Publications by authors named "Zhaoqing Yang"

130 Publications

Characterization of Coxsackievirus A6 Strains Isolated From Children With Hand, Foot, and Mouth Disease.

Front Cell Infect Microbiol 2021 16;11:700191. Epub 2021 Aug 16.

Institute of Medical Biology, Chinese Academy of Medical Sciences, and Peking Union Medical College, Kunming, China.

Coxsackievirus A6 (CVA6) is a key pathogen causing hand, foot and mouth disease (HFMD). However, there are currently no specific antiviral drugs or vaccines for treating infections caused by CVA6. In this study, human rhabdomyosarcoma (RD), African green monkey kidney (Vero), and human embryonic lung diploid fibroblast (KMB17) cells were used to isolate CVA6 from 327 anal swab and fecal samples obtained during HFMD monitoring between 2009 and 2017. The VP1 genes of the isolates were sequenced and genotyped, and the biological characteristics of the representative CVA6 strains were analyzed. A total of 37 CVA6 strains of the D3 gene subtypes were isolated from RD cells, all of which belonged to the epidemic strains in mainland China. Using the adaptive culture method, 10 KMB17 cell-adapted strains were obtained; however, no Vero cell-adapted strains were acquired. Among the KMB17 cell-adapted strains, only KYN-A1205 caused disease or partial death in suckling mice, and its virulence was stronger than its RD cell-adapted strain. The pathogenic KYN-A1205 strain caused strong tropism to the muscle tissue and led to pathological changes, including muscle necrosis and nuclear fragmentation in the forelimb and hindlimb. Sequence analysis demonstrated that the KYN-A1205 strain exhibited multiple amino acid mutations after KMB17 cell adaptation. Moreover, it showed strong pathogenicity, good immunogenicity and genetic stability, and could be used as an experimental CVA6 vaccine candidate.
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http://dx.doi.org/10.3389/fcimb.2021.700191DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8418080PMC
August 2021

Characterization of coxsackievirus A10 strains isolated from children with hand, foot, and mouth disease.

J Med Virol 2021 Aug 13. Epub 2021 Aug 13.

Institute of Medical Biology, Chinese Academy of Medical Sciences and Peking Union Medical College, Kunming, China.

Hand, foot, and mouth disease (HFMD) is a contagious disease that threatens the health of children under 5 years of age. Coxsackievirus A10 (CV-A10) is one of the main pathogens of HFMD. Currently, preventive vaccines and specific therapeutic drugs are not available for CV-A10. In this study, a total of 327 stool specimens were collected from pediatric patients from 2009 to 2017 during HFMD surveillance, among which 14 CV-A10 strains could only be isolated from rhabdomyosarcoma cells, but not from KMB17 and Vero cells. Through adaptive culture, 2 and 11 CV-A10 strains were recovered from Vero and KMB17 cell cultures, respectively. The growth of CV-A10 strains in Vero cells was better than that in KMB17 cells. The 14 CV-A10 strains belonged to the F genotype, and the nucleotides and amino acids of their complete genomes shared 92.6%-96.3% and 98.4%-98.9% identities, respectively. The different CV-A10 strains exhibited varying virulence in vivo, but had similar effects on tissue injury, with the hind limb muscles, kidneys, and lungs being severely affected. Additionally, the hind limb muscles had the highest viral loads. CV-A10 was found to exhibit a strong tropism to muscle tissue. The results of this study are critical to developing vaccines against CV-A10 infections.
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http://dx.doi.org/10.1002/jmv.27268DOI Listing
August 2021

Automated material identification with a Raman spectrometer based on the contribution enhancement of small differences and the adaptive target Raman peak subtraction.

Appl Opt 2021 Jul;60(19):5682-5690

There is only a small difference in Raman peaks between two materials, but they also represent different molecular materials. Therefore, the accurate identification ability for similar materials with small differences among their Raman peaks plays a key role in Raman spectrometers for material identification. However, the noises, the baseline (i.e., fluorescence backgrounds), and the requirements, such as fast and automated detection, of excellent user experiences cause many difficulties. In this paper, the target Raman peak is directly subtracted from the detected Raman spectrum by the adaptive minimum root mean square error (RMSE) estimation for a residual spectrum. Unlike the usual methods in which the detected Raman peak needs to be first recovered by removing the baseline from its Raman spectrum and then to be compared with the target Raman peak, our method can effectively enhance the contribution of small differences between the detected and the target Raman peak on the residual spectrum so as to make the RMSE of the residual spectrum more sensitive with increasing differences. On the other hand, the obtained RMSE of the residual spectrum only has a small change for the detected Raman spectrum with various baselines. So the common criteria (i.e., the third-order polynomials describing RMSE) to identify the detected Raman spectrum with various baselines and the target Raman spectrum is presented. Simulation results show that the small difference, where there is only an additional small Raman peak as low as 1/25 of the maximum peak height, can also be accurately identified. Experiments also demonstrate that similar materials can be accurately identified, whereas some commercial Raman spectrometers fail to identify them. Our method effectively deals with the problem in which the error of the complex baseline correction causes erroneous judgement in Raman spectrometers for material identification.
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http://dx.doi.org/10.1364/AO.428528DOI Listing
July 2021

Polymorphism of Antifolate Drug Resistance in From Local Residents and Migrant Workers Returned From the China-Myanmar Border.

Front Cell Infect Microbiol 2021 24;11:683423. Epub 2021 Jun 24.

Department of Pathogen Biology and Immunology, Kunming Medical University, Kunming, China.

Drug-resistant  malaria impedes efforts to control, eliminate, and ultimately eradicate malaria in Southeast Asia. resistance to antifolate drugs derives from point mutations in specific parasite genes, including the dihydropteroate synthase (), dihydrofolate reductase (), and GTP cyclohydrolase I () genes. This study aims to investigate the prevalence and spread of drug resistance markers in populating the China-Myanmar border. Blood samples were collected from symptomatic patients with acute infection. Samples with single-clone infections were sequenced for and genesand genotyped for 6 flanking microsatellite markers. Copy number variation in the gene was also examined. Polymorphisms were observed in six different codons of the  gene (382, 383, 512, 549, 553, and 571) and six different codons of the  gene (13, 57, 58, 61, 99, 117) in two study sites. The quadruple mutant haplotypes 57I/L/58R/61M/117T of gene were the most common (comprising 76% of cases in Myitsone and 43.7% of case in Laiza). The double mutant haplotype 383G/553G of  gene was also prevalent at each site (40.8% and 31%). Microsatellites flanking the gene differentiated clinical samples from wild type and quadruple mutant genotypes ( = 0.259-0.3036), as would be expected for a locus undergoing positive selection. The lack of copy number variation of suggests that SP-resistant may harbor alternative mechanisms to secure sufficient folate.
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http://dx.doi.org/10.3389/fcimb.2021.683423DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8265503PMC
July 2021

Increasing proportions of relapsing parasite species among imported malaria in China's Guangxi Province from Western and Central Africa.

Travel Med Infect Dis 2021 Sep-Oct;43:102130. Epub 2021 Jun 21.

Department of Pathogen Biology and Immunology, Kunming Medical University, Kunming, Yunnan Province, 650500, China. Electronic address:

Background: Travel-related malaria in non-endemic areas returning from endemic areas presents important challenges to diagnosis and treatment. Imported malaria to newly malaria-free countries poses further threats of malaria re-introduction and potential resurgence. For those traveling to places with high Plasmodium falciparum prevalence, prophylaxis against this parasite is recommended, whereas causal prophylaxis against relapsing malaria is often overlooked.

Methods: We analyzed a cluster of imported malaria among febrile patients in Shanglin County, Guangxi Province, China, who had recent travel histories to Western and Central Africa. Malaria was diagnosed by microscopy and subsequently confirmed by species- and subspecies-specific PCR. Plasmodium vivax was genotyped using a barcode consisting of 42 single nucleotide polymorphisms.

Results: Investigations of 344 PCR-confirmed malaria cases revealed that in addition to Plasmodium falciparum being the major parasite species, the relapsing parasites Plasmodium ovale and P. vivax accounted for ~40% of these imported cases. Of the 114 P. ovale infections, 65.8% and 34.2% were P. ovale curtisi and P. ovale wallikeri, respectively, with the two subspecies having a ~2:1 ratio in both Western and Central Africa. Phylogenetic analysis of 14 P. vivax isolates using a genetic barcode demonstrated that 11 formed a distinct clade from P. vivax populations from Eastern Africa.

Conclusion: This study provides support for active P. vivax transmission in areas with the predominant Duffy-negative blood group. With relapsing malaria making a substantial proportion of the imported malaria, causal prophylaxis should be advocated to travelers with a travel destination to Western and Central Africa.
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http://dx.doi.org/10.1016/j.tmaid.2021.102130DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8429216PMC
June 2021

Loop-mediated isothermal amplification (LAMP) assays targeting 18S ribosomal RNA genes for identifying P. vivax and P. ovale species and mitochondrial DNA for detecting the genus Plasmodium.

Parasit Vectors 2021 May 24;14(1):278. Epub 2021 May 24.

Department of Pathogen Biology and Immunology, Kunming Medical University, Kunming, 650500, Yunnan, People's Republic of China.

Background: Loop-mediated isothermal amplification (LAMP) has been widely used to diagnose various infectious diseases. Malaria is a globally distributed infectious disease attributed to parasites in the genus Plasmodium. It is known that persons infected with Plasmodium vivax and P. ovale are prone to clinical relapse of symptomatic blood-stage infections. LAMP has not previously been specifically evaluated for its diagnostic performance in detecting P. ovale in an epidemiological study, and no commercial LAMP or rapid diagnostic test (RDT) kits are available for specifically diagnosing infections with P. ovale.

Methods: An assay was designed to target a portion of mitochondrial DNA (mtDNA) among Plasmodium spp., the five human Plasmodium species and two other assays were designed to target the nuclear 18S ribosomal DNA gene (18S rDNA) of either P. vivax or P. ovale for differentiating the two species. The sensitivity of the assays was compared to that of nested PCR using defined concentrations of plasmids containing the target sequences and using limiting dilutions prepared from clinical isolates derived from Chinese workers who had become infected in Africa or near the Chinese border with Myanmar.

Results: The results showed that 10 copies of the mitochondrial target or 10 and 10 copies of 18S rDNA could be detected from Plasmodium spp., P. vivax and P. ovale, respectively. In 279 clinical samples, the malaria Pan mtDNA LAMP test performed well when compared with a nested PCR assay (95% confidence interval [CI] sensitivity 98.48-100%; specificity 90.75-100%). When diagnosing clinical cases of infection with P. vivax, the 18S rDNA assay demonstrated an even great sensitivity (95.85-100%) and specificity (98.1-100%). The same was true for clinical infections with P. ovale (sensitivity 90.76-99.96%; specificity 98.34-100%). Using plasmid-positive controls, the limits of detection of Malaria Pan, 18S rDNA P. vivax and 18S rDNA P. ovale LAMP were 100-, 100- and tenfold lower than those of PCR, respectively.

Conclusion: The novel LAMP assays can greatly aid the rapid, reliable and highly sensitive diagnosis of infections of Plasmodium spp. transmitted among people, including P. vivax and P. ovale, cases of which are most prone to clinical relapse.
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http://dx.doi.org/10.1186/s13071-021-04764-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8147439PMC
May 2021

Susceptibility of Isolates from the China-Myanmar Border Area to Piperaquine and Association with Candidate Markers.

Antimicrob Agents Chemother 2021 Mar 8. Epub 2021 Mar 8.

Department of Internal Medicine, Morsani College of Medicine, University of South Florida, 3720 Spectrum Boulevard, Suite 304, Tampa, FL, USA

from the Greater Mekong subregion has evolved resistance to the artemisinin-based combination therapy dihydroartemisinin and the partner drug piperaquine. To monitor the potential westward spread or independent evolution of piperaquine resistance, we evaluated the susceptibility of 120 isolates collected at the China-Myanmar border during 2007-2016. The parasite isolates displayed a relatively wide range of piperaquine susceptibility estimates. While 56.7% of the parasites showed bimodal drug response curves, all but five generated area-under-the-curve (AUC) estimates consistent with a susceptible phenotype. Using the piperaquine survival assay (PSA), 5.6% parasites showed reduced susceptibility. Of note, parasites from 2014-2016 showed the highest AUC value and the highest proportion with a bimodal curve, suggesting falling effectiveness in these later years. Unsupervised K-mean analysis of the combined data assigned parasites into three clusters and identified significant correlations between IC, IC and AUC values. No parasites carried the E415G mutation in a putative exo-nuclease, new mutations in PfCRT, or amplification of the genes, suggesting mechanisms of reduced piperaquine susceptibility that differ from those described in other countries of the region. The association of increased AUC, IC, and IC values with major PfK13 mutations (F446I and G533S) suggests that piperaquine resistance may evolve in these PfK13 genetic backgrounds. Additionally, the Pfmdr1 F1226Y mutation was associated with significantly higher PSA values. Further elucidation of piperaquine resistance mechanisms and continuous surveillance are warranted.
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http://dx.doi.org/10.1128/AAC.02305-20DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8092910PMC
March 2021

Three Novel Genetic Variants in the FAM110D, CACNA1A, and NLRP12 Genes Are Associated With Susceptibility to Hypertension Among Dai People.

Am J Hypertens 2021 08;34(8):874-879

The Department of Medical Genetics, Institute of Medical Biology, Chinese Academy of Medical Sciences and Peking Union Medical College, Kunming, China.

Background: Although the genetic factors associated with hypertension remain unknown, genetic variations in genes related to ion channels, inflammation, and the cell cycle may affect susceptibility to hypertension. In the present study, the association between hypertension and 10 candidate single-nucleotide polymorphisms (SNPs) was evaluated among Chinese Dai people, who have a smaller gene pool than Han individuals.

Methods: A total of 1,193 samples from Dai people were collected, including 488 with hypertension and 705 with normal blood pressure. Based on the preliminary results of whole-genome sequencing among pools of individuals (Pool-seq), 10 candidate SNPs in 6 genes (FAM110D, ADD1, RAG1, CACNA1C, CACNA1A, and NLRP12) were genotyped in the case and control groups by multiplex PCR for SNP genotyping with next-generation sequencing (MultiPCR-NGS). The relationship between hypertension and each candidate SNP was evaluated using the χ 2 test and multiple logistic regression analysis.

Results: The χ 2 test showed that the allele frequencies of rs3748856 in FAM110D, rs139118504 in CACNA1A, and rs34436714 in NLRP12 were significantly different between the case and control groups (P < 0.005). After adjusting for age, body mass index, total cholesterol, triglyceride, and low-density lipoprotein, logistic regression analyses revealed that the association between the 3 SNPs and hypertension among Dai people remained significant (P = 0.012, 2.71 × 10-4, and 0.017, respectively).

Conclusions: These findings indicate that there may be different molecular pathogeneses of hypertension among Dai people, which should be noted in future studies.
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http://dx.doi.org/10.1093/ajh/hpab040DOI Listing
August 2021

Efficacy of artemether-lumefantrine for treating uncomplicated Plasmodium falciparum cases and molecular surveillance of drug resistance genes in Western Myanmar.

Malar J 2020 Aug 27;19(1):304. Epub 2020 Aug 27.

Department of Internal Medicine, Morsani College of Medicine, University of South Florida, Tampa, FL, 33612, USA.

Background: Currently, artemisinin-based combination therapy (ACT) is the first-line anti-malarial treatment in malaria-endemic areas. However, resistance in Plasmodium falciparum to artemisinin-based combinations emerging in the Greater Mekong Sub-region is a major problem hindering malaria elimination. To continuously monitor the potential spread of ACT-resistant parasites, this study assessed the efficacy of artemether-lumefantrine (AL) for falciparum malaria in western Myanmar.

Methods: Ninety-five patients with malaria symptoms from Paletwa Township, Chin State, Myanmar were screened for P. falciparum infections in 2015. After excluding six patients with a parasite density below 100 or over 150,000/µL, 41 P. falciparum patients were treated with AL and followed for 28 days. Molecular markers associated with resistance to 4-amino-quinoline drugs (pfcrt and pfmdr1), antifolate drugs (pfdhps and pfdhfr) and artemisinin (pfk13) were genotyped to determine the prevalence of mutations associated with anti-malarial drug resistance.

Results: For the 41 P. falciparum patients (27 children and 14 adults), the 28-day AL therapeutic efficacy was 100%, but five cases (12.2%) were parasite positive on day 3 by microscopy. For the pfk13 gene, the frequency of NN insert after the position 136 was 100% in the day-3 parasite-positive group as compared to 50.0% in the day-3 parasite-negative group, albeit the difference was not statistically significant (P = 0.113). The pfk13 K189T mutation (10.0%) was found in Myanmar for the first time. The pfcrt K76T and A220S mutations were all fixed in the parasite population. In pfmdr1, the Y184F mutation was present in 23.3% of the parasite population, and found in both day-3 parasite-positive and -negative parasites. The G968A mutation of pfmdr1 gene was first reported in Myanmar. Prevalence of all the mutations in pfdhfr and pfdhps genes assessed was over 70%, with the exception of the pfdhps A581G mutation, which was 3.3%.

Conclusions: AL remained highly efficacious in western Myanmar. Pfk13 mutations associated with artemisinin resistance were not found. The high prevalence of mutations in pfcrt, pfdhfr and pfdhps suggests high-degree resistance to chloroquine and antifolate drugs. The pfmdr1 N86/184F/D1246 haplotype associated with selection by AL in Africa reached > 20% in this study. The detection of > 10% patients who were day-3 parasite-positive after AL treatment emphasizes the necessity of continuously monitoring ACT efficacy in western Myanmar.
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http://dx.doi.org/10.1186/s12936-020-03376-5DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7450958PMC
August 2020

High-throughput sequencing analysis of differences in intestinal microflora between ulcerative colitis patients with different glucocorticoid response types.

Genes Genomics 2020 10 25;42(10):1197-1206. Epub 2020 Aug 25.

Department of Gastroenterology, The First Affiliated Hospital of Kunming Medical University, 295 Xichang Road, Kunming, 650032, People's Republic of China.

Background: Previous investigations reported that the imbalance of intestinal microflora may be the initiation and promotion factor in the pathogenesis of inflammatory bowel disease such as ulcerative colitis (UC). Glucocorticoid is a very important class of regulatory molecules in the body. The response of different individuals to glucocorticoids can be divided into glucocorticoid sensitive, glucocorticoid resistance and glucocorticoid dependence.

Objective: We aimed to investigate the differences in intestinal microflora composition and related metabolic pathways in UC patients with these three different glucocorticoid response types.

Methods: The whole genomic DNA was extracted from fecal specimens. High-throughput sequencing technology was used to analyze the fecal 16S rRNA genome of UC patients with different glucocorticoid response types, and functional prediction was performed by PICRUSTs software.

Results: The results showed that the intestinal microflora of the three groups were mainly composed of Firmicutes, Proteobacteria and Bacteroidetes. Although the species abundance and diversity of intestinal microflora in UC patients differed little among the three groups, the composition of intestinal microflora showed significant heterogeneity, which directly led to differences in the function of intestinal microbiota of UC patients with different glucocorticoid responses. Furthermore, of the 240 pathways, "PANTO-PWY: phosphopantothenate biosynthesis I", "COA-PWY-1: coenzyme A biosynthesis II (mammalian)" and "PWY-4242: pantothenate and coenzyme A biosynthesis III" were significantly different in the three groups.

Conclusions: These results indicate that UC patients with different glucocorticoids response types have different bacterial compositions and functions, which lays a foundation for further study of glucocorticoid resistance in UC patients.
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http://dx.doi.org/10.1007/s13258-020-00986-wDOI Listing
October 2020

Molecular Surveillance and in vitro Drug Sensitivity Study of Isolates from the China-Myanmar Border.

Am J Trop Med Hyg 2020 09;103(3):1100-1106

Department of Pathogen Biology and Immunology, Kunming Medical University, Kunming, China.

The emergence and spread of resistance in to the frontline treatment artemisinin-based combination therapies in Southeast Asia require close monitoring of the situation. Here, we collected 36 clinical samples of from the China-Myanmar border in 2014-2016, adapted these parasites to continuous culture, and performed in vitro drug assays on seven antimalarial drugs. Data for 23 parasites collected in 2010 and 2012 from the same area reported in an early study were used to assess longitudinal changes in drug sensitivity. Parasites remained highly resistant to chloroquine (CQ) and pyrimethamine, whereas they were generally sensitive to mefloquine (MFQ), lumefantrine (LMF), naphthoquine (NQ), and pyronaridine (PND). Parasites showed a similar temporal trend in sensitivity to CQ, NQ, and PND, with gradual reduction in the half-maximal inhibitory concentrations (ICs) after 2012. The ICs to the aminoalcohol drugs MFQ, LMF, and quinine (QN) all significantly declined in 2014, followed by various degrees of increase in 2016. Pyrimethamine displayed a continuous increase in IC over the years. The Dd2-like mutations were fixed or nearly fixed in the parasite population. The F1226Y mutation was detected in 80% parasites in 2016 and associated with reduced sensitivity to LMF and QN ( < 0.05). The N51I in and K540E/N and A581G in that are associated with antifolate resistance were either fixed or were approaching fixation in recent years. This study provides an updated picture and temporal trend of antimalarial drug resistance in the China-Myanmar border region, which will serve as a reference for antimalarial treatment.
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http://dx.doi.org/10.4269/ajtmh.20-0235DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7470591PMC
September 2020

Ex vivo susceptibilities of Plasmodium vivax isolates from the China-Myanmar border to antimalarial drugs and association with polymorphisms in Pvmdr1 and Pvcrt-o genes.

PLoS Negl Trop Dis 2020 06 12;14(6):e0008255. Epub 2020 Jun 12.

Department of Internal Medicine, Morsani College of Medicine, University of South Florida, Tampa, Florida, United States of America.

Background: Vivax malaria is an important public health problem in the Greater Mekong Subregion (GMS), including the China-Myanmar border. Previous studies have found that Plasmodium vivax has decreased sensitivity to antimalarial drugs in some areas of the GMS, but the sensitivity of P. vivax to antimalarial drugs is unclear in the China-Myanmar border. Here, we investigate the drug sensitivity profile and genetic variations for two drug resistance related genes in P. vivax isolates to provide baseline information for future drug studies in the China-Myanmar border.

Methodology/principal Findings: A total of 64 P. vivax clinical isolates collected from the China-Myanmar border area were assessed for ex vivo susceptibility to eight antimalarial drugs by the schizont maturation assay. The medians of IC50 (half-maximum inhibitory concentrations) for chloroquine, mefloquine, pyronaridine, piperaquine, quinine, artesunate, artemether, dihydroartemisinin were 84.2 nM, 34.9 nM, 4.0 nM, 22.3 nM, 41.4 nM, 2.8 nM, 2.1 nM and 2.0 nM, respectively. Twelve P. vivax clinical isolates were found over the cut-off IC50 value (220 nM) for chloroquine resistance. In addition, sequence polymorphisms in pvmdr1 (P. vivax multidrug resistance-1), pvcrt-o (P. vivax chloroquine resistance transporter-o), and difference in pvmdr1 copy number were studied. Sequencing of the pvmdr1 gene in 52 samples identified 12 amino acid substitutions, among which two (G698S and T958M) were fixed, M908L were present in 98.1% of the isolates, while Y976F and F1076L were present in 3.8% and 78.8% of the isolates, respectively. Amplification of the pvmdr1 gene was only detected in 4.8% of the samples. Sequencing of the pvcrt-o in 59 parasite isolates identified a single lysine insertion at position 10 in 32.2% of the isolates. The pvmdr1 M908L substitutions in pvmdr1 in our samples was associated with reduced sensitivity to chloroquine, mefloquine, pyronaridine, piperaquine, quinine, artesunate and dihydroartemisinin.

Conclusions: Our findings depict a drug sensitivity profile and genetic variations of the P. vivax isolates from the China-Myanmar border area, and suggest possible emergence of chloroquine resistant P. vivax isolates in the region, which demands further efforts for resistance monitoring and mechanism studies.
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http://dx.doi.org/10.1371/journal.pntd.0008255DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7314094PMC
June 2020

Cellular analysis of a novel mutation p. Ser287Tyr in TOR1A in late-onset isolated dystonia.

Neurobiol Dis 2020 07 31;140:104851. Epub 2020 Mar 31.

The Department of Medical Genetics, Institute of Medical Biology, Chinese Academy of Medical Sciences and Peking Union Medical College, Kunming, China. Electronic address:

Background: Variations in TOR1A were thought to be associated with early-onset isolated dystonia. The variant S287Y (NM_000113.2: c.860C > A, p. Ser287Tyr, rs766483672) was found in our late-onset isolated dystonia patient. This missense variant is adjacent to R288Q (c.863G > A, p. Arg288Gln), which was reported to be associated with isolated dystonia. The potentially pathogenic role of S287Y is not conclusively known.

Methods: Cytological and molecular biological analyses were performed in vitro to determine whether this variant damages the structure and function of the cell.

Results: Compared with the SH-SY5Y cells overexpressing wild-type TOR1A, the cells overexpressing the protein with S287Y have an enlarged peri-nuclear space. The same changes in nuclear morphology were also found in the cells overexpressing the pathogenic variants ΔE (NM_000113.2:c.904_906delGAG, p. Glu302del), F205I (NM_000113.2:c.613 T > A, p. Phe205Ile), and R288Q (NM_000113.2:c.863G > A, p. Arg288Gln). Mutated proteins with S287Y presented a higher tendency to form dimers under reducing conditions. The same tendencies were observed in other mutated proteins but not in wild-type torsinA.

Conclusions: TorsinA with S287Y damages the structure of the cell nucleus and may be a novel pathogenic mutation that causes isolated dystonia.
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http://dx.doi.org/10.1016/j.nbd.2020.104851DOI Listing
July 2020

Association between gene polymorphisms of voltage-dependent Ca channels and hypertension in the Dai people of China: a case-control study.

BMC Med Genet 2020 02 28;21(1):44. Epub 2020 Feb 28.

Institute of Medical Biology Chinese Academy of Medical Sciences and Peking Union Medical College, Kunming, China.

Background: Abnormal calcium homeostasis related to the development of hypertension. As the key regulator of intracellular calcium concentration, voltage-dependent calcium channels (VDCCs), the variations in these genes may have important effects on the development of hypertension. Here we evaluate VDCCs variability with respect to hypertension in the Dai ethnic group of China.

Methods: A total of 1034 samples from Dai individuals were collected, of which 495 were used as cases, and 539 were used as controls. Blood pressure was measured using a standard mercury measurement method, three times with a rest for 5 min, and the average was used for analyses. Seventeen single nucleotide polymorphisms (SNPs) in the four protein-coding genes (CACNA1A, CACNA1C, CACNA1S, CACNB2) of VDCCs were identified by multiplex PCR-SNP typing technique. Chi-square tests and regression models were used to analyse the associations of SNPs with hypertension.

Results: The results of chi-square tests showed that the allele frequencies of 5 SNPs were significantly different between the case and the control groups (P < 0.05), but the statistical significance was lost after Bonferroni's correction. However, after adjusting for BMI, age, sex and other factors by logistic regression analyses, the results showed that 5 SNPs consistent with chi-square tests (rs2365293, rs17539088, rs16917217, rs61839222 and rs10425859) were still statistically positive.

Conclusions: This finding suggested that the significant association of these SNPs with hypertension may be noteworthy in future studies.
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http://dx.doi.org/10.1186/s12881-020-0982-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7049211PMC
February 2020

Evolution of the Plasmodium vivax multidrug resistance 1 gene in the Greater Mekong Subregion during malaria elimination.

Parasit Vectors 2020 Feb 12;13(1):67. Epub 2020 Feb 12.

Division of Infectious Diseases and International Medicine, Department of Internal Medicine, Morsani College of Medicine, University of South Florida, Tampa, FL, USA.

Background: The malaria elimination plan of the Greater Mekong Subregion (GMS) is jeopardized by the increasing number of Plasmodium vivax infections and emergence of parasite strains with reduced susceptibility to the frontline drug treatment chloroquine/primaquine. This study aimed to determine the evolution of the P. vivax multidrug resistance 1 (Pvmdr1) gene in P. vivax parasites isolated from the China-Myanmar border area during the major phase of elimination.

Methods: Clinical isolates were collected from 275 P. vivax patients in 2008, 2012-2013 and 2015 in the China-Myanmar border area and from 55 patients in central China. Comparison was made with parasites from three border regions of Thailand.

Results: Overall, genetic diversity of the Pvmdr1 was relatively high in all border regions, and over the seven years in the China-Myanmar border, though slight temporal fluctuation was observed. Single nucleotide polymorphisms previously implicated in reduced chloroquine sensitivity were detected. In particular, M908L approached fixation in the China-Myanmar border area. The Y976F mutation sharply decreased from 18.5% in 2008 to 1.5% in 2012-2013 and disappeared in 2015, whereas F1076L steadily increased from 33.3% in 2008 to 77.8% in 2015. While neutrality tests suggested the action of purifying selection on the pvmdr1 gene, several likelihood-based algorithms detected positive as well as purifying selections operating on specific amino acids including M908L, T958M and F1076L. Fixation and selection of the nonsynonymous mutations are differently distributed across the three border regions and central China. Comparison with the global P. vivax populations clearly indicated clustering of haplotypes according to geographic locations. It is noteworthy that the temperate-zone parasites from central China were completely separated from the parasites from other parts of the GMS.

Conclusions: This study showed that P. vivax populations in the China-Myanmar border has experienced major changes in the Pvmdr1 residues proposed to be associated with chloroquine resistance, suggesting that drug selection may play an important role in the evolution of this gene in the parasite populations.
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http://dx.doi.org/10.1186/s13071-020-3934-5DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7017538PMC
February 2020

Associations among Soil-Transmitted Helminths, G6PD Deficiency and Asymptomatic Malaria Parasitemia, and Anemia in Schoolchildren from a Conflict Zone of Northeast Myanmar.

Am J Trop Med Hyg 2020 04;102(4):851-856

Department of Pathogen Biology and Immunology, Kunming Medical University, Kunming, China.

In tropical areas of developing countries, the interactions among parasitic diseases such as soil-transmitted helminths (STHs) and malaria, and glucose-6-phosphate dehydrogenase deficiency (G6PDd), are complex. Here, we investigated their interactions and impact on anemia in school students residing in a conflict zone of northeast Myanmar. A cross-sectional survey was conducted between July and December 2015 in two schools located along the China-Myanmar border. Stool samples from the schoolchildren were analyzed for STH infections, whereas finger-prick blood samples were analyzed for G6PDd, hemoglobin concentrations, and infections. Among 988 enrolled children, , , hookworm, , and infections occurred in 3.3%, 0.8%, 31.5%, 1.2%, and 0.3%, respectively. Glucose-6-phosphate dehydrogenase deficiency was present in 16.9% of the children, and there was a very high prevalence of anemia (73%). Anthropometric measures performed on all children showed that 50% of the children were stunted and 25% wasted. Moderate to severe anemia was associated with STH infections, stunting, and wasting. In addition, children had increasing odds of anemia with increasing burden of infections. This study revealed a high prevalence of G6PDd, STHs, and anemia in schools located in a conflict zone. In areas where malnutrition and STH infections are rampant, testing for both glucose-6-phosphate dehydrogenase and anemia should be considered before treating vivax malaria with 8-aminoquinolines.
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http://dx.doi.org/10.4269/ajtmh.19-0828DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7124928PMC
April 2020

Characterization of a novel echovirus 21 strain isolated from a healthy child in China in 2013.

Arch Virol 2020 Mar 7;165(3):757-760. Epub 2020 Jan 7.

Institute of Medical Biology, Chinese Academy of Medical Sciences, Peking Union Medical College (CAMS and PUMC), 935 Jiao Ling Road, Kunming, 650118, Yunnan, People's Republic of China.

Echovirus 21 (E21) belongs to the species Enterovirus B, whose members are frequently associated with acute flaccid paralysis. E21 strain 553/YN/CHN/2013 was isolated from a healthy child in Yunnan, China, in 2013. This is the first report of the complete genome sequence of E21 in China. This strain shared 81.7% nucleotide sequence identity and 96.8% amino acid sequence identity with the E21 prototype strain Farina. Although strain 553/YN/CHN/2013 belongs to the E21 serotype, the only similarity to the E21 strain was in the VP1 region, as other genomic regions, including VP2-VP4, were more similar to other EV-B members. Recombination analysis showed evidence of recombination events between E21 and other EV-B viruses. E21 strain 553/YN/CHN/2013 failed to infect suckling mice via intracerebral injection. Surveillance of E21 is very important to help forecast the potential of emerging E21 outbreaks and related diseases.
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http://dx.doi.org/10.1007/s00705-019-04506-4DOI Listing
March 2020

Widespread resistance mutations to sulfadoxine-pyrimethamine in malaria parasites imported to China from Central and Western Africa.

Int J Parasitol Drugs Drug Resist 2020 04 29;12:1-6. Epub 2019 Nov 29.

Department of Pathogen Biology and Immunology, Kunming Medical University, Kunming, 650500, Yunnan, PR China. Electronic address:

Background: Imported cases of infectious disease provide invaluable information about epidemiological conditions abroad, and should guide treatment decisions at home and abroad. Here, we examined cases of malaria imported from Africa to China for mutations eroding the efficacy of sulfadoxine-pyrimethamine (SP), sometimes used as an intermittent preventive treatment during for pregnant women and infants.

Methods: A total of 208 blood samples were collected from P. falciparum-infected workers who had returned from Western and Central Africa to Guangxi Province Frequency distribution. Samples were analyzed for the mutations in dhfr and dhps genes by PCR -sequencing. The prevalence of dhfr and dhps polymorphisms was analyzed. Among the isolates, polymorphisms were detected in mutants N51I, C59R, S108N and I164L of Pfdhfr and I431V, S436 A/F, A437G, K540 E/N, A581G and A613T of pfdhps.

Results: Mutations promoting drug resistance were widespread in this cohort. For pfdhfr and pfdhps, wild types were equally rare among patients returned from Western Africa and Central Africa. A triple-mutant dhfr haplotype was most prevalent (>70%). We report for the first time mutation I164L-dhfr and I431V-dhps in Ghana, and for the first time we found A581G to exceed a clinically-relevant threshold that may counter-indicate current clinical practices. For Pfdhps, the double-mutant IAGKAA was high prevalent haplotype in Ghana, Western Africa. The single-mutant ISGKAA was a majority haplotype in Cameroon. Alarmingly, a "super resistance" quintuple mutant was detected, for the first time, in parasites of West African origin (defined by IAGKAA/IRNI in combination with pfdhps 581G and dhfr I164L). This may limit the efficacy of this drug combination for even intermittent clinical applications.

Conclusions: These data are cause for great concern and call for continued surveillance of the efficacy of SP in source and recipient populations, and should be considered when developing treatment policy for imported malaria cases in China and elsewhere.
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http://dx.doi.org/10.1016/j.ijpddr.2019.11.002DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6909128PMC
April 2020

Efficacy of directly-observed chloroquine-primaquine treatment for uncomplicated acute Plasmodium vivax malaria in northeast Myanmar: A prospective open-label efficacy trial.

Travel Med Infect Dis 2020 Jul - Aug;36:101499. Epub 2019 Oct 8.

Department of Internal Medicine, Morsani College of Medicine, University of South Florida, 3720 Spectrum Blvd, Suite 304, Tampa, FL, 33612, USA. Electronic address:

Background: Chloroquine (CQ) and primaquine (PQ) remain the frontline drugs for radical cure of uncomplicated P. vivax malaria in the Greater Mekong Sub-region (GMS). Recent reports of decreased susceptibility of P. vivax to CQ in many parts of the GMS raise concerns.

Methods: From April 2014 to September 2016, 281 patients with uncomplicated P. vivax infection attending clinics in border settlements for internally displaced people in northeast Myanmar were recruited into this study. Patients were treated with standard regimen of 3-day CQ and concurrent 14-day PQ (3.5 mg/kg total dose) as directly observed therapy, and followed for recurrent parasitemia within 28 days post-patency.

Results: Within the 28-day follow-up period, seven patients developed recurrent parasitemia, resulting in a cumulative rate of parasite recurrence of 2.6%. Five of the seven parasitemias recurred within two weeks, and two of those failed to clear within seven days, indicating high-grade resistance.

Conclusion: Although failure of CQ/PQ treatment of P. vivax was relatively infrequent in northeast Myanmar, this study nonetheless confirms that CQ/PQ-resistant strains do circulate in this area, some of them of a highly resistant phenotype. It is thus recommended that patients who acquire vivax malaria in Myanmar be treated an artemisinin-combination therapy along with hypnozoitocidal primaquine therapy to achieve radical cure.
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http://dx.doi.org/10.1016/j.tmaid.2019.101499DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7816571PMC
August 2021

Fabrication of CuO-Ag nanocomposites with enhanced durability and bactericidal activity.

J Colloid Interface Sci 2019 Dec 5;557:156-167. Epub 2019 Sep 5.

School of Materials Science and Engineering, Ocean University of China, Qingdao 266100, China. Electronic address:

Hybrid Cuprous oxide-silver (CuO-Ag) have attracted tremendous attention due to their various applications in photocatalysis, surface enhanced Raman scattering (SERS), and optical features. Here we expanded the application to exhibit excellent chemical stability and synergistic bactericidal. We prepared CuO-Ag heterostructure through thermally decomposing Ag-acetate to deposit Ag nanoparticles (Ag NPs) onto CuO surface. CuO-Ag heterostructure bears exceptional stability while exposing to oxygen, water, and light, owing to the physical coating of Ag NPs and transferring the electrons and holes inside the CuO to the surface through a Schottky barrier to prevent photocorrosion. The deposition of Ag NPs also improved the intensity and time of oxidative stress reaction of CuO, proved by reactive oxygen species (ROS) examination. Ag NPs distributed on the surface of CuO particles formed a large of ion release channel, resulting in excellent sustained release of copper ions. Density functional theory (DFT) calculations were used to investigate the mechanism of photocatalysis and ROS generation. The constructed CuO-Ag heterostructure exhibit highly long-term sterilization activity against Staphylococcus aureus (S. aureus) and Pseudomonas aeruginosa (P. aeruginosa) which were maintained around 70% and 80% and were increased by 40% and 50% compared with free CuO after being immersed in phosphate buffer saline (PBS) solutions within 14 days.
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http://dx.doi.org/10.1016/j.jcis.2019.09.015DOI Listing
December 2019

Increasing trends of malaria in a border area of the Greater Mekong Subregion.

Malar J 2019 Sep 12;18(1):309. Epub 2019 Sep 12.

Division of Infectious Diseases and International Medicine, Department of Internal Medicine, Morsani College of Medicine, University of South Florida, 3720 Spectrum Boulevard, Suite 304, Tampa, FL, 33612, USA.

Background: Intensive malaria transmission along international borders is a significant impediment to malaria elimination in the Greater Mekong Subregion (GMS) of Southeast Asia. Passive case detection (PCD) was used to study the dynamics and trends of malaria transmission at the China-Myanmar border to provide epidemiologic information for improved malaria control.

Methods: PCD was conducted in one hospital and 12 clinics near the Laiza town in northeast Myanmar from 2011 to 2016. Clinical malaria was diagnosed by microscopy and demographic information was captured using a structured questionnaire at the time of the patient's presentation for care.

Results: Over the study period, 6175 (19.7%) malaria cases were confirmed by microscopy from 31,326 suspected cases. The four human malaria parasite species were all identified, with Plasmodium vivax and Plasmodium falciparum accounting for 5607 (90.8%) and 481 (7.8%) of the confirmed cases, respectively. In contrast to the steady decline of malaria in the general GMS, the study site had an upward trend of malaria incidence with vivax malaria outbreaks in 2013 and 2016. Adult males, children under the age of 15, and those with occupations such as farming, being a soldier or student, had significantly higher risks of clinical malaria compared to having fevers from other aetiologies. A self-reported history of clinical malaria was also associated with a higher risk of confirmed malaria.

Conclusions: The China-Myanmar border area has experienced an overall upward trend of malaria incidence in recent years with P. vivax becoming the predominant species. Evidence-based control strategies need to focus on high-risk populations.
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http://dx.doi.org/10.1186/s12936-019-2924-6DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6739967PMC
September 2019

A novel mutation causes Hermansky-Pudlak syndrome type 4 with pulmonary fibrosis in 2 siblings from China.

Medicine (Baltimore) 2019 Aug;98(33):e16899

Department of Medical Genetics, Institute of Medical Biology, Peking Union Medical University & Chinese Academy of Medical Sciences.

Hermansky-Pudlak syndrome (HPS) is a rare autosomal recessive multisystem disorder characterized by oculocutaneous albinism (OCA) and bleeding diathesis, although it displays both genetic and phenotypic heterogeneity. Several genetic subtypes of HPS have been identified in human; however, the characterizations of HPS type 4 (HPS-4) genotype and phenotype remain unclear. This study was aimed to identify gene mutation responsible for HPS-4 with pulmonary fibrosis (PF).Two Chinese siblings in their 50 s afflicted with OCA and progressive dyspnea were recruited and underwent clinical and genetic examinations. In both patients, chest high-resolution computerized tomography showed severe interstitial PF in bilateral lung fields, and the pulmonary function test indicated restrictive lung disease. A novel homozygous frameshift mutation (NM_022081: c.630dupC; p.A211fs) in the HPS4 gene was identified by whole-exome sequencing analysis followed by Sanger DNA sequencing, and it segregated with the phenotypes. The c.630dupC mutation was not found in unaffected healthy controls. The patients were considered as HPS-4 with interstitial PF and eventually died of respiratory failure.This is the first report on the genotype and clinical phenotype of HPS-4 in China. Our results demonstrate the association between a novel frameshift mutation in HPS4 and severe PF with poor prognosis in HPS is presented.
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http://dx.doi.org/10.1097/MD.0000000000016899DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6831253PMC
August 2019

Multiple relapses of Plasmodium vivax malaria acquired from West Africa and association with poor metabolizer CYP2D6 variant: a case report.

BMC Infect Dis 2019 Aug 9;19(1):704. Epub 2019 Aug 9.

Department of Pathogen Biology and Immunology, Kunming Medical University, Kunming, Yunnan, 650500, People's Republic of China.

Background: Plasmodium vivax transmission in West Africa, dominant for the Duffy-negative blood group, has been increasingly recognized from both local residents as well as international travelers who contracted P. vivax malaria there. However, the relapsing pattern and sensitivity to antimalarial treatment of P. vivax strains originated from this region are largely unknown. There is evidence that the efficacy of primaquine for radical cure of relapsing malaria depends on host factors such as the hepatic enzyme cytochrome P450 (CYP) 2D6.

Case Presentation: A 49-year-old Chinese man was admitted to the Shanglin County Hospital in Guangxi Province, China, on December 19, 2016, 39 days after he returned from Ghana, where he stayed for one and a half years. He was diagnosed by microscopy as having uncomplicated P. vivax malaria. Treatment included 3 days of intravenous artesunate (420 mg total), and 3 days of chloroquine (1550 mg total), and 8 days of primaquine (180 mg total). Although parasites and symptoms were cleared rapidly and he was malaria-negative for almost two months, he suffered four relapses with relapse intervals ranging from 58 to 232 days. The last relapse occurred at 491 days from his first vivax attack. For the first three relapses, he was treated similarly with chloroquine and primaquine, sometimes supplemented with additional artemisinin combination therapies (ACTs). For the last relapse, he was treated with intravenous artesunate, 3 days of an ACT, and 7 days of azithromycin, and had remained healthy for 330 days. Molecular studies confirmed P. vivax infections for all the episodes. Although this patient was diagnosed to have normal glucose-6-phosphate dehydrogenase (G6PD) activity, his CYP2D6 genotype corresponded to a *2A/*36 allele variant suggesting of an impaired primaquine metabolizer phenotype.

Conclusions: This clinical case suggests that P. vivax malaria originating from West Africa may produce multiple relapses extending beyond one year. The failures of primaquine as an anti-relapse therapy may be attributed to the patient's impaired metabolizer phenotype of the CYP2D6. This highlights the importance of knowing the host G6PD and CYP2D6 activities for effective radical cure of relapsing malaria by primaquine.
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http://dx.doi.org/10.1186/s12879-019-4357-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6688248PMC
August 2019

The glucose-6-phosphate dehydrogenase Mahidol variant protects against uncomplicated Plasmodium vivax infection and reduces disease severity in a Kachin population from northeast Myanmar.

Infect Genet Evol 2019 11 24;75:103980. Epub 2019 Jul 24.

Department of Cell Biology and Medical Genetics, Kunming Medical University, Kunming, Yunnan Province, China. Electronic address:

Glucose-6-phosphate dehydrogenase (G6PD) deficiency is one of the most common red cell disorders in the world. The aim of this study was to investigate whether the G6PD Mahidol variant and haplotype 1311 T/93C, which are prevalent in the Kachin ethnic population along the China-Myanmar border area, offer protection against Plasmodium vivax infection. Malaria was monitored in nine villages near the Laiza township, Kachin State, Myanmar, where 258 cases of uncomplicated P. vivax were identified in 2013-2017. From the same villages, 250 unrelated, malaria-free participants were recruited to serve as the control cohort. Quantitative enzyme activity analysis in 100 healthy individuals identified that both male hemizygotes and female heterozygotes of the G6PD Mahidol variant had on average ~40% lower enzyme activity relative to the wild-type individuals. Compared with the overall prevalence of 25.2% in the control cohort, the G6PD Mahidol variant had a significantly lower prevalence (7.0%) among the 258 vivax patients (P <  .0001, χ test). Logistic regression analysis of G6PD genotypes stratified by sex showed that the individuals with the Mahidol 487A allele had dramatically reduced odds of having acute vivax malaria (adjusted odds ratio = 0.213 for male 487A hemizygotes, P < .0001, and 0.248 for female 487GA heterozygotes, P < .001). Furthermore, both 487A hemizygous male and 487GA heterozygous female patients had significantly lower asexual parasitemias than the wild-type patients, suggesting a potential effect on alleviating disease severity. In contrast, the silent mutation haplotype 1311 T/93C was highly prevalent (49.6%) in the study population, but it was not associated with altered G6PD enzymatic activities nor did it seem to provide protection against vivax infection or disease severity. Taken together, this study provided evidence that the Mahidol G > A mutation offers protection against P. vivax infection and potentially reduces disease severity in a Kachin population.
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http://dx.doi.org/10.1016/j.meegid.2019.103980DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6832843PMC
November 2019

Interactions of unstable hemoglobin Rush with thalassemia and hemoglobin E result in thalassemia intermedia.

Hematology 2019 Dec;24(1):459-466

a Department of Medical Genetics, Institute of Medical Biology , Chinese Academy of Medical Sciences & Peking Union Medical College , Kunming , People's Republic of China.

: The clinical consequences and significance of many unstable hemoglobins interacting with other hemoglobinopathies remain unrecognized. Here we first explore molecular and hematological characterizations of previously undescribed compound heterozygosity states for unstable hemoglobin Rush (Hb Rush, Beta 101 Glu > Gln, HBB:c.304G > C) with Hb E and different forms of thalassemia. : Hematological assays, globin gene mutation assays and β-globin gene cluster haplotype were conducted in 11 patients from 8 unrelated Chinese ethnic families with unexplained hemoglobin separation fraction in hemoglobin gel electrophoresis. : Hb Rush in various combinations with Hb E, β-thalassemias and α-thalassemia were identified. Hb Rush simple heterozygote was generally associated with mild hemolytic anemia, and the compound heterozygotes of Hb Rush and the other β-globin variants led to thalassemia intermedia phenotypes with moderate anemia. Hemoglobin electrophoreses showed that the co-presence of Hb Rush with either Hb E or β-thalassemias increased proportion of Hb Rush due to relative decrease of other globin chain synthesis. Beta-globin gene cluster haplotype analysis suggested a common origin of the Hb Rush variant in the Chinese families of different ethnic ancestry. : Unstable Hb Rush interacting with β-thalassemia result in thalassemia intermedia phenotypes, which demonstrated the clinical significance of Hb Rush and new insights into complex mechanism of clinical heterogeneity of thalassemia.
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http://dx.doi.org/10.1080/16078454.2019.1621020DOI Listing
December 2019

Identification of a new recombinant strain of echovirus 33 from children with hand, foot, and mouth disease complicated by meningitis in Yunnan, China.

Virol J 2019 05 8;16(1):63. Epub 2019 May 8.

Institute of Medical Biology, Chinese Academy of Medical Sciences and Peking Union Medical College, Kunming, 650118, People's Republic of China.

Background: Hand, foot, and mouth disease (HFMD) is a common childhood disease, which is usually caused by enterovirus A (EV-A) serotypes. Enterovirus A71 (EV-A71) and coxsackievirus A16 (CV-A16) are the main etiologic agents. Multiple serotypes of enterovirus B serotypes (EV-B) have been detected in outbreaks or sporadic cases of HFMD.

Results: During HFMD surveillance in Yunnan, China in 2013, two echovirus 33 (E-33) isolates were recovered in cell culture and typed by molecular methods from the cerebrospinal fluid (CSF) and feces of two sporadic cases of HFMD complicated by meningitis. Sequence analysis indicated that the study isolates, YNK35 and YNA12, formed an independent branch, and belonged to E-33 genotype H. Recombination analysis indicated multiple recombination events in the genomic sequence of isolate YNK35. The recombination mainly occurred in the non-structural coding region of P2 and P3, and involved intra-species recombination of species B.

Conclusion: In this study, the complete sequences of two E-33 isolates were determined. This is the first report of severe HFMD associated with E-33 in Yunnan China, and it enriches the number of full-length genome sequences of E-33 in the GenBank database.
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http://dx.doi.org/10.1186/s12985-019-1164-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6506940PMC
May 2019

In vitro susceptibility of Plasmodium falciparum isolates from the China-Myanmar border area to artemisinins and correlation with K13 mutations.

Int J Parasitol Drugs Drug Resist 2019 08 10;10:20-27. Epub 2019 Apr 10.

Department of Pathogen Biology and Immunology, Kunming Medical University, Kunming, Yunnan Province, 650500, China. Electronic address:

Mutations in the Kelch domain of the K13 gene (PF3D7_1343700) were previously associated with artemisinin resistance in Plasmodium falciparum. This study followed the dynamics of the K13 polymorphisms in P. falciparum parasites from the China-Myanmar border area obtained in 2007-2016, and their in vitro sensitivities to artesunate (AS) and dihydroartemisinin (DHA). The 50% effective concentration (EC) values of 133 culture-adapted field isolates to AS and DHA, measured by the conventional 72 h SYBR Green I-based assay, varied significantly among the parasites from different years; all were significantly higher than that of the reference strain 3D7. Compared with parasites from 2007 to 2008, ring survival rates almost doubled in parasites obtained in later years. Sequencing the full-length K13 genes identified 11 point mutations present in 85 (63.9%) parasite isolates. F446I was the predominant (55/133) variant, and its frequency was increased from 17.6% (3/17) in 2007 to 55.9% (19/34) in 2014-2016. No wild-type (WT) Kelch domain sequences were found in the 34 samples obtained from 2014 to 2016. In the 2014-2016 samples, a new mutation (G533S) appeared and reached 44.1% (15/34). Collectively, parasites with the Kelch domain mutations (after amino acid 440) had significantly higher ring survival rates than the WT parasites. Individually, F446I, G533S and A676D showed significantly higher ring survival rates than the WT. Although the drug sensitivity phenotypes measured by the RSA and EC assays may be intrinsically linked to the in vivo clinical efficacy data, the values determined by these two assays were not significantly correlated. This study identified the trend of K13 mutations in parasite populations from the China-Myanmar border area, confirmed an overall correlation of Kelch domain mutations with elevated ring-stage survival rates, and emphasized the importance of monitoring the evolution and spread of parasites with reduced artemisinin sensitivity along the malaria elimination course.
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http://dx.doi.org/10.1016/j.ijpddr.2019.04.002DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6479106PMC
August 2019

Complete Genome Sequence of a Human Enterovirus C99 Strain Isolated from a Healthy Child in Yunnan, China, in 2013.

Microbiol Resour Announc 2019 Apr 18;8(16). Epub 2019 Apr 18.

Institute of Medical Biology, Chinese Academy of Medical Sciences, and Peking Union Medical College, Kunming, People's Republic of China

The complete genome sequence of a human enterovirus C99 strain isolated from a healthy child in Yunnan, China, in 2013 was determined. The isolate belonged to genotype C, according to phylogenetic and homogeneity analyses.
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http://dx.doi.org/10.1128/MRA.01489-18DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6473154PMC
April 2019

Zinc oxide/vanadium pentoxide heterostructures with enhanced day-night antibacterial activities.

J Colloid Interface Sci 2019 Jul 19;547:40-49. Epub 2019 Mar 19.

Integrated Composites Laboratory (ICL), Department of Chemical & Biomolecular Engineering, University of Tennessee, Knoxville, TN 37934, USA. Electronic address:

Low photocatalytic efficiency of visible light and fast recombination of photo-generated carriers are two challenges facing the applications of photocatalyst sterilant zinc oxide (ZnO). Meanwhile, both light and dark photocatalytic activities are important. It is of great theoretical and practical significance to construct a day-night photocatalytic antibacterial material, which is beneficial to the effective use of energy and to tackle the limitation of using photocatalytic bacteriostat. ZnO nanoflowers decorated vanadium pentoxide (VO) nanowires heterojunction (ZVH) was firstly fabricated using a facile water-bathing method. The designed ZVH structure efficiently produced abundant reactive oxygen species (ROS) in both light and darkness. It yielded 99.8% and 99.0% of antibacterial rate against S. aureus due to oxidative stress induced by ROS in light and darkness, respectively. The generation of ROS played a major role in the antibacterial activities against S. aureus under both light and dark conditions. The prepared ZVH with improved antibacterial properties provides an alternative for day-night antibacterial agents.
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http://dx.doi.org/10.1016/j.jcis.2019.03.061DOI Listing
July 2019

Geographical heterogeneity in prevalence of subclinical malaria infections at sentinel endemic sites of Myanmar.

Parasit Vectors 2019 Feb 18;12(1):83. Epub 2019 Feb 18.

Department of Immunology, College of Basic Medical Sciences, China Medical University, Shenyang, 110122, Liaoning, China.

Background: The malaria burden of Myanmar still remains high within the Greater Mekong Subregion of Southeast Asia. An important indicator of progress towards malaria elimination is the prevalence of parasite infections in endemic populations. Information about malaria epidemiology is mostly derived from reports of confirmed acute malaria cases through passive case detection, whereas the prevalence of baseline subclinical malaria infections is much less known.

Methods: In this study, cross-sectional surveys were conducted during the rainy season of 2017 in four townships (Bilin, Thabeikkyin, Banmauk and Paletwa) of Myanmar with divergent annual malaria incidences. A total of 1991 volunteers were recruited from local villages and Plasmodium subclinical infections were estimated by light microscopy (LM), rapid diagnostic tests (RDTs) and nested PCR. The nested PCR analysis was performed with a modified pooling strategy that was optimized based on an initial estimate the infection prevalence.

Results: The overall malaria infection prevalence based on all methods was 13.9% (277/1991) and it differed drastically among the townships, with Paletwa in the western border having the highest infection rate (22.9%) and Thabeikkyin in central Myanmar having the lowest (3.9%). As expected, nested PCR was the most sensitive and identified 226 (11.4%) individuals with parasite infections. Among the parasite species, Plasmodium vivax was the most prevalent in all locations, while Plasmodium falciparum also accounted for 32% of infections in the western township Paletwa. Two RDTs based on the detection of the hrp2 antigen detected a total of 103 P. falciparum infections, and the ultrasensitive RDT detected 20% more P. falciparum infections than the conventional RDT. In contrast, LM missed the majority of the subclinical infections and only identified 14 Plasmodium infections.

Conclusions: Cross-sectional surveys identified considerable levels of asymptomatic Plasmodium infections in endemic populations of Myanmar with P. vivax becoming the predominant parasite species. Geographical heterogeneity of subclinical infections calls for active surveillance of parasite infections in endemic areas. The pooling scheme designed for nested PCR analysis offers a more practical strategy for large-scale epidemiological studies of parasite prevalence. Such information is important for decision-makers to put forward a more realistic action plan for malaria elimination.
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http://dx.doi.org/10.1186/s13071-019-3330-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6378722PMC
February 2019
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