关键词： 结直肠癌   益气健脾   化学疗法   FOLFOX方案   Meta分析  

摘要： 目的 系统评价益气健脾活血法联合FOLFOX方案治疗结直肠癌患者的有效性及安全性,为临床用药提供依据。方法 检索PubMed、中国知网、万方、维普等数据库,纳入有关益气健脾活血法联合FOLFOX方案治疗结直肠癌患者的随机对照试验。检索时间为建库起至2023年11月。采用Revman 5.3软件对结果进行Meta分析。结果 共纳入15篇文献,涉及927例患者,其中治疗组患者488例,对照组患者439例。Meta分析结果显示:益气健脾活血法联合FOLFOX方案对结直肠癌患者临床症状缓解有效率(OR=4.52;95%CI:2.98~6.85,I^(2)=0%)及控显率(OR=5.51;95%CI:3.26~9.31,I^(2)=12%)高于对照组,并可提高患者的生活质量(OR=3.12;95%CI:1.44~6.75,I^(2)=0%),但对肿瘤缓解情况无明显改善(OR=1.57;95%CI:0.93~2.67,I^(2)=0%)。益气健脾活血法联合FOLFOX方案对结直肠癌化疗患者的神经毒性(OR=0.73;95%CI:0.44~1.22,I^(2)=0%)、总骨髓抑制(OR=0.78;95%CI:0.35~1.74,I^(2)=0%)发生率及血小板下降(OR=0.72;95%CI:0.44~1.17,I^(2)=0%)无明显改善,但可减轻白细胞(OR=0.46;95%CI:0.30~0.69,I^(2)=0%)及血红蛋白(OR=0.56;95%CI:0.37~0.84,I^(2)=0%)下降情况。结论 益气健脾活血法联合FOLFOX方案对结直肠癌患者临床症状改善有较好的效果,并可减轻部分不良反应。

关键词： 高血压脑出血   小骨窗侧裂入路   大骨瓣开颅手术   术后并发症发生率   炎症反应  

摘要： 本研究旨在对比小骨窗侧裂入路与标准大骨瓣开颅手术在治疗高血压脑出血患者的有效性及安全性。方法 回顾性分析2020年1月至2023年1月,共计60名诊断为高血压脑出血的患者被随机分为两组,每组30人。实验组采用小骨窗侧裂入路进行手术,对照组接受标准大骨瓣开颅手术。术后并发症发生率、住院时间,以及各项指标被用于评估治疗的有效性及安全性。结果 显示,实验组患者在手术后舒张压降低更显著(P<0.05);其次,实验组患者的手术时间更短、术中出血量更少、切口长度更小以及术后恢复更快(P<0.05);此外,在术后并发症方面,实验组的发生率显著低于对照组(P<0.05);同样,实验组在炎症反应控制上也表现出更好的效果,术后第三天白细胞计数明显低于对照组(P<0.05)。结论 小骨窗侧裂入路在治疗高血压脑出血方面与标准的大骨瓣开颅手术相比,可提供相似的治疗效果,并且具有更低的并发症发生率,较短的手术时间,说明其在临床应用中具有潜在的有效性及更高的安全性。

关键词： 老年2型糖尿病   二甲双胍   门冬胰岛素30注射液   血糖   胰岛功能  

摘要： 目的分析二甲双胍联合门冬胰岛素30注射液治疗对老年2型糖尿病患者血糖水平、胰岛功能、炎症反应的影响,为该疾病的临床治疗提供参考。方法以随机数字表法将2021年1月至2024年1月杭州九和医院收治的60例老年2型糖尿病患者分为对照组(30例,门冬胰岛素30注射液治疗)和观察组(30例,二甲双胍联合门冬胰岛素30注射液治疗)。两组患者均治疗12周,比较两组患者治疗后血糖控制临床疗效,治疗前后血糖指标水平、胰岛功能指标、血清炎症因子水平、BMI,以及治疗期间不良反应发生情况。结果与对照组比,观察组患者血糖控制临床疗效更优;治疗后两组患者血清空腹血糖(FBG)、餐后2 h血糖(2 hPG)、糖化血红蛋白(HbA1c)水平较治疗前均降低,且观察组均低于对照组;治疗后两组患者胰岛素分泌指数(HOMA-β)较治疗前均升高,胰岛素抵抗指数(HOMA-IR)、空腹胰岛素(FINS)水平较治疗前均降低,且观察组变化幅度均大于对照组;治疗后两组患者血清白细胞介素-6(IL-6)、肿瘤坏死因子-α(TNF-α)水平及BMI较治疗前均降低,且观察组均低于对照组(均P<0.05);两组患者治疗期间不良反应总发生率比较,差异无统计学意义(P>0.05)。结论应用二甲双胍与门冬胰岛素30注射液联合治疗,能改善老年2型糖尿病患者的血糖控制效果和胰岛功能,减轻炎症反应,且安全性良好。

关键词： 石杉碱甲   心脑舒通   血管性痴呆   影像学变化   认知功能   痴呆程度   日常生活能力  

摘要： 目的分析石杉碱甲联合心脑舒通治疗血管性痴呆(VD)患者临床疗效、大脑影像学及认知功能的影响。方法2021年3月至2023年6月商洛市中心医院收治的血管性痴呆患者206例,采用根据随机数字表法分为心脑舒通组(n=103)、石杉碱甲联合组(n=103),心脑舒通组予以心脑舒通等血管性痴呆常规治疗,石杉碱甲联合组在心脑舒通组基础上增加石杉碱甲治疗。对比两组临床疗效、大脑影像学变化、认知功能[简易精神状态检查量表(MMSE)]、痴呆程度[长谷川痴呆量表(HDS)]及日常生活能力[日常生活能力量表(ADL)],并对比治疗安全性。结果石杉碱甲联合组的治疗总有效率为93.21%(96/103)高于心脑舒通组的84.47%(87/103)(χ^(2)=3.964,P=0.046);治疗后,石杉碱甲联合组和心脑舒通组大脑影像显示下皮层下动脉梗死、基底节出血、顶叶梗死、颞叶梗死及额叶梗死率(分别是2.91%、4.85%、3.88%、6.80%、5.83%、9.71%、12.62%、11.65%、15.53%、13.59%),低于治疗前(分别是22.33%、30.10%、13.59%、19.42%、14.56%、20.39%、25.24%、15.53%、21.36%、17.48%),且石杉碱甲联合组各部位梗死率均低于心脑舒通组(均P<0.05);治疗后,石杉碱甲联合组和心脑舒通组MMSE、HDS及ADL评分[分别是(24.46±4.13)分、(25.65±3.87)分、(66.94±7.21)分、(20.41±3.87)分、(21.06±3.22)分、(58.41±6.57)分],均高于治疗前[分别是(18.06±3.47)分、(17.88±2.41)分、(47.51±6.02)分、(17.69±3.52)分、(17.52±2.48)分、(46.84±5.87)分],且石杉碱甲联合组评分均高于心脑舒通组(均P<0.05);在不良反应总发生率方面,心脑舒通组为16.50%(17/103),石杉碱甲联合组为19.41%(20/103),两组比较差异无统计学意义(χ^(2)=0.296,P>0.05)。结论石杉碱甲+心脑舒通更有利于改善血管性痴呆患者认知功能、痴呆程度及日常生活能力,脑梗死率影像改变效果更佳,临床效果更为显著,具有安全性。

关键词： 草鱼   脂质蓄积   脂肪细胞   线粒体自噬   细胞凋亡   PINK1/Parkin  

摘要： 草鱼脂肪组织脂质过度沉积是水产养殖生产中常见的突出问题之一,而诱导脂肪细胞凋亡是降脂的有效手段。为探究草鱼脂肪细胞中线粒体自噬与细胞凋亡的关系,开展在体和离体两个试验。在水温24~30℃的在体试验中,将体质量约20 g的草鱼饲养在网箱中,投喂添加0(对照组)、10、20 mg/kg和40 mg/kg线粒体自噬激活剂羰基氰化物-3-氯苯腙56 d;离体试验中,分离原代草鱼脂肪细胞培养分化成熟后,用0(对照组)和20μmol/L羰基氰化物-3-氯苯腙处理细胞24 h。在体试验结果显示:与对照组相比,40 mg/kg线粒体自噬激活剂羰基氰化物-3-氯苯腙显著降低了草鱼腹腔脂肪指数(P<0.05)和甘油三酯含量(P<0.05),显著提高了自噬相关基因pink1、parkin、atg12、atg5和凋亡相关基因caspase3、caspase9的mRNA水平(P<0.05);与对照组相比,各个处理组的脂肪细胞面积大小无显著变化(P>0.05)。离体试验结果表明:羰基氰化物-3-氯苯腙处理极显著升高了细胞线粒体自噬相关基因pink1、parkin、atg4、atg7和atg12的mRNA水平(P<0.01)和细胞凋亡相关基因bax、caspase9的mRNA水平及bax/bcl-2比值(P<0.05或P<0.01),显著降低了抗凋亡基因bcl-2的mRNA水平(P<0.05)及细胞甘油三酯含量(P<0.05)。综合试验结果可知,激活草鱼脂肪细胞线粒体自噬可能会诱导脂肪细胞凋亡,降低草鱼腹腔脂质的蓄积。

关键词： Neurogranin   Ameloblast   Calmodulin   Tooth development  

摘要： Differentiation and proliferation of odontogenic cells are regulated by specific genes, driving the morphological changes during tooth germ development. While substantial data have been gathered on genes involved in early tooth development, knowledge about the terminal differentiation of odontogenic cells-particularly ameloblasts-remains limited. To identify molecules involved in cytodifferentiation, gene expression profiles in maxillary cap stage and root stage molar germs of rats at postnatal day 9, respectively were compared using differential display-PCR. This analysis unexpectedly revealed the upregulation of neurogranin, a brain-specific calmodulin-binding protein, at the cap stage. The expression of neurogranin at both transcriptional and translational levels progressively decreased from the early bell stage, through the crown stage, to the root stage in molar germs. Similar temporal expression patterns were observed for other calmodulin-binding proteins, including neuromodulin and PEP-19. Immunofluorescence confirmed the presence of neurogranin in the inner enamel epithelium of cap and early bell stage molar germs. Correspondingly, the expression levels of calmodulin and PKC gamma mRNA displayed dynamic changes during the developmental timeline. Notably, the ablation of neurogranin in SF2 ameloblastic cells enhanced ameloblast differentiation and mineralization. These findings, for the first time, suggest that neurogranin may play a critical role in the temporospatial regulation of the differentiation of inner enamel epithelial cells into ameloblasts.

关键词： Mutant p53   Glutathionylation   Glutathione reductase   GSH/GSSG ratio   Ubiquitin-proteasome system   Mutant p53-carrying cancer  

摘要： Mutp53 level is widely variable among individual cancer cells in tumor tissues, and within cells a higher level of mutp53 is usually observed in the nucleus as compared to the cytoplasm. This spatial heterogeneity in mutp53 expression has been well documented and likely plays an important role in tumor therapeutic resistance. However, its underlying mechanism remains poorly understood. In this study, we first revealed a critical role of micro-environmental reducing status in regulating mutp53 stability and spatially heterogeneous accumulation. Immunofluorescence and ThiolTracker Violet dye staining demonstrated a clear correlation between the cellular mutp53 level and the reducibility in the patient-derived tumor tissues and mutp53-expressing cancer cell lines. The nucleus exhibited both higher reducibility and more mutp53 accumulation than the cytoplasm did. Supplementing GSH exacerbated the accumulation of mutp53, while consuming GSH led to extensive depletion of mutp53, suggesting that the environmental reducing status kept mutp53 stability. Mechanistically, S-glutathionylation could trigger ubiquitination and proteasomal degradation of mutp53. A highly-reducing local environment preserved mutp53 stability by inhibiting glutathionylation and subsequent proteasomal degradation of mutp53, which also provided an explanation for the differential accumulation of mutp53 proteins in the nucleus and cytoplasm. Thirdly, we revealed that the expression level of glutathione reductase (GR) was positively correlated with mutp53 accumulation across the cultured mutp53-expressing cell lines, patient-derived tumor tissues and patient databases. Over-expression of GR reinforced the environmental reducibility, affected glutathionylation and improved mutp53 accumulation, while inhibiting GR either by chemical inhibitors or genetic approach induced massive clearance of a variety of mutp53 and effectively retarded the growth of p53-mutated cell-derived xenografts in mice. These studi

关键词： CBP60 proteins   Colletotrichum gloeosporioides   Transcriptional regulation   Poplar  

摘要： The calmodulin-binding protein 60 (CBP60) family members play pivotal roles in plant immunity in plants. Most studies have concentrated on AtCBP60a, AtCBP60b and AtCBP60g in Arabidopsis thaliana. However, there are few reports on the CBP60 gene family in woody plants, particularly the function of CBP60e in plant-pathogen interactions. In this investigation, 14 Populus trichocarpa (Pt) CBP60 (PtCBP60) genes were identified and these genes were unevenly dispersed across eight chromosomes. The detection of collinearity and the presence of tandem gene clusters suggested that segmental duplication and tandem duplication might be the critical impetus for expanding gene members in poplar. Notably, PtCBP60E1 and PtCBP60E2 not only showed segmental duplication events, but shared similar physicochemical properties. PtCBP60E1 was further evaluated by the temporal expression pattern analysis at different hours post-inoculation (hpi) with Colletotrichum gloeosporioides, which showed that its expression was significantly induced (9.7-fold) at 24 hpi. Intriguingly, the area of leaf lesions (2.8 mm2) in overexpression (OE) of PtCBP60E1 (OE-31) lines was notably smaller than that (15.35 mm2) in non-transgenic poplar 84 K (wild-type, WT) lines at 3 days post-inoculation. Higher ROS accumulation was detected in OE lines after C. gloeosporioides infection compared to WT lines. These results showed that PtCBP60E1 positively regulated the resistance response of poplar to C. gloeosporioides infection. Overall, this study provided a comprehensive characterization of the PtCBP60 gene family in poplar and identified PtCBP60E1 as an essential regulatory gene in response to C. gloeosporioides infection, offering new insights into the genomic evolution and molecular mechanisms of poplar CBP60.

关键词： biomolecular condensates   cancer   p53   phase separation   prion diseases   protein aggregation  

摘要： Biomolecular condensates, formed through phase separation (PS), are essential in various physiological processes, but they can also transition into amyloid-like structures, contributing to diseases like cancer and neurodegenerative disorders. This review centers on the tumor suppressor protein p53 and its paralogs, p63 and p73, which play significant roles in cancer biology. Mutations in the TP53 gene, present in over half of all malignant tumors, disrupt the function of p53 and contribute to cancer progression. Mutant p53 not only misfolds but also forms biomolecular condensates and amyloid-like aggregates, like the toxic amyloids seen in neurodegenerative diseases. These amyloid-like structures, characteristic of mutant p53, might be associated with its gain of function (GoF) in cancer. Recent in vitro and in cell studies demonstrate that mutant p53 can exert a prion-like effect on its paralogs, p63 and p73, which typically do not form amyloids under physiological conditions. Heparin inhibits the prion-like effect of mutant p53 on p63 and p73. These findings underscore the critical role of mutant p53 in promoting the aggregation of p63 and p73, and likely of other transcription factors, suggesting new therapeutic targets. The amyloid-like aggregation of mutant p53 is an excellent candidate target for cancer, as evidenced by recent studies. By understanding the phase transitions and amyloid formation of mutant p53, innovative diagnostic and treatment strategies have been explored to reveal and disrupt these processes, offering hope for improved cancer ***

关键词： Cerebral ischemia-reperfusion injury   Calcium/calmodulin-dependent protein kinase II Beta   Amphiregulin   Jun proto-oncogene   Embryonic lethal abnormal vision-like 1   Autophagy-dependent ferroptosis  

摘要： Ferroptosis is an iron-dependent regulatory cell death characterized by lipid peroxidation. The molecular mechanism of calcium/calmodulin-dependent protein kinase II beta (CAMK2B) affecting cerebral ischemic injury through autophagy-dependent ferroptosis is still unclear. Here, we aimed to study the regulatory effect of CAMK2B on autophagy-dependent ferroptosis and its effect on cerebral ischemic injury. We found that CAMK2B was significantly upregulated in oxygen and glucose deprivation/recovery (OGD/R)-induced PC12 cells and primary hippocampal neurons. CAMK2B knockdown inhibited OGD/R-induced autophagy-dependent ferroptosis in PC12 cells and primary hippocampal neurons. In addition, CAMK2B was co-localized with amphiregulin (AREG) in PC12 cells, and overexpression of AREG reversed the effect of CAMK2B knockdown on OGD/R-induced autophagy-dependent ferroptosis in PC12 cells and primary hippocampal neurons. Further molecular mechanism studies showed that AREG enhanced the transcriptional activation of embryonic lethal abnormal vision-like 1 (ELAVL1) through Jun Proto-Oncogene (c-Jun), thereby inducing autophagy-dependent ferroptosis in PC12 cells and primary hippocampal neurons. Moreover, CAMK2B was significantly upregulated in the ipsilateral penumbra neurons of cerebral ischemia-reperfusion (I/R) mice, and the level of autophagy-dependent ferroptosis was increased in the brain tissue of I/R mice. Knockdown of CAMK2B alleviated neuronal damage by inhibiting autophagy-dependent ferroptosis in the brain tissue of model mice. This study suggests that CAMK2B plays a key role in regulating neuronal autophagy-dependent ferroptosis, and CAMK2B may be a potential target for the treatment of cerebral I/R injury.