Artemisinin resistance-associated markers in Plasmodium falciparum parasites from the China-Myanmar border: predicted structural stability of K13 propeller variants detected in a low-prevalence area.

BACKGROUND: Malaria reduction and future elimination in China is made more difficult by the importation of cases from neighboring endemic countries, particularly Myanmar, Laos, and Vietnam, and increased travel to Africa by Chinese nationals. The increasing prevalence of artemisinin resistant parasites across Southeast Asia highlights the importance of monitoring the parasite importation into China. Artemisinin resistance in the Mekong region is associated with variants of genes encoding the K13 kelch domain protein (pf13k), found in specific genetic backgrounds, including certain alleles of genes encoding the chloroquine resistance transporter (pfcrt) and multidrug resistance transporter PgH1 (pfmdr1). METHODS: In this study we investigated the prevalence of drug resistance markers in 72 P. falciparum samples from uncomplicated malaria infections in Tengchong and Yingjiang, counties on the Yunnan-Myanmar border. Variants of pf13k, pfcrt and pfmdr1 are described. RESULTS: Almost all parasites harboured chloroquine-resistant alleles of pfcrt, whereas pfmdr1 was more diverse. Major mutations in the K13 propeller domain associated with artemisinin resistance in the Mekong region (C580Y, R539T and Y493H) were absent, but F446I and two previously undescribed mutations (V603E and V454I) were identified. Protein structural modelling was carried out in silico on each of these K13 variants, based on recently published crystal structures for the K13 propeller domain. Whereas F446I was predicted to elicit a moderate destabilisation of the propeller structure, the V603E substitution is likely to lead to relatively high protein instability. We plotted these stability estimates, and those for all previously described variants, against published values for in vivo parasitaemia half-life, and found that quadratic regression generates a useful predictive algorithm. CONCLUSION: This study provides a baseline of P. falciparum resistance-associated mutations prevalent at the China-Myanmar border. We also show that protein modelling can be used to generate testable predictions as to the impact of pfk13 mutations on in vivo (and potentially in vitro) artemisinin susceptibility.

Effects of psoralen isoflavones on the treatment of PC12 cells injured by Aβ / 国际中医中药杂志

Objective To study the effect of psoralen isoflavone on the treatment of PC12 cells injured by Aβ and the mechanism on the effect of the psoralen isoflavones on the expression of related proteins. Methods The PC12 cells were divided into blank group, model group, E2 group, and psoralen isoflavones group by random number table method, In addition to the blank group the rest of each group culture medium were added 20μmol/L of Aβ25-35 modeling, The E2 group was added to the 10-3μmol/L oestrogen and psoralen isoflavones group for the intervention of 102-10-6 μmol/L.The proliferation rate of PC12 cells was detected by MTT assay, and the expression of APP, BACE1, ERβ, p-ERK and Aβ protein was detected by Western Blot. Results Compared with the model group, the proliferation of PC12 cells induced by 10-1μmol/L of psoralen isoflavone increased (101％ vs. 52％, P<0.01); The expression of p-ERK (0.751± 0.066 vs. 0.364 ± 0.015), ERβ(0.756 ± 0.105 vs. 0.337 ± 0.045) increased significantly (P<0.01); APP (0.382 ± 0.039 vs. 0.479 ± 0.015), BACE1 (0.517 ± 0.024 vs. 0.622 ± 0.029), Aβ (0.430 ± 0.032 vs. 0.581 ± 0.030) expression amount were significantly lower (P<0.05). Conclusions Psoralen isoflavones have a certain therapeutic effect on PC12 cells injured by Aβ.

Investigation of tick bites in outpatients with fever from health care facilities in Tengchong County / 中国血吸虫病防治杂志

Objective To study the prevalence of tick bites and relative factors of outpatients with fever from health care fa?cilities in Tengchong County. Methods From July to August,2014,the outpatients with fever in five health care facilities namely Tengchong Center for Disease Control and Prevention,Hehua Health Center,Jietou Health Center,Qushi Health Cen?ter and Xinhua Health Center were investigated by questionnaires. The factors related to tick bites were explored with the univari?ate analysis and multiple regression models. Results Totally 884 effect questionnaires were acquired. Among the 884 partici?pants,85(9.6%)had experienced tick bites. The frequency of tick bites was associated with locations,gender,age group,own?ership of cattle,working at foreign country,firewood cutting and lumbering in the forest(all P<0.05). The multiple regression revealed that the male and people raising cattle,working at foreign country,engaging in firewood cutting and lumbering in the forest had a more risk for tick bites. Conclusions Tick bites are common in the residents of Tengchong County. The risk of be?ing bitten varies in different populations. The local health departments should promote health education in the high?risk popula?tion to reduce the risk of infecting tick?borne diseases.

Malaria epidemiological analysis in Tengchong City from 2010 to 2015 / 中国血吸虫病防治杂志

Objective To analyze the malaria epidemiological characteristics in Tengchong City from 2010 to 2015,so as to provide the evidence for adjusting and formulating measures in the elimination stage. Methods The malaria data were collected and analyzed by using Microsoft Excel 2010 in Tengchong City from 2010 to 2015. Results There were 1 408 malaria cases re?ported in Tengchong City from 2010 to 2015,including 1 091 cases of Plasmodium vivax infection,256 cases of P. falciparum infection,5 cases of P. malariae infection,1 case of P. ovale infection,1 case of mixed infections,and 54 unclassified cases. Totally 1 390 imported cases were recorded and 98.06%of them(1 363/1 390)were imported from Myanmar. Most of the pa?tients(n=908)were aged from 21 to 40 years,and the male to female ratio was 11.03∶1. The highest?risk populations were farmers and migrant workers. The most cases were observed in April and June,and at that time,most of the floating workers re?turned. Conclusion Imported malaria is severe in Tengchong City,and there is a great challenge to malaria elimination.

Assistant Effects of Longman Ampelopsis Grossedentata on Serum Lipid / 中国药师

Objective:To study the effect of Longman Ampelopsis grossedentata on the level of serum lipid. Methods:The exper-imental rats were given high-fat diet during the experiment. The rats were randomly divided into the model group, high dose group (37. 80 g·kg-1), medium dose group (12. 60 g·kg-1), low dose group (6. 30 g·kg-1) and lipid-lowering drug group (180 mg· kg-1 ) . All the groups were administrated continuously for 30 days, and the effect on body weight, serum TC, TG and HDL-C were measured. Results:Compared with that of the model group, the increase of body weight in the other groups was not significant ( P>0. 05), and all the rats had no obvious poisoning symptom. TC and TG were higher after the high-fat diet administration than those be-fore the experiment in the model group, and the differences were statistically significant (P<0. 05). After the 30-day treatment, the levels of TC and TG in the high-dose group were significantly decreased compared with those of the model group (P<0. 05). Conclu-sion:Longman Ampelopsis grossedentata shows assistant therapeutic effect on serum lipid.

Diagnostic performance of CareStart™ malaria HRP2/pLDH (Pf/pan) combo test versus standard microscopy on falciparum and vivax malaria between China-Myanmar endemic borders.

BACKGROUND: Rapid diagnostic test (RDT) is becoming an alternative way of establishing quickly the diagnosis of malaria infections, by detecting specific malaria antigens in suspected patients' blood between the China-Myanmar endemic borders areas, towards achieving the National Malaria Elimination programme by 2020. The objective of this study is to evaluate the performance of CareStart™ Malaria Pf/Pan RDT kit for the diagnosis of malaria infections in suspected patients. Blood examination by microscopy was taken as gold standard to evaluate CareStart™ kit's sensitivity, specificity and predictive value and corrected with PCR assay. RESULTS: Overall 126 of 241 (52.28%) malaria cases were detected by microscopy compared to 115 of 241(47.72%) CareStart™ kit and 128 of 241 (53.11%) PCR corrected assay. CareStart™ kit's sensitivity and specificity for the diagnosis of malaria were 89.68% and 98.26% respectively, compared to standard microscopy, whereas the sensitivity and specificity for falciparum malaria were 88.52% and 98.26%, and for vivax malaria: 90.77% and 100%. The CareStart™ positive predictive values were 98.26% (93.88-99.52%, 95% CI) compared to 100% (96.77-100%, 95% CI) for PCR-corrected, and the negative predictive values of 89.68% (83.15-93.87%, 95% CI) were the same in microscopy as PCR-corrected. The diagnostic accuracy of CareStart™ kit versus microscopy and PCR were 93.78% (89.99-96.19%, 95% CI) and 94.61% (90.99-96.82%, 95% CI) respectively. The likelihood of diagnostic of malaria positive was almost similar between microscopy and CareStart™ kit, with an entropy reduction of 60.0% compared to a weak likelihood of misdiagnosis of 0.10 (0.09-0.12, 95% CI), with an entropy reduction of 36.01%. CONCLUSION: The accuracy of CareStart™ kit is comparable to gold standard microscopy in these areas, it is easy to perform and suitable for cross-border diagnosis and monitoring of local or imported malaria patterns by any local health staff in endemic remotes.