Antibacterial mechanism of kojic acid and tea polyphenols against Escherichia coli O157:H7 through transcriptomic analysis

Escherichia coli O157:H7 is one of the major foodborne pathogenic bacterial that cause infectious diseases in humans.The previous found that a combination of kojic acid and tea polyphenols exhibited better activity against E.coli O157:H7 than using either alone.This study aimed to explore responses underlying the antibacterial mechanisms of kojic acid and tea polyphenols from the gene level.The functional enrichment analysis by comparing kojic acid and tea polyphenols individually or synergistically against E.coli O157:H7 found that acid resistance systems in kojic acid were activated,and the cell membrane and genomic DNA were destructed in the cells,resulting in“oxygen starvation”.The oxidative stress response triggered by tea polyphenols inhibited both sulfur uptake and the synthesis of ATP,which affected the bacteria's life metabolic process.Interestingly,we found that kojic acid combined with tea polyphenols hindered the uptake of iron that played an essential role in the synthesis of DNA,respiration,tricarboxylic acid cycle.The results suggested that the iron uptake pathways may represent a novel approach for kojic acid and tea polyphenols synergistically against E.coli O157:H7 and provided a theoretical basis for bacterial pathogen control in the food industry.

Total flavonoids of Astragalus membranaceus protect against 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine-induced neurotoxicity in mice by inhibiting ferroptosis through SLC7A11/GPX-4 signaling pathway

Parkinson’s disease(PD)is a common neurodegenerative disorder with no cure.Astragalus membranaceus is used in Chinese culture as a food supplement to boost immunity.The present study aimed to explore the neuroprotective effects of total flavonoids extracted from A.membranaceus(TFA)and their protective mechanisms.TFA offered neuroprotection against 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine(MPTP)in the mouse model of Parkinsonism,by improving behavior performance in the gait analysis and pole test,and inhibiting the decline of tyrosine hydroxylase(TH)positive neurons and TH protein expression in substantia nigra of mice.TFA also prevented 1-methyl-4-phenylpyridinium(MPP+)induced neurotoxicity in SHSY5Y cells,by increasing GSH and GSH/GSSG ratio,and reducing reactive oxygen species.In addition,the neuroprotective effects of TFA were associated with its ability to restore MPTP/MPP+induced downregulation of SLC7A11 and glutathione peroxidase 4(GPX-4).In conclusion,we demonstrated that TFA exerted significant neuroprotection against MPTP/MPP+induced neurodegeneration by inhibiting ferroptosis through the regulation of SLC7A11/GPX-4 axis,suggesting the use of TFA as a possible food supplement in the prevention of PD.

Early monitoring values of oncogenic signalling molecules for hepatocellular carcinoma

The prevention and early diagnosis of liver cancer remains a global medical challenge.During the malignant transformation of hepatocytes,a variety of oncogenic cellular signalling molecules,such as novel high mobility group-Box 3,angiopoietin-2,Golgi protein 73,glypican-3,Wnt3a(a signalling molecule in the Wnt/β-catenin pathway),and secretory clusterin,can be expressed and secreted into the blood.These signalling molecules are derived from different signalling pathways and may not only participate in the malignant transformation of hepatocytes but also become early diagnostic indicators of hepatocarcinogenesis or specific targeted molecules for hepatocellular carcinoma therapy.This article reviews recent progress in the study of several signalling molecules as sensitive biomarkers for monitoring hepatocarcinogenesis.

Reduction of the oxidative damage to H_(2)O_(2)-induced HepG2 cells via the Nrf2 signalling pathway by plant flavonoids Quercetin and Hyperoside

Hyperoside and quercetin are similar in molecular structures.In this study,the antioxidant regulatory targets of hyperoside and quercetin are mainly in the nuclear factor(erythroid-2-derived)-related factor 2(Nrf2)pathway predicted by network pharmacology.And the antioxidant effect and mechanism of hyperoside and quercetin were measured and compared in H_(2)O_(2)-induced Hep G2 cells and Caenorhabditis elegans.The findings indicated that quercetin was more effective than hyperoside in reducing oxidative damage,which was proved by improved cell viability,decreased reactive oxygen species(ROS)production,decreased cellular apoptosis,and alleviated mitochondrial damage.In addition,quercetin was more efficient than hyperoside in enhancing the expression of Nrf2-associated m RNAs,increasing the activities of superoxide dismutase(SOD),glutathione peroxidase(GSH-Px),and catalase(CAT),and reducing the cellular malondialdehyde(MDA)content.Quercetin was superior to hyperoside in prolonging the lifespan of worms,decreasing the accumulation of lipofuscin,inhibiting ROS production,and increasing the proportion of skn-1 in the nucleus.With the Nrf2 inhibitor ML385,we verified that quercetin and hyperoside primarily protected the cells against oxidative damage via the Nrf2 signalling pathway.Furthermore,molecular docking and dynamics simulations demonstrated that the quercetin-Kelch-like ECH-associated protein 1(Keap1)complex was more stable than the hyperoside-Keap1 complex.The stable structure of the complex might hinder the binding of Nrf2 and Keap1 to release Nrf2 and facilitate its entry into the nucleus to play an antioxidant role.Overall,quercetin had a better antioxidant than hyperoside.

加味四妙散对急性痛风性关节炎大鼠的疗效及对滑膜组织中嘌呤能离子通道型受体7 NOD样受体热蛋白结构域相关蛋白3表达的影响

目的通过研究加味四妙散干预急性痛风性关节炎大鼠滑膜组织中嘌呤能离子通道型受体7(P2X7R)、NOD样受体热蛋白结构域相关蛋白3(NLRP3)表达的影响,探讨加味四妙散在防治急性痛风性关节炎的疗效及抗炎作用机制。方法选择雄性SD大鼠60只,按照随机数字表法分为6组,分别为空白对照组、模型组、秋水仙碱组、加味四妙散低剂量组、加味四妙散中剂量组、加味四妙散高剂量组,每组10只。空白对照组给予等体积0.9%氯化钠注射液在相应的部位,其余5组复制高尿酸血症并急性痛风性关节炎大鼠模型。加味四妙散组予加味四妙散低、中、高剂量水提液(4.24 g/kg、8.48 g/kg、16.96 g/kg)灌胃、秋水仙碱组予秋水仙碱混悬液(3 mg/kg)灌胃。模型组予等量0.9%氯化钠注射液灌胃。经过4 h、8 h、12 h、24 h和48 h的治疗,对右踝关节的肿胀情况及大鼠步态进行观察。末次给药2 h后,通过腹主动脉采血,采用生化法检测血清尿酸浓度、肝肾功能及血清三磷酸腺苷(ATP)水平,酶联免疫吸附试验(ELISA)测定血清中白细胞介素(IL)-1β、IL-8含量,取受试踝关节滑膜组织,苏木精-伊红染色(HE)观察滑膜组织病理情况,利用蛋白免疫印迹法检测滑膜组织中NLRP3、P2X7R蛋白的表达。结果除空白对照组外,各组大鼠的踝关节肿胀率从造模后4~8 h开始上升,24 h达高峰后下降。在造模48 h后,秋水仙碱组和加味四妙散的低、中、高剂量组的肿胀率减轻,步态逐渐改善(P<0.05),与空白组比较,模型组中滑膜组织表现出关节炎病理改变,显微镜下可见滑膜脱落、坏死,滑膜细胞增生,相较于模型组,加味四妙散的低、中、高剂量组以及秋水仙碱组在血清ATP、IL-1β、血尿酸、IL-8均降低,滑膜组织关节炎病理情况得到改善。滑膜组织P2X7R、NLRP3蛋白表达均降低(P<0.05),与秋水仙碱组相比,加味四妙散对大鼠肝肾功能的损害较小(P<0.05)。结论加味四妙散可以降低高尿酸血症和痛风模型大鼠的血尿酸水平,减少对肝肾功能的损害,抑制急性痛风性关节炎大鼠踝关节滑膜组织中NLRP3、P2X7R蛋白的表达,降低局部组织炎症反应,从而发挥治疗作用。

Human herpesvirus 7 meningitis in an adolescent with normal immune function:A case report

BACKGROUND Human herpesvirus type 7(HHV-7)is a less common herpes virus that usually causes mild,self-limiting illnesses.However,in recent years,there have been increasing reports of HHV-7 causing serious central nervous system infections,especially meningitis.The pathogenesis and clinical features of HHV-7 meningitis,particularly in adolescents with normal immune function,remain incompletely studied.Therefore,the purpose of this report is to share a case of HHV-7 meningitis in an immunocompetent adolescent with a view to deepening our understanding of the disease.CASE SUMMARY A 12-year-old female was admitted with fever,headache,and vomiting.4 d before admission,the patient developed a fever without obvious induction,with a temperature up to 39.5℃,no convulsions,accompanied by chills,headaches,fatigue,and no muscle aches.The patient was treated with fever reduction,which could be reduced to 38℃;repeated high fever,accompanied by vomiting 7-8 times;and no abdominal pain or diarrhea.The patient was diagnosed with"acute suppurative tonsillitis"in a local hospital,and the blood routine was generally normal.The patient was given symptomatic support treatment such as"ceftriaxone sodium"and antiemetic rehydration for 2 d,and his condition did not improve.The patient's physical examination showed pharyngeal congestion,bilateral tonsil grade I hypertrophy,regression of purulent secretions,and cervical resistance.Ocular B-ultrasound:Opacity of the vitreous body and edema of the optic disc in both eyes.Optical coherence tomography examination showed that the macular fovea was generally normal in both eyes,with edema of the optic disc.DNA virus monitoring results:HHV-7.We gave ganciclovir antiviral therapy,dexamethasone anti-inflammatory treatment,mannitol to reduce cranial pressure,omeprazole to protect gastrointestinal mucosa,and calcium and potassium supplementation.CONCLUSION This study reports a case of HHV-7 meningitis in an adolescent with normal immune function.Through comprehensive analysis of the clinical manifestations,laboratory tests,and treatment methods of the patient,it is found that early identification and antiviral treatment are essential for the outcome of the disease.This case suggests that despite normal immune function,adolescents may still suffer from herpes virus type 7 meningitis,so clinicians should be vigilant and take effective treatment measures in time.

Recombinant adeno-associated virus 8-mediated inhibition of microRNA let-7a ameliorates sclerosing cholangitis in a clinically relevant mouse model

BACKGROUND Primary sclerosing cholangitis(PSC)is characterized by chronic inflammation and it predisposes to cholangiocarcinoma due to lack of effective treatment options.Recombinant adeno-associated virus(rAAV)provides a promising platform for gene therapy on such kinds of diseases.A microRNA(miRNA)let-7a has been reported to be associated with the progress of PSC but the potential therapeutic implication of inhibition of let-7a on PSC has not been evaluated.AIM To investigate the therapeutic effects of inhibition of a miRNA let-7a transferred by recombinant adeno-associated virus 8(rAAV8)on a xenobiotic-induced mouse model of sclerosing cholangitis.METHODS A xenobiotic-induced mouse model of sclerosing cholangitis was induced by 0.1% 3,5-Diethoxycarbonyl-1,4-Dihydrocollidine(DDC)feeding for 2 wk or 6 wk.A single dose of rAAV8-mediated anti-let-7a-5p sponges or scramble control was injected in vivo into mice onset of DDC feeding.Upon sacrifice,the liver and the serum were collected from each mouse.The hepatobiliary injuries,hepatic inflammation and fibrosis were evaluated.The targets of let-7a-5p and downstream molecule NF-κB were detected using Western blot.RESULTS rAAV8-mediated anti-let-7a-5p sponges can depress the expression of let-7a-5p in mice after DDC feeding for 2 wk or 6 wk.The reduced expression of let-7a-5p can alleviate hepato-biliary injuries indicated by serum markers,and prevent the proliferation of cholangiocytes and biliary fibrosis.Furthermore,inhibition of let-7a mediated by rAAV8 can increase the expression of potential target molecules such as suppressor of cytokine signaling 1 and Dectin1,which consequently inhibit of NF-κB-mediated hepatic inflammation.CONCLUSION Our study demonstrates that a rAAV8 vector designed for liver-specific inhibition of let-7a-5p can potently ameliorate symptoms in a xenobiotic-induced mouse model of sclerosing cholangitis,which provides a possible clinical translation of PSC of human.

Clinical manifestations and the prenatal diagnosis of trisomy 7 mosaicism:Two case reports

BACKGROUND The clinical manifestations of trisomy 7 mosaicism are diverse and nonspecific,so prenatal diagnosis is very difficult.CASE SUMMARY Two pregnant women with abnormal prenatal screening results were included.One was a 22-year-old woman(G1P0).At 31st week of gestation,ultrasound revealed that the posterior horn of the left lateral ventricle was 10 mm and the right renal pelvis had a separation of 7 mm.The other pregnant woman was 33 years old(G2P1L1A0),and her fetus was found to have a cardiac malformation at the 24th week of gestation.Copy number variation sequencing,whole-exome sequencing and karyotype analysis were carried out after amniocentesis,and both fetuses were diagnosed with trisomy 7 mosaicism.After parental counseling,one woman continued the pregnancy,and the other woman terminated the pregnancy.CONCLUSION In trisomy 7 mosaicism,the low proportion of trisomy does not lead to abortion,but can result in abnormal fetal development,which can be detected via ultrasound.Therefore,clinicians need to pay more attention to various aspects of fetal growth and development,combining with imaging,cellular,molecular genetics and other methods to perform comprehensive evaluations of fetuses to provide more reliable genetic counseling for pregnant women.

Review and prospects on the low-voltage Na_(2)Ti_(3)O_(7) anode materials for sodium-ion batteries

Due to its low cost and natural abundance of sodium,Na-ion batteries(NIBs)are promising candidates for large-scale energy storage systems.The development of ultralow voltage anode materials is of great significance in improving the energy density of NIBs.Low-voltage anode materials,however,are severely lacking in NIBs.Of all the reported insertion oxides anodes,the Na_(2)Ti_(3)O_(7) has the lowest operating voltage(an average potential of 0.3 V vs.Na^(+)/Na)and is less likely to deposit sodium,which has excellent potential for achieving NIBs with high energy densities and high safety.Although significant progress has been made,achieving Na_(2)Ti_(3)O_(7) electrodes with excellent performance remains a severe challenge.This paper systematically summarizes and discusses the physicochemical properties and synthesis methods of Na_(2)Ti_(3)O_(7).Then,the sodium storage mechanisms,key issues and challenges,and the optimization strategies for the electrochemical performance of Na_(2)Ti_(3)O_(7) are classified and further elaborated.Finally,remaining challenges and future research directions on the Na_(2)Ti_(3)O_(7) anode are highlighted.This review offers insights into the design of high-energy and high-safety NIBs.

Nomogram based on multimodal magnetic resonance combined with B7-H3mRNA for preoperative lymph node prediction in esophagus cancer

Accurate preoperative prediction of lymph node metastasis(LNM)in esophageal cancer(EC)patients is of crucial clinical significance for treatment planning and prognosis.AIM To develop a clinical radiomics nomogram that can predict the preoperative lymph node(LN)status in EC patients.METHODS A total of 32 EC patients confirmed by clinical pathology(who underwent surgical treatment)were included.Real-time fluorescent quantitative reverse transcription-polymerase chain reaction was used to detect the expression of B7-H3 mRNA in EC tissue obtained during preoperative gastroscopy,and its correlation with LNM was analyzed.Radiomics features were extracted from multi-modal magnetic resonance imaging of EC using Pyradiomics in Python.Feature extraction,data dimensionality reduction,and feature selection were performed using XGBoost model and leave-one-out cross-validation.Multivariable logistic regression analysis was used to establish the prediction model,which included radiomics features,LN status from computed tomography(CT)reports,and B7-H3 mRNA expression,represented by a radiomics nomogram.Receiver operating characteristic area under the curve(AUC)and decision curve analysis(DCA)were used to evaluate the predictive performance and clinical application value of the model.RESULTS The relative expression of B7-H3 mRNA in EC patients with LNM was higher than in those without metastasis,and the difference was statistically significant(P<0.05).The AUC value in the receiver operating characteristic(ROC)curve was 0.718(95%CI:0.528-0.907),with a sensitivity of 0.733 and specificity of 0.706,indicating good diagnostic performance.The individualized clinical prediction nomogram included radiomics features,LN status from CT reports,and B7-H3 mRNA expression.The ROC curve demonstrated good diagnostic value,with an AUC value of 0.765(95%CI:0.598-0.931),sensitivity of 0.800,and specificity of 0.706.DCA indicated the practical value of the radiomics nomogram in clinical practice.CONCLUSION This study developed a radiomics nomogram that includes radiomics features,LN status from CT reports,and B7-H3 mRNA expression,enabling convenient preoperative individualized prediction of LNM in EC patients.

1700V EcOnoDUAL3 IGBT7产品及其在690V变频器中的应用

1700V EcOnoDUAL3封装的IGBT4模块已经在变频器中得到了广泛应用。随着芯片技术的进步和市场对更高效和更高电流等级产品需求的不断增加,英飞凌基于最新的1700V IGBT7芯片开发了新一代的ECOnODUAL3IGBT模块。本文首先介绍了1700V IGBT7模块的系列产品、IGBT7芯片特性和ECOnoDULA3模块的封装升级。然后通过与IGBT4的最大电流模块FF600R17ME4_B11进行参数对比,分析了两款IGBT7模块FF450R17ME7_B11和FF600R17ME7_B11的产品优势。最后,根据690V变频器的典型应用工况,通过仿真对比阐明了新一代IGBT7产品可以显著的降低功率损耗和提升变频器的功率密度。

Unraveling the therapeutic mechanisms of myristic acid and luteolin 7-rutinoside in oral cancer: insights from network pharmacology and molecular docking analysis

Background:The compound Luteolin-7-rutinoside(L7R)is a flavone derivative of luteolin,predominantly identified in plant species belonging to the families Asteraceae.Conversely,Myristic acid is characterized by its structure as a 14-carbon,unsaturated fatty acid.In this investigation,we endeavor to elucidate the putative mechanisms underlying the therapeutic effects of Myristic Acid and Luteolin 7-rutinoside in the context of oral cancer treatment,employing network pharmacology coupled with molecular docking methodologies.Methods:The protein targets of Myristic Acid and Luteolin 7-rutinoside were identified through a search on the Swiss Target Database.Subsequently,a compound-target network was constructed using Cytoscape 3.9.1.Targets associated with OC were retrieved from the OMIM and GeneCards databases.The overlap between compound targets and OC-related targets was determined,and the resulting shared targets were subjected to protein-protein interaction(PPI)network analysis using the STRING database.Additionally,gene ontology(GO)and Kyoto Encyclopedia of Genes and Genomes(KEGG)enrichment analyses were conducted on the identified targets.Molecular docking were performed to investigate the interactions between the core target and the active compound.Results:The component target network comprises 103 nodes and 102 edges.Among the proteins in the protein-protein interaction(PPI)network,those with higher degrees are TNF,PPARG,and TP53.Analysis through Gene Ontology(GO)and Kyoto Encyclopedia of Genes and Genomes(KEGG)pathways indicates that the treatment of OC with Myristic Acid and Luteolin 7-rutinoside primarily involves the regulation of miRNA transcription and inflammatory response.The identified signaling pathways include Pathways in cancer,PPAR signaling pathway,EGFR signaling pathway,and TNF signaling pathway.Molecular docking studies reveal that Luteolin 7-rutinoside and Myristic acid exhibit higher affinity towards TNF,PPARG,TP53,and EGFR.Conclusion:This study reveals the potential molecular mechanism of Myristic Acid and Luteolin 7-rutinoside in the treatment of oral cancer,and provides a reference for subsequent basic research.

Extending the solid solution range of sodium ferric pyrophosphate:Off‐stoichiometric Na_(3)Fe(2.5)(P_(2)O_(7))_(2)as a novel cathode for sodium‐ion batteries

Iron‐based pyrophosphates are attractive cathodes for sodium‐ion batteries due to their large framework,cost‐effectiveness,and high energy density.However,the understanding of the crystal structure is scarce and only a limited candidates have been reported so far.In this work,we found for the first time that a continuous solid solution,Na_(4−α)Fe_(2+α)_(2)(P_(2)O_(7))_(2)(0≤α≤1,could be obtained by mutual substitution of cations at center‐symmetric Na3 and Na4 sites while keeping the crystal building blocks of anionic P2O7 unchanged.In particular,a novel off‐stoichiometric Na_(3)Fe(2.5)(P_(2)O_(7))_(2)is thus proposed,and its structure,energy storage mechanism,and electrochemical performance are extensively investigated to unveil the structure–function relationship.The as‐prepared off‐stoichiometric electrode delivers appealing performance with a reversible discharge capacity of 83 mAh g^(−1),a working voltage of 2.9 V(vs.Na^(+)/Na),the retention of 89.2%of the initial capacity after 500 cycles,and enhanced rate capability of 51 mAh g^(−1)at a current density of 1600 mA g^(−1).This research shows that sodium ferric pyrophosphate could form extended solid solution composition and promising phase is concealed in the range of Na_(4−α)Fe_(2+α)_(2)(P_(2)O_(7))_(2),offering more chances for exploration of new cathode materials for the construction of high‐performance SIBs.

改进YOLOv7算法的钢材表面缺陷检测研究

当前,基于深度学习的智能检测技术逐步应用于钢材表面缺陷检测领域,针对钢材表面缺陷检测精度低的问题,提出一种高精度实时的缺陷检测算法CDN-YOLOv7。加入CARAFE轻量化上采样算子来改善网络特征融合能力,融合级联注意力机制和解耦头重新设计YOLOv7检测头网络,旨在解决原始头网络特征利用效率不高的问题,使其充分利用各尺度、通道、空间的多维度信息,提升复杂场景下模型表征能力。引入归一化Wasserstein距离重新设计Focal-EIoU损失函数,提出NF-EIoU替换CIoU损失,平衡各尺度缺陷样本对Loss的贡献,降低各尺度缺陷的漏检率。实验结果表明,CDN-YOLOv7的检测精度可达80.3%,较于原YOLOv7精度提升了6.0个百分点,模型推理速度可达60.8帧/s,满足实时性需求,CDN-YOLOv7在提升各尺度缺陷检测精度的同时显著降低了缺陷的漏检率。

辣椒新品种云干椒7号的选育

云干椒7号是以自交系258-1-2-3-1X-1为母本,以丘北辣椒优异单株390-1-1为父本配制而成的干制辣椒一代杂种。植株生长势及分枝性强,中熟,定植至采收约100 d(天),坐果率高;果实线形,老熟果深红色,平均果长11.5 cm,横径1.1 cm,干制后果面光滑油亮,平均单果干质量1.3 g,香辣味浓,辣椒素含量0.12%,VC含量1570.13 mg·kg^(-1);抗疫病,每667 m^(2)鲜椒产量920~1080 kg,干椒产量230~270 kg,制干率约25%,适宜云南省文山、曲靖、昭通、楚雄等干椒主产区及海拔2200 m以下的小果干椒类型地区春季栽培。

2021-2022年河南省猪细小病毒1~7型检测与分析

旨在了解猪细小病毒1~7型(PPV1~PPV7)在河南省的流行情况。利用PCR检测了2021-2022年河南省猪场送检的748份样品,并对检测数据进行了分析。结果表明,PPV1/2/3/5/6/7在河南省各地区一年四季广泛流行,而秋、冬季节是感染高峰期,PPV2(16.04%)的感染率最高,PPV7(15.11%)次之。产房仔猪未检出PPV1/3/5,PPV2/6/7在各生长阶段猪群中均有检出,患呼吸系统疾病的保育和育肥猪中PPV各型检出率均较高,尤以PPV2常见。PPV2和PPV7在口腔液、血样、肺脾淋巴结中检出率均较高,血样中较低,PPV3常存在于血清和组织中,PPV5多见于口腔液,PPV6多见于血样。研究证实,除PPV4未检出外,其他6种PPV在河南均存在,并且多与其他病原混合感染,PPV2、PPV7可与多种病原混合感染,PPV7与PCV2混合感染最常见。

电针预处理对切口痛大鼠中脑导水管周围灰质5-HT_(7)受体表达的影响

目的:建立足趾部切口痛大鼠模型,探讨重复电针预处理对切口痛大鼠镇痛效果及其对中脑导水管周围灰质(periaqueductal gray,PAG)5-HT_(7)受体(5-HT_(7)R)表达的影响。方法:40只成年雄性SD大鼠按随机数字表法均等分为对照组(Control,Con组)、切口痛模型组(Incision pain,IP组)、正常+电针预处理组(Control+Electroacupuncture,Con+EA组)、模型+电针预处理组(Incision Pain+Electroacupuncture,IP+EA组)。IP组和IP+EA组大鼠右足趾部行疼痛造模,且造模前,Con+EA组和IP+EA组大鼠行右侧“足三里”穴和“环跳”穴电针刺激(2/10 Hz疏密波,刺激强度数值为1档,每日1次30 min),连续5天。于第1次电针预处理前2 h(T1)、术前2 h(T2)、术后4 h(T3)、术后24 h(T4)测定大鼠机械刺激缩足反射阈值(mechanical withdrawal threshold,MWT)和热缩足潜伏期(thermal withdrawal latency,TWL);酶联免疫吸附法检测脑脊液中5-HT浓度;免疫组化和免疫荧光方法分别检测大鼠PAG中c-Fos和5-HT_(7)R蛋白表达情况。结果:与Con组比较,IP组大鼠T3、T4时间点MWT和TWL均明显降低,脑脊液中5-HT浓度增加,PAG中c-Fos蛋白和5-HT_(7)R表达明显上调(P<0.05);Con+EA组和IP+EA组脑脊液中5-HT含量和PAG中5-HT_(7)R表达均上升(P<0.05)。与IP组相比,IP+EA组大鼠T3、T4时间点的MWT和TWL显著升高,PAG中c-Fos蛋白表达减少,5-HT_(7)R蛋白表达增加(P<0.05)。结论:电针预处理可能通过上调PAG中5-HT_(7)R蛋白表达发挥镇痛作用。

miR-7抑制剂治疗MRL/lpr小鼠的实验性研究

目的:探讨miR-7抑制剂治疗MRL/lpr小鼠的疗效。方法:选取30只MRL/lpr小鼠,随机分为miR-7抑制剂(miR-7 antagomir)组、环磷酰胺(CTX)组和生理盐水(Saline)对照组,10只/组。MRL/lpr小鼠13周时开始治疗,以上药物分别连续给药5周。每周观察各组小鼠一般状况并称重,留取血清和尿液标本。ELISA检测13~17周三组小鼠血清ANA、抗ds-DNA抗体、C3水平,并检测上述各周三组小鼠尿蛋白水平。流式细胞术检测三组小鼠Tfh细胞比例变化。RT-PCR检测三组小鼠脾脏和淋巴结miR-7和PTEN mRNA表达水平。HE、PAS、PASM染色观察光镜下三组小鼠的肾脏病理情况。结果:治疗5周后,形态学方面:与Saline组相比,miR-7 antagomir组和CTX组小鼠一般状况良好,体质量随周龄增加而增加。血清学方面:miR-7 antagomir组和CTX组血清ANA和抗ds-DNA抗体较Saline组明显下降,补体C3水平明显上升,但两治疗组间上述指标差异均无统计学意义。细胞学方面:miR-7 antagomir组小鼠脾脏Tfh细胞比例明显低于Saline组。与Saline组比较,miR-7 antagomir组小鼠脾B细胞miR-7表达水平降低,PTEN mRNA表达水平升高。此外,miR-7 antagomir组和CTX组小鼠光镜下肾脏病理改变均较Saline组有所好转,但该两组间肾脏病理改变无明显差异。结论:miR-7可作为系统性红斑狼疮的潜在治疗靶点,miR-7 antagomir能够显示出与经典免疫抑制剂CTX相近的治疗效果,有效地改善了MRL/lpr小鼠的狼疮样疾病表现,延缓了病情进展。

7^(OE)+8^(*)亚基对东北强筋小麦品种品质性状影响研究

小麦品质改良是东北春麦区强筋小麦育种的主要目标之一。Glu-B1位点7^(OE)+8^(*)亚基为超强筋小麦品种必备基因。为了明确该亚基在东北春麦区强筋小麦遗传背景下的品质遗传效应,本研究利用分子标记和选择回交相结合的手段,将7^(OE)+8^(*)亚基定向导入到强筋小麦品种龙麦26和龙麦35(Glu-B1位点均为7+9亚基)的遗传背景之中,对BC5F1、BC6F1群体和自交BC6F2鉴定获得的纯合品系进行7^(OE)+8^(*)亚基遗传效应评价。结果表明,在强筋小麦品种龙麦26(7+9)和龙麦35(7+9)遗传背景下转入7^(OE)+8^(*)亚基后,其干面筋、面筋指数、形成时间、稳定时间、断裂时间、拉伸面积、延伸性和最大抗延阻力等品质指标3年平均分别提高1.3%(P=0.82)和1.8%(P=0.49)、6.6%(P=0.59)和4.7%(P=0.37)、55.0%(P=0.24)和35.8%(P=0.56)、44.5%(P=0.43)和32.8%(P=0.73)、41.4%(P=0.31)和30.0%(P=0.66)、28.0%(P=0.05)和23.4%(P=0.37)、6.5%(P=0.47)和5.8%(P=0.42)、19.5%(P=0.31)和18.0%(P=0.38);Zeleny沉降值2年平均分别提高6.8%和11.4%。以上结果表明,在2个强筋小麦品种遗传背景下,Glu-B1位点转入7^(OE)+8^(*)亚基较7+9亚基对各项品质指标改良均存在正向效应,但提高幅度存在差异,对形成时间、稳定时间、断裂时间、最大抗延阻力、拉伸面积等衡量面筋质量的指标提高幅度更大,表明该亚基对面筋质量改良效应显著。综上所述,7^(OE)+8^(*)亚基可作为东北春麦区强筋小麦遗传背景下品质性状进一步改良的优选基因,为超强筋小麦育种的重要基因资源。

子宫内膜癌组织中dMMR蛋白和miRNA Let-7表达水平及临床价值的研究

目的探讨子宫内膜癌(endometrial carcinoma,EC)中微小RNA Let-7(miRNA Let-7)表达水平与DNA错配修复(DNA mismatch repair,dMMR)蛋白表达缺失的关系及意义。方法选取2016年5月~2022年12月在江苏省连云港市妇幼保健院行根治性手术切除的子宫内膜癌患者74例,分别用免疫组织化学法检测dMMR蛋白(包括MLH1,PMS2,MSH2,MSH6)的表达、实时荧光定量聚合酶链反应(qRT-PCR)检测miRNA Let-7的相对表达量,按照dMMR蛋白表达情况,将EC患者分为表达完整组(n=43)和表达缺失组(n=31),采用Logistic多因素回归分析与dMMR蛋白缺失相关的危险因素、绘制受试者工作特征(receiver operating characteristic,ROC)曲线评估相关因素的预测价值。结果74例EC病例中,miRNA Let-7的表达水平在肌层浸润<1/2组显著高于肌层浸润≥1/2组,差异具有统计学意义(t=1.79,P=0.04);dMMR蛋白表达的缺失率为41.89%,且年龄<55岁组和miRNA Let-7低表达组(<0.715)患者中的dMMR蛋白缺失率高于≥55岁组和miRNA Let-7高表达组(≥0.715),差异具有统计学意义(χ2=3.92,4.50,均P<0.05);Logistic多因素回归分析结果显示miRNA Let-7表达水平是发生dMMR表达缺失的独立危险因素(P=0.012);Spearman相关分析表明,miRNA Let-7的表达水平与dMMR蛋白缺失呈明显负相关(r=-0.247,P=0.034);ROC曲线分析结果显示,miRNA Let-7表达水平对于预测EC患者中发生dMMR蛋白的缺失具有一定的价值,其AUC为0.737,最佳临界值为0.77,敏感度和特异度分别为0.651,0.806。结论子宫内膜癌患者中miRNA Let-7的表达水平与dMMR蛋白缺失具有相关性,也是发生dMMR蛋白缺失的危险因素,有望为预测dMMR的表达缺失提供帮助。