Correction of RNA splicing defect in β654-thalassemia mice using CRISPR/Cas9 gene-editing technology

β⁶⁵⁴-thalassemia is a prominent Chinese subtype of β-thalassemia, representing 17% of all cases of β-thalassemia in China. The molecular mechanism underlying this subtype involves the IVS-2-654 C→T mutation leading to aberrant β-globin RNA splicing. This results in an additional 73-nucleotide exon between exons 2 and 3 and leads to a severe thalassemia syndrome. Herein, we explored a CRISPR/Cas9 genome editing approach to eliminate the additional 73-nucleotide by targeting both the IVS-2-654 C→T and a cryptic acceptor splice site at IVS-2-579 in order to correct aberrant β-globin RNA splicing and ameliorate the clinical β-thalassemia syndrome in β⁶⁵⁴ mice. Gene-edited mice were generated by microinjection of sgRNA and Cas9 mRNA into one-cell embryos of β⁶⁵⁴ or control mice: 83.3% of live-born mice were gene-edited, 70% of which produced correctly spliced RNA. No off-target events were observed. The clinical symptoms, including hematologic parameters and tissue pathology of all of the edited β⁶⁵⁴ founders and their offspring were significantly improved compared to those of the non-edited β⁶⁵⁴ mice, consistent with the restoration of wild-type β-globin RNA expression. Notably, the survival rate of gene-edited heterozygous β⁶⁵⁴ mice increased significantly, and live-born homozygous β⁶⁵⁴ mice were observed. Our study demonstrated a new and effective gene-editing approach that may provide groundwork for the exploration of β⁶⁵⁴-thalassemia therapy in the future.     

立体定向辅助显微手术切除脑内海绵状血管瘤

目的 探讨利用立体定向技术,辅助皮层电极监测,开放显微手术切除导致顽固性癫痫的脑内海绵状血管瘤,提高微创手术的治疗效果.方法 26例顽固性癫痫病例,MRI示脑内海绵状血管瘤(直径在0.5～2.5 cm),视频脑电图检查诊断与MRI定位一致.10例采用常规显微手术切除,16例利用立体定向技术,放置硅胶管引导显微手术切除病灶,辅助皮层脑电图监测确认致痫灶切除.结果 手术时间:常规组为3.5小时,定向组为2.3小时.病灶全切率:常规组80%(8/10),定向组93.7%(15/16).全部病例得到随访,时间平均18个月,常规组癫痫消失8例,脑电图记录到癫痫波2例,临床癫痫发作2例.定向组癫痫消失14例,脑电图记录到癫痫波2例,临床癫痫发作1例.结论 在没有导航系统的条件下,立体定向引导显微开放手术,辅助皮层电极监测,切除以顽固性癫痫为症状的海绵状血管瘤是一种定位精确、微创、安全、有效的方法.     

伽玛刀联合替莫唑胺治疗脑胶质瘤的临床观察

目的 探讨伽玛刀联合替莫唑胺和伽玛刀治疗恶性脑胶质瘤的效果和安全性.方法 选择2003～2006年经病理证实为恶性胶质瘤的病人,采用病例对照研究的方法,随机分为二组,实验组(35例)在伽玛刀术后采用替莫唑胺5个周期化疗,对照组(48例)仅行伽玛刀治疗.长期随访,观察病人的无进展生存时间和总的生存时间以及药物的安全性.结果 实验组的平均平均生存期为14.2个月,对照组为7.8个月.实验组的2年生存率为20.5%,对照组为10.1%.常见的不良反应为恶心、呕吐等.结论 伽玛刀联合替莫唑胺治疗恶性胶质瘤有效,能提高生存率而毒副反应小.     

肺癌患者术后并发肺部感染的危险因素分析

目的 分析肺癌患者术后并发肺部感染(postoperative pulmonary infection in patients with lung cancer,PPILC)的危险因素.方法 回顾性分析中山大学肿瘤防治中心2018年1-12月收治的472例行肺癌手术患者的资料,包括临床基本资料和实验室检查结果等,应用单...     

Differential Associations of Intakes of Whole Grains and Coarse Grains with Risks of Cardiometabolic Factors among Adults in China

There is a lack of studies on the association between whole grain intake and cardiometabolic risk factors in China and the current definition of whole grains is inconsistent. This study defined whole grains in two ways, Western versus traditional, and examined their associations with the risks of major cardiometabolic factors (CMFs) among 4706 Chinese adults aged ≥18 years, who participated in surveys both in 2011 and in 2015. Diet data were collected by consecutive 3 d 24 h recalls, together with household seasoning weighing. Whole grains were defined as grains with a ratio of fiber to carbohydrate of ≥0.1, while coarse grains were defined as grains except for rice and its products, and wheat and its products. Multivariable logistic regressions were modeled to analyze the associations of intakes of whole grains and coarse grains, respectively, with risks of major CMFs including obesity-, blood pressure-, blood glucose- and lipid-related factors, which were defined by International Diabetes Federation and AHA/NHLBI criteria. After adjusting for potential confounders, the odds of elevated LDL-C decreased with the increasing intake levels of whole grains (OR 0.64, 95% CI 0.46–0.88, p-trend < 0.05). Moreover, adults with the whole grain intake of 50.00 to 150.00 g/day had 27% lower odds of overweight and obesity (OR 0.73, 95% CI 0.54–0.99) and 31% lower odds of elevated LDL-C (OR 0.69, 95% CI 0.49–0.96), as compared with non-consumers. In conclusion, given the significant nutrient profiles of whole grains and coarse grains, the adults with higher intakes of whole grains only may have a lower risk of LDL-C and overweight and obesity.     

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.     

Microstructure Evolution of Al6061 Alloy Made by Additive Friction Stir Deposition

In this paper, the phase structure, composition distribution, grain morphology, and hardness of Al6061 alloy samples made with additive friction stir deposition (AFS-D) were examined. A nearly symmetrical layer-by-layer structure was observed in the cross section (vertical with respect to the fabrication-tool traversing direction) of the as-deposited Al6061 alloy samples made with a back-and-forth AFS-D strategy. Equiaxed grains were observed in the region underneath the fabrication tool, while elongated grains were seen in the “flash region” along the mass flow direction. No clear grain size variance was discovered along the AFS-D build direction except for the last deposited layer. Grains were significantly refined from the feedstock (~163.5 µm) to as-deposited Al6061 alloy parts (~8.5 µm). The hardness of the as-fabricated Al6061 alloy was lower than those of the feedstock and their heat-treated counterparts, which was ascribed to the decreased precipitate content and enlarged precipitate size.     

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.     

不同模式新辅助治疗食管癌的疗效分析

目的 探讨食管癌不同模式新辅助治疗的疗效分析。方法 回顾性分析2015年1月至2022年5月于安阳市肿瘤医院行新辅助治疗的食管鳞癌(ESCC)患者的资料,共纳入542例患者,其中放化疗(NCRT)组137例,化疗(NCT)组241例,免疫加化疗(NICT)组164例;女性198例,男性344例;≤65岁289例,＞65岁253例。首要研究终点包括主要病理缓解(MPR)率、病理完全缓解(pCR) 率,次要研究终点包括总生存(OS)、无进展生存(PFS)和安全性。生存分析采用Kaplan-Meier方法,并采用Log-rank检验进行组间比较。采用Cox比例风险回归模型进行预后因素分析。结果 NCRT组的MPR率和pCR率分别为66.4%(91/137)和35.8%(49/137),NCT组分别为35.3%(85/241)和6.6%(16/241),NICT组分别为63.4%(104/164)和31.1%(51/164)(χ²=1.67, P＜0.001)。NCRT组的1、2、3年的OS分别为89.8%、82.3%、72.3%,NCT组分别为85.9%、71.4%、61.4%,NICT组分别为91.9%、81.5%、77.8%,差异有统计学意义(χ²=9.20,P＜0.01);NCRT组的1、2、3年的PFS分别为81.5%、67.9%、66.6%,NCT组分别75.9%、61.0%、53.5%,NICT组分别为80.1%、65.5%、65.3%,差异有统计学意义(χ²=4.62,P＜0.05)。多因素分析显示,治疗方式、T分期、N分期是OS的独立影响因素(P＜0.05)。3组不良反应及术后并发症差异无统计学意义(P＞0.05)。结论 与NCT对比,NICT与NCRT有更高的pCR、MPR和生存获益,因此新辅助免疫可作为食管癌术前治疗手段之一,但仍需大型的随机对照研究进一步证实。     

视觉因素对前交叉韧带重建患者足底压力中心的影响

目的 分析患者前交叉韧带重建(anterior cruciate ligament reconstruction, ACLR)术后早期与术后 1 年在视觉因素影响下足底压力中心面积(center of pressure area, COPA)和压力中心速度(center of pressure speed, COPS)等参数的变化。 方法 纳入 ACLR 患者 17 例,于术后早期和术后 1 年测试足底 COPA 和 COPS 等数据;匹配 17 例健康受试者作为对照组。 进行睁、闭眼不同视觉状态站立平衡测试,对各测量状态进行相关性分析。 结果 双足站立测试时,短期组 COPA 和 COPS 在睁眼和闭眼对比均有统计学差异(P<0. 05);长期组 COPS 睁眼和闭眼对比有统计学差异(P<0. 001)。 健侧站立时,各组间差异具有统计学意义(P<0. 05),伤侧站立时各组间差异无统计学意义(P>0. 05)。 健侧站立睁眼条件下,长期组 COPA 高于短期组和对照组,对照组 COPS 低于短期组和长期组(P<0. 01)。 健侧站立闭眼条件下,对照组 COPA 低于短期组和长期组,对照组 COPS 低于长期组(P<0. 01)。 双足睁眼与双足闭眼之间、双足睁眼与伤侧睁眼之间、健侧睁眼和伤侧睁眼之间、健侧闭眼和伤侧闭眼之间在 COPA 和COPS 上均呈正相关。 结论 通过对 ACLR 患者站立位压力中心相关数据的分析,发现视觉对姿势稳定控制有重要影响。 术后 1 年患者双足和单足站立时对比正常人稳定性波动较大,提示在临床上要加强术后长期训练以巩固康复效果,并对开展长期评估和制定精准训练计划具有一定的指导作用,以防止术后长时间功能退化和降低再次损伤的风险。