Objective:To evaluate the potential causal relationship between tinnitus and the risk of Alzheimer's disease(AD)onset using the two-sample Mendelian randomization(MR)method and to clarify its mechanism of action,so as to provide new ideas for early warning of AD.Methods:Genome-wide association study(GWAS)database was used to search the keywords"tinnitus"and"Alzheimer"to obtain the related datasets of exposure factor tinnitus and outcome AD;the tinnitus datasets included ukb-d-4803_11,ukb-d-4803_12,ukb-d-4803_13,ukb-b-14254 and ukb-a-384;the AD datasets included ieu-b-5067,ieu-b-2,ieu-a-297,ebi-a-GCST90027158 and ebi-a-GCST002245.The single nucleotide polymorphisms(SNPs)closely and independently associated with tinnitus were screened as instrumental variables(IVs),and the SNPs associated with AD were used as outcomes.Inverse variance weighted(IVW)method was used to conduct MR analysis to evaluate its odds ratio(OR)value,95%confidence interval(CI)and P value;P<0.05 indicated significant causal relationship.Sensitivity detection used Cochran's Q test to detect the heterogeneity of IVs to evaluate its Q value,df value and P value;when IVW method P>0.05,it indicated no significant heterogeneity;MR-Egger intercept was used to detect horizontal pleiotropy;when the intercept was 0 or close to 0 and P>0.05,it indicated no significant horizontal pleiotropy;meanwhile,leave-one-out method was used for sensitivity analysis.Finally,visualization results were performed using forest plot,scatter plot,funnel plot and leave-one-out plot.Results:A total of 286 SNPs were screened as IVs.All instrumental variables satisfied F>10,suggesting no weak instrumental variable;after screening by PhenoScanner web tool,all SNPs were unrelated to confounding factors.When the tinnitus and AD datasets were ukb-d-4803 and ebi-a-GCST90027158 respectively,there was a significant positive correlation between tinnitus and the risk of AD onset(IVW:OR=1.842,95%CI:1.065-3.188,P=0.029);Cochran's Q test suggested no significant heterogeneity of IVs(Q=9.788,df=10.000,P=0.459);MR-Egger intercept indicated no horizontal pleiotropy(Egger intercept=-0.006,P=0.147);leave-one-out method showed stable results,and no SNP with significant influence on the results was detected.Conclusion:There is a positive causal relationship between tinnitus and the risk of AD onset.Neuroinflammation accompanied by persistent microglial activation to varying degrees may be the common pathogenesis of tinnitus and AD;in addition,depression may also act as an upstream factor to hyperactivate the hypothalamic-pituitary-adrenal(HPA)axis,leading to the progression of relationship between tinnitus and AD.

This paper explores the traditional Chinese medicine （TCM） pathomechanism， as well as pattern differentiation and treatments for sundowning syndrome in Alzheimer's disease through midnight-noon and ebb-flow theory. The syndrome's onset aligns with three critical time periods governed by three specific channels， including the bladder channel （3：00—5：00 pm， Shen period）， the kidney channel （5：00—7：00 pm， You period）， and the pericardium channel （7：00—9：00 pm， Xu period）. It is believed that when the symptoms occurred at the bladder channel （Shen period）， the pathomechanism manifested as yang qi floating upward and internal heat-blood stasis， and the treatment should supplement the kidney and essence， expelling stasis and discharging heat， as well as returning fire to its origin， using modified Taohe Chengqi Decoction （桃核承气汤） combined with Erzhi Pill （二至丸）. When the symptoms occurred at the kidney channel （You period）， the pathomechanism characterized by marrow sea deficiency and yin failing to anchor yang， so treatment follows the principles of supplementing the kidney and filling essence， as well as calming the mind and subduing yang， using modified Liuwei Dihuang Pill （六味地黄丸） combined with Erzhi Pill （二至丸）. When the symptoms occurred at the pericardium channel （Xu period）， the pathomechanism characterized as phlegm-turbidity clouding the mind and obstructing the brain， then the intervention need clear heat and dissolve phlegm， as well as open the orifices and calm the mind， using modified Wendan Decoction （温胆汤）. Additionally， comprehensive therapy combining oral administration of TCM decoctions with acupuncture， pressure pills on ear points， and point application therapy， which provides clinical insights for the treatment of this disease.

This article reviewed the concept, current status influencing factors and interventions of burden among family caregivers of chronic critical illness survivors, aiming to provide theoretical basis and practical guidance for the research on the burden of family caregivers of chronic critical illness survivors, effectively reduce the burden of family caregivers of chronic critical illness survivors, promote the recovery of chronic critical illness survivors, and improve the quality of life.

This article reviewed the concept, current status influencing factors and interventions of burden among family caregivers of chronic critical illness survivors, aiming to provide theoretical basis and practical guidance for the research on the burden of family caregivers of chronic critical illness survivors, effectively reduce the burden of family caregivers of chronic critical illness survivors, promote the recovery of chronic critical illness survivors, and improve the quality of life.

GGGGCC repeat expansions in the C9ORF72 gene are the most common cause of amyotrophic lateral sclerosis and frontotemporal dementia (c9ALS/FTD). It has been reported that hexanucleotide repeat expansions in C9ORF72 produce five dipeptide repeat (DPR) proteins by an unconventional repeat-associated non-ATG (RAN) translation. Within the five DPR proteins, poly-PR and poly-GR that contain arginine are more toxic than the other DPRs (poly-GA, poly-GP, and poly-PA). Here, we demonstrated that poly-PR peptides transferred into cells by endocytosis in a clathrin-dependent manner, leading to endoplasmic reticulum stress and cell death. In SH-SY5Y cells and primary cortical neurons, poly-PR activated JUN amino-terminal kinase (JNK) and increased the levels of p53 and Bax. The uptake of poly-PR peptides by cells was significantly inhibited by knockdown of clathrin or by chlorpromazine, an inhibitor that blocks clathrin-mediated endocytosis. Inhibition of clathrin-dependent endocytosis by chlorpromazine significantly blocked the transfer of poly-PR peptides into cells, and attenuated poly-PR-induced JNK activation and cell death. Our data revealed that the uptake of poly-PR undergoes clathrin-dependent endocytosis and blockade of this process prevents the toxic effects of synthetic poly-PR peptides.

Objective To explore the application of olfactory assessment and substantia nigra ultrasonography in early diagnosis of Parkinson's disease (PD).Methods Thirty PD patients,admitted to our hospital from March 2015 to March 2017,were served as PD group and 30 healthy subjects were served as control group.Olfactory assessment tool Sniffm Sticks-1 6 and substantia nigra ultrasonography were performed;the sensitivity,specificity and positive predictive value of olfactory assessment,transcranial ultrasonography,and combined measurement for diagnosis of PD were calculated,respectively.Correlations of results of olfactory assessment,transcranial ultrasonography with age,gender,course of disease,and Unified Parkinson's Disease Rating Scale Ⅲ (UPDRS Ⅲ) scores were analyzed.Results There were 25 PD patients with olfactory test (SS-16) scores≤ 10 and 22 control subjects;the olfactory test (SS-16) scores in PD patients were 7.83±2.23,which were significantly lower as compared with those in control subjects (12.03±1.96,P＜0.05);the incidence of olfactory dysfunction in PD group was 83.33％ and that in control group was 26.67％,with statistical significance (P＜0.05).There were 23 PD patients with area of substantia nigra hyperecho≥ 0.20 cm2 and 26 control subjects;area of substantia nigra hyperecho was (0.22±0.06) cm2 in PD group,which was signfciantly increased as compared with control group ([0.11 ±0.07] cm2,P＜0.05);the incidence of pathological substantia nigra hyperecho in PD group was 76.67％ and that in control group was 13.33％,with significant difference (P＜0.05).The sensitivity of olfactory assessment,transcranial ultrasonography,and combined measurement for diagnosis of PD was 83.33％,76.67％,86.67％,indicating that combined measurement had significantly higher sensitivity that the other two method (P＜0.05).SS-16 scores and area of substantia nigra hyperecho were unrelated with gender,age,duration and UPDRS Ⅲ scores (P＞0.05).Conclusion Combination of olfactory test and substantia nigra hyperecho can improve the diagnosis sensitivity of PD.

Objective To investigate the demands and problems of the sharing and construc-tion of teaching resources in medical universities. Method A self-designed questionnaire named The questionnaire of the present situation and demand of teaching resources sharing platforms in medical universities in China was used to conducted in all the attainders during a national teaching resources meeting, and SPSS 17.0 was used to analyze the data. Results Among 125 valid questionnaires, 117 people (93.6%) think it's necessary to establish the resources sharing platform, what's more 108 people (86.4%) believe that education resources sharing platform is very helpful for teaching, and multimedia materials, online courses, course wares, teaching cases, website of subject resources and other educa-tion resources should be widely shared. Our investigation has involved 48 medical universities from all over the country, in which 33 medical universities have teaching resources sharing platform. However, 20 (60.6%) of the universities have still not updated the content on time. There are 10 main factors which influence the using of the education resource sharing platform, in which 105 (84%) of them have con-sidered the factor as backward concepts, 91 (72.8%) think that there exist problems in resource con-struction mechanism, 76 (60.8%) think to be the standardized and universal problems. Conclusion It is necessary to build the education resource sharing platform. In all, we should change the traditional education concept and consciousness, strengthen mechanism of management, and exploit high quality education resource to improve the sharing level of education resource in medical universities.

This review presents the most recent chemical and biological investigations on one of the marine invertebrates, gorgonian octocoral. It summarizes all 432 new compounds published in 2002-2009, which consists of 46 sesquiterpenoids (including 2 new natural products, NNP), 282 diterpenoids (including 4 from Pennatulacea octocoral and one artifact), 76 steroids, and 29 alkaloids or other types (2 NNP included). In this paper, according to the structure division, the new compounds are described in combination with the taxonomy of the investigated animals, and its simultaneous bioactivity results. Novel skeletons and complex structures are paid most emphasis on its features, means of structural elucidation and the proposed biogenesis pathway. The source of all new compounds and the different diterpenoid skeleton types are all listed and analyzed, as well as the commonly used Chinese names or some proposed ones for diterpenoid skeletons. Furthermore, this papers deals with all biological test toward the gorgonian new metabolites, i.e. anti-cancer, anti-inflammatory, anti-bacterial(against Staphylococcus aureus bacteria, Mycobacterium tuberculosis etc), anti-malaria, and anti-fouling as well, in which anti-cancer activity and cytotoxicity were additionally, a discussion and prospect are proposed regarding chemical overview on gorgonian. This review, hopefully, can be useful in proving data and references for further chemical and biological research of China sea gorgonian, for the studies on chemical ecology, and for the discovery of new and bioactive compounds or the marine-derived leading targets.
Alkaloids ; analysis ; Animals ; Anthozoa ; chemistry ; physiology ; Diterpenes ; analysis ; Sesquiterpenes ; analysis ; Steroids ; analysis