosyltransferase in interactions among pathogenic bacteria, phages and plant hosts, which provide insights into balanced coevolution from environmental perspectives.     

Molecular Analysis of Caprine Enterovirus Circulating in China during 2016–2021: Evolutionary Significance

Here, we report the characterization of 13 novel caprine/ovine enterovirus strains isolated from different regions in China during 2016–2021. Immunoperoxidase monolayer assay showed that these viral strains shared strong cross-reaction with the previously reported caprine enterovirus CEV-JL14. Alignment analysis of the complete nucleotide sequences revealed 79.2%–87.8% and 75.0%–76.7% sequence identity of these novel caprine enterovirus strains to CEV-JL14 and TB4-OEV, respectively. Phylogenetic analyses clustered these novel strains to EV-G based on the amino acid sequences of P1 and 2C+3CD. Moreover, phylogenetic analysis of these caprine enterovirus strains identified three new EV-G types using VP1 sequences. These results demonstrate the genetic variations and the evolution of caprine enterovirus.     

Ruthenium-catalyzed asymmetric hydrogenation of aromatic and heteroaromatic ketones using cinchona alkaloid-derived NNP ligands

A series of cinchona alkaloid-based NNP ligands, including a new one, have been employed for the asymmetric hydrogenation of ketones. By combining ruthenium complexes, various aromatic and heteroaromatic ketones were smoothly reacted, yielding valuable chiral alcohols with extremely high 99.9% ee. Moreover, a proposed reaction mechanism was discussed and verified by NMR.

A series of cinchona alkaloid-based NNP ligands including a new one has been employed for the asymmetric hydrogenation of ketones. By combining ruthenium complexes, various ketones were smoothly reacted with up to 99.9% ee.

Since the well-known failure of using racemic thalidomide, attention has been paid to the manufacture of optically pure compounds as effective components in pharmaceuticals and agrochemicals. Asymmetric hydrogenation of ketones, especially heteroaromatic ketones, has emerged as a popular facile route to approach enantiopure secondary alcohols as essential intermediates for the construction of biologically active molecules.^1–4 Knowles et al.⁵ pioneered the production of enantioenriched chiral compounds in 1968, and Noyori and co-workers^6–8 laid the cornerstone of asymmetric hydrogenation in 1990s. Subsequently, numerous catalytic systems have been developed. Ru-BICP-chiral diamine-KOH was developed and proved to be effective for asymmetric hydrogenation of aromatic ketones by Xumu Zhang.⁹ Cheng-yi Chen reported asymmetric hydrogenation of ketone using trans-RuCl₂[(R)-xylbinap][(R)-daipen] and afforded secondary alcohol in 92–99% ee.¹⁰ Mark J. Burk and Antonio Zanotti-Gerosa disclosed Phanephos-ruthenium-diamine complexes catalyzing the asymmetric hydrogenation of aromatic and heteroaromatic ketones with high activity and excellent enantioselectivity.¹¹ Qi-Lin Zhou et al. designed and synthesized chiral spiro diphosphines as a new chiral scaffold applied in the asymmetric hydrogenation of simple ketones with extremely high activity and up to 99.5% ee.^12–15 Similarly, Kitamura and co-workers have developed a set of tridentate binan-Py-PPh₂ ligands for the asymmetric hydrogenation of ketones affording excellent results.¹⁶ Recently, chiral diphosphines and tridentate ligands based on ferrocene have been developed for the asymmetric hydrogenation of carbonyl compound with a remarkable degree of success.^17–21 Despite many ligands for asymmetric hydrogenation of ketones have been reported, expensive reagent and multistep complicated reactions were employed to synthesize most of them.^22–24 In light of increasing industrial demand, easily obtained, cheap and practical chiral ligands are still highly desirable. In addition to chiral ligands, the selection of metals was essential for asymmetric hydrogenation.^25–27 Although Mn,^28–30 Fe,^31–34 Co,^35–37 Ni^38,39 and Cu^40,41 metals were proved to be effective for asymmetric hydrogenation in recent years, Rh,^42–44 Ir^45,46 and especially Ru remained the most preferred metals. Ruthenium^47–51 was chosen owing to its superior performances in terms of low price, selectivity and activity. Takeshi Ohkuma,⁵² Hanmin Huang^53,54 and Johannes G. de Vries⁵⁵ all successfully used ruthenium catalysts for asymmetric hydrogenation of ketones. Admittedly, there is a continuing interest in the development of cheaper, simpler and more efficient catalysts for the asymmetric hydrogenation of ketones under mild conditions to access corresponding secondary alcohols. Recently, we developed new NNP chiral ligands derived from cinchona alkaloid for the asymmetric hydrogenation of various ketones in extremely excellent results using a iridium catalytic system.⁵⁶ Prompted by these encouraging results, we were interested in exploring a ruthenium-catalyzed asymmetric hydrogenation of ketones with NNP chiral ligands derived from cinchona alkaloid. Here, we showed that changing from iridium to ruthenium, with the same simple synthetic ligands, delivered a catalyst catalyzed asymmetric hydrogenation of ketones to give the industrially important chiral alcohols with up to 99.9% ee. Although the catalytic activity of ruthenium catalyst was not as high as that of the iridium catalyst, the enantioselectivity could be maintained, and even showed higher enantioselectivity in the hydrogenation of some substrates.Chiral tridentate ligand NNP (L1–L10) were synthesized and characterized as reported in our previous publication. With tridentate ligands in hand, we began to evaluate the catalytic performance in benzylidene-bis(tricyclohexylphosphine) dichlororuthenium-catalyzed asymmetric hydrogenation of acetophenone employed as a standard substrate (Fig. 2). MeOH was found to be a better one as the conversion and enantioselectivity were 99.9% and 98.2%, respectively. Bases screening showed that Ba(OH)₂ was superior to the others, giving >99.9% conversion and 98.8% ee in the present catalytic system (Fig. 1). Ligand screening revealed that the configuration of chiral centers of cinchona alkaloids of the ligand markedly affected the catalytic performance. NNP ligands derived from cinchonine and quinidine appeared to benefit both the reaction rate and enantioselectivity, while those derived from cinchonidine and quinine had the opposite effect. Further, different NNP ligands that bearing different substituents on the phenyl rings were evaluated. Similar to our previous research, ligands with electron-withdonating substituents showed better catalytic performance than those with electron-withdrawing substituents. However, it was noted that the more electron-withdonating substituents furnished lower activity but same enantioselectivity. The optimal ligand L5 derived from quinidine with one methoxy group on benzene ring provided the corresponding chiral alcohol with 99.9% conversion and 98.8% ee. Considering that L3 derived from cinchonine had similar catalytic performance to L4 derived from quinidine, new ligand L10 similar to L5 with one methoxy group on benzene ring was synthesized and applied to the asymmetric hydrogenation of template substrate. 99.6% conversion and 97.6% ee was obtained. Hence, L5 was employed as better ligand in subsequent experiments.Open in a separate windowFig. 1The effect of different bases for the asymmetric hydrogenation of acetophenone (substrate/Ru/L5 = 500/1/2, ketones: 0.429 mol L⁻¹, base: 0.15 mol L⁻¹, MeOH: 2 mL, 30 °C, 6 MPa, 2 h.).Open in a separate windowFig. 2The effect of different solvents for the asymmetric hydrogenation of acetophenone. (substrate/Ru/L5 = 1000/1/2, ketones: 0.858 mol L⁻¹, Ba(OH)₂: 0.15 mol L⁻¹, solvent: 2 mL, 30 °C, 6 MPa, 2 h.).The effect of different ligand for the asymmetric hydrogenation of acetophenone^a

Relationships between self-reflectiveness and clinical symptoms in individuals during pre-morbid and early clinical stages of psychosis

BackgroundSelf-reflectiveness, one dimension of cognitive insight, plays a protective role in an individual’s mental state. Both high and low levels of self-reflectiveness have been reported in patients with schizophrenia and individuals at clinical high risk for the illness.AimsThis study aimed to explore the relationship patterns between self-reflectiveness and clinical symptoms in individuals during the pre-morbid and early clinical stages of psychosis.MethodsA total of 181 subjects, including individuals with attenuated positive symptoms (APS, n=122) and patients with first-episode psychosis (FEP, n=59), completed the Beck Cognitive Insight Scale and were evaluated using the Schedule of Assessment of Insight and Positive and Negative Syndrome Scale. All subjects were classified into three groups according to their level of self-reflectiveness: low level (LSR, n=59), medium level (MSR, n=67) and high level (HSR, n=55). Both linear and non-linear relationships between self-reflectiveness and clinical symptoms were explored.ResultsMore individuals with APS were classified into the MSR group, while more patients with FEP were classified into the LSR group. The LSR group demonstrated less awareness of illness than the MSR and HSR groups, more stereotyped thinking and poorer impulse control but less anxiety than the MSR group, and lower levels of blunted affect and guilt feelings than the HSR group. The MSR group demonstrated lower stereotyped thinking than the HSR group. Compared to the LSR group, the MSR group had increased self-reflectiveness, improved awareness of illness, decreased stereotyped thinking, and better impulse control, but increased feelings of guilt. The HSR group showed increased stereotyped thinking when compared to the MSR group, but the other variables did not change significantly between these two groups. Overall, self-reflectiveness demonstrated an approximately inverse S-shaped relationship with the awareness of illness, a U-shaped relationship with stereotyped thinking and poor impulse control, and an almost linear relationship with anxiety and guilt feelings.ConclusionsSelf-reflectiveness demonstrates complex relationships with clinical symptoms and fails to exert significant positive effects when reaching a certain high level.