[Frequency of bowel movements and risk of Parkinson's disease: a prospective cohort study in adults in China].

Objective: To evaluate the association between the frequency of bowel movement (BMF) and the risk of Parkinson's disease (PD). Methods: In this study, 510 134 participants from the China Kadoorie Biobank (CKB) were included after excluding those who reported to had been diagnosed with cancer at baseline survey. The baseline survey was conducted from 2004 to 2008. The study used the data from the baseline survey and follow-up until December 31, 2016. Cox proportional hazards regression models were used to estimate the HRs and the 95%CIs of risk of PD diagnosis with BMF. Results: During an average follow-up period of (9.9±1.9) years, 808 participants were diagnosed with PD. Compared with participants who had bowel movements every day, the multivariable-adjusted HR (95%CI) for those who had bowel movements<3 times/week, once every 2-3 days, and>1 time/day were 3.62 (2.88-4.54), 2.13 (1.74-2.60), and 0.81 (0.63-1.05), respectively. The linear trend test results of the association between BMF and risk of PD diagnosis was significant (P<0.001). Compared with the participants who had bowel movements ≥1 time/day, the multivariable-adjusted HR (95%CI) for those who had bowel movements<1 time/day was 3.13 (2.32-4.23) within the 5 years of follow- up and was 2.48 (2.05-3.01) beyond the 5 years of follow-up. The gender specific results were similar. The association of BMF<1 time/day with risk of PD diagnosis was stronger in older participants. Conclusions: The participants with low BMF at baseline survey would have higher risk for PD diagnosis in the subsequent 10 years on average. Since abnormal decrease of BMF is easy to be found, programs could be set up for the early screening of PD in older people, along with other early symptoms of PD.

[Clinical diagnosis and treatment of eosinophilic otitis media].

Objective: Eosinophilic otitis media(EOM) is a rare,refractory otitis media.This article summarizes the clinical manifestations and diagnosis and treatment experience of EOM. Method: Retrospective analysis of 3 cases of EOM patients with medical history, clinical manifestations, and related auxiliary examinations.Discuss the EOM clinical features,diagnosis and treatment in conjunction with the literature. Result: The clinical features of 3 patients with EOM were summarized as: a large amount of yellowish white secretions or polyps formation, obvious itching symptoms; polyp biopsy showed a large amount of eosinophil infiltration;topical use of hormone-containing ear drops treatment is effective.Conclusion: EOM is a new type of chronic otitis media.It has characteristic clinical manifestations,a comprehensive treatment based on glucocorticoids should be given..

[Association between body mass index and both total and cause-specific mortality in China: findings from data through the China Kadoorie Biobank].

Objective: To evaluate the associations between body mass index (BMI) and both total and cause-specific mortality. Methods: After excluding participants with heart disease, stroke, cancer, chronic obstructive pulmonary disease, and diabetes at baseline study, 428 593 participants aged 30-79 in the China Kadoorie Biobank study were chosen for this study. Participants were categorized into 9 groups according to their BMI status. Cox regression analysis was used to estimate the hazard ratios (HRs) and 95% confidence intervals (CIs) of mortality on BMI. Results: Among 3 085 054 person-years of the follow-up program between 2004 and 2013 (median 7.2 years), a total of 7 862 men and 6 315 women died. After adjusting for known or potential confounders, an increased risks of all-cause deaths were shown among participants with a BMI less than 18.5 (HR=1.40, 95%CI: 1.31-1.50), between 18.5-20.4 (HR=1.11, 95%CI: 1.05-1.17), and more than 35.0 (HR=2.05, 95%CI: 1.60-2.61), when compared to those with BMI between 20.5-22.4. Ranges of BMI with lower risk of cause-specific mortality were: 18.5-23.9 for ischemic heart disease, <26.0 for cerebro-vascular disease, 26.0-34.9 for cancers, and 24.0-25.9 for respiratory diseases. Conclusions: In this large prospective study, both underweight and obesity were associated with the increased total and certain cause-specific mortality, which were independent from other risk factors of death. Programs related to extensive follow-up, thorough analysis BMI and the risks of incidence on major chronic diseases all need to be developed, in order to better understand the impact of BMI on human health.

Selective Sparing of Human Tregs by Pharmacologic Inhibitors of the Phosphatidylinositol 3-Kinase and MEK Pathways.

Phosphatidylinositol 3-kinase (PI3K) and mitogen-activated protein kinase/extracellular signal-regulated (MEK) signaling are central to the survival and proliferation of many cell types. Multiple lines of investigation in murine models have shown that control of the PI3K pathway is particularly important for regulatory T cell (Treg) stability and function. PI3K and MEK inhibitors are being introduced into the clinic, and we hypothesized that pharmacologic inhibition of PI3K, and possibly MEK, in mixed cultures of human mononuclear cells would preferentially affect CD4(+) and CD8(+) lymphocytes compared with Tregs. We tested this hypothesis using four readouts: proliferation, activation, functional suppression, and signaling. Results showed that Tregs were less susceptible to inhibition by both δ and α isoform-specific PI3K inhibitors and by an MEK inhibitor compared with their conventional CD4(+) and CD8(+) counterparts. These studies suggest less functional reliance on PI3K and MEK signaling in Tregs compared with conventional CD4(+) and CD8(+) lymphocytes. Therefore, the PI3K and MEK pathways are attractive pharmacologic targets for transplantation and treatment of autoimmunity.

Supraventricular tachyarrhythmias after hematopoietic stem cell transplantation: incidence, risk factors and outcomes.

Recent studies suggest that cancer patients may be at increased risk for supraventricular tachyarrhythmias (SVTA). We have observed clinically significant SVTA in patients undergoing hematopoietic stem cell transplantation occurring at a median of 6 days post transplant, manifesting as atrial fibrillation/flutter or regular narrow-complex tachycardia and persisting for a median of 3 days (range, 0-8). All patients received aggressive medical therapy and/or electrical cardioversion to restore sinus rhythm and to re-establish hemodynamic stability. Non-Hodgkin's lymphoma (NHL) was the most common diagnosis (53%), and a case control analysis in those patients demonstrated that SVTA occurred in 12% of patients and was associated with older age and pre-existing cardiac conditions. In conclusion, patients undergoing HSCT are at moderate risk for developing SVTA, particularly older patients with a diagnosis of NHL. These arrhythmias are clinically significant, and are a marker for increased mortality and prolonged hospital stay. Additional studies are needed to identify high-risk patients who may benefit from prophylactic anti-arrhythmic therapy.

Determination of genome size and restriction fragment length polymorphism of four Chinese rickettsial isolates by pulsed-field gel electrophoresis.

Pulsed-field gel electrophoresis (PFGE) was used to determine the genome size and the restriction fragment length polymorphism (RFLP) of four new Chinese isolates of spotted fever group (SFG) rickettsiae. The genome size of the isolates Ha-91, BJ-90, 054 and 036 was 1,253 kb, 1,236 kb, 1,272 kb, and 1,272 kb, respectively. The isolates 054 and 036 had identical RFLP profiles. All the isolates differed in the properties under study from the so far known SFG rickettsiae. The unique RFLP profiles of the isolates supported our opinion that they are new strains of SFG rickettsiae or even new species of SFG rickettsiae.

Genetic classification of "Rickettsia heilongjiangii" and "Rickettsia hulinii," two Chinese spotted fever group rickettsiae.

To determine the phylogenetic position of two new rickettsial strains isolated from ticks in China, 16S ribosomal DNA, gltA, and ompA (apart from the tandem repeat units) genes were amplified by PCR and sequenced. The phylogenetic relationships between these strains and other rickettsiae were inferred from the comparison of sequences of the three genes by the parsimony, neighbor-joining, and maximum-likelihood methods. The results demonstrated that the 054 strain, a rickettsia pathogenic in humans, and the HL-93 strain were related and clustered together with Rickettsia japonica. Significant statistical bootstrap values (100 and 92%) supported the nodes in this cluster. Based on previous genotypic and antigenic data and the phylogenetic analysis presented here, the 054 and HL-93 strains should be considered as new species, and we formally propose that they be named "Rickettsia heilongjiangii" and "Rickettsia hulinii," respectively.

Heterogeneity in the response of vascular smooth muscle to heparin: altered signaling in heparin-resistant cells.

OBJECTIVE: Vascular smooth muscle cells show phenotypic heterogeneity in vivo that affects the extent to which they respond to the antimitogenic effects of heparin. In vitro, heparin-resistant cells are readily selected. This study was undertaken to determine whether differences in the antiproliferative response to heparin involve differences in activity of heparin-sensitive signal transduction pathways. METHODS: Rat thoracic aorta smooth muscle cells (ASMC) at early passage together with two established vascular smooth muscle lines, PAC-1 and A10, were examined before and after selection for growth in the presence of heparin (10 micrograms/ml). Cells were rendered quiescent and then stimulated with serum. RESULTS: The three cell types showed different sensitivities to the antimitogenic effects of heparin. With respect to [3H]thymidine incorporation, A10 cells were insensitive to 1 microgram/ml heparin whereas PAC-1 cells responded down to 0.05 microgram/ml and ASMC were of intermediate sensitivity. ASMC and PAC-1 cells but not A10 showed a decrease in c-fos mRNA in response to 1 microgram/ml heparin, and a decrease in the c-Fos content of AP-1 DNA binding activity. None of the cells had decreased c-jun mRNA in the presence of heparin. Although induction of c-fos by serum is thought to signal through the Erk mitogen activated protein kinase family, Erk activity was decreased more by 1 microgram/ml heparin in A10 cells than in PAC-1 or ASMC. When cells were selected by growth in the presence of 10 micrograms/ml heparin, A10 cells were unaffected but PAC-1 and ASMC showed a blunted effect of heparin on serum stimulation. In contrast to A10 and their controls not exposed to continuous heparin, heparin-selected PAC-1 and ASMC showed a diminished ability to induce c-fos in response to serum. CONCLUSIONS: Smooth muscle cell lines show different responses to the antimitogenic effects of heparin that correlate with the heparin sensitivity of c-Fos/c-Jun expression. Although Erk is implicated in c-fos induction, cells comparatively resistant to heparin still show heparin-dependent inhibition of Erk activation, suggesting that other pathways may be more important for heparin resistance. Furthermore, cells selected for heparin resistance may develop c-fos-independent pathways for proliferation.

Sequence analysis of a fragment of rOmpA gene of several isolates of spotted fever group rickettsiae from China.

The nucleotide sequence of rOmpA gene fragment of three Chinese isolates of spotted fever group rickettsiae (SFGR) (BJ-90, Ha-91 and HLJ-054) was determined. The obtained nucleotide and putative amino acid sequences were compared with those of another Chinese SFGR isolate (HL-93) and several prototype SFGR strains. This comparison showed that the isolates BJ-90 and Ha-91 are closely related to each other and R. sibirica but different from the isolates HLJ-054 and HL-93. We assume that with exception of the isolates HLJ-054 and HL-93 that represent new, unique members of SFGR, the isolates BJ-90 and Ha-91 are closely related to R. sibirica, one of the prototype SFGR strains.

Detection of Rickettsia sibirica in ticks and small mammals collected in three different regions of China.

The primers Rr 190.70p and Rr 190.602n were used to detect spotted fever group (SFG) rickettsiae by polymerase chain reaction (PCR) in ticks and small mammals collected in three different regions of China. The obtained results indicated that specific DNA fragments of SFG rickettsiae were amplified from Dermacentor silvarum, D. sinicus, D. auratus, Haemaphysalis concinna, H. wellingtoni, H. yeni, Apodemus agrarius, Microtus fortis. Clethrionomys rufocanus, Ondatra zibethica, Rattus flavipectus and hedgehog. The PCR product were digested with restriction endonucleases PstI and RsaI and the obtained electrophoretic profiles were compared with those of the prototype strains of SFG rickettsiae by the restriction fragment length polymorphism (RFLP) technique. The comparisons showed that the profiles were identical to those of Rickettsia sibirica. In addition, three new isolates of R. sibirica were obtained from H. yeni, D. sinicus and hedgehog, and designated NH-95, BJ-95 and BHJ-95, respectively. These results not only demonstrated a horizontal transmission of the rickettsiae between ticks and hosts but also suggested that R. sibirica is widely distributed in China and its hosts and vectors are various, all that indicating the existence of natural foci of North Asia tick-borne spotted fever specific to China.

[A molecular epidemiologic investigation of north Asia fever in scenic spots of Beijing suburb].

PCR/RFLP technique was used to detect spotted fever group rickettsiae (SFGR) in ticks and small mammals collected in eleven scenic spots of Beijing suburb. We not only detected Rickettsia sibirica in D. sinicus and hedgehog collected nearby the Museum of Aviation, but also isolated two strains of SFGR from them, named as BJ-95 strain and BJH-95 strain respectively. The two strains were identified as R. sibirica by SDS-PAGE, Western blot and PCR/RFLP. The results demonstrated the existence of horizontal transmission of R. sibirica between ticks and small mammals and showed the most scenic spots except the vicinity of Museum of Aviation being investigated were safe to North Asia Fever. This is the first report on the isolation of R. sibirica in hedgehogs.

Sequence analysis and comparison of 190 K surface antigen gene fragment of a new species of spotted fever group rickettsiae.

A 533 bp long PCR product amplified from rickettsial strain HL-93 DNA with the primer pair Rr 190.70p and Rr 190.602n, designed from DNA sequence encoding 190 K protein antigen of R. rickettsii, was cloned into plasmid vector PGEM-T and sequenced. The primer-flanking region of the product, an open reading frame, was 491 bp long. The sequence of the product was compared with those of the corresponding regions of DNAs of R. rickettsii (strain R), R. japonica (strain VR 1363) and R. conorii (strain Malish 7) which were reported earlier by other authors. The results showed that 23, 31 and 52 nucleotides in the compared sequence in strain HL-93 differed from those in R. japonica, R. rickettsii and R conorii, respectively. The homologies of strain HL-93 with R. japonica, R. rickettsii and R. conorii were 95.6%, 94% and 90% in nucleotide, and 89%, 87% and 80% in putative amino acid sequences. We consider strain HL-93 as a new member of the spotted fever group (SFG) rickettsiae on the basis of a high degree of homology and genetic divergence in the nucleotide sequence of a part of the 190 K protein gene.

[Detection of north-Asia tick-borne spotted fever in ticks and rodents along the Heilongjiang river-side by restriction fragment length polymorphism of PCR products].

In order to elucidate the natural foci of North-Asia tick-borne spotted fever along the bank of Heilongjiang river, we used PCR/RFLP to detect spotted fever group rickettsiae in ticks and rodents. The results showed that the wild samples of Dermacentor silvarum, Haemaphysalis concinna and Apodemus agrarius, Microtus fortis, Clethrionomys rufocanus and Ondatra zibethica were all positive with amplification, but typhus rickettsiae, tsutsugamushi fever rickettsiae and Q fever rickettsiae were all negative. Futher RFLP analysis of amplified products with PstI and Rsal demonstrated that their restriction endonuclease profiles were identical to Rickettsia sibirica, but were different from the other prototype strains of SFG rickettsiae, suggesting the possible existance of natural foci of North-Asia tick borne spotted fever in these areas.

Posttranscriptional effects of glucose on proteoglycan expression in mesangial cells.

Hyperglycemic conditions are known to increase mRNA and protein levels of several extracellular matrix molecules in cultured mesangial cells, but accompanying increases in proteoglycan mRNA have not been found, and there are discrepant reports of normal or decreased proteoglycan synthesis with or without undersulfation in diabetic kidneys and hyperglycemic cultures. We examined the effects in proliferating cells of glucose on [35S]Sulfate incorporation into heparan and dermatan sulfates and on mRNA levels of decorin, biglycan, and basement membrane perlecan. In both mesangial cells and vascular smooth muscle cells, 30 mmol/L glucose caused a decrease of 15% to 25% in the amount of sulfate incorporated into each proteoglycan in cultures confluent for 1 to 4 days, compared with 10 mmol/L glucose. The effect showed no specificity for the class of proteoglycan and was not a consequence of changes in total protein synthesis, which increased, or cell proliferation, which was unaffected. No decrease in charge density of any of the proteoglycan fractions was observed by ion-exchange chromatography. Therefore, the decrease in labeling was due to a decrease in synthesis and not undersulfation. mRNA levels for biglycan and perlecan increased slightly and transiently, and these changes cannot account for the decreased synthesis. Decorin mRNA was detected only in smooth muscle cells, where it and biglycan were differentially affected by glucose, apparently at the transcriptional level; stabilities of the two messages were unaffected by glucose. Although transforming growth factor-beta 1 (TGF-beta 1) mRNA levels increased in response to glucose, the cytokine did not appear to regulate proteoglycan synthesis, because structural changes in proteoglycans elicited by addition of TGF-beta 1 to the culture medium did not occur in the hyperglycemic cultures. On the other hand, inhibition and downregulation of protein kinase C (PKC), while decreasing net sulfate incorporation into mesangial cell proteoglycans, prevented the effect of high glucose. We conclude that a high glucose concentration causes a general decrease in the synthesis of all classes of proteoglycans at a posttranscriptional level, and can do so without affecting the charge density of individual proteoglycan molecules.

Genotypic identification of three new strains of spotted fever group rickettsiae isolated in China.

Polymerase chain reaction (PCR) and restriction endonuclease fragment length polymorphism (RFLP) analysis were used to characterize the genotypic diversity of three isolates of spotted fever group (SFG) rickettsiae isolated from ticks in China. A primer pair designed from DNA sequence encoding 190 K protein antigen of R. rickettsii and genomic DNAs obtained from the isolates were used in PCR. The PCR products were cleaved with restriction endonucleases PstI and RsaI, and the digestion patterns were analyzed by polyacrylamide gel electrophoresis (PAGE) and compared with those of all known species and strains of SFG rickettsiae. The results showed that three isolates had the same PCR products as the other SFG rickettsiae under comparison. HL-93 strain, isolated from Hemophysalis concinna ticks collected in Hulin County, Heilongjiang Province, had unique PstI digestion pattern among SFG rickettsiae; strains BJ-93 and 053, isolated from Dermacentor sinicus and Haemaphysalis concinna ticks collected in Changping County, Beijing City, and Suifenhe City, Heilongjiang Province, respectively, had the same PstI and RsaI digestion patterns as strains R. sibirica 246, BJ-90 and IMTO-85. The present study demonstrated that the BJ-93 and 053 strains were genotypically identical with R. sibirica and the HL-93 strain was genotypically unique among SFG rickettsiae.

Detection of spotted fever group rickettsiae in ticks and rodents by polymerase chain reaction technique in People's Republic of China.

The polymerase chain reaction (PCR) technique for amplification of genomic fragments of spotted fever group (SFG) rickettsiae directly from field samples of ticks, tick ova, tick larvae, tick faeces and organs of wild mice was employed for the first time in P.R. of China. Ticks and rodents were collected in Beijing and Heilongjiang, Hainan and Hebei Provinces. The PCR primers were designed from the DNA sequence encoding the 190 K protein of R. rickettsii for a 532 bp long product. Seven of ten tick samples, three of four tick ovum samples, one of two tick larva samples, four of seven tick faeces samples (the samples represented pools of several individuals), and two of twenty-seven wild mouse organs were found PCR-positive. In comparison with PCR assay, the haemolymph test gave similar but not so clear-cut results. PCR assay is recommended as a rapid, sensitive and convenient tool for the detection of SFG rickettsiae in endemic foci. The fact that tick faeces were found to certain extent PCR-positive for the presence of SFG rickettsiae is apparently the first report on this subject and contributes to the knowledge of the transmission of these micro-organisms in the nature.