Hepatocellular carcinoma:An analysis of the expression status of stress granules and their prognostic value

BACKGROUND Hepatocellular carcinoma(HCC)is a global popular malignant tumor,which is difficult to cure,and the current treatment is limited.AIM To analyze the impacts of stress granule(SG)genes on overall survival(OS),survival time,and prognosis in HCC.METHODS The combined The Cancer Genome Atlas-Liver Hepatocellular Carcinoma(TCGA-LIHC),GSE25097,and GSE36376 datasets were utilized to obtain genetic and clinical information.Optimal hub gene numbers and corresponding coefficients were determined using the Least absolute shrinkage and selection operator model approach,and genes for constructing risk scores and corresponding correlation coefficients were calculated according to multivariate Cox regression,respectively.The prognostic model’s receiver operating characteristic(ROC)curve was produced and plotted utilizing the time ROC software package.Nomogram models were constructed to predict the outcomes at 1,3,and 5-year OS prognostications with good prediction accuracy.RESULTS We identified seven SG genes(DDX1,DKC1,BICC1,HNRNPUL1,CNOT6,DYRK3,CCDC124)having a prognostic significance and developed a risk score model.The findings of Kaplan-Meier analysis indicated that the group with a high risk exhibited significantly reduced OS in comparison with those of the low-risk group(P<0.001).The nomogram model’s findings indicate a significant enhancement in the accuracy of OS prediction for individuals with HCC in the TCGA-HCC cohort.Gene Ontology and Gene Set Enrichment Analysis suggested that these SGs might be involved in the cell cycle,RNA editing,and other biological processes.CONCLUSION Based on the impact of SG genes on HCC prognosis,in the future,it will be used as a biomarker as well as a unique therapeutic target for the identification and treatment of HCC.

Stress granules inhibit endoplasmic reticulum stress-mediated apoptosis during hypoxia-induced injury in acute liver failure

BACKGROUND Stress granules(SGs)could be formed under different stimulation to inhibit cell injury.AIM To investigate whether SGs could protect hepatocytes from hypoxia-induced damage during acute liver failure(ALF)by reducing endoplasmic reticulum stress(ERS)mediated apoptosis.METHODS The agonist of SGs,arsenite(Ars)was used to intervene hypoxia-induced hepatocyte injury cellular model and ALF mice models.Further,the siRNA of activating transcription factor 4(ATF4)and SGs inhibitor anisomycin was then used to intervene in cell models.RESULTS With the increase of hypoxia time from 4 h to 12 h,the levels of HIF-1α,ERS and apoptosis gradually increased,and the expression of SGs marker G3BP1 and TIA-1 was increased and then decreased.Compared with the hypoxia cell model group and ALF mice model,the levels of HIF-1α,apoptosis and ERS were increased in the Ars intervention group.After siRNA-ATF4 intervention,the level of SGs in cells increased,and the levels of HIF-1α,ERS and apoptosis decreased.Compared with the siRNA-ATF4 group,the levels of G3BP1 in the siRNAATF4+anisomycin group were decreased,and the levels of HIF-1α,ERS and apoptosis were increased.Moreover,compared with the ALF group,the degree of liver injury and liver function,the levels of HIF-1α,ERS and apoptosis in the Ars intervention group were decreased,the level of SGs was increased.CONCLUSION SGs could protect hepatocytes from hypoxia-induced damage during ALF by reducing ERSmediated apoptosis.

基于SG-I6000 2.0+CMBD的电力智能运维系统设计与实现

为促使电网公司运维工作规范化、便捷化,提高电网运维效率,在原有SG-I6000 2.0系统架构基础上,融入配置管理数据库(CMBD),构建基于SG-I6000 2.0+CMBD的电力智能运维系统。该系统自上而下分为应用层、中台服务层和运维感知层,相比原系统新增了资源配置、流程服务、健康履历、自动审计、业务流微应用、构建自主流程微应用、资源全过程管理等。并发测试结果表明,新系统最大可承受1000个并发用户同时使用的需求。压力测试结果表明,在最大500个用户数量同时操作情况下,平均事务响应时间仅为40.8 s,相比原系统降低了63%,运维效率得到显著提升。

Diverse CMT2 neuropathies are linked to aberrant G3BP interactions in stress granules

Complex diseases often involve the interplay between genetic and environmental factors. Charcot-Marie-Tooth type 2neuropathies (CMT2) are a group of genetically heterogeneous disorders, in which similar peripheral neuropathology isinexplicably caused by various mutated genes. Their possible molecular links remain elusive. Here, we found that uponenvironmental stress, many CMT2-causing mutant proteins adopt similar properties by entering stress granules (SGs), where theyaberrantly interact with G3BP and integrate into SG pathways. For example, glycyl-tRNA synthetase (GlyRS) is translocated fromthe cytoplasm into SGs upon stress, where the mutant GlyRS perturbs the G3BP-centric SG network by aberrantly binding toG3BP. This disrupts SG-mediated stress responses, leading to increased stress vulnerability in motoneurons. Disrupting thisaberrant interaction rescues SG abnormalities and alleviates motor deficits in CMT2D mice. These findings reveal a stressdependentmolecular link across diverse CMT2 mutants and provide a conceptual framework for understanding geneticheterogeneity in light of environmental stress.

Xiaotan Tongfu granules contribute to the prevention of stress ulcers

AIM:To investigate the efficacy and potential mechanism of Xiaotan Tongfu granules(XTTF)in stress ulcers.METHODS:One hundred sixty rats were randomly divided into 4 groups(n=10)as follows:the model group(MP group),the control group(CP group),the ranitidine group(RP group)and the XTTF granule group(XP group).Rats in the MP group received no drugs,rats in the CP group received 0.2 mL of a 0.9%sodium chloride solution via oral gavage,and rats in the RP and XP groups received the same volume of ranitidine(50 mg/kg)or XTTF granule(4.9 g/kg).The cold-restraint stress model was applied to induce stress ulcers after 7 consecutive days of drug administration.Afterwards,rats were sacrificed at 0,3,6 and24 h.Gastric pH was measured by a precise pH meter;gastric emptying rate(GER)was measured by using a methylcellulose test meal;myeloperoxidase activity(MPO),macrophage migration inhibitory factor(MIF),proliferating cell nuclear antigen(PCNA),and heat shock protein 70(HSP70)were measured by immunohistochemical staining;and mucosal cell apoptosis was measured by transferase dUTP nick end labeling.RESULTS:In the cold-restraint stress model,the development of stress ulcers peaked at 3 h and basically regressed after 24 h.Gastric lesions were significantly different in the RP and XP groups at each time point.Interestingly,although this index was much lower in the RP group than in the XP group immediately following stress induction(7.00±1.10 vs 10.00±1.79,P<0.05.Concerning gastric pH,between the RP and XP groups,we detected a statistically significant difference immediately after stress induction(0 h:4.56±0.47 vs 3.34±0.28,P<0.05)but not at any of the subsequent time points.For GER,compared to the RP group,GER was remarkably elevated in the XP group because a statistically significant difference was detected(3 h:46.84±2.70 vs 61.16±5.12,P<0.05;6 h:60.96±6.71 vs 73.41±6.16,P<0.05;24 h:77.47±3.17 vs 91.31±4.34,P<0.05).With respect to MPO and MIF,comparisons between the RP and XP groups revealed statistically significant differences at 3 h(MPO:18.94±1.20 vs 13.51±0.89,P<0.05;MIF:150.67±9.85 vs 122.17±5.67,P<0.05)and 6 h(MPO:13.22±1.54 vs 8.83±0.65,P<0.05;MIF:135.50±9.46 vs 109.83±6.40,P<0.05).With regard to HSP70,HSP70 expression was significantly increased in the RP and XP groups at 3 and 6 h compared to the MP and CP groups.In addition,comparing the RP and XP groups also showed statistically significant differences at 3 and 6 h.The expression of PCNA was higher in the RP and XP groups 3 h after stress induction.Between these two groups,small but statistically significant differences were observed at all of the time points(3 h:69.50±21.52 vs 79.33±15.68,P<0.05;6 h:107.83±4.40 vs 121.33±5.71,P<0.05;24 h:125.33±5.65 vs 128.50±14.49,P<0.05)except 0 h.With regard to apoptosis,the apoptotic activity in the RP and XP groups was significantly different from that in the MP and CP groups.The XP group exhibited a higher inhibition of cell apoptosis than the RP group at3 h(232.58±24.51 vs 174.46±10.35,P<0.05)and6 h(164.74±18.31 vs 117.71±12.08,P<0.05).CONCLUSION:The Xiaotan Tongfu granule was demonstrated to be similar to ranitidine in preventing stress ulcers.It exhibited multiple underlying mechanisms and deserves further study.

Bufei Yishen granules suppress oxidative stress in rats with chronic obstructive pulmonary disease via Nrf2 signaling

OBJECTIVE To explore the antioxidant effect of Bufei Yishen granules on chronic obstructive pulmo⁃nary disease(COPD)and investigate its underlying mechanism.METHODS Forty-eight rats were randomly divided into normal,model,Bufei Yishen granules(BY)and N-acetylcysteine(NAC)groups,12 rats in each group.The stable COPD rat model was duplicated by using repeated cigarette smoke exposure combined with Klebsiella bacterial infection for 12 weeks(week 1-12),and the corresponding drugs were administered for the next 8 weeks(week 13-20).Minute volume(MV),tidal volume(TV)and peak expiratory flow(PEF)were measured by whole body plethysmography(WBP)system every 4 weeks.Before sacrificed,forced vital capacity(FVC)and forced expiratory volume 0.1(FEV0.1)were measured byPFT system.The pathological changes of lung tissue were observed by pathological techniques.Heme oxygenase 1(HO-1),superoxide dismutase 1(SOD1)and Nrf2 in lung tissue were measured by immunohisto-hemical method.The total anti oxidizing capability(T-AOC),lipid peroxide(LPO)in rat serum were measured.The expression of Nrf2,HO-1 andγ-glutamyl cysteine synthetase(γ-GCS)mRNA in lung tissue was detected by quantitative polymerase chain reac⁃tion(qPCR).The protein expression of Keap1,Nrf2 and HO-1 in lung tissue were detected by Western blotting.RESULTS①Lung function:compared with normal group,the MV in model group was significantly decreased at week 8(P<0.01),the TV and PEF were significantly decreased at week 4(P<0.01).At week 20,compared with model group,MV,TV,and PEF in the BY and NAC groups were significantly increased(P<0.01);compared with the NAC group,MV,TV,and PEF in BY group were significantly increased(P<0.01).At the end of week 20,the FVC and FEV0.1 in model group were significantly lower than that in normal group(P<0.01).Compared with model group,the FVC and FEV0.1 in the BY and NAC groups were significantly increased(P<0.05).②Oxidative indexes:Compared with Normal group,T-AOCin serum was significantly decreased in Model group,while LPO was significantly increased(P<0.01).Compared with the Model,T-AOC in BY and NAC groups was significantly increased(P<0.01),and the LPO was significantly decreased(P<0.05,P<0.01).There were no difference between the BTG and NAC.③Nrf2 signaling:Nrf2 and HO-1 in lung tissue were mainly expressed in the cytoplasm and part of the nucleus of alveolar epithelial cells.SOD1 protein was mainly distributed in bronchial epithelial cells and alveolar septa.Compared with normal group,the expression of Nrf2 in the model group was increased(P<0.01),and HO-1 and SOD1 were decreased(P<0.01).Compared with the model,the expression of Nrf2 in the BY group was significantly increased(P<0.05),and HO-1 and SOD1 in BY and NAC groups were both increased(P<0.01).Compared with the NAC group,the expression of HO-1 in BY group was increased(P<0.01).Compared with normal group,the Nrf2 mRNA expression of lung tissue in the model was significantly increased(P<0.01),the HO-1 andγ-GCS mRNA was decreased(P<0.01).Compared with model group,the Nrf2,HO-1,andγ-GCS mRNA in the BY group were increased(P<0.01),the HO-1,andγ-GCS mRNA in NAC group were increased(P<0.01).Compared with normal group,the Nrf2 protein expression of lung tissue in the model group was significantly increased(P<0.01),and HO-1 protein expression was significantly decreased(P<0.01).Compared with the model,the Nrf2 and HO-1 protein in NAC and BY groups was significantly increased(P<0.01).CONCLUSION Bufei Yishen gran⁃ules has beneficial curative effect in COPD rats,and has the same antioxidation effect as NAC,the mechanism may be involved in upregulating Nrf2 signaling.

Paclitaxel-induced stress granules increase LINE-1 mRNA stability to promote drug resistance in breast cancer cells

Abnormal expression of long interspersed element-1(LINE-1)has been implicated in drug resistance,while our previous study showed that chemotherapy drug paclitaxel(PTX)increased LINE-1 level with unknown mechanism.Bioinformatics analysis suggested the regulation of LINE-1 mRNA by drug-induced stress granules(SGs).This study aimed to explore whether and how SGs are involved in drug-induced LINE-1 increase and thereby promotes drug resistance of triple negative breast cancer(TNBC)cells.We demonstrated that SGs increased LINE-1 expression by recruiting and stabilizing LINE-1 mRNA under drug stress,thereby adapting TNBC cells to chemotherapy drugs.Moreover,LINE-1 inhibitor efavirenz(EFV)could inhibit drug-induced SG to destabilize LINE-1.Our study provides the first evidence of the regulation of LINE-1 by SGs that could be an important survival mechanism for cancer cells exposed to chemotherapy drugs.The findings provide a useful clue for developing new chemotherapeutic strategies against TNBCs.

针刺联合息风化痰通络颗粒对急性脑梗死溶栓患者的影响及机制研究

目的:评估针刺联合息风化痰通络颗粒对急性脑梗死(ACI)后溶栓患者的疗效,探讨其作用机制。方法:纳入ACI溶栓患者178例,按随机数字表法分为观察组和对照组各89例,最终164例完成研究,观察组81例,对照组83例。对照组接受常规治疗,观察组在对照组的基础上加用针刺联合息风化痰通络颗粒治疗,两组均治疗2周。评估比较两组的临床疗效、美国国立卫生研究院卒中量表(NIHSS)评分、日常生活活动能力量表(ADL)评分、血清炎症因子水平、氧化应激因子水平以及脑血流动力学。结果:治疗后,两组ADL评分、白细胞介素-10(IL-10)、超氧化物歧化酶(SOD)、谷胱甘肽过氧化物酶(GSH-Px)、过氧化氢酶(CAT)水平均较治疗前升高(P<0.05),NIHSS评分、白细胞介素-1β(IL-1β)、超敏C反应蛋白(hs-CRP)、丙二醛(MDA)水平较治疗前降低(P<0.05),观察组NIHSS评分、IL-1β、IL-10、hs-CRP、MDA水平低于对照组(P<0.05),ADL评分、SOD、GSH-Px、CAT水平高于对照组(P<0.05)。两组脑血流动力学指标均较治疗前改善,且观察组改善情况优于对照组(P<0.05)。观察组治疗总有效率95.06%,对照组84.34%,两组疗效比较,差异有统计学意义(P<0.05)。结论:针刺联合息风化痰通络颗粒能够促进ACI溶栓患者脑血流动力学恢复,改善缺血再灌注损伤的神经功能,其作用机制可能与减轻炎症反应、抑制氧化应激反应有关。

疏肝利胆颗粒治疗原发性胆汁性胆管炎72例的疗效观察

目的:探讨疏肝利胆颗粒治疗原发性胆汁性胆管炎(PBC)胆腑郁热证患者效果。方法:纳入兰州大学第一医院普外科就诊的72例胆腑郁热证PBC患者,根据数字奇偶法分为对照组和治疗组,每组36例。对照组服用熊去氧胆酸胶囊治疗,治疗组服用熊去氧胆酸胶囊+疏肝利胆颗粒治疗。比较两组临床症状、微炎症指标[白细胞介素6(IL-6)、白细胞介素17(IL-17)、肿瘤坏死因子-α(TNF-α)]、肝功能[谷草转氨酶(AST)、总胆红素(TBIL)、谷丙转氨酶(ALT)]、氧化应激指标[丙二醛(MDA)、谷胱甘肽过氧化物酶(GSH-Px)、超氧化物歧化酶(SOD)]、肝纤维化[血清透明质酸(HA)、层粘连蛋白(LN)、Ⅲ型前胶原、Ⅳ型胶原]、免疫球蛋白M(IgM)变化及疗效情况。结果:两组治疗后身热不退、身目发黄、胁肋胀痛、大便秘结、呕吐呃逆、口苦咽干中医证候积分对比,治疗组均低于对照组(P<0.05)。两组治疗后IL-17、IL-6、TNF-α水平均下降(P<0.05),治疗组比对照组更低(P<0.05)。两组TBIL、AST、ALT水平治疗后均下降(P<0.05),治疗组比对照组更低(P<0.05)。两组治疗后MDA水平均降低(P<0.05),治疗组更低(P<0.05),两组治疗后GSH-Px、SOD水平均升高(P<0.05),治疗组更高(P<0.05)。两组治疗后肝纤维化、免疫指标HA、LN、III型前胶原、IV型胶原、IgM水平均下降(P<0.05),治疗组比对照组更低(P<0.05)。治疗后治疗组总有效率显著高于对照组(91.67%vs 72.22%)。结论:疏肝利胆颗粒治疗胆腑郁热证PBC临床疗效显著,能有效促进临床症状及肝功能改善,减轻机体炎症反应及氧化应激反应,改善机体免疫功能、肝纤维化程度,具有较高的临床推广价值。

基于网络药理学和实验验证探究生血通便颗粒治疗慢传输型便秘的作用机制

目的采用网络药理学预测生血通便颗粒治疗慢传输型便秘(slow transit constipation,STC)的潜在作用机制,并进行动物实验验证。方法利用TCMSP数据库和BATMAN-TCM数据库筛选生血通便颗粒的活性成分及作用靶点,通过GeneCards数据库和OMIM数据库筛选STC疾病相关靶点,构建“活性成分-疾病靶点”网络,使用R语言对交集基因进行GO及KEGG富集分析。大鼠采用盐酸洛哌丁胺混悬液[3 mg/(kg·d)]灌胃建立STC模型。将大鼠分为正常组(等体积蒸馏水)、模型组(等体积蒸馏水)、莫沙比利组[1.35 mg/(kg·d)]、生血通便颗粒低剂量组[1.44 g/(kg·d)]、生血通便颗粒高剂量组[2.88 g/(kg·d)],每组8只,每日灌胃1次,连续治疗14 d。记录治疗后肠道推进率;HE染色观察结肠组织病理学改变;免疫组织化学法检测结肠组织酪氨酸激酶受体(tyrosine kinase receptor,c-Kit)表达;TUNEL染色检测结肠组织Cajal间质细胞(interstitial cells of Cajal,ICC)凋亡情况;Western blot检测结肠组织葡萄糖调节蛋白78(glucose regulated protein 78,GRP78)、C/EBP同源蛋白(C/EBP homologous protein,CHOP)、B细胞淋巴瘤-2(B-cell lymphoma-2,Bcl-2)、Bcl-2相关X蛋白(Bcl-2 associated X protein,Bax)、活化型胱天蛋白酶-3(cleaved cysteine aspartic acid specific protease-3,cleaved Caspase-3)蛋白表达水平。结果筛选出生血通便颗粒活性成分74个,对应的作用靶点为492个,CASP3(Caspase-3)、Bcl-2、Bax凋亡基因是STC的核心靶点之一,其相关的作用通路为内质网应激信号通路。动物实验结果表明,与正常组比较,模型组大鼠肠道推进率降低(P<0.01);结肠黏膜萎缩、变薄,黏膜上皮层有缺失,固有层腺体缺损破坏明显,可见炎性改变;结肠组织中c-Kit表达降低(P<0.01);凋亡细胞绿色荧光增加、c-Kit红色荧光减少,ICC凋亡指数升高(P<0.01);结肠组织GRP78、CHOP、Bax、cleaved Caspase-3蛋白表达水平升高(P<0.01),Bcl-2蛋白表达水平降低(P<0.01)。与模型组相比,莫沙必利组及生血通便颗粒低、高剂量组大鼠肠道推进率提高(P<0.01);结肠黏膜结构较完整,炎性情况有所恢复,腺体排列较整齐;结肠组织中c-Kit表达升高(P<0.01);凋亡细胞绿色荧光减少、c-Kit红色荧光增加,ICC凋亡指数降低(P<0.01);结肠组织GRP78、CHOP、Bax、cleaved Caspase-3蛋白表达水平降低(P<0.01),Bcl-2蛋白表达水平升高(P<0.01)。与莫沙必利组相比,生血通便颗粒高剂量组肠道推进率提高(P<0.05)、c-Kit表达升高(P<0.05)、ICC凋亡指数降低(P<0.05);生血通便颗粒低、高剂量组结肠组织中GRP78、CHOP、Bax、cleaved Caspase-3蛋白表达水平降低(P<0.01),生血通便颗粒高剂量组Bcl-2蛋白表达水平升高(P<0.01)。结论生血通便颗粒可通过抑制内质网应激GRP78/CHOP信号通路,调控Bax、Bcl-2、cleaved Caspase-3凋亡蛋白表达,从而抑制ICC凋亡以达到治疗STC的作用。

失眠颗粒对疫情后PTSD患者卒中预防作用的网络药理学及动物实验研究

目的:采用网络药理学方法和动物实验验证探讨陕西省中医医院院内制剂失眠颗粒治疗疫情后创伤后应激障碍(post‑traumatic stress disorder,PTSD)远期预防卒中(stroke)的作用机制。方法:使用TCMIP和BATMAN‑TCMTCMSP等数据库筛选失眠颗粒成分中各味中药的有效成分及靶点,基于GEO数据库采用基因表达图谱分析技术通过基因共表达网络分析(WGCNA)获得PTSD和卒中的差异基因。利用R语言软件进行数据挖掘和统计分析,以筛选出PTSD发生卒中的风险基因。将失眠颗粒的靶点与PTSD发生卒中的风险基因取交集,通过STRING数据库构建靶点互作网络,在Cytoscape软件进行拓扑分析筛选核心靶点,对交集靶点进行GO功能分析和KEGG富集分析,构建“失眠颗粒中药‑成分‑靶点”网络图,选取核心靶点进行动物实验验证。结果:失眠颗粒筛选出642个化合物成分,对应2082个靶点,筛选出PTSD发生卒中的风险基因2379个,通过VENN分析获得失眠颗粒成分和疾病共同靶点165个。PPI分析后最终获得68个关键靶点,即为失眠颗粒治疗PTSD并对卒中远期预防的核心靶点。在CytoNCA进行拓扑分析,排名前10的核心靶点分别是MAPK3、MAPK1、NCOA2、MAPK14、NR3C1、RARA、PRKACA、SMARCD3、FOS、FOXO1。KEGG富集分析后得到104条相关通路,GO功能分析得到10条BP通路、10条MF通路和3条CC通路。在动物实验中,与模型组比较,失眠颗粒可明显改善PTSD的焦虑样行为,同时降低p38 MAPK蛋白的表达水平。结论:失眠颗粒通过抑制p38 MAPK介导的MAPK通路来抑制创伤后应激障碍的抑郁焦虑样行为和记忆能力。PTSD患者卒中的发生率高,失眠颗粒通过治疗PTSD并对卒中的远期预防有迹可循。

The pathogenic mechanism of TAR DNA-binding protein 43(TDP-43)in amyotrophic lateral sclerosis

The onset of amyotrophic lateral sclerosis is usually characterized by focal death of both upper and/or lower motor neurons occurring in the motor cortex,basal ganglia,brainstem,and spinal cord,and commonly involves the muscles of the upper and/or lower extremities,and the muscles of the bulbar and/or respiratory regions.However,as the disease progresses,it affects the adjacent body regions,leading to generalized muscle weakness,occasionally along with memory,cognitive,behavioral,and language impairments;respiratory dysfunction occurs at the final stage of the disease.The disease has a complicated pathophysiology and currently,only riluzole,edaravone,and phenylbutyrate/taurursodiol are licensed to treat amyotrophic lateral sclerosis in many industrialized countries.The TAR DNA-binding protein 43 inclusions are observed in 97%of those diagnosed with amyotrophic lateral sclerosis.This review provides a preliminary overview of the potential effects of TAR DNAbinding protein 43 in the pathogenesis of amyotrophic lateral sclerosis,including the abnormalities in nucleoplasmic transport,RNA function,post-translational modification,liquid-liquid phase separation,stress granules,mitochondrial dysfunction,oxidative stress,axonal transport,protein quality control system,and non-cellular autonomous functions(e.g.,glial cell functions and prion-like propagation).

四君子汤治疗脾虚型慢性疲劳综合征临床研究

目的:观察四君子汤治疗脾虚型慢性疲劳综合征的临床疗效。方法:选取脾虚型慢性疲劳综合征患者72例作为研究对象,采用随机数字表法分为对照组和试验组各36例。2组均提供健康宣教,试验组采用四君子汤颗粒剂治疗,对照组给予安慰剂颗粒干预。比较2组临床疗效和安全性,以及治疗前后疲劳症状评分、中医证候评分、疲劳度[Chalder疲劳问卷评分表(Chalder)]评分、SF-36健康调查量表中文版(SF-36)评分、五水平五维健康量表(EQ-5D-5L)评分及血清氧化应激指标[皮质醇稳定蛋白(CORT)、丙二醛(MDA)、超氧化物歧化酶(SOD)及谷胱甘肽过氧化物酶(GSH-PX)]水平。结果:治疗后,试验组总有效率为94.44%,对照组为77.78%,2组比较,差异有统计学意义(P<0.05)。治疗1、2个月后,2组睡眠障碍、紧张焦虑和记忆力减退等疲劳症状评分均较治疗前降低(P<0.05),且试验组3项评分在相同时间点均低于对照组(P<0.05)。治疗1、2个月后,2组中医证候评分、Chalder评分均较治疗前降低(P<0.05),且试验组中医证候评分、Chalder评分在相同时间点均低于对照组(P<0.05)。治疗1、2个月后,2组SF-36、EQ-VAS评分评分均较治疗前升高(P<0.05);且试验组2项评分在相同时间点均高于对照组(P<0.05)。治疗1、2个月后,2组血清中CORT、SOD及GSH-PX水平均较治疗前升高(P<0.05),MDA水平均较治疗前降低(P<0.05),且试验组CORT、SOD及GSH-PX水平在相同时间点均高于对照组(P<0.05),MDA水平在相同时间点低于对照组(P<0.05)。结论:四君子汤治疗脾虚型慢性疲劳综合征疗效显著,可改善脾虚症状,提高患者生活质量,改善氧化应激反应,且安全性较好。

肺纤康颗粒联合吡非尼酮治疗肺虚络瘀型特发性肺纤维化的临床研究

目的探讨肺纤康颗粒治疗肺虚络瘀型特发性肺纤维化(IPF)患者的临床疗效。方法纳入2023年11月~2024年5月就诊于南华大学附属第一医院中医科及衡阳市中医医院肺病科的42例IPF患者,随机分为对照组与治疗组,每组各21例。对照组采用吡非尼酮联合安慰剂口服,治疗组采用吡非尼酮联合肺纤康颗粒口服,两组均治疗3个月。治疗后,比较两组临床疗效及治疗前后的中医证候积分、圣乔治呼吸问卷(SGRQ)评分、6分钟步行距离(6MWD)、肺功能、动脉血氧分压(PaO_(2))、胸部高分辨CT(HRCT)评分以及血清Ⅲ型胶原蛋白(Ⅲ-C)、Ⅳ型胶原蛋白(Ⅳ-C)、超氧化物歧化酶(SOD)、丙二醛(MDA)水平的差异。结果对照组和治疗组的总有效率分别为71.43%和90.47%,差异有统计学意义(P<0.05)。与对照组治疗后比较,治疗组中医证候积分、SGRQ症状评分及疾病影响评分、血清MDA、Ⅲ-C、Ⅳ-C水平明显降低(P<0.05);一氧化碳弥散量(DLCO)、PaO_(2)、血清SOD水平明显升高(P<0.05)。结论肺纤康颗粒与吡非尼酮合用具有协同增效作用,能延缓IPF病情进展,其疗效优于吡非尼酮单药治疗。作用机制可能与抑制MDA产生、提高SOD水平,减轻氧化应激反应有关。

坤宁颗粒对痛经模型大鼠的抗炎镇痛作用研究

[目的]研究坤宁颗粒对痛经模型大鼠COX-2/PGF2α通路、内分泌激素、炎症因子和氧化应激水平的影响,探讨其保护作用及机制。[方法]取SD雌性大鼠,随机分为6组,正常对照组、模型组、益母草颗粒(3.5 g/kg)阳性对照组、坤宁颗粒低(1.4 g/kg)、中(2.8 g/kg)、高(5.6 g/kg)剂量组,除正常对照组外,其余组建立痛经模型,第1、10天灌胃戊酸雌二醇每只0.2 mg,第2~9天每只0.1 mg,从第5天各给药组灌胃给药,正常对照组和模型组灌胃蒸馏水,每日1次,第10天正常对照组大鼠腹腔注射生理盐水,其余各组大鼠腹腔注射缩宫素每只10 U。观察各组大鼠扭体反应次数;采用酶联免疫吸附实验(ELISA)检测大鼠血清前列腺素F2α(PGF2α)、前列腺素E_(2)(PGE_(2))、β-内啡肽(β-EP)、雌二醇(E_(2))、孕酮(PROG)、白介素-1β(IL-1β)、白介素-6(IL-6)、肿瘤坏死因子-α(TNF-α)含量;比色法检测大鼠血清超氧化物歧化酶(SOD)、谷胱甘肽过氧化物酶(GSH-Px)、丙二醛(MDA)水平;蛋白免疫印迹法(Western Blot)检测大鼠子宫组织环氧合酶-2(COX-2)、前列腺素E_(2)受体(PTGER2)、雌激素受体α(ERα)蛋白表达;苏木精-伊红(HE)染色观察子宫组织病理形态。[结果]与正常对照组相比,模型组大鼠扭体反应次数显著增加,大鼠血清中PGF2α、E_(2)、IL-1β、IL-6、TNF-α、MDA水平和子宫组织COX-2、ERα蛋白表达显著升高,而血清PGE_(2)、β-EP、PROG、SOD、GSH-Px水平显著降低,子宫PTGER2蛋白表达显著降低,子宫组织可见明显充血、水肿。与模型组相比,坤宁颗粒可以显著降低大鼠扭体反应次数和血清中PGF2α、E_(2)、IL-1β、IL-6、TNF-α、MDA水平,升高PGE_(2)、β-EP、PROG、SOD、GSH-Px水平,显著抑制子宫组织COX-2、ERα蛋白表达,升高PTGER2蛋白表达,组织病理学明显改善。[结论]坤宁颗粒对痛经模型大鼠具有显著的改善作用,其机制可能与调节COX-2/PGF2α通路和PGE_(2)、β-EP、E_(2)、PROG等内分泌激素、降低炎症因子水平、改善氧化应激水平有关。

玉米根尖淀粉对渗透胁迫的响应

玉米根尖淀粉的特征以及在渗透胁迫中的作用尚不清楚.本研究以玉米杂交种郑单958为材料,用15%的聚乙二醇(PEG-6000)对幼苗根系进行不同时长的渗透胁迫处理,分析根尖淀粉的形态和含量变化、淀粉酶活性及相关基因表达水平变化.结果表明,根尖淀粉粒大小为0.3~2.5μm,大部分呈球状,少数为片状或无规则形状.随着胁迫时间延长,根尖淀粉逐渐降解,淀粉酶(尤其是β淀粉酶)活性增强,导致可溶性糖含量增加;相应地,多种淀粉酶基因表达明显上调.根尖淀粉在渗透胁迫下的降解将增加根细胞的渗透调节能力,从而缓解胁迫伤害.该结果有助于认识玉米根系响应渗透胁迫的分子生理机制.

Rice Grains from Slightly Saline Field Exhibited Unchanged Starch Physicochemical Properties but Enhanced Nutritional Values

This study aims to investigate grain quality and nutritional values of rice(Pokkali,a salt-tolerant cultivar;RD73,a new cultivar improved from KDML105 introgressed with Saltol QTL from Pokkali,and KDML105,a moderately salt-susceptible cultivar)grown under non-saline(0.04–0.87 dS/m)and slightly saline(1.08–4.83 dS/m)field conditions.The results revealed that salinity caused significant reduction in grain size but significant increments in reducing sugar and total protein contents in the grains.Nevertheless,the amounts of starch in the grains of KDML105 and Pokkali rice genotypes were unaffected by the stress.The starch granule size distribution was also unaffected by salinity.Interestingly,only starch from Pokkali was significantly diminished in amylose content,from 19.18%to 16.99%.Accordingly,parameters relating to starch gelatinization,retrogradation,and pasting properties of KDML105 and RD73 were unaffected by salinity;only Pokkali showed a significant increase in percentage of retrogradation along with a significant reduction in gelatinization enthalpy.In the saline field,total phenolic content and antioxidant capacity in the grains of all rice cultivars tended to increase,particularly in Pokkali.On average,essential element contents in grains from the saline-treated plants showed a 33%,32%,32%,22%,20%,11%,and 10%increase in total P,N,K,Mg,Zn,Fe,and Ca content,respectively.Interestingly,total Fe content exhibited the greatest percentage of increments in KDML105(187%).Taken together,cultivation of rice in the slightly saline field did not alter its eating and cooking qualities,while enhanced some nutritional properties such as proteins,minerals,and secondary metabolites like phenolic compounds.

贞芪颗粒对仔猪断奶应激的影响

本研究利用断奶仔猪模型探究复方中兽药贞芪颗粒对断奶仔猪生长、腹泻及断奶应激的影响。通过测定仔猪生长性能、腹泻率、空肠绒毛形态、生长及应激相关激素水平,发现21日龄断奶相比于28日龄断奶对仔猪的增重、腹泻率、肠道损伤的影响更大,表明21日龄断奶可对仔猪造成更严重的断奶应激。利用21日龄断奶仔猪模型,比较了贞芪颗粒给药组和不给药组仔猪的断奶应激相关指标,发现贞芪颗粒可显著降低仔猪腹泻率并缩短腹泻持续时间,27日龄时给药组仔猪皮质醇激素水平显著降低(P<0.05),43日龄时给药组仔猪血清中生长激素(GH)含量极显著升高(P<0.01)。以上结果表明,贞芪颗粒具有一定的缓解仔猪断奶腹泻、提高仔猪抗应激及促生长效果。

彝医药金薄清咽颗粒制备工艺及对慢性咽炎模型大鼠的疗效机制

目的:研究彝医药金薄清咽颗粒(JBQYG)的制剂工艺及其对慢性咽炎(CP)模型大鼠的改善机制。方法:选择最优辅料,进行成型工艺筛选和高效液相色谱法(HPLC)分析;用JBQYG干预CP大鼠,检测咽喉组织表观、病理、转录因子p65(NF-κB p65)蛋白表达及炎性和氧化水平。结果:最优辅料为乳糖,成型工艺为:纯浸膏∶乳糖=8∶1、乙醇浓度95%、乙醇用量10%,制剂标准成分芍药苷稳定达标;JBQYG降低了CP大鼠咽喉NF-κB p65蛋白的磷酸化水平和,逆转了氨水诱导的炎性和氧化应激,从而改善了咽喉的表观和病理改变;且JBQYG较阿司匹林更有效地改善了氧化应激,差异有统计学意义(P<0.05)。结论:研究确定的制剂制备工艺合理;JBQYG通过降低NF-κB p65的磷酸化水平和提升总抗氧化能力,改善CP咽喉的炎性和氧化状态、表观及病理改变。

基于PERK/eIF2α/ATF4/CHOP通路探讨健骨颗粒对UMR-106细胞内质网应激凋亡的影响

目的探讨健骨颗粒含药血清对UMR-106成骨样细胞内质网应激ERS凋亡的影响和作用机制。方法选用UMR-106成骨样细胞,采用0、0.01、0.02、0.03、0.04、0.05μmol/L不同浓度的GSK2606414(PERK抑制剂)对细胞进行干预,采用CCK8法筛选GSK2606414最佳干预浓度。将生长状态较好的UMR-106细胞随机分为阴性对照组(NC组)、模型组(H_(2)O_(2)组)、健骨颗粒组(H_(2)O_(2)+JG组)和阳性对照组(H_(2)O_(2)+GSK2606414组)4组。NC组和H_(2)O_(2)组采用10%生理盐水血清干预12 h,H_(2)O_(2)+JG组采用10%健骨颗粒含药血清干预12 h,H_(2)O_(2)+GSK2606414组采用0.03μmol/L的GSK2606414和10%生理盐水血清干预12 h,除NC组外,其余各组在不更换新培养基的情况下,再分别加入10μmol/L H_(2)O_(2)干预12 h。采用激光共聚焦显微镜观察细胞内NC组和H_(2)O_(2)组GRP78和Caspase-12荧光表达情况,DCFH-DA检测活性氧(ROS)含量,激光共聚焦显微镜观察细胞内钙离子实时动态变化判断ROS/ERS模型是否成立。再采用An⁃nexin V-FITC/PI检测4组细胞晚期凋亡率,qPCR和Western blot检测4组ERS相关标志指标GRP78、PERK、eIf2α、ATF4和CHOP mRNA转录水平和蛋白相对表达量。结果与0μmol/L组比较,0.03μmol/L的GSK2606414是干预UMR-106细胞12 h后对细胞活力没有影响的最大浓度,故使用该浓度作为后续H_(2)O_(2)+GSK2606414组的实验干预条件。与NC组相比,H_(2)O_(2)组ROS含量显著增高(P<0.01),GRP78和Caspase-12的蛋白荧光表达量明显增加,细胞内钙离子流动速度加快并持续增高,表明H_(2)O_(2)诱导UMR-106细胞ROS/ERS模型的成功建立。与NC组相比,H_(2)O_(2)组凋亡率显著增高(P<0.05),GRP78、PERK、eIf2α、ATF4、CHOP mRNA转录水平和蛋白相对表达量均显著增高(P<0.01)。与H_(2)O_(2)组相比,H_(2)O_(2)+JG组和H_(2)O_(2)+GSK2606414组ROS含量显著降低(P<0.01),凋亡率显著降低(P<0.05),GRP78、PERK、eIf2α、ATF4、CHOP mRNA转录水平(P<0.05)和蛋白相对表达量(P<0.01)均显著降低。结论健骨颗粒可通过PERK/eIF2α/ATF4/CHOP信号通路缓解内质网过度应激,降低成骨细胞凋亡率,发挥防治绝经后骨质疏松症的作用。