Molecular mechanisms of melatonin-induced alleviation of synaptic dysfunction and neuroinflammation in Parkinson's disease: a review.

This review focuses on melatonin's role in advancing Parkinson's disease (PD) pathogenesis by inhibiting synaptic dysfunction and neuroinflammation. The early pathological changes in PD, caused by SNCA/PARK1 and LRRK2/PARK8-mediated synaptic vesicle endocytosis during the early pathogenesis of PD, are briefly reviewed. The pathological changes related to synaptic plasticity and dendrites caused by synaptic dysfunction in neurotoxin 6-hydroxydopamine (6-OHDA) and 1-methl-4-phenyl-1,2,3,6-tetrahydropyridin (MPTP)-induced PD models are also discussed. The molecular mechanisms of pathological changes in PD, caused by the activation of microglia, astrocytes, and inflammatory vesicles, are discussed. The effectiveness of melatonin (MLT) in the restoration of dopaminergic neurons in the substantia nigra (SNc) has been established. MLT can upregulate dendritic numbers and restore synaptic plasticity by inhibiting alpha-synuclein aggregation and neurotoxicity. These functions of MLT improve sleep patterns in PD patients and suppresses synaptic dysfunction by inhibiting the overactivation of the PKA/CREB/BDNF signaling pathway and reactive oxygen species (ROS) production. MLT can maintain the typical transport and release of neurotransmitters. MLT also reduces neuroinflammation by promoting microglia 2 (M2) polarization, which reduces the expression of inflammatory cytokines. Additionally, MLT stimulates the activation of the retinoic acid receptor-related orphan receptor α (RORα) ligand and inhibits the activation of the Recombinant Sirtuin 1 (SIRT1)-dependent pathway, the NLR family pyridine structure domain 3 (NLRP3) inflammasome. By integrating the latest advances in synaptic dysfunction and neuroinflammation-related PD, researchers can develop clinical interventions for treating PD and further explore the pathological hallmarks of prodromal PD.

Effects of physical fitness training on metabolic syndrome among military personnel in Taiwan.

INTRODUCTION: Metabolic syndrome (MS) is strongly associated with cardiovascular diseases and diabetes but can be prevented with regular physical activity. This study aimed to assess the impact of a physical fitness training programme on MS among military personnel. METHODS: This retrospective observational study included volunteer army soldiers who underwent annual health examinations between 2011 and 2014. In 2011, the reformed physical fitness training programme and physical fitness test were introduced to the participants. MS evaluation and physical fitness performances were evaluated before and after implementing the training programme using a mixed-effects model and generalised estimating equation, adjusted for sex, age and smoking. RESULTS: From 2011 to 2014, 1720 soldiers underwent the annual health examination. In 2011, before the fitness programme, 246 soldiers (14.3%) had MS. After implementation, decreases in blood pressure and fasting glucose levels were observed and maintained for 3 years. Running performance was negatively correlated to triglycerides (ß=-11.37; p<0.001) and waist circumference (ß=-0.42; p<0.001) and positively correlated to high-density lipoprotein cholesterol levels (ß=2.14; p<0.001). The severity of MS was reduced following introduction of the physical fitness programme. CONCLUSIONS: MS and its components improved after introducing the reformed fitness programme, with running performance proving to be most relevant to MS. Clinicians should encourage increased physical activity to prevent MS among military personnel.

Clinical and genetic characteristics of familial hypercholesterolemia patients with type 2 diabetes.

PURPOSE: Though type 2 diabetes mellitus (T2DM) is an important and independent risk factor for coronary artery disease (CAD) in the general population, the impact of T2DM on CAD in patients with familial hypercholesterolemia (FH) is less understood. Thus, the current study aimed to examine the features of FH patients with T2DM and explore the effects of T2DM on CAD in FH. METHODS: A total of 289 clinical heterozygous FH (HeFH) patients diagnosed with Dutch Lipid Clinic Criteria were consecutively recruited and divided into a T2DM group (n = 58) and non-T2DM group (n = 231). Clinical characteristics and laboratory findings were compared between the two groups. Target exome sequencing was used for gene mutation analysis. RESULTS: HeFH patients with T2DM had significantly higher levels of triglycerides, body mass index and free fatty acids than did non-T2DM patients; moreover, patients with T2DM more frequently exhibited hypertension. However, the spectrum of FH-causing mutations was not significantly different (p = 0.061). Notably, patients with T2DM had higher prevalence of CAD (p = 0.012) and higher Gensini Score (p = 0.002). The regression analysis confirmed that HbA1c was an independent risk factor for both the presence and severity of CAD [OR 2.321 (1.098-4.904), p = 0.027; OR 1.349 (1.032-1.762), p = 0.028, respectively] in patients with HeFH. CONCLUSIONS: Although there were not many differences in the clinical, lipid and genetic aspects of HeFH patients with and without T2DM, T2DM and HbA1c were associated with worse coronary lesions, suggesting that diabetes and the degree of blood glucose control are also important determinants of cardiovascular disease in these patients.

Elevated lipoprotein (a) levels are associated with the presence and severity of coronary artery disease in patients with type 2 diabetes mellitus.

BACKGROUND AND AIMS: The role of lipoprotein (a) [Lp(a)] in coronary artery diseases (CAD) with special clinical background such as type 2 diabetes mellitus (T2DM) has not been fully determined. The aim of the present study was to investigate the relation of Lp(a) to type 2 diabetic patients with or without CAD. METHODS AND RESULTS: A total of 2040 consecutive patients with T2DM who received selective coronary angiography (CAG) due to angina-like chest pain were enrolled. The patients were subsequently divided into CAD and non-CAD groups according to the results of CAG. The severity of CAD was evaluated by the Gensini Score (GS), number of stenotic vessels, and history of myocardial infarction (MI). Data showed that Lp(a) levels were higher in the CAD group than in the non-CAD group (median: 15.00 mg/dL vs. 11.88 mg/dL, P = 0.025). The results from CAD subgroup analysis indicated that the patients with MI, multiple-vessel disease and high GS had higher Lp(a) levels compared with those in their matched subgroups (P < 0.05, respectively). After adjustment for confounders, Lp(a) levels were independently related to the presence and severity of CAD (CAD:OR = 1.564; MI:OR = 1.523; high GS:OR = 1.388; multiple-vessel disease:OR = 1.455; P < 0.05, respectively). CONCLUSION: Elevated Lp(a) levels were independently associated with the presence and severity of CAD in patients with T2DM. More studies are necessary to confirm our findings.

Efficacy and safety of sublingual immunotherapy with Dermatophagoides farinae drops in pre-school and school-age children with allergic rhinitis

Background: The safety and efficacy of sublingual immunotherapy (SLIT) have been confirmed by many studies. However, in China, the research on efficacy and safety in young and older children with allergic rhinitis (AR) is still rare. Objective: The aim of this retrospective study is to evaluate the efficacy and safety of SLIT with Dermatophagoides farinae drops in pre-school and school-age children with AR. Methods: A total of 282 subjects aged 2-13 years with AR received a two-year course of sublingual immunotherapy along with pharmacotherapy. According to the age, patients were defined as the pre-school group (2-6 years old, n = 116) and school-age group (7-13 years old, n = 166). Total nasal rhinitis symptom scores (TNSS), visual analogue score (VAS) and total medication scores (TMS) were evaluated at four time points: baseline, after SLIT for half a year, one year and two years. The adverse events (AEs) were evaluated at each visit. Results: After two-year SLIT, the four rhinitis symptom scores, TNSS, VAS and TMS scores were significantly lower than baseline (all P < 0.05). The comparison of efficacy between one and two-year duration showed no significant difference in global clinical outcomes (all P > 0.05). In addition, there were no significant differences between the pre-school and school-age group in TNSS (all P > 0.05), VAS (all P > 0.05) and TMS scores (P > 0.05) after SLIT for half a year, one year and two years. No severe systemic AEs were reported. Conclusion: SLIT with D. farinae drops is clinically effective and safe in pre-school and school-age patients with house dust mites (HDMs)-induced AR (AU)

No disponible

Efficacy and safety of sublingual immunotherapy with Dermatophagoides farinae drops in pre-school and school-age children with allergic rhinitis.

BACKGROUND: The safety and efficacy of sublingual immunotherapy (SLIT) have been confirmed by many studies. However, in China, the research on efficacy and safety in young and older children with allergic rhinitis (AR) is still rare. OBJECTIVE: The aim of this retrospective study is to evaluate the efficacy and safety of SLIT with Dermatophagoides farinae drops in pre-school and school-age children with AR. METHODS: A total of 282 subjects aged 2-13 years with AR received a two-year course of sublingual immunotherapy along with pharmacotherapy. According to the age, patients were defined as the pre-school group (2-6 years old, n=116) and school-age group (7-13 years old, n=166). Total nasal rhinitis symptom scores (TNSS), visual analogue score (VAS) and total medication scores (TMS) were evaluated at four time points: baseline, after SLIT for half a year, one year and two years. The adverse events (AEs) were evaluated at each visit. RESULTS: After two-year SLIT, the four rhinitis symptom scores, TNSS, VAS and TMS scores were significantly lower than baseline (all P<0.05). The comparison of efficacy between one and two-year duration showed no significant difference in global clinical outcomes (all P>0.05). In addition, there were no significant differences between the pre-school and school-age group in TNSS (all P>0.05), VAS (all P>0.05) and TMS scores (P>0.05) after SLIT for half a year, one year and two years. No severe systemic AEs were reported. CONCLUSION: SLIT with D. farinae drops is clinically effective and safe in pre-school and school-age patients with house dust mites (HDMs)-induced AR.

Analysis of the association between plasma PCSK9 and Lp(a) in Han Chinese.

PURPOSE: It has been reported that proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors can significantly reduce lipoprotein(a) [Lp(a)], and the mechanism for Lp(a) reduction remains unclear. Recently an interesting clinical research with a small sample showed a positive correlation between plasma PCSK9 and Lp(a) levels in diabetes. Here we aimed to use a relatively large sample to investigate whether such an association exists in Han Chinese. METHODS: A total of 783 inpatients were consecutively enrolled and composed of 172 patients with type 2 diabetes mellitus (T2DM) and 611 non-T2DM subjects. Plasma PCSK9 level was measured by ELISA, and its association with Lp(a) was assayed by Spearman's correlation and multiple regression. Clinical and biochemical parameters were determined in all subjects studied. RESULTS: No significant differences in PCSK9 and Lp(a) levels were found between T2DM and non-T2DM patients. PCSK9 level was not related to Lp(a) level either in T2DM or non-T2DM group in bivariate correlation and multiple linear regression analysis. Additionally, no association between the levels of PCSK9 and Lp(a) was found in well, poorly controlled T2DM patients or in T2DM patients with or without coronary artery disease (CAD). Besides, no difference was found among the PCSK9 values across tertiles of Lp(a) level. CONCLUSION: We found no association of plasma PCSK9 levels with Lp(a) level in Han Chinese with or without T2DM, suggesting that Lp(a) reduction by PCSK9 inhibitors may not be achieved simply through PCSK9 pathway at least in Chinese.

Association of plasma small dense LDL cholesterol with PCSK9 levels in patients with angiographically proven coronary artery disease.

BACKGROUND AND AIMS: Proprotein convertase subtilisin-kexin type 9 (PCSK9) is a novel regulator of low-density lipoprotein (LDL) metabolism. Recently, small dense LDL (sdLDL) particles have been suggested to be a very atherogenic subspecies of LDL. To date, the association of sdLDL with PCSK9 is still unclear. The aim of the present study is to determine the association of sdLDL, as assayed by sdLDL-cholesterol (sdLDL-C), with PCSK9 in a cohort of subjects undergoing coronary angiography. METHODS AND RESULTS: Four hundred and ninety consecutive subjects were enrolled and classified into stable coronary artery disease (CAD) and non-CAD group. LDL separation was performed by Lipoprint System: 7 LDL subfractions were obtained and LDL score (% sdLDL) was calculated. The plasma PCSK9 levels were measured by ELISA. The data indicated that PCSK9 levels were significantly increased by sdLDL-C quartiles (p = 0.028). In age- and sex-adjusted analysis plasma sdLDL-C was positively correlated with PCSK9 levels (r = 0.157, p < 0.01). To rule out the confounding effect of dyslipidemia, we performed the analysis in subjects with and without dyslipidemia separately. Interestingly, the positive correlation of sdLDL-C with PCSK9 was only significant in patients with dyslipidemia and stable CAD (r = 0.177, p < 0.01). In a model adjusting for traditional risk factors including dyslipidemia, PCSK9 was an independent predictor of high sdLDL-C in CAD group (OR = 12.919, 95% CI 1.427-116.952) but not in non-CAD group. CONCLUSION: This study firstly demonstrated that plasma sdLDL-C was positively related to PCSK9 in patients with stable CAD, suggesting an interaction between sdLDL-C and PCSK9 in atherosclerotic coronary disease.

Bacterial vaginosis is conducive to the persistence of HPV infection.

We investigated the effects of bacterial vaginosis (BV) on the outcomes of high-risk human papillomavirus infection (HR-HPV). BV was diagnosed on Papanicolaou-stained cytology slides of 707 HPV-positive patients. HR-HPV DNA expression was analysed using the Hybrid Capture II (HC-II) assay. Of the 707 HR-HPV-positive female patients, 298 (42.1%) exhibited clearance of HR-HPV. The remaining 409 patients had persistent HR-HPV infection. The persistent HR-HPV group and the clearing group had similar rates of BV at the beginning of the study. At the end of the study, the persistent HR-HPV group had a BV prevalence of 11.2% while the clearing group had a significant lower BV prevalence of 5.0%. A decreased clearance of HPV was found in women with current BV, compared with women without BV. Furthermore, the natural history of HPV was not affected by the HPV viral load or the BV prevalence at the beginning of the study (P > 0.05). Bacterial vaginosis appears conducive to the persistence of HPV infection.

Optimization of Pulse Sequences for Lactate Detection and Its Diagnostic Value in Acute Cerebral Infarction Using (1)H MR Spectroscopy.

Cerebral infarction will cause ischemic encephalopathy and lactate accumulation in the brain in acute cerebral infarction. This study investigated the optimization of pulse sequences for lactate detection and its diagnostic value in acute cerebral infarction using proton MR spectroscopy ((1)H MRS). The studies were performed on a phantom and on 17 patients with acute cerebral infarction. Examinations were performed with a GE 1.5T MRI system (Signa). The spectra were obtained using both PRESS and STEAM sequences. The spectra were processed using a GE Advantage workstation (ADW 4.3). Moreover, the optimal sequence combined with other sequences, including conventional MRI sequences and MR DWI, were used to acquire proton MRI data for 17 patients with acute cerebral infarction and 20 healthy volunteers. The maximum lactate peaks using TE=135 ms were down doublet whereas the peaks using 270 ms were up doublet. Lactate peaks were ascending in 17 patients with cerebral infarction. Optimized (1)H MRS sequences are useful for better detection of lactate in acute cerebral infarction.

Genotyping and drug resistance patterns of Mycobacterium tuberculosis strains in five provinces of China.

OBJECTIVE: To evaluate the distribution of the Mycobacterium tuberculosis Beijing genotype and the association of the genotype with drug-resistant M. tuberculosis strains in five provinces in China. DESIGN: M. tuberculosis strains (n = 158) isolated from five provinces of China were subjected to insertion sequence 6110 restriction fragment length polymorphism (RFLP), spoligotyping and mycobacterial interspersed repetitive units (MIRU) analyses. The prevalence of the Beijing genotype strains in each province was determined and compared. The proportion method was used to test the drug susceptibility of all strains. RESULT: Of the 158 strains, 123 (77.8%) were identified as the Beijing genotype by RFLP and spoligotyping. Nearly all the strains (n = 152, 96.2%) were grouped into 14 shared spoligotypes. Six other spoligotypes were unique to China. The prevalence of the Beijing genotype was significantly higher in the interior than in coastal areas (P < 0.001, OR 5.4, 95%CI 2.3-12.7). Resistance to rifampicin (RMP) was associated with the Beijing strain (P = 0.05, OR 3.7, 95%CI 1.2-11.1). CONCLUSION: The M. tuberculosis Beijing genotype varies in prevalence in different regions of China and is solely associated with RMP resistance.

First Report of Crown Rot of Grafted Cucumber Caused by Fusarium solani in China.

Grafting has been widely and effectively used in cucumber (Cucumis sativus) cultivation for approximately 30 years in China to avoid Fusarium wilt caused by Fusarium oxysporum Schl. f. sp. cucumerinum Owen. In greenhouses, 90% of cucumbers are grafted onto pumpkin (Cucurbita moschata) rootstock. However, in March 2009, a severe crown rot causing yellowing and wilting of the leaves was observed on grafted cucumber in a large number of greenhouses in Lingyuan, western Liaoning Province in China. Symptoms consisted of dark brown, water-soaked lesions and a dense, white mycelial mat at the base of the stem. Lingyuan is the largest district for cucumber cultivation using grafting techniques in solar greenhouses in China. In 30 surveyed greenhouses in Sanshijiazi Village in the city of Lingyuan, the incidence of affected plants ranged from 10 to 40%, which caused serious economic losses. Fusarium spp. were isolated from the surface-sterilized basal stems of symptomatic plants on potato dextrose agar and incubated on potato sucrose agar for 4 days at 25°C. Colonies of the isolates produced a brown pigmentation and sparse, aerial mycelia, with a cream color on the underside. Conidiophores were elongated and branched or unbranched. Microconidia were abundant, hyaline, ellipsoid to ovoid, and 6 to 14 × 2.5 to 3.5 µm. Macroconidia were cylindrical, abundant, mostly two to six septate, 22 to 63 × 3.2 to 5.0 µm, with the apical cell rounded and blunt, and the basal cell rounded. On the basis of morphological characteristics, the fungus was identified as F. solani (C. Booth). For confirmation, the internal transcribed spacer region of rDNA was amplified and sequenced. A 449-bp sequence shared 99% homology with that of a F. solani GenBank accession previously reported from Japan (No. AF150473.1). The new sequence was deposited in GenBank (Accession No. HM015882). Pathogenicity of three isolates was determined in two experiments using different methods of inoculation. In one, 30 seedlings of pumpkin (C. moschata) with one true leaf each were inoculated by dipping their roots in a suspension of 106 spores ml-1, while control plants were mock inoculated with sterile water. Plants were then potted in a sterile mix of peat moss and vermiculite (2:1 vol/vol). In the other, pregerminated pumpkin seeds were sown in the same medium with a conidial suspension added at a rate of 106 spores ml-1, while other seeds were sown in sterile soil as controls. Plants for both experiments were maintained in a greenhouse at 25°C. Twelve days after inoculation, inoculated plants in both experiments showed a cortical rot on the crown and stem base with a brown, water-soaked appearance. Twenty-one days later, inoculated plants developed wilting and yellowed leaves. Disease incidence was 100%. No symptoms occurred on the control plants. Both experiments were repeated once with the same results. The pathogen was recovered from symptomatic tissue, confirming Koch's postulates. F. solani has been previously reported to cause root rot on cucurbit in California (2) and crown rot on grafted cucumber in the Netherlands (1). To our knowledge, this is the first report of crown rot of grafted cucumber caused by F. solani in China. References: (1) L. C. P. Kerling and L. Bravenboer. Neth. J. Plant Pathol. 73:15, 1967. (2) T. A. Tousson and W. C. Snyder. Phytopathology 51:17, 1961.

Predicting risk for early infantile atopic dermatitis by hereditary and environmental factors.

BACKGROUND: Hereditary and environmental factors contribute to the occurrence of atopic dermatitis (AD). However, the interaction of these two factors is not totally understood. OBJECTIVES: To evaluate the early risk factors for infantile AD at the age of 6 months and to develop a predictive model for the development of AD. METHODS: In 2005, a representative sample of mother and newborn pairs was obtained by multistage, stratified systematic sampling from the Taiwan national birth register. Information on hereditary and environmental risk factors was collected by home interview when babies were 6 months old. Multivariate regression analysis was applied to determine the risk factors for AD in the infants. RESULTS: A total of 20 687 pairs completed the study satisfactorily. AD was diagnosed in 7.0% of 6-month-old infants by physicians. Parental asthma, atopic dermatitis and allergic rhinitis, and maternal education levels were risk factors for AD in infants. Among environmental factors, fungus on walls at home and renovation/painting in the house during pregnancy were significantly associated with early infantile AD. Using these factors, the probability of having infantile AD was estimated and grouped into low, high and very high. With five runs of tests in mutually exclusive subsets of this population, the likelihood of AD for 6-month-old infants was consistent in all the groups with the predictive model. The highest predicted probability of AD was 70.1%, among boys with maternal education levels > 12 years, both parents with AD, renovation and painting of the house during pregnancy and fungus on walls at home. The lowest probability was 3.1%, among girls with none of the above factors. CONCLUSIONS: This investigation provides a technique for predicting the risk of infantile AD based on hereditary and environmental factors, which could be used for developing a preventive strategy against AD, especially among those children with a family history of atopy.

Choroid plexus papillary carcinoma associated with hemorrhage. A case report.

Choroid plexus papillary carcinoma is a rare intracranial malignant epithelial tumor. We describe a case of choroid plexus tumor arising in the periventricular parenchyma. A 52-year-old man presented with headache for five months, aggravated by vomiting for three days. Brain computed tomography scan revealed an inhomogeneous density lesion in the right temporoparietal lobe with mild enhancement, and hemorrhage anterior to the lesion. Histological and immunohistochemical findings indicated a choroid plexus papillary carcinoma.

Two faces of high-molecular-weight kininogen (HK) in angiogenesis: bradykinin turns it on and cleaved HK (HKa) turns it off.

High-molecular-weight kininogen (HK) is a plasma protein that possesses multiple physiological functions. Originally identified as a precursor of bradykinin, a bioactive peptide that regulates many cardiovascular processes, it is now recognized that HK plays important roles in fibrinolysis, thrombosis, and inflammation. HK binds to endothelial cells where it can be cleaved by plasma kallikrein to release bradykinin (BK). The remaining portion of the molecule, cleaved HK, is designated cleaved high-molecular-weight kininogen or HKa. While BK has been intensively studied, the physiological implication of the generation of HKa is not clear. Recent studies have revealed that HKa inhibits angiogenesis while BK promotes angiogenesis. These findings represent novel functions of the kallikrein-kinin system that have not yet been fully appreciated. In this review, we will briefly discuss the recent progress in the studies of the molecular mechanisms that mediate the antiangiogenic effect of HKa and the proangiogenic activity of BK.

Thin sectional anatomy, three-dimensional reconstruction and visualization of the heart from the Chinese Visible Human.

The research aimed to provide sectional anatomic and three-dimensional (3D) virtual anatomic bases for imaging diagnosis and surgical operation by the use of data from the heart of the first Chinese digitized Visible Human. Data from the series of thin sections of the heart were analyzed and input into an SGI workstation, and 3D reconstruction and virtualization of the heart were performed. Each image of sectional anatomy was clear and the 3D structures of the heart were reconstructed in their entirety. All reconstructed structures can be displayed by multiple structural and color modes, individually or jointly, and can be rotated continuously in any plane. The model of the virtual heart clearly showed fine structures of the heart in random orientation. The dataset of the sectional anatomy provides a fine and integrated morphologic base for imaging diagnosis. The 3D reconstructed images clearly show the internal and entire structures of the heart.

Polymorphisms in GSTT1 and p53 and urinary transitional cell carcinoma in south-western Taiwan: a preliminary study.

Little is known about the relevance of genetic polymorphisms to arsenic-related bladder cancer. A preliminary case-control study was conducted to explore the association between genetic polymorphisms of GSTT1, p53 codon 72 and bladder cancer in southern Taiwan, a former high arsenic exposure area. Fifty-nine urinary transitional cell carcinoma (TCC) patients from a referral centre in south-western Taiwan and 81 community controls matched on residence were recruited from 1996 to 1999. A questionnaire was administered to obtain arsenic exposure and general health information. Genotypes of p53 codon 72 and GSTT1 were analysed by polymerase chain reaction-restriction fragment length polymerase. The combined variant genotypes (heterozygous or homozygous variant) of p53 codon 72 and GSTT1 null were observed in 29% of cases and in 44% of controls, respectively. In this preliminary study, bladder cancer risk was slightly elevated for subjects carrying the variant genotype of p53 codon 72 or in subjects carrying the GSTT1 null genotype. Variants in p53 codon 72 increased the risk of bladder cancer among smokers. However, the results were not statistically significant and larger confirmatory studies are needed to clarify the role of candidate gene polymorphisms and bladder cancer risk in arsenic exposed populations.