Tanshinone ⅡA improves Alzheimer’s disease via RNA nuclearenriched abundant transcript 1/microRNA-291a-3p/member RAS oncogene family Rab22a axis

BACKGROUND Alzheimer’s disease(AD)is a neurodegenerative condition characterized by oxidative stress and neuroinflammation.Tanshinone ⅡA(Tan-ⅡA),a bioactive compound isolated from Salvia miltiorrhiza plants,has shown potential neuroprotective effects;however,the mechanisms underlying such a function remain unclear.AIM To investigate potential Tan-ⅡA neuroprotective effects in AD and to elucidate their underlying mechanisms.METHODS Hematoxylin and eosin staining was utilized to analyze structural brain tissue morphology.To assess changes in oxidative stress and neuroinflammation,we performed enzyme-linked immunosorbent assay and western blotting.Additionally,the effect of Tan-ⅡA on AD cell models was evaluated in vitro using the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay.Genetic changes related to the long non-coding RNA(lncRNA)nuclear-enriched abundant transcript 1(NEAT1)/microRNA(miRNA,miR)-291a-3p/member RAS oncogene family Rab22a axis were assessed through reverse transcription quantitative polymerase chain reaction.RESULTS In vivo,Tan-ⅡA treatment improved neuronal morphology and attenuated oxidative stress and neuroinflammation in the brain tissue of AD mice.In vitro experiments showed that Tan-ⅡA dose-dependently ameliorated the amyloid-beta 1-42-induced reduction of neural stem cell viability,apoptosis,oxidative stress,and neuroinflammation.In this process,the lncRNA NEAT1-a potential therapeutic target-is highly expressed in AD mice and downregulated via Tan-ⅡA treatment.Mechanistically,NEAT1 promotes the transcription and translation of Rab22a via miR-291a-3p,which activates nuclear factor kappa-B(NF-κB)signaling,leading to activation of the pro-apoptotic B-cell lymphoma 2-associated X protein and inhibition of the anti-apoptotic B-cell lymphoma 2 protein,which exacerbates AD.Tan-ⅡA intervention effectively blocked this process by inhibiting the NEAT1/miR-291a-3p/Rab22a axis and NF-κB signaling.CONCLUSION This study demonstrates that Tan-ⅡA exerts neuroprotective effects in AD by modulating the NEAT1/miR-291a-3p/Rab22a/NF-κB signaling pathway,serving as a foundation for the development of innovative approaches for AD therapy.

Diverse phenotype of Méenière’s disease associated with family history,thyroid disorder,migraine and associated disorders

Objective:To better understand the clinical phenotype of Méenière’s disease(MD),we examined family history,thyroid disorder,migraine,and associated disorders in complaints of people living with MD.Method:We designed the study as a retrospective and examined data gathered from 912 participants with MD.Their data were originally collected by the Finnish M′eni`ere Federation(FMF).The survey data included individual case histories for environmental factors,comorbidities,disease-specific complaints,impact-related questions,cognitive complaints,health-related quality of life(HRQoL),and sense of coherence(SOC).Results:We observed significant differences between those with and without sporadic occurrence,family history,thyroid disorder,and migraine-associated complaints.Family history explained 20%of variability in patient complaints.Patients with a family history of MD whose disease started at younger age experienced balance problems,more severe vertigo spells,more severe vestibular drop attacks(VDA),and less nausea,although they had good SOC.Thyroid disorder explained 14%of variability in patient complaints.MD patients with a thyroid disorder comorbidity suffered more often from constant dizziness,balance problems,greater impact of hearing problems,cognitive complaints,and poor HRQoL.Migraine explained 12%of variability in patients’complaints and was associated with poor SOC and cognitive balance problems.MD patients with both thyroid disorder and migraine used antidepressants more often than other groups.Logistic regression analysis showed comorbidities of ischemic brain disorder(among 7.1%),kidney insufficiency(among 1.2%),and diabetes(among 7.3%)had statistically significant but restricted association with balance and gait problems,VDA,and reduced HRQoL.Conclusions:Family history of MD and thyroid disorder or migraine comorbidities in MD influence the complaint pattern and partially explain complex symptom profiles,including symptoms of cognitive problems.Confounders play a minimal role in complaint profile and impact of MD whereas comorbidities influence the complaint structure and partly explain the complex symptom profile in MD.

The Impact of Nursing Staff’s Work Attitude on the Fear of Patients Recovering from Benign Tumors:Family Support as a Mediating Variable

The perception of nursing staff’s attitude influences patient fear.Understanding this dynamic is crucial for fostering a supportive environment conducive to patient well-being and effective healthcare practices.The purpose of this research is to investigate how the attitudes and behaviours of nursing staff influence the fear and anxiety levels of patients recovering from benign tumors,aiming to improve patient care and recovery outcomes.Data was collected from a sample of 100 participants,comprising 20 nursing staff and 80 patients recovering from benign tumors.Surveys were administered to gather quantitative data on attitudes and fear levels.Participants were selected randomly from hospital records and outpatient clinics.Our analysis encompassed nursing staff attitude,patient fear levels,the influence of family support,progression of tumor recovery,patient-reported satisfaction,and the quality of healthcare services provided.The quantitative aspect utilized PLS-SEM software to perform regression analysis,evaluating both direct and indirect effects.Statistical analysis assessed the relationships between nursing staff attitudes,patient fear during benign tumor recovery,and the mediating role of family support.The findings of the study demonstrate that better nurse attitudes(Hypothesis 1,β=0.45,p<0.001)and stronger family support(Hypothesis 2,β=0.32;p<0.001) are linked to lower levels of patient fear.Partially mediating the relationship between nurse attitudes and patient fear,according to Hypothesis 3(β=0.28,p<0.002),is family support.Patients’perceptions of family support are highly influenced by nursing behaviour,as demonstrated by Hypothesis 4(β=0.38;p<0.001).Our research showed a strong relationship between the attitudes of nursing personnel and patient fear levels.Family support demonstrated a strong mediating effect on patient fear.Patient-reported satisfaction is positively correlated with family support.However,no significant relationship was found between healthcare service quality and patient fear.

Research on the Influence of Family Education on Children’s Behavioral Habits

Under the background of the all-round deepening of quality education,the cultivation of comprehensive quality has become the main theme of contemporary education reform.Good behavior and habits are of great significance to children’s future learning,growth,and development.Through literature review and other methods,this paper analyzes the current situation of children’s family education and the influence of family education on the cultivation of children’s behavioral habits and provides some strategies for cultivating children’s good behavioral habits in family education.

PARK1 gene mutation of autosomal dominant Parkinson's disease family

Studies have shown that PARK1 gene is associated with the autosomal dominant inheritance of Parkinson＇s disease. PARK1 gene contains two mutation sites, namely Ala30Pro and Ala53Thr, which are located on exons 3 and 4, respectively. However, the genetic loci of the pathogenic genes remain unclear. In this study, blood samples were collected from 11 members of a family with high prevalence of Parkinson＇s disease, including four affected cases, five suspected cases and two non-affected cases. Point mutation screening of common mutation sites on PARK1 gene exon 4 was conducted using PCR, to determine the genetic loci of the causative gene for Parkinson＇s disease. Gene identification and sequencing results showed that a T base deletion mutation was observed in the PARK1 gene exon 4 of all 11 collected samples. It was confirmed that the PARK1 gene exon 4 gene mutation is an important pathogenic mutation for Parkinson＇s disease.

A Story About Mary's Family

The students were having an English class. "Today you can write a story about your family.I want you to tell me something about your parents and your brothers and sisters, "said Mr Shute. Mary raised her hand."What kind of thing shall I write about my parents? "she asked. "Well,"said Mr Shute. "Write about

两种依他尼酸衍生物对人类谷胱甘肽-S-转移酶Mu的抑制动力学研究

目的:考察所设计依他尼酰乙胺、双依他尼酰丁二胺及对应产物对人类谷胱甘肽-S-转移酶Mu(glutathione-S-transferase Mu,GSTM)的抑制动力学。方法:重组表达GSTM,以2,4-二硝基氯苯(1-chloro-2,4-dinitrobenzene,CDNB)和还原型谷胱甘肽(glutathione,GSH)为底物,跟踪酶反应过程的紫外吸收变化,测定酶活性。比较GSTM存在下依他尼酰乙胺、双依他尼酰丁二胺与GSH孵育前后对酶的半抑制浓度(IC50)、抑制类型。结果:依他尼酰乙胺、双依他尼酰丁二胺对GSTM的IC50分别为(44.0±2.2)μmol/L、(0.090±0.012)μmol/L(n=3),两者相对GSH是反竞争性抑制剂、相对CDNB是竞争性抑制剂。与酶和GSH孵育原位生成产物后,对GSTM的IC50分别为(8.9±0.1)μmol/L和(0.006±0.001)μmol/L(n=3);依他尼酰乙胺与GSH孵育后相对GSH是竞争性抑制剂、相对CDNB是混合型抑制剂;双依他尼酰丁二胺与GSH孵育后相对GSH和CDNB均为混合型抑制剂。两种依他尼酸衍生物与GSH孵育后产物IC50明显降低,双依他尼酰丁二胺及其GSH孵育产物IC50较依他尼酰乙胺及其产物均明显降低。结论:依他尼酰乙胺、双依他尼酰丁二胺是潜抑制剂,其产物对GSTM的抑制作用更强,抑制类型发生明显改变;双依他尼酰丁二胺及其产物较依他尼酰乙胺抑制作用更强。

基于Matlab/Simulink的光伏电池建模与仿真

为了研究光伏发电系统,该文根据光伏电池的数学模型,利用Matlab软件在Matlab/Simulink下搭建了一种光伏电池仿真模型。通过对搭建模型运行仿真得出了光伏电池的特性曲线,并且经过改变外界参数对不同环境下的光伏电池的输出特性曲线进行了比较,得出了相应结论:不同环境下光伏电池的输出特性是不同的,且按照一定的规律变化,但每一种环境下光伏电池都有唯一的最大功率输出点。这对光伏并网系统的研究具有重要意义。

Family and twin studies in inflammatory bowel disease

Studies examining the inheritance of inflammatory bowel disease （IBD） within different family groups have been the basis for recent molecular advances in the genetics of IBD. The derived heritability in Crohn＇s disease （CD） is higher than in many other complex diseases. The risk of IBD is highest in first-degree relatives of a CD proband, but first-degree relatives of a proband suffering from ulcerative colitis （UC） and more distant relatives are also at increased risk. Disease concordance rates in IBD have been examined in multiplex families and in three large European twin studies.

Structure and function of the contactin-associated protein family in myelinated axons and their relationship with nerve diseases

The contactin-associated protein （Caspr） family participates in nerve excitation and conduction, and neurotransmitter release in myelinated axons. We analyzed the structures and functions of the Caspr family- CNTNAP1 （Casprl）, CNTNAP2 （Caspr2）, CNTNAP3 （Caspr3）, CNTNAP4 （Caspr4） and CNTNAP5 （Caspr5）, Casprl-5 is not only involved in the formation of myelinated axons, but also participates in maintaining the stability of adjacent connections. Casprl participates in the formation, differentiation, and proliferation of neurons and astrocytes, and in motor control and cognitive function. We also analyzed the relationship between the Caspr family and neurodegenerative diseases, multiple sclerosis, and autoimmune encephalitis. However, the effects of Caspr on disease course and prognosis remain poorly understood. The effects of Caspr on disease diagnosis and treatment need further investigation.

Bortezomib effect on E2F and cyclin family members in human hepatocellular carcinoma cell lines

AIM: To evaluate the effects of the proteasome inhibitor bortezomib (BZB) on E2Fs and related genes in hepatocellular carcinoma (HCC) cells.

Similar clinical characteristics of familial and sporadic inflammatory bowel disease in South Korea

AIM: To investigate differences of clinical characteristics and disease courses between familial and sporadic inflammatory bowel disease (IBD) patients.

Increased oxidative damage of sperm and seminal plasma in men with idiopathic infertility is higher in patients with glutathione S-transferase Mu-1 null genotype

Aim： To examine whether a relationship exists between glutathione S-transferase Mu-1 （GSTM1） gene polymorphism and the susceptibility of sperm and seminal plasma from patients with idiopathic infertility to oxidative stress. Methods： Fifty-two men with idiopathic infertility and 60 healthy fertile men were recruited to this study. GSTM1 gene polymorphism was determined by polymerase chain reaction （PCR） and both the infertile and control individuals were divided into GSTM1 null and GSTM1 positive groups according to their GSTM1 gene structure. We compared reactive oxygen species （ROS） generation, malondialdehyde （MDA）, protein carbonyls and glutathione （GSH） concentrations, and glutathione S-transferase （GST） activity in seminal plasma and spermatozoa from infertile patients and controls with respect to GSTM1 genotype. Results： Significantly higher levels of oxidative stress and damage markers were found in idiopathic infertile men with the GSTM1 null genotype compared with those with the GSTM1 positive genotype. There was no significant difference in genotype distribution for theGSTM1 variant between the idiopathic infertile subjects and fertile subjects. Patients with the GSTM1 null genotype also had lower sperm concentrations than those with GSTM1 positive genotype. Conclusion： Our results suggest that the susceptibility of sperm and seminal plasma to oxidative stress is significantly greater in idiopathic infertile men with the GSTM1 null genotype compared with those possessing the gene. Therefore, in patients with idiopathic infertility, GSTM1 polymorphism might be an important source of variation in susceptibility of spermatozoa to oxidative damage.

Adenomas of the common bile duct in familial adenomatous polyposis

Familial adenomatous polyposis(FAP)or Gardner’s syndrome is often accompanied by adenomas of the stomach and duodenum.We experienced a case of adenomas of the common bile duct in a 40-year-old woman with FAP presenting with acute cholangitis.Only 8 cases of adenomas or adenocarcinoma ofthe common bile duct have been reported in the literature in patients with FAP or Gardner’s syndrome.Those patients presented with acute cholangitis or pancreatitis.Local excision or Whipple procedure may be the reasonable surgical option.

Family history and disease outcomes in patients with Crohn's disease:A comparison between China and the United States

AIM To investigate the differences in family history of inflammatory bowel disease(IBD) and clinical outcomes among individuals with Crohn's disease(CD) residing in China and the United States.METHODS We performed a survey-based cross-sectional study of participants with CD recruited from China and the United States.We compared the prevalence of IBD family history and history of ileal involvement,CD-related surgeries and IBD medications in China and the United States,adjusting for potential confounders.RESULTS We recruited 49 participants from China and 145 from the United States.The prevalence of family history of IBD was significantly lower in China compared with the United States(China:4.1%,United States:39.3%).The three most commonly affected types of relatives were cousin,sibling,and parent in the United States compared with child and sibling in China.Ileal involvement(China:63.3%,United States:63.5%) and surgery for CD(China:51.0%,United States:49.7%) were nearly equivalent in the two countries.CONCLUSION The lower prevalence of familial clustering of IBD in China may suggest that the etiology of CD is less attributed to genetic background or a family-shared environment compared with the United States.Despite the potential difference in etiology,surgery and ileal involvement were similar in the two countries.Examining the changes in family history during the continuing rise in IBD may provide further insight into the etiology of CD.

Research on the effects of family care degree on stigma and psychosocial adaptation among the patients with Parkinson’s disease

Objective:This study aimed to investigate the status quo of family care degree,stigma and psychosocial adaptation of the patients with Parkinson’s disease(PD),and discuss the effects of family care degree on stigma and psychosocial adaptation among the patients with PD.Methods:This study was conducted between September 2018 and April 2019 on patients with PD who were admitted to a Ter tiary Grade A hospital in Dalian city.A total of 246 PD patients were investigated by convenience sampling method using self-designed general information questionnaire,along with family care index(APGAR),24-item Stigma Scale for Chronic Illness(SSCI),and Psychosocial Adjustment Scale(PAS)for PD.And patients were divided into two groups according to the level of family care degree and compared with stigma and psychosocial adaptation.Results:The total score of family care for patients with PD was 6.97±2.46,family function was good in 132 cases(53.7%),moderate barrier in 92 cases(37.4%),and severe barrier in 22 cases(8.9%).The scores of stigma and psychosocial adaptability and their dimensions in the group with high degree family care were higher than the low degree group.Conclusions:The overall level of family care for PD patients was poor.Improving family care degree can help patients with PD to reduce stigma and improve psychosocial adaptation.

The role of DJ-1 complexes and catecholamine metabolism： relevance for familial and idiopathic Parkinson＇s disease

Autosomal recessive mutations in the PARK7 gene,which encodes for the protein DJ-1,result in a loss of function and are a cause of familial Parkinson’s disease（PD）,while increased wild-type DJ-1protein levels are associated with some forms of cancer.Several functions of DJ-1 have been described,with the greatest evidence indicating that DJ-1 is a redox-sensitive protein involved in the regulation of oxidative stress and cell survival.

A Family of Global Attractors for a Class of Generalized Kirchhoff-Beam Equations

The initial boundary value problem for a class of high-order Beam equations with quasilinear and strongly damped terms is studied. Firstly, the existence and uniqueness of the global solution of the equation are proved by prior estimation and Galerkin finite element method. Then the bounded absorption set is obtained by prior estimation, and the family of global attractors for the high-order Kirchhoff-Beam equation is obtained. The Frechet differentiability of the solution semigroup is proved after the linearization of the equation, and the decay of the volume element of the linearization problem is further proved. Finally, the Hausdorff dimension and Fractal dimension of the family of global attractors are proved to be finite.

苯氧乙酸类化合物对人谷胱甘肽-S-转移酶Mu抑制性能表征

目的 设计合成4个苯氧乙酸类化合物,通过不同方法表征其对人谷胱甘肽-S-转移酶Mu(glutathione-S-transferase Mu, GSTM)的抑制性能,考察苯氧乙酸类化合物与GSTM之间的构效关系。方法 设计合成含α,β-不饱和酮结构的4-丙烯酰苯氧乙酰乙胺(Ⅰa)、N,N’-(4-(丙烯酰基)苯氧乙酰基)丁二胺(Ⅱa)和不含α,β-不饱和酮结构的4-丙酰苯氧乙酰乙胺(Ⅰb)、N,N’-(4-(丙酰基)苯氧乙酰基)丁二胺(Ⅱb),利用初速度法表征4个化合物对GSTM的半抑制浓度(50%inhibiting concentration,IC)和表观抑制常数(inhibition constant,K),利用荧光光谱法表征4个化合物对GSTM的解离常数(dissociation constant,K)。结果 含α,β-不饱和酮结构的Ⅰa、Ⅱa可与谷胱甘肽(glutathione, GSH)发生亲电加成反应,与酶和GSH孵育原位生成产物后,其对GSTM的IC分别为(67±6)μmol/L、(0.10±0.02)μmol/L (n=2);不含α,β-不饱和酮结构的Ⅰb、Ⅱb对GSTM无明显抑制作用。Ⅰa相对GSH的K为(19.9±1.6)μmol/L,相对CDNB的K为(9.1±0.7)μmol/L (n=3);Ⅱa相对GSH的K为(0.063±0.005)μmol/L,相对CDNB的K为(0.079±0.006)μmol/L (n=3);可见Ⅱa较Ⅰa的K低(P<0.05)。荧光光谱法测得Ⅰa、Ⅰb、Ⅱa、Ⅱb的K分别为(41.5±1.8)μmol/L、(38.9±1.7)μmol/L、(18.0±0.9)μmol/L、(19.5±1.0)μmol (n=2);可见Ⅰa与Ⅰb、Ⅱa与Ⅱb之间的K无显著差异(P>0.05),而Ⅱa较Ⅰa、Ⅱb较Ⅰb的K低(P<0.05)。结论 α,β-不饱和酮结构是苯氧乙酸类化合物抑制作用的必须官能团;二价抑制剂Ⅱa、Ⅱb较单价抑制剂Ⅰa、Ⅰb对GSTM具有更高亲和力,Ⅱa的产物较Ⅰa的产物抑制作用更强。

Treatment of Crohn's disease and familial Mediterranean fever by leukopheresis:Single shot for two targets

Coexistence of Crohn's disease(CD) and familial Mediterranean fever(FMF) is a rare condition and knowledge about this clinical situation is limited with a few case reports in the literature. The treatment of both diseases depends on their individual therapies. However, it is very hard to deal with this coexistence when CD is refractory to standard therapies. Ongoing activity of CD triggers the clinical attacks of FMF and the symptoms like abdominal pain interfere with both disease presentations which can cause problems about diagnostic and therapeutic approach. The main therapeutic agent for FMF is colchicine and diarrhea is the most common side effect of this drug. This side effect also causes problems about management of these diseases when both of them are clinically active. Here we report probably the first case in the literature with coexisting CD and FMF who was successfully treated by leukopheresis since he was refractory to conventional therapies for CD.