Background Fungal keratitis has a high incidence in China and its clinical treatment is very difficult,and its etiology diagnosis and appraisal is the premise to improve the prognosis of disease.With the changes of regional environment and climate in recent years,whether the spectrum of fungal keratitis change in South China is remarkable.Objective The purpose of this study was to investigate recent pathogenic distribution of fungal keratitis in South China area.Methods The consecutive fungal culture resuhs of 3 350 purulent keratitis at Zhongshan Ophthalmic Center from January 2009 to December 2014 were retrospectively reviewed.The positive rate of fungal culture,genus or species distribution,seasonal distribution and different term distribution were analyzed.Results The culture-positive rate was 31.34％ in this study (1 050/3 350),and the average culture-positive number was 175 strains per year.In the positive fungus,the highest positive rate was Fusarium SP (32.10％,337/1 050),and followed by Aspergillus SP (25.71％,270/1 050),Heminthosporium SP (14.29 ％,150/1 050) and Mucor SP (9.14％,96/1 050).The fungal culture-positive rate was 36.05％ (367/1 018) in 2009 to 2010,32.45％ (324/1 014) in 2011 to 2012,and 26.86％ (354/1 318) in 2013 to 2014,respectively,with a significant difference among the three periods (x2 =22.37,P＜0.01),showing a decreasing tendency of incidence.Two hundreds and sixtyone strains were isolated from January to March (31.15 ％,261/838),182 strains from April to June (25.53 ％,182/713),237 strains from July to September (30.00％,237/790),370 strains from October to December (36.67％,370/1 009),showing a statistically significant difference among them (x2 =25.19,P ＜ 0.01).The number of infectious strains was most during October to December and fewest during April to June.Conclusions The leading pathogenic fungi of fungal keratitis is Fusarium SP and followed by Aspergillus SP,Helminthosporium SP,Mucor SP in turn.Fungal keratitis is usually prevalent from October to December,and its incidence is still rising in Chinese mainland recently.However,the increasing tendency in South China has been prevented in recent six years.

Objective To explore the association between the tag single nucleotide polymorphism (tag SNP) of the adenylyl cyclase 3 (ADCY3) and the essential hypertension (EH).Methods From April to July 2013,a total of 1 061 subjects diagnosed with EH and 1 218 control subjects were recruited from Ningbo,Zhejiang Province.Information was collected by face-to-face interview.Twelve tag SNPs were detected by ligase detection reaction technique.Results After adjusted for age,gender,body mass index and other related factors,logistic regression analysis showed that 3 loci (rs11689546,rs7593130,rs2241759) were associated with EH.AG genotype of rs11689546 was associated with 0.494 times lower risk of EH (OR =0.494,95％ CI0.246-0.993;compared with AA genotype).CT genotype of rs7593130 was associated with 1.596 times higher risk of EH (OR =1.596,95％ CI 1.009-2.524;compared with TT genotype),and CT/CC genotype of rs7593130 was associated with 1.627 times higher risk of EH (OR =1.627,95％ CI 1.034-2.559;compared with TT genotype).AG genotype of rs2241759 was associated with 0.669 times lower risk of EH (OR =0.669,95％ CI 0.503-0.891;compared with AA genotype),and CT/CC genotype of rs2241759 was associated with 0.687 times lower risk of EH (OR =0.687,95％ CI 0.518-0.911;compared with TT genotype).Conclusion The polymorphisms of ADCY3 are associated with lower (G allele of the rs11689546 locus and G allele of the rs2241759 locus) or higher (C allele of the rs7593130 locus) risk of essential hypertension.

Alzheimer's disease(AD)is a severe threat to human health and one of the three major causes of human death.Double-stranded RNA-dependent protein kinase(PKR)is an interferon-induced protein kinase involved in innate immunity.In the occurrence and development of AD,PKR is upregulated and continu-ously activated.On the one hand,the activation of PKR triggers an integrated stress response in brain cells.On the other hand,it indirectly upregulates the expression of 3-site amyloid precursor protein cleaving enzyme 1 and facilitates the accumulation of amyloid-β protein(Aβ),which could activate PKR activator to further activate PKR,thus forming a sustained accumulation cycle of Aβ.In addition,PKR can promote Tau phosphorylation,thereby reducing microtubule stability in nerve cells.Inflammation in brain tissue,neurotoxicity resulted from Aβaccumulation,and disruption of microtubule stability led to the progression of AD and the declines of memory and cognitive function.Therefore,PKR is a key molecule in the development and progression of AD.Effective PKR detection can aid in the diagnosis and prediction of AD progression and provide opportunities for clinical treat-ment.The inhibitors targeting PKR are expected to control the activity of PKR,thereby controlling the progression of AD.Therefore,PKR could be a target for the development of therapeutic drugs for AD.

Cognitive reserve referred to the cumulative flexibility of an individual's cognitive processes,whereas accurately assessing an individual's cognitive reserve and intervening was important for preventing the occurrence of cognitive dysfunction as well as promoting cognitive health.This article reviewed the main contents and applications of cognitive reserve assessment tools,and compared the characteristics and limitations of each assessment tool.The purpose was to provide ideas for the development of cognitive reserve assessment tools suitable for China's cultural background and population characteristics,and to provide a basis for accurately assessing the current status of China's cognitive reserve and formulating targeted cognitive reserve enhancement programs.

Objective:To establish a nucleic acid detection and genotyping method for Mycoplasma pneumoniae ( Mp) based on nucleic acid in clinical samples. Methods:Through genomic comparison, the specific target sequences of Genotype 1 and Genotype 2 Mp strains were selected to design synthetic primers and probes, and a PCR detection and classification method for Mp dual fluorescent probe was established, and the specificity, accuracy, detection limit and repeatability of the method were evaluated. The established fluorescence PCR method was used to detect the nucleic acid of clinical specimens and compared with the reported fluorescent PCR methods. Results:The nucleic acid of 18 pathogens, including other species of Mycoplasma and common respiratory bacteria and viruses, which were closely related to the Mp species, were detected, and the results showed that there was no cross-reactivity. The accuracy of detection and typing of 90 Mp nucleic acid was 100%. The detection limits of Genotype 1 and Genotype 2 Mp samples were 1.0 copy/μl, and the experimental coefficient of variation of repeatability within groups and between groups was less than 2.5%. In the detection of 88 nucleic acid of clinical specimens, the Kappa value was 0.675 and the P value was 0.267 compared with the reported real-time PCR method, showing a high degree of agreement. Conclusions:The method for detecting and genotyping Mp in this study has high sensitivity, specificity, and accuracy, which can be applied to the monitoring and prevention and control of Mp in the disease control system of provinces and cities at all levels in China. This method promotes the improvement of the Mp prevention and control system in China, strengthens the surveillance ability, and is of great significance for the early warning and prediction of Mp.

Intelligent responsive drug delivery system opens up new avenues for realizing safer and more effective combination immunotherapy. Herein, a kind of tumor cascade-targeted responsive liposome (NLG919@Lip-pep1) is developed by conjugating polypeptide inhibitor of PD-1 signal pathway (AUNP-12), which is also a targeted peptide that conjugated with liposome carrier through matrix metalloproteinase-2 (MMP-2) cleavable peptide (GPLGVRGD). This targeted liposome is prepared through a mature preparation process, and indoleamine-2,3-dioxygenase (IDO) inhibitor NLG919 was encapsulated into it. Moreover, mediated by the enhanced permeability and retention effect (EPR effect) and AUNP-12, NLG919@Lip-pep1 first targets the cells that highly express PD-L1 in tumor tissues. At the same time, the over-expressed MMP-2 in the tumor site triggers the dissociation of AUNP-12, thus realizing the precise block of PD-1 signal pathway, and restoring the activity of T cells. The exposure of secondary targeting module II VRGDC-NLG919@Lip mediated tumor cells targeting, and further relieved the immunosuppressive microenvironment. Overall, this study offers a potentially appealing paradigm of a high efficiency, low toxicity, and simple intelligent responsive drug delivery system for targeted drug delivery in breast cancer, which can effectively rescue and activate the body's anti-tumor immune response and furthermore achieve effective treatment of metastatic breast cancer.