Comparative analyses of mitogenomes in the social bees with insights into evolution of long inverted repeats in the Meliponini

The insect mitogenome is typically a compact circular molecule with highly conserved gene contents.Nonetheless,mitogenome structural variations have been reported in specific taxa,and gene rearrangements,usually the tRNAs,occur in different lineages.Because synapomorphies of mitogenome organizations can provide information for phylogenetic inferences,comparative analyses of mitogenomes have been given increasing attention.However,most studies use a very few species to represent the whole genus,tribe,family,or even order,overlooking potential variations at lower taxonomic levels,which might lead to some incorrect inferences.To provide new insights into mitogenome organizations and their implications for phylogenetic inference,this study conducted comparative analyses for mitogenomes of three social bee tribes(Meliponini,Bombini,and Apini)based on the phylogenetic framework with denser taxonomic sampling at the species and population levels.Comparative analyses revealed that mitogenomes of Apini and Bombini are the typical type,while those of Meliponini show diverse variations in mitogenome sizes and organizations.Large inverted repeats(IRs)cause significant gene rearrangements of protein coding genes(PCGs)and rRNAs in Indo-Malay/Australian stingless bee species.Molecular evolution analyses showed that the lineage with IRs have lower dN/dS ratios for PCGs than lineages without IRs,indicating potential effects of IRs on the evolution of mitochondrial genes.The finding of IRs and different patterns of gene rearrangements suggested that Meliponini is a hotspot in mitogenome evolution.Unlike conserved PCGs and rRNAs whose rearrangements were found only in the mentioned lineages within Meliponini,tRNA rearrangements are common across all three tribes of social bees,and are significant even at the species level,indicating that comprehensive sampling is needed to fully understand the patterns of tRNA rearrangements,and their implications for phylogenetic inference.

Changes in macrophage infiltration and podocyte injury in lupus nephritis patients with repeated renal biopsy: Report of three cases

BACKGROUND In this study,we retrospectively analysed macrophage infiltration and podocyte injury in three patients with diffuse proliferative lupus nephritis(LN)who un-derwent repeated renal biopsy.CASE SUMMARY Clinical data of three diffuse proliferative LN patients with different pathological characteristics(case 1 was LN IV-G(A),case 2 was LN IV-G(A)+V,and case 3 was LN IV-G(A)+thrombotic microangiopathy)were reviewed.All patients underwent repeated renal biopsies 6 mo later,and renal biopsy specimens were studied.Macrophage infiltration was assessed by CD68 expression detected by immunohistochemical staining,and an immunofluorescence assay was used to detect podocin expression to assess podocyte damage.After treatment,Case 1 changed to LN III-(A),Case 2 remained as type V LN lesions,and Case 3,which changed to LN IV-S(A),had the worst prognosis.We observed reduced macro-phage infiltration after therapy.However,two of the patients with active lesions after treatment still showed macrophage infiltration in the renal interstitium.Before treatment,the three patients showed discontinuous expression of podocin.Notably,the integrity of podocin was restored after treatment in Case 1.CONCLUSION It may be possible to reverse podocyte damage and decrease the infiltrating ma-crophages in LN patients through effective treatment.

DNA Tandem Repeats as Iterable Objects to Count Cell Divisions: A Computational Model

Cell lineages of nematodes are completely known: the adult male of Caenorhabditis elegans contains 1031 somatic cells, the hermaphrodite 959, not one more, not one less;cell divisions are strictly deterministic (as in the great majority of invertebrates) but so far nothing is known about the mechanism used by cells to count precise numbers of divisions. In vertebrates, each species has its invariable deterministic numbers of somites, vertebrae, fingers, and teeth: counting the number of iterations is a widespread process in living beings;nonetheless, it remains an unanswered question and a great challenge in cell biology. This paper introduces a computational model to investigate the possible role of satellite DNA in counting cell divisions, showing how cells may operate under Boolean logic algebra. Satellite DNA, made up of repeated monomers and subject to high epigenetic methylation rates, is very similar to iterable sequences used in programming: just like in the “iteration protocol” of algorithms, the epigenetic machinery may run over linear tandem repeats (that hold cell-fate data), read and orderly mark one monomer per cell-cycle (cytosine methylation), keep track and transmit marks to descendant cells, sending information to cell-cycle regulators.

Migration routes of the endangered Oriental Stork(Ciconia boyciana)from Xingkai Lake,China,and their repeatability as revealed by GPS tracking

The Oriental Stork(Ciconia boyciana)is listed as'Endangered'on the International Union for the Conservation of Nature(IUCN)Red List of Threatened Species and is classified as a first category nationally protected bird species in China.Understanding this species'seasonal movements and migration will facilitate effective conservation to promote its population.We tagged 27 Oriental Stork nestlings at Xingkai Lake on the Sanjiang Plain in Heilongjiang Province,China,used GPS tracking to follow them over the periods of 2014-2017 and 2019-2022,and confirmed their detailed migratory routes using the spatial analysis function of ArcGIS 10.7.We discovered four migration routes during autumn migration:one common long-distance migration route in which the storks migrated along the coastline of Bohai Bay to the middle and lower reaches of the Yangtze River for wintering,one short-distance migration route in which the storks wintered in Bohai Bay and two other migration routes in which the storks crossed the Bohai Strait around the Yellow River and wintered in South Korea.There were no significant differences in the number of migration days,residence days,migration distances,number of stopovers and average number of days spent at stopover sites between the autumn and spring migrations(P>0.05).However,the storks migrated significantly faster in spring than in autumn(P=0.03).The same individuals did not exhibit a high degree of repetition in their migration timing and route selection in either autumn or spring migration.Even storks from the same nest exhibited considerable between-individual variation in their migration routes.Some important stopover sites were identified,especially in the Bohai Rim Region and on the Songnen Plain,and we further explored the current conservation status at these two important sites.Overall,our results contribute to the understanding of the annual migration,dispersal and protection status of the endangered Oriental Stork and provide a scientific basis for conservation decisions and the development of action plans for this species.

OsTHA8 encodes a pentatricopeptide repeat protein required for RNA editing and splicing during rice chloroplast development

In higher plants, the chloroplast is the most important organelle for photosynthesis and for numerous essential metabolic processes in the cell. Although many genes involved in chloroplast development have been identified, the mechanisms underlying such development are not fully understood. In this study, a rice(Oryza sativa) mutant exhibiting pale green color and seedling lethality was isolated from a mutant library. The mutated gene was identified as an ortholog of THA8(thylakoid assembly 8) in Arabidopsis and maize. This gene is designated as OsTHA8 hereafter. OsTHA8 showed a typical pentatricopeptide repeat(PPR) characteristic of only four PPR motifs. Inactivation of OsTHA8 led to a deficiency in chloroplast development in the rice seedling stage. OsTHA8 was expressed mainly in young leaves and leaf sheaths.The OsTHA8 protein was localized to the chloroplast. Loss of function of OsTHA8 weakened the editing efficiency of ndhB-611/737 and rps8-182 transcripts under normal conditions. Y2H and BiFC indicated that OsTHA8 facilitates RNA editing by forming an editosome with multiple organellar RNA editing factor(OsMORF8) and thioredoxin z(OsTRXz), which function in RNA editing in rice chloroplasts. Defective OsTHA8 impaired chloroplast ribosome assembly and resulted in reduced expression of PEP-dependent genes and photosynthesis-related genes. Abnormal splicing of the chloroplast gene ycf3 was detected in ostha8. These findings reveal a synergistic regulatory mechanism of chloroplast biogenesis mediated by RNA, broaden the function of the PPR family, and shed light on the RNA editing complex in rice.

Molecular characterization of sweet potato(Ipomoea batatas[L.]Lam)germplasms for desirable traits by using simple sequence repeats markers

Every breeding program that aims to create new and improved cultivars with desired traits mostly relies on information related to genetic diversity.Therefore,molecular characterization of germplasms is important to obtain target cultivars with desirable traits.Sweet potato[Ipomoea batatas(L.)Lam]is widely considered the world’s most important crop,with great diversity in morphological and phenotypic traits.The genetic diversity of 20 sweet potato germplasms originating from Bangladesh,CIP,Philippines,Taiwan,and Malaysia were compared,which was accomplished by genetic diversity analysis by exploring 20 microsatellite DNA markers for germplasm characterization and utilization.This information was effective in differentiating or clustering the sweet potato genotypes.A total of 64 alleles were generated using the 20 primers throughout the 20 germplasm samples,with locus IBS97 having the highest number of alleles(5),whereas locus IbU33 had the fewest alleles(2).The alleles varied in size from 105(IbU31)to 213 base pairs(IBS34).The Polymorphism Information Content(PIC)values for the loci IbL46 and IBS97 varied from 0.445 to 0.730.IBS97 has the highest number of effective alleles(3.704),compared to an average of 2.520.The average Shannon’s diversity index(H)was 1.003,ranging from 0.673 in IbU3 to 1.432 in IBS97.The value of gene flow(Nm)varied between 0.000 and 0.005,with an average of 0.003,whereas genetic differentiation(FST-values)ranged between 0.901 and 1.000.The sweet potato germplasm included in this study had a broad genetic base.SP1 vs.SP9 and SP12 vs.SP18 germplasm pairings had the greatest genetic distance(GD=0.965),while SP1 vs.SP2 germplasm couples had the least genetic diversity(GD=0.093).Twenty genotypes were classified into two groups in the UPGMA dendrogram,with 16 genotypes classified as group“A”and the remaining four genotypes,SP10,SP18,SP19,and SP20,classified as group“B.”According to cluster analysis,the anticipated heterozygosity(gene diversity)of Nei(1973)was 0.591 on average.In summary,SSR markers successfully evaluated the genetic relationships among the sweet potato accessions used and generated a high level of polymorphism.The results of the present study will be useful for the management of germplasm,improvement of the current breeding strategies,and the release of new cultivars as varieties.

Axial length shortening in myopic children with Stickler syndrome after repeated low-level red-light therapy

AIM:To report the myopia-controlling effect of repeated low-level red-light(RLRL)therapy in patients with Stickler syndrome(STL),an inherited collagenic disease typically presenting with early onset myopia.METHODS:Three STL children,aged 3,7,and 11y,received RLRL therapy throughout the follow-up period of 17,3,and 6mo,respectively after exclusion of fundus anomalies.Data on best-corrected visual acuity(BCVA),intraocular pressure,cycloplegic subjective refraction,ocular biometrics,scanning laser ophthalmoscope,optical coherence tomography,genetic testing,systemic disease history,and family history were recorded.RESULTS:At the initiation of the RLRL therapy,the spherical equivalent(SE)of 6 eyes from 3 patients ranged from-3.75 to-20.38 D,axial length(AL)were from 23.88 to 30.68 mm,and BCVA were from 0.4 to 1.0(decimal notation).Myopia progression of all six eyes slowed down after RLRL therapy.AL in five out of the six eyes shortened-0.07 to-0.63 mm.No side effects were observed.CONCLUSION:Three cases of STL whose progression of myopic shift and AL elongation are successfully reduced and even reversed after RLRL therapy.

F-box and leucine-rich repeat 6 promotes gastric cancer progression via the promotion of epithelial-mesenchymal transition

BACKGROUND F-box and leucine-rich repeat 6(FBXL6)have reportedly been associated with several cancer types.However,the role and mechanisms of FBXL6 in gastric cancer(GC)require further elucidation.AIM To investigate the effect of FBXL6 in GC tissues and cells and the underlying mechanisms.METHODS TCGA and GEO database analysis was performed to evaluate the expression of FBXL6 in GC tissues and adjacent normal tissues.Reverse transcription-quantitative polymerase chain reaction,immunofluorescence,and western blotting were used to detect the expression of FBXL6 in GC tissue and cell lines.Cell clone formation,5-ethynyl-2’-deoxyuridine(EdU)assays,CCK-8,transwell migration assay,and wound healing assays were performed to evaluate the malignant biological behavior in GC cell lines after transfection with FBXL6-shRNA and the overexpression of FBXL6 plasmids.Furthermore,in vivo tumor assays were performed to prove whether FBXL6 promoted cell proliferation in vivo.RESULTS FBXL6 expression was upregulated more in tumor tissues than in adjacent normal tissues and positively associated with clinicopathological characteristics.The outcomes of CCK-8,clone formation,and Edu assays demonstrated that FBXL6 knockdown inhibited cell proliferation,whereas upregulation of FBXL6 promoted proliferation in GC cells.Additionally,the transwell migration assay revealed that FBXL6 knockdown suppressed migration and invasion,whereas the overex pression of FBXL6 showed the opposite results.Through the subcutaneous tumor implantation assay,it was evident that the knockdown of FBXL6 inhibited GC graft tumor growth in vivo.Western blotting showed that the effects of FBXL6 on the expression of the proteins associated with the epithelial-mesenchymal transition-associated proteins in GC cells.CONCLUSION Silencing of FBXL6 inactivated the EMT pathway to suppress GC malignancy in vitro.FBXL6 can potentially be used for the diagnosis and targeted therapy of patients with GC.

Prognostic role of ring finger and WD repeat domain 3 and immune cell infiltration in hepatocellular carcinoma

We have found that the expression of ring finger and WD repeat domain 3(RFWD3)is significantly higher in unpaired and paired hepatocellular carcinoma(HCC)tissues than in normal tissues.Moreover,this expression has a significant correlation with the infiltration level of 14 immune cell types and when the detected RFWD3 expression levels were grouped as high and low,a prominent difference was revealed for overall survival,disease-specific survival,and progression-free interval.Through statistical analysis(univariate Cox),we were also able to identify RFWD3 as an independent prognostic element for HCC,with RFWD3 having an ability to accurately predict HCC prognosis(area under the curve of 0.863).Finally,we have generated prognostic nomograms for probabilities of 1-,3-and 5-year overall survival in HCC via integrating the factors of age,pathologic stage,alpha-fetoprotein level,and RFWD3 expression.

Energy Based Random Repeat Trust Computation in Delay Tolerant Network

As the use of mobile devices continues to rise,trust administration will significantly improve security in routing the guaranteed quality of service(QoS)supply in Mobile Ad Hoc Networks(MANET)due to the mobility of the nodes.There is no continuance of network communication between nodes in a delay-tolerant network(DTN).DTN is designed to complete recurring connections between nodes.This approach proposes a dynamic source routing protocol(DSR)based on a feed-forward neural network(FFNN)and energybased random repetition trust calculation in DTN.If another node is looking for a node that swerved off of its path in this situation,routing will fail since it won’t recognize it.However,in the suggested strategy,nodes do not stray from their pathways for routing.It is only likely that the message will reach the destination node if the nodes encounter their destination or an appropriate transitional node on their default mobility route,based on their pattern of mobility.The EBRRTC-DTN algorithm(Energy based random repeat trust computation)is based on the time that has passed since nodes last encountered the destination node.Compared to other existing techniques,simulation results show that this process makes the best decision and expertly determines the best and most appropriate route to send messages to the destination node,which improves routing performance,increases the number of delivered messages,and decreases delivery delay.Therefore,the suggested method is better at providing better QoS(Quality of Service)and increasing network lifetime,tolerating network system latency.

Timing of Elective Repeat Cesarean Delivery at 38 Weeks versus 39 Weeks: Rate of Spontaneous Onset of Labor before Planned Cesarean Section and Impact on Maternal Outcome: A Retrospective Cohort Study

Background: The timing of elective repeat cesarean delivery at 38 weeks versus 39 weeks is still a debatable subject, both regarding maternal and neonatal outcomes. In the Saudi context, there is lack of local data to aid decision-making regarding the timing of elective repeat cesarean delivery. Objectives: To estimate the rate of spontaneous onset of labor before the planned gestational age for repeat cesarean section in women who were booked at gestational age of (39 0/7 - 39 6/7) weeks (W39) versus (38 0/7 - 38 6/7) weeks (W38) and to compare the rate of maternal composite outcome between these groups. Design: Retrospective cohort. Setting: This study was conducted at King Abdulaziz Medical City, Jeddah, KSA. Method: Delivery registry books were reviewed to identify all deliveries from 1 January 2014 to 31 December 2016 (3 years). All low-risk pregnant women who had 2 or more cesarean deliveries and who met the inclusion criteria were included. Results: A total of 440 women were included of whom 318 (72.3%) were planned for elective cesarean section at W38 gestational age and 122 women at W39 gestational age. Mothers planned at W39 had higher rate of emergency cesarean deliveries versus those planned at W38 (18.0% versus 10.4%, p = 0.030;RR = 13.06), most frequently due to early onset of contractions (16.4% versus 8.2%, p = 0.012;RR = 12.17) or cervical dilatation (11.6% versus 5.4%, p = 0.024, RR = 16.15). No difference in the incidence of individual or composite maternal complications was noted between the two groups. Mother’s age (OR 0.93, p = 0.018) and schedule date at W39 (OR = 1.94, p = 0.028) were independently associated with spontaneous onset of labor before the scheduled gestational age, while no association was found with parity, previous number of spontaneous vaginal deliveries, number of previous cesarean deliveries or interval from last cesarean delivery. Conclusion: Elective cesarean section scheduled at 39 weeks of gestation or beyond carries a higher risk of emergency cesarean section, with no significant increase in maternal complications. The identification of factors associated with spontaneous onset of labor before the planned gestational age should be carefully identified to determine the optimal timing.

Design and Implementation of Quantum Repeaters:Insights on Quantum Entanglement Purification

Quantum communication is a groundbreaking technology that is driving the future of information transmission and communication technologies to a new paradigm.It relies on quantum entanglement to facilitate the transmission of quantum states between parties.Quantum repeaters are crucial for facilitating long-distance quantum communication.These quantum devices act as intermediaries between adjacent communication channel segments within a fragmented quantum network,allowing for entanglement swapping between the channel segments.This entanglement swapping process establishes entanglement links between the endpoints of adjacent segments,gradually creating a continuous entanglement connection over the entire length of the transmission channel.The established quantum link can be utilized for secure and efficient quantum communication between distant sender and receiver nodes.This study focuses on quantum entanglement purification,a protocol aimed at maintaining high fidelity entangled states above the operational threshold of the communication channel.This study investigates the optimal stage for executing the purification protocol and applies optimization schemes to evaluate various purification protocols.We use IBM Qiskit for circuit implementation and simulation.The results offer valuable insights into future approaches to implementing practical quantum repeaters and shed light on existing and anticipated challenges.

非小细胞肺癌组织中circBIRC6、APPBP2表达及临床预后意义

目的 探讨非小细胞肺癌(NSCLC)组织中环状核糖核酸杆状病毒IAP重复序列6(circBIRC6)、β淀粉样蛋白前体蛋白结合蛋白2(APPBP2)表达及临床预后意义。方法 收集2018年6月~2020年1月90例在河北北方学院附属第一医院行手术切除的NSCLC组织及癌旁组织,采用实时荧光定量聚合酶链式反应检测circBIRC6、APPBP2表达,并分析二者与NSCLC患者临床病理特征的关系。通过Pearson相关性分析NSCLC组织中circBIRC6与APPBP2 mRNA表达的相关性,Kaplan-Meier法绘制不同表皮生长因子受体(EGFR)基因突变、TNM分期和circBIRC6、APPBP2 mRNA表达的NSCLC患者生存曲线,多因素Cox回归分析NSCLC患者预后的影响因素。结果 与癌旁组织比较,NSCLC组织中circBIRC6、APPBP2 mRNA表达升高(P<0.05)。NSCLC组织中circBIRC6与APPBP2 mRNA表达呈正相关(r=0.817,P<0.001)。NSCLC患者不同分化程度、TNM分期、淋巴结转移组织中circBIRC6、APPBP2 mRNA表达比较有差异(P<0.05)。随访3年,90例NSCLC患者总生存率为55.56%(50/90)。EGFR基因突变阳性/阴性NSCLC患者总生存率比较无差异(P>0.05);TNM分期Ⅰ~Ⅱ期NSCLC患者总生存率高于Ⅲ期NSCLC患者(P<0.05);circBIRC6、APPBP2 mRNA高表达组生存率低于circBIRC6、APPBP2 mRNA低表达组(P<0.05)。低分化、TNM分期Ⅲ期、淋巴结转移和circBIRC6≥10.97、APPBP2 mRNA≥2.48为NSCLC患者死亡的独立危险因素[OR(95%CI)=3.586(1.080~11.909)、3.632(1.193~11.057)、3.197(1.060~9.640)、3.223(1.086~9.570)、2.767(1.022~7.492)]。结论 NSCLC组织中circBIRC6、APPBP2 mRNA高表达,与分化程度、TNM分期、淋巴结转移和预后有关。

自适应光学视觉模拟器测量波前像差的重复性及与OPD-Scan Ⅲ的一致性研究

目的:评价自适应光学视觉模拟器(VAO)测量全眼高阶像差的重复性及与OPD-ScanⅢ测量全眼高阶像差的一致性。方法:采用横断面研究方法。纳入2023-08/09在成都东区爱尔眼科医院屈光科就诊的近视患者204例204眼(均取右眼数据)。由同一位操作熟练的检查者分别使用两种设备进行检查,使用VAO测量4.5 mm瞳孔直径下3-6阶的高阶像差,VAO和OPD-ScanⅢ测量3-6 mm瞳孔直径下全眼总高阶像差(tHOA)、球差(SA)、彗差(Coma)和三叶草像差(Trefoil),评估VAO测量全眼像差的重复性及两种设备的一致性。结果:VAO测量全眼的高阶像差均显示较高的重复性(0.767≤ICC≤0.941、Sw<0.01μm、TRT<0.1μm)。4-6 mm瞳孔直径下VAO与OPD-ScanⅢ的Coma测量值无差异(P>0.05),其余瞳孔直径下全眼总高阶像差的测量值均有差异(均P<0.05)。VAO与OPD-ScanⅢ的3 mm瞳孔直径下各阶像差以及4、5 mm瞳孔直径下的SA、4 mm瞳孔直径下的Coma测量值的95%LoA<0.1,显示一致性较好,其余瞳孔直径下的像差测量值的95%LoA>0.1,显示一致性较差,两种设备3 mm(r=0.218-0.317,P<0.01)、4 mm(r=0.406-0.672,P<0.01)、5 mm(r=0.538-0.839,P<0.01;r=0.030-0.109,P>0.01)以及6 mm(r=0.369-0.766,P<0.01)瞳孔直径下高阶像差测量值差异较大。结论:VAO测量3-6 mm瞳孔直径下全眼高阶像差结果时具有良好的重复性,但VAO与OPD-ScanⅢ的3-6 mm瞳孔直径下的全眼高阶像差测量值存在差异性,一致性较差,临床应用不可互换。

玉米逆境胁迫响应基因ZmTPR1的表达和功能分析

在前期干旱-复水处理玉米转录组测序基础上,发现了一个响应干旱胁迫的基因ZmTPR1(Tetratricopeptide repeat 1),对该基因进行生物信息学分析,并探究其在不同组织及逆境胁迫下的表达模式,利用CRISPR-Cas9技术敲除拟南芥中的同源基因AtTPR1,分析干旱胁迫条件下纯合突变体植株的表型和生理生化指标,初步探究该基因的功能,为培育抗旱玉米品种提供基因资源。结果表明,ZmTPR1基因位于玉米的第3号染色体,编码421个氨基酸,具有保守的卷曲螺旋结构域,可能参与玉米对植物激素、干旱等胁迫的响应。ZmTPR1基因在玉米各组织中均表达,在幼茎中的表达量最高;干旱、高温、盐和缺氮胁迫均可诱导ZmTPR1基因的表达,干旱胁迫后表达量上调最明显;干旱胁迫后ZmTPR1基因在抗旱玉米自交系郑36中的表达量均极显著高于敏旱玉米自交系B73。敲除AtTPR1基因后拟南芥抗旱能力下降,Attpr1突变体在干旱胁迫下生长受到严重抑制,叶片萎蔫甚至干死,同时相对含水量、叶绿素含量、净光合速率及过氧化物酶和超氧化物歧化酶活性极显著降低,丙二醛含量极显著升高。综合来看,ZmTPR1基因参与玉米对多种非生物胁迫的响应过程,并在响应干旱胁迫中发挥着重要的作用。

LRRK2基因R1067Q和GBA基因R202Q双变异致早发型帕金森病一例

患者男性,42岁。主因左手抖动18个月,左下肢抖动伴运动迟缓6个月,于2023年7月8日入院。患者18个月前(2022年1月)无明显诱因出现左上肢不自主抖动,静止时出现、持物及动作时消失,无动作迟缓、反应变慢等其他伴随症状。于2022年11月至外院就诊,头部MRI检查无明显异常,结合临床症状,考虑帕金森病(PD),服用普拉克索0.375 mg/d并逐渐增量至0.375 mg/次、2次/d长期治疗,症状无明显改善。6个月前(2023年1月)出现左下肢不自主抖动,并逐渐出现动作迟缓,左侧肢体活动不灵活,体位变化或行走时偶有头晕,不伴视物旋转及恶心呕吐等,持续数分钟后头晕可自行好转,无嗅觉丧失、情绪低落,睡眠质量尚可,无多梦、呓语、乱喊乱叫、手舞足蹈等症状。

经典藏药如意珍宝片多次给药的靶器官-脑组织的成分探究

目的:探讨经典藏药如意珍宝片多次给药后,其靶器官脑组织的活性成分,分析其可能的作用特点。方法:6只斯泼累格·多雷(SD)雄性大鼠分为对照组和观察组2组,连续给药7 d,在最后一次给药后1 h处死动物,取血浆和脑组织,分析入血成分,并对潜在入脑成分进行检测和验证。结果:采用Full mass/dd-MSMS模式,以目标峰的一级谱图的分子量的组成及二级质谱图的分子离子峰进行定性分析;并依据入血成分作为潜在入脑成分,将其输入到包含列表内,进行样品检测。结合数据库mzcloud和ChemSpider的结果,对潜在入脑成分进行搜索,根据保留时间、一级质量数和二级质谱数据,共发现了13个入脑成分,其中大豆苷、胆酸、紫苜蓿酮、3′-O-methylviolanone、胡椒碱已用标准品验证。色氨酸、茴香脑、异木香酸和腺苷已通过mzCloud数据库进行二级碎片信息比对。结论:如意珍宝片中的降香、荜茇、甘草膏、肉桂、木香、黄葵子、牛黄、红花等药物的有效成分能够进入靶器官脑组织中,发挥其疗效作用。

食蟹猴重复给予溶瘤病毒药物HSV-1/hPD-1的毒性研究

目的:考察食蟹猴重复给予溶瘤病毒药物HSV-1/hPD-1后的体内毒性,探索安全剂量范围,为后续临床试验提供参考信息。方法:30只食蟹猴随机分成3组,包括溶媒对照组和低、高剂量(1.0×10^(8)、4.0×10^(8)pfu)组,每组10只,雌雄各半。采用肌肉注射给药,每周给药2次,连续给药6周,恢复期8周。试验期间,每天观察动物的临床症状和摄食量,每次给药后1~2天观察注射部位症状,每周称量体重。分别在检疫期、首次给药后、给药期结束、恢复期结束的不同时间点进行安全药理(体温、血压、心电图)测定、临床病理(血液学、血凝、血清生化、尿生化)检查、免疫学(T淋巴细胞、细胞因子、免疫原性)测定、组织病理学检查和脏器称重。结果:给药后,动物未见异常症状、注射部位刺激性、体重和摄食量改变,未见安全药理和临床病理指标有意义的变化。与溶媒对照组比较,第41天,低剂量会引起动物CD3^(+)CD4^(+)T细胞比例升高,高剂量未见明显变化。第13至97天,低、高剂量均能引起动物产生抗载体结合抗体、抗抗体,以及个别动物检出hPD-1表达产物。证明药物在体内产生免疫活性和介导免疫原性。组织病理学检查显示,给药期结束时,低、高剂量组动物注射部位极轻度至中度混合细胞浸润,高剂量组动物坐骨神经极轻度髓鞘/轴突变性;恢复期结束时注射部位病变减为极轻度,坐骨神经病变未见恢复趋势。低、高剂量组动物未见组织脏器重量改变。结论:食蟹猴重复给予溶瘤病毒药物HSV-1/hPD-1后,动物体内耐受良好,受试物未见毒性反应剂量(NOAEL)是1.0×10^(8)pfu。上述研究结果为药物开展临床试验提供了数据支持。

盐酸多奈哌齐联合孙氏经颅重复针刺法治疗阿尔茨海默病的效果

目的 观察盐酸多奈哌齐联合孙氏经颅重复针刺法治疗阿尔茨海默病(AD)的临床效果。方法 选取2022年9月至2023年9月黑龙江中医药大学附属第二医院哈南分院针灸门诊收治的90例AD患者,按照随机数字表法将其分为观察组、对照A组、对照B组,各30例。对照A组给予口服盐酸多奈哌齐治疗,对照B组行孙氏经颅重复针刺法治疗,观察组为盐酸多奈哌齐联合孙氏经颅重复针刺法治疗,均治疗8周。评价其临床疗效。比较三组治疗前及治疗后4、8周简易智力状态检查量表(MMSE)、阿尔茨海默病认知评估量表(ADAS-cog)和日常生活活动能力量表(ADL)评分及血清同型半胱氨酸(Hcy)水平。结果 观察组临床疗效优于对照A组及对照B组,差异有统计学意义(P<0.05)。三组治疗后4、8周MMSE评分高于治疗前,ADAS-cog、ADL评分和血清Hcy水平低于治疗前,差异有统计学意义(P<0.05);三组治疗后8周MMSE评分高于治疗后4周,ADAS-cog、ADL评分和血清Hcy水平低于治疗后4周,差异有统计学意义(P<0.05)。治疗后8周,观察组MMSE评分高于对照A组和对照B组,ADAS-cog、ADL评分和血清Hcy水平低于对照A组和对照B组,差异有统计学意义(P<0.05)。结论盐酸多奈哌齐联合孙氏经颅重复针刺法可改善轻中度AD患者的认知功能及行为能力,降低血清Hcy水平,且效果优于单纯口服多奈哌齐和孙氏经颅重复针刺法,值得临床推广。

雾天桥梁可变限速值的效用评估及优化

为改善高速公路桥梁路段雾天环境的交通安全,文中考虑可变限速标志设置对驾驶行为的影响,从服从效应角度提出其量化评估方法,以期获得最优作用效能。文中以鄂东长江大桥为原型,选取该桥梁近年最低能见度(100 m)和自由流服务水平作为测试环境,设计3种限速策略,分别为对照组SⅠ(无限速策略)、实验组SⅡ(90~70 km/h限速策略)、实验组SⅢ(90~70~50 km/h逐级限速策略);依托驾驶模拟器,实现不同限速条件的雾天桥梁场景微观驾驶行为数据的细粒度感知,采用重复测量方差分析方法从驾驶人响应的快速性、稳定性及准确性剖析可变限速标志的作用机理及驾驶人特征表现,并通过模糊综合评价方法评估不同限速策略的有效性。研究结果表明:雾天桥梁可变限速标志能够使驾驶人更早地采取减速措施,车辆在雾区行驶过程的稳定性更好;在雾天能见度100 m情况下,90~70~50 km/h逐级限速策略的稳态频数更大,空间稳定性更好,且速度超调量和跟随比更小,响应准确性更高。模糊综合评估结果显示,90~70~50 km/h逐级限速策略作为最优方案,能够有效地提升雾区驾驶行为的调节适应能力,降低驾驶风险,提高车辆运行的稳定性。本研究成果为雾天桥梁可变限速标志的优化设置提供了解决方案,可为雾天桥梁的主动安全防控提供有效支撑。