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AIMS: To investigate the associations of conicity index (C-index) and relative fat mass (RFM) with incident type 2 diabetes mellitus (T2DM) among adults in China. MATERIALS AND METHODS: A total of 10 813 participants aged over 18 years in Shenzhen Longhua district were enrolled in a follow-up study conducted from 2018 to 2022. The participants were categorized based on quartiles (Q) of C-index and RFM. The Cox proportional hazards model was performed to examine the relationships between C-index, RFM and the risk of T2DM. RESULTS: After adjusting for potential confounding factors, including age, sex, occupation, marital status, education level, smoking status, alcohol consumption, physical exercise, hypertension status, fasting blood glucose (FBG) and total cholesterol (TC), both C-index and RFM showed positive and independent associations with risk of T2DM. The multivariable-adjusted hazard ratios (95% confidence intervals) for T2DM risk in participants in C-index Q3 and Q4 compared with those in C-index Q1 were 1.50 (1.12, 2.02) and 1.73 (1.29, 2.30), and 1.94 (1.44, 2.63), 3.18 (1.79, 5.64), 4.91 (2.68, 9.00) for participants in RFM Q2, Q3 and Q4 compared with RFM Q1. These differences were statistically significant (all p < 0.05). CONCLUSION: C-index and RFM are strongly associated with new-onset T2DM and could be used to identify the risk of diabetes in large-scale epidemiological studies.
Subject(s)
Diabetes Mellitus, Type 2 , Humans , Diabetes Mellitus, Type 2/epidemiology , Female , Male , China/epidemiology , Middle Aged , Adult , Follow-Up Studies , Risk Factors , Anthropometry , Aged , Incidence , Adiposity , Body Mass Index , East Asian PeopleABSTRACT
Global warming is increasing the frequency and intensity of heat waves and droughts. One important phase in the life cycle of plants is seed germination. To date, the association of the temperature and water potential thresholds of germination with seed traits has not been explored in much detail. Therefore, we set up different temperature gradients (5-35 °C), water potential gradients (-1.2-0 MPa), and temperature × water potential combinations for nine native plants in the Loess Plateau region to clarify the temperature and water combinations suitable for their germination. Meanwhile, we elucidated the temperature and water potential thresholds of the plants and their correlations with the mean seed mass and flatness index by using the thermal time and hydrotime models. According to our findings, the germination rate was positively correlated with the germination percentage and water potential, with the former rising and the latter decreasing as the temperature increased. Using the thermal time and hydrotime models, the seed germination thresholds could be predicted accurately, and the germination thresholds of the studied species varied with an increase in germination percentage. Moreover, temperature altered the impact of water potential on the germination rate. Overall, the base water potential for germination, but not the temperature threshold, was negatively correlated with mean seed mass and was lower for rounder seeds than for longer seeds. This study contributes to improving our understanding of the seed germination characteristics of typical plants and has important implications for the management and vegetation restoration of degraded grasslands.
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This study aimed to evaluate spectacle-wearing compliance and identify the determinants associated with it in infants with bilateral corrective refractive errors. Infants agedâ <â 3 years with bilateral corrective refractive errors who were supplied with spectacles forâ >â 1 month were enrolled at the pediatric comprehensive clinic of Zhongshan Ophthalmic Center. Spectacle-wearing compliance was evaluated by calculating the percentage of spectacle-wearing time in the awake time (STIT), and its potential determinants were identified based on interviews with the infants' caregivers using univariate and multivariate logistic regression analysis. Pearson correlation analysis was performed to further determine the degree of correlation between spectacle-wearing compliance and weight of spectacles. A total of 366 infants (age: 20.85â ±â 9.06 months, male: 54.92%) were included. The mean percentage of STIT was 64.00%±41.69%. The communication between caregivers of different infants regarding spectacle-wearing experience (Pâ =â .004, ORâ =â 2.290, 95% confidence interval [CI] for ORâ =â 1.301-4.029), perceptions of spectacle-wearing importance (Pâ =â .000, ORâ =â 6.337, 95% CI for ORâ =â 3.664-10.961), and weight of spectacles (Pâ =â .000, ORâ =â 7.271, 95% CI for ORâ =â 4.141-12.769) were significantly associated with spectacle-wearing compliance. Besides, spectacle-wearing compliance was positively correlated with the weight of spectacles (Pâ <â .01), exhibiting a decreasing trend with the weight of spectacles. Overall, spectacle-wearing compliance requires improvement. Moreover, efficient strategies aimed at improving spectacle-wearing compliance, such as enhancing communication between caregivers of different infants regarding spectacle-wearing experience, raising awareness about the importance of wearing spectacles, and reducing the weight of spectacles, are urgently needed.
Subject(s)
Eyeglasses , Refractive Errors , Child , Humans , Male , Infant , Child, Preschool , Refractive Errors/therapy , Ambulatory Care Facilities , Communication , Correlation of Data , Patient ComplianceABSTRACT
BACKGROUND: Although the majority of pregnancies with preeclampsia are characterised by elevated blood pressure, preeclampsia is often associated with nephrotic syndrome with similar symptoms such as high proteinuria and bilateral lower limb oedema. In this study, we compared the maternal-foetal outcomes of pregnant women with preeclampsia in a population with nephrotic syndrome and explored the factors that contribute to the corresponding outcomes and disease development. METHODS: A total of 90 pregnant women were included in this study, of whom 30 had nephrotic syndrome and were diagnosed with preeclampsia during pregnancy, and 60 had nephrotic syndrome alone. Descriptive statistical analyses of baseline data were performed to analyse the effect of combined preeclampsia on maternal and foetal pregnancy outcomes using unadjusted and adjusted logistic regression models. RESULTS: In this study, the baseline data of the two study populations demonstrated no differences except for the history of caesarean section and 24-h proteinuria results, which were significantly different (P < 0.05). The risk of preterm birth in the nephrotic syndrome with preeclampsia group was 8.25 (95% CI:3.041-22.084 P < 0.05); for a low birth weight, the risk was 6.00 (95% CI:2.302-15.638 P < 0.05); for foetal distress,the risk was 5.667 (95% CI:2.070-15.514 P < 0.05); and the risk of foetal birth restriction was 7.429 (95% CI: 2.642-20.885 P < 0.05). A risk-based analysis of adverse maternal outcomes yielded a risk of miscarriage of 2.200 (95% CI: 0.584-8.291; P > 0.05). After adjusting the model for each outcome, significant risks of preterm labour, foetal birth restriction, and low birth weight were revealed (P < 0.05). CONCLUSION: Combined preeclampsia has a significantly higher risk of adverse pregnancy outcomes for the foetus.Therefore, the prevention and control of eclampsia in pregnant women should be improved to ensure maternal and neonatal health.
Subject(s)
Nephrotic Syndrome , Pre-Eclampsia , Premature Birth , Pregnancy , Infant, Newborn , Female , Humans , Pre-Eclampsia/epidemiology , Pre-Eclampsia/diagnosis , Premature Birth/epidemiology , Nephrotic Syndrome/complications , Nephrotic Syndrome/epidemiology , Cesarean Section , Pregnancy Outcome/epidemiology , Proteinuria/epidemiologyABSTRACT
Background: Triglyceride-glucose (TyG) index is a simple marker of insulin resistance. However, insufficient data is available on whether the TyG index is associated with worsening renal function (WRF) in the elderly. Therefore, this study was designed to explore the association between the TyG index and WRF based on a community elderly cohort. Methods: In this study, 7,822 elderly (aged ≥ 65 years) adults from southern China were enrolled and divided into four groups according to the TyG index quartiles. The primary endpoint was incident chronic kidney disease (CKD), defined as incident estimated glomerular filtration rate (eGFR) < 60 mL/min/1.73 m2. Additional endpoints included a decline in eGFR of 30% and 40% during the follow-up period. Results: During the median 2.04 year follow-up period, 1,541 (19.7%) participants developed CKD. After adjusting for confounding factors, multivariable Cox regression models revealed significant associations between TyG index and incident CKD (HR per SD increase, 1.21; 95% CI: 1.14-1.29), a decline in eGFR of 30% (HR per SD increase, 1.38; 95% CI: 1.26-1.50), and decline in eGFR of 40% (HR per SD increase, 1.42; 95% CI: 1.24-1.63). Furthermore, compared with those in Q1, participants in Q4 demonstrated a higher risk of developing CKD (HR, 1.59; 95% CI: 1.35-1.88). These positive associations remained consistent across different subgroup populations. Conclusion: Our study suggests a positive and independent association between the TyG index and WRF in the elderly.
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Background: Hypertension is a common complication in injection drug users (IDU), especially a high proportion of resistant hypertension occurs among them. However, the involving mechanisms remain largely unknown. Methods: We here investigated the key signaling moieties in resistant hypertension in drug users. Analyses were performed with high-throughput transcriptomic sequencing data of peripheral blood from individuals with drug-sensitive hypertension (Ctrl-DS), IDU with resistant hypertension (IDU-DR), and IDU with sensitive hypertension (IDU-DS). Results: We showed that 17 and 1 genes in IDU-DS, 48 and 4 genes in IDU-DR were upregulated and downregulated compared Ctrl-DS, and 2 and 4 genes were upregulated and downregulated in IDU-DR compared with IDU-DS, respectively (p ≤ 0.01 and |log2(FC)| ≥ 1). Differentially expressed genes (DEGs) between Ctrl-DS and IDU-DS were mainly involved in Gene ontology terms of immunoglobulin complex and blood microparticle. DEGs between IDU-DS and IDU-DR were mainly involved in immune system process and immunoglobulin complex. DEGs between Ctrl-DS and IDU-DR were mainly involved in immunoglobulin complex, blood microparticle and cytoplasmic vesicle lumen. We identified 2 gene clusters (brown modules, MEbrown; turquoise module, MEturquoise) correlated with IDU-DR and a gene cluster (magenta module, MEmagenta) correlated with IDU-DS by weighted gene co-expression network analysis (WGCNA). Functional analysis demonstrated that pathways of focal adhesion and focalin-1-rich granule lumen were involved in the development of IDU-DR, and the cytosolic large ribosomal subunit may relate to IDU-DR. Further, immune cell infiltration analysis demonstrated that the abundance of dendritic cells (DCs), natural Treg cells (nTreg), and exhausted T cells (Tex) in IDU-DR and IDU-DS, naïve CD8+ T cells in IDU-DS was significantly different compared with that in Ctrl-DS. The abundance of cytotoxic T cells (Tc) was significantly different between IDU-DS and IDU-DR. Conclusion: Our findings indicated a potential function of immunoregulation mechanisms for resistant hypertension.
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BACKGROUND: Disease situations are more aggressive in patients with childhood-onset systemic lupus erythematosus (cSLE) than in those with adult-onset SLE (aSLE). However, information on pregnant women with cSLE and its association with pregnancy outcomes is limited. This study aimed to compare pregnancies in patients with cSLE vs. aSLE, and further analyse the characteristics of cSLE in pregnant women and explore its association with adverse pregnancy outcomes. METHODS: Altogether, data of 167 pregnancies from 150 women, including 22 pregnancies with cSLE and 145 pregnancies with aSLE, were retrospectively analysed. Characteristics and disease activity were compared between the cSLE and aSLE groups during pregnancy. Associations between cSLE and the risk of active SLE (SLEPDAI > 4), active lupus nephritis (LN), and adverse pregnancy outcomes were analysed using logistic regression. RESULTS: The cSLE group had a higher incidence of active SLE (12/22 vs. 30/145, P = 0.001) and active LN (11/22 vs. 26/145, P = 0.001) than the aSLE group. In the multivariable analysis, cSLE was a risk factor for active SLE and active LN during pregnancy, with ORs of 4.742 (95%CI 1.678-13.405, P = 0.003) and 4.652 (95%CI 1.630-13.279, P = 0.004), respectively. No significant association between cSLE and the risk of composite adverse gestational outcomes was identified after sequentially adjusting pre-pregnancy characteristics and pregnancy factors (P > 0.05). CONCLUSION: Disease activity of women with cSLE in pregnancy was more aggressive than that of women with aSLE, which was similar to the characteristics of non-pregnant women with SLE. cSLE might have indirect effects on the risk of adverse pregnancy outcomes through LN and active disease. Therefore, closely monitoring patients with cSLE during pregnancy is crucial.
Subject(s)
Lupus Erythematosus, Systemic , Adult , Age of Onset , Cohort Studies , Female , Humans , Lupus Erythematosus, Systemic/complications , Lupus Erythematosus, Systemic/diagnosis , Lupus Erythematosus, Systemic/epidemiology , Pregnancy , Retrospective Studies , Risk FactorsABSTRACT
OBJECTIVE: To investigate the effect of artesunate and arsenous acid and their combination on the proliferation and apoptosis of human multiple myeloma cells and their mechanism. METHODS: Human multiple myeloma cell line RPMI 8226 cells were cultured and treated with 0, 1, 2, 4, 8 nmol/L arsenous acid and 0, 40, 80, 160, 320 µmol/L artesunate, respectively. The inhibition of cell growth was detected by CCK-8 assay. The apoptosis rate was detected by flow cytometry. QPCR was used to detect the mRNA expression of cell proliferation and apoptosis-related factors. The expression of cell proliferation, apoptosis-related factors and PI3K/AKT pathway protein were detected by Western blot. RESULTS: CCK-8 assay showed that the growth of multiple myeloma cells was inhibited by arsenous acid and artesunate. The IC50 of arsenous acid was 1.96 nmol/L, and artesunate was 153.96 µmol/L. Flow cytometry showed that arsenous acid, artesunate, and their combination could significantly increase the apoptosis of multiple myeloma cells. QPCR and Western blot showed that the arsenous acid, artesunate, and their combination treatment could inhibit the expression of mRNA and protein of cell proliferation-related factors interleukin-6 and vascular endothelial growth factor (P<0.05), inhibit apoptosis-related factor BCL-xl and promote the expression of mRNA and protein of Bax (P<0.05), and reduce the protein expression of p-PI3K and p-AKT in PI3K/AKT signaling pathway (P<0.05). Moreover, the combination effect of the two drugs on cell apoptosis and the above mentioned factors was obviously stronger than that of the two drugs alone. CONCLUSION: Artesunate combined with arsenous acid inhibits proliferation and promotes apoptosis of tumor cells through PI3K/AKT signaling pathway, and is superior to the effect of two drugs alone.
Subject(s)
Multiple Myeloma , Proto-Oncogene Proteins c-akt , Apoptosis , Artesunate , Cell Line, Tumor , Cell Proliferation , Humans , Phosphatidylinositol 3-Kinases/metabolism , Proto-Oncogene Proteins c-akt/metabolism , Signal Transduction , Vascular Endothelial Growth Factor AABSTRACT
BACKGROUND: Norovirus (NoV) is the main cause of non-bacterial acute gastroenteritis (AGE) outbreaks worldwide. From September 2015 through August 2018, 203 NoV outbreaks involving 2500 cases were reported to the Shenzhen Center for Disease Control and Prevention. METHODS: Faecal specimens for 203 outbreaks were collected and epidemiological data were obtained through the AGE outbreak surveillance system in Shenzhen. Genotypes were determined by sequencing analysis. To gain a better understanding of the evolutionary characteristics of NoV in Shenzhen, molecular evolution and mutations were evaluated based on time-scale evolutionary phylogeny and amino acid mutations. RESULTS: A total of nine districts reported NoV outbreaks and the reported NoV outbreaks peaked from November to March. Among the 203 NoV outbreaks, 150 were sequenced successfully. Most of these outbreaks were associated with the NoV GII.2[P16] strain (45.3%, 92/203) and occurred in school settings (91.6%, 186/203). The evolutionary rates of the RdRp region and the VP1 sequence were 2.1 × 10-3 (95% HPD interval, 1.7 × 10-3-2.5 × 10-3) substitutions/site/year and 2.7 × 10-3 (95% HPD interval, 2.4 × 10-3-3.1 × 10-3) substitutions/site/year, respectively. The common ancestors of the GII.2[P16] strain from Shenzhen and GII.4 Sydney 2012[P16] diverged from 2011 to 2012. The common ancestors of the GII.2[P16] strain from Shenzhen and previous GII.2[P16] (2010-2012) diverged from 2003 to 2004. The results of amino acid mutations showed 6 amino acid substitutions (*77E, R750K, P845Q, H1310Y, K1546Q, T1549A) were found only in GII.4 Sydney 2012[P16] and the GII.2[P16] recombinant strain. CONCLUSIONS: This study illustrates the molecular epidemiological patterns in Shenzhen, China, from September 2015 to August 2018 and provides evidence that the epidemic trend of GII.2[P16] recombinant strain had weakened and the non-structural proteins of the recombinant strain might have played a more significant role than VP1.
Subject(s)
Caliciviridae Infections , Gastroenteritis , Norovirus , Caliciviridae Infections/epidemiology , China/epidemiology , Disease Outbreaks , Gastroenteritis/epidemiology , Genotype , Humans , Norovirus/genetics , Phylogeny , Retrospective StudiesABSTRACT
Objective To prepare monoclonal antibodies (mAbs) against GII.4 norovirus P domain by multiple antigens in an immunization program. Methods BALB/c mice were immunized with the multiple GII.4 NoV P domain, namely 1996cluster (VA387), 2004cluster, 2006b cluster and 2010 cluster. The spleen cells from the immunized mice were fused with SP2/0 cells and the hybridoma cells were screened by ELISA. The supernatant of the mAbs was collected and purified by the limiting dilution assay. Its subtype was identified, and the specificity and neutralization were analyzed by indirect ELISA and HBGA blocking, respectively. Results We obtained thirteen hybridoma cell lines that stably secreted mAbs against GII.4 NoV P domain. Their titers reached above 10-4 after purification. The subtypes of the mAbs were identified as IgG1. Indirect ELISA showed that all the mAbs specifically bound to all GII.4 norovirus variants. Five mAbs specifically bound to GII.17, GII.3 and GII.6 variants. Three mAbs specifically bound to GII.2 variants and strongly blocked NoV P particle from binding to the histo-blood group antigen (HBGA) receptors. Conclusion The mAbs against GII.4 norovirus P domain have been obtained by combined antigens immunization program. Multi-antigen immunization can enhance immune response significantly and cross-react with other GII.4 norovirus variants. The findings provide a basis for further development of novel GII.4 norovirus vaccines and for the optimization of the immunization programs of combined multi-antigen vaccine candidates.
Subject(s)
Antibodies, Monoclonal , Antibodies, Viral , Caliciviridae Infections , Norovirus , Animals , Antibodies, Monoclonal/immunology , Antibodies, Viral/immunology , Caliciviridae Infections/immunology , Mice , Mice, Inbred BALB C , Norovirus/genetics , Norovirus/immunologyABSTRACT
BACKGROUND: The accurate interpretation of BRCA1/2 variants becomes increasingly important in breast cancer and other related cancers including ovarian cancer, prostate cancer, pancreatic cancer and so forth. In the past decades, especially before year 2015, limitations of techniques and lack of databases and guidelines have led to possible misinterpretation of the clinical significance of sequence variants of BRCA1/2. A published study reported reclassification of some BRCA1/2 variants previously classified as variants of uncertain significance (VUS) to likely pathogenic in breast or ovarian cancer patients from Korea. However, little is known about the situation in Chinese population. METHODS: We retrospectively retrieved 109 publications studying about BRCA1/2 variants of Chinese population from the year 1999 to year 2019 (March). After excluding publications of meta-analysis and publications with missing data, 72 publications were eventually retained for subsequent analysis. In total, 1,351 BRCA variants (673 BRCA1 variants and 678 BRCA2 variants) derived from 42,430 Chinese cancer patients were standardized and reinterpreted using ACMG/AMP 2015 guidelines and China Expert Consensus on BRCA variant interpretation by genetic counselors. RESULTS: Among the 1,351 BRCA variants, the majority of interpretation (91.7%, 1,239/1,351) remained the same as previously published. However, there were 112 (8.3%, 112/1,351) variants (64 BRCA1, 48 BRCA2) reclassified with different categories. CONCLUSIONS: Our results demonstrated that clinical significance of not only VUS, but also pathogenic/likely pathogenic variants varied from time to time in the Chinese population. Precise reinterpretation of BRCA1/2 variants is of crucial importance to genetic counseling or clinical decision-making for risk individuals or patients.
Subject(s)
Asian People/genetics , BRCA1 Protein/genetics , BRCA2 Protein/genetics , Breast Neoplasms, Male/diagnosis , Breast Neoplasms/diagnosis , Genetic Testing/standards , Adult , Breast/pathology , Breast Neoplasms/epidemiology , Breast Neoplasms/genetics , Breast Neoplasms/therapy , Breast Neoplasms, Male/epidemiology , Breast Neoplasms, Male/genetics , Breast Neoplasms, Male/therapy , China/epidemiology , Clinical Decision-Making/methods , Databases, Genetic , Female , Genetic Counseling/standards , Genetic Predisposition to Disease , Genetic Variation , Humans , Male , Middle Aged , Practice Guidelines as Topic , Retrospective Studies , Risk Assessment/methods , Risk Assessment/standards , Risk FactorsABSTRACT
Parechovirus A (PeV-A), which causes a wide variety of diseases, is prevalent among young children. However, little is currently known about PeV-A infections in children with acute gastroenteritis in mainland China. In this study, we investigated the molecular epidemiology of acute gastroenteritis in Shenzhen, southern China, with an emphasis on PeV-A infections. A total of 1220 stool specimens from 1220 outpatient children under 5 years old with acute gastroenteritis were collected from January 2016 to December 2018. Viral RNA was detected by a real-time RT-PCR and PCR method. The PeV-A isolates were genotyped by sequencing the VP3/VP1 region. Of 1220 specimens, 148 (12.1%) were positive for PeV-A. The predominant genotype was PeV-A 1B (68.9%), followed by PeV-A 4 (12.2%), PeV-A 14 (6.1%), PeV-A 1A (5.4%), PeV-A 6 (2.7%), PeV-A 3 (2.7%) and PeV-A 5 (2.0%). It was found that 68.2% of PeV-A infections occurred in the summer and rainy months (June to September) in southern China. The majority of PeV-A-positive patients (97.3%) were younger than 24 months old. PeV-A coinfection with norovirus, rotavirus, astrovirus and adenovirus was found in thirty specimens (30/148, 20.3%), five specimens (5/148, 3.4%), five specimens (5/148, 3.4%), and two specimens (2/148, 1.4%), respectively. Coinfections with more than one other enteric virus were not observed in any of the PeV-A-positive specimens. Phylogenetic analysis revealed that the PeV-A isolates from Shenzhen were closely related to each other and to strains circulating in China, suggesting endemic circulation of PeV-A in China. The results of this study indicate that PeV-A is one of important pathogens of acute gastroenteritis in young children and that coinfection is a possible mode of PeV-A infection. PeV-A associated with acute gastroenteritis exhibited high genotypic diversity in Shenzhen, southern China.
Subject(s)
Feces/virology , Gastroenteritis/epidemiology , Parechovirus/genetics , Parechovirus/isolation & purification , Picornaviridae Infections/epidemiology , Adenoviridae/isolation & purification , Astroviridae/isolation & purification , Child, Preschool , China/epidemiology , Diarrhea/epidemiology , Diarrhea/virology , Female , Gastroenteritis/virology , Genotype , Humans , Infant , Infant, Newborn , Male , Molecular Epidemiology , Norovirus/isolation & purification , Phylogeny , RNA, Viral/genetics , Real-Time Polymerase Chain Reaction , Rotavirus/isolation & purificationABSTRACT
Jiangmen is one of the Guangdong-Hong Kong-Macao Greater Bay Areas with frequent commercial intercourse, which is responsible for human immunodeficiency virus type 1 (HIV-1) rapid circulation and genetic evolution for recent years. As a novel HIV-1 second-generation recombinant was previously reported in Jiangmen but the systematic molecular epidemiological investigation was still unknown. A retrospective study on HIV-1 genotypic characteristics and the emergence of transmitted drug resistance in this region was necessary. A total of 224 newly diagnosed HIV-positive cases were randomly selected in Jiangmen City of Guangdong Province between 2018 and 2019. The partial gag (1080 bp), pol (840 bp), and env (460 bp) genes were amplified using nested polymerase chain reaction followed by sequencing. The phylogenetic and recombination analysis as well as HIV-1 drug resistance were performed to surveillance. Sexual transmission was determined to be the major risk factor in Jiangmen. Phylogenetic analysis detected the genotypic distribution as follows: CRF01_AE (36.65%,70 of 191), CRF07_BC (32.46%, 62 of 191), CRF08_BC (4.71%, 9 of 191), CRF55_01B (5.24%, 10 of 191), CRF59_01B (3.14%, 6 of 191), subtype B (4.71%, 9 of 191), subtype C (1.05%, 2 of 191) as well as unique recombinant forms (12.04%, 23 of 191) consisted of seven recombinant patterns, which originated from multiple regions of China. Low-level prevalence of Surveillance Drug Resistance Mutations (2.1%) were predicted but drug-resistant mutations showed at a high level (15.4%) especially mutations in RT gene at position 179 were found to be the most frequent in the therapy-naïve population. Our study highlighted the critical importance of monitoring the emerge of recombinant strains among newly diagnosed HIV-1 individuals along with drug resistance regularly to prevent multi-channel introduction and breakout of new HIV strains.
ABSTRACT
New recombinant variants are a predominant challenge for preventing the spread of the HIV-1 epidemic. In this study, we confirmed a novel HIV-1 CRF07_BC/CRF55_01B recombinant form for the first time, which was isolated from a male patient in Jiangmen, China. The genomic sequence of the variant with four CRF55_01B segments inserted into the CRF07_BC backbone is 8,510 bp in length, extending from nucleotides 669 to 9,293 according to the HXB2 genome. Specifically, the recombinant strain contains site mutations associated with drug resistance.
Subject(s)
Genome, Viral , HIV Infections/virology , HIV-1/genetics , HIV-1/isolation & purification , Recombination, Genetic , China , Drug Resistance, Viral/genetics , Genotype , Humans , Male , Mutation , Phylogeny , RNA, Viral/genetics , Sequence Analysis, DNAABSTRACT
BACKGROUND: Routine data on the use of preventive therapy (PT) for latent tuberculosis infection (LTBI) in students are scarce in high tuberculosis (TB) burden countries. This study aimed to investigate the effects of PT and identify factors related to PT abandonment during the school TB epidemic in Guangzhou, southern China. METHODS: Purified protein derivative (PPD) skin testing was performed on all staff and students in a vocational school in Guangzhou, southern China during December 2014. Subjects (n=362) with a reactive PPD induration ≥15 mm, or with papules, blisters, and a normal chest X-ray image were recommended for PT. The subjects were assigned to a PT group (n=156) and control group (n=206), respectively, on a voluntary basis. Subjects in the PT group received isoniazid (INH) combined with rifampicin (RFP) for 3 consecutive months; after which, the incidence of TB and protective rate of PT for reducing TB were observed during a 2-year follow up period. An improved questionnaire was used to identify factors that influenced treatment abandonment. All data were subjected to univariate and multivariate logistic regression analyses. RESULTS: Two cases in the PT group and 20 cases in the control group developed TB. The protective rate of PT for reducing TB was 86.8%. In the PT group, 69 cases finished PT, with a completion rate of 44.2%, and the incidence rates of adverse events and hepatotoxicity were 12.2% and 1.9%, respectively. Among 362 LTBI cases, a total of 293 cases abandoned PT. Discrimination (OR =7.173, 95% CI, 3.361-15.307), worry about adverse drug reactions (OR =2.752, 95% CI, 1.459-5.192), a low parental education level (OR =2.605, 95% CI, 1.420-4.777), and accepting the opinion of a non-TB specialist (OR =6.017, 95% CI, 3.077-11.765) were identified as high-risk factors for abandoning PT. CONCLUSIONS: A PT regimen consisting of INH combined with RFP for 3 consecutive months is reasonable for use in schools. Discrimination, worry about adverse drug reactions, a low parental education level, and accepting the opinion of a non-TB specialist are all factors that may increase the risk for treatment abandonment among LTBI cases. To overcome psychological obstacles is critical for improving treatment adherence.
ABSTRACT
Enterovirus 71 (EV71) is one of the most common pathogens of hand, foot, and mouth disease (HFMD). A rapid reverse transcription recombinase polymerase amplification (RT-RPA) assay was established to detect EV71 subgenotype C4 (EV71-C4). The 95% detection limit of the RT-RPA was 3.767 log10 genomic copies (LGC)/reaction. The specificity was 100%. In a clinical sample evaluation, this approach demonstrated sufficient clinical performance when compared with a commercial RT-qPCR diagnostic kit. Thus, the RT-RPA assay may be a promising alternative for the detection of EV71-C4.
Subject(s)
Enterovirus A, Human/isolation & purification , Hand, Foot and Mouth Disease/virology , Nucleic Acid Amplification Techniques/methods , Enterovirus A, Human/classification , Enterovirus A, Human/genetics , Hand, Foot and Mouth Disease/diagnosis , Humans , Limit of Detection , Recombinases/chemistry , Reverse TranscriptionABSTRACT
We examined sequence variation in the HIV-1 gag p6 region from 27 individuals infected with HIV-1 CRF07_BC. An additional 269 gag p6 sequences of CRF07_BC from the Los Alamos National Laboratory database were also analyzed. A unique deletion of seven amino acid (aa) (p6Δ7) (aa 30-36, PIDKELY, in the HXB2 genome) was observed to exist exclusively in CRF07_BC. Indeed, 54.1% (160/296) of the CRF07_BC sequences contained the p6Δ7 mutation. The prevalence of the p6Δ7 mutation was 37.2% (29/78) and 92.3% (48/52) in CRF07_BC-infected intravenous drug users and men who have sex with men (MSM), respectively. Our results demonstrate that the p6Δ7 mutation dominates in MSM infected by HIV-1 CRF07_BC in China and suggests that this deletion could serve as a useful marker for monitoring HIV-1 evolution and epidemic. In future studies, it will be of interest to determine whether such genotypic variation influences viral replication capacity and disease progression.
Subject(s)
Amino Acids/genetics , Genes, gag/genetics , HIV Infections/virology , HIV-1/genetics , Sequence Deletion/genetics , gag Gene Products, Human Immunodeficiency Virus/genetics , China , Genotype , Humans , Male , Mutation/genetics , Phylogeny , Sequence Analysis, DNA/methodsABSTRACT
Here, we report the genetic diversity of HIV-1 and emergence of novel HIV-1 unique recombinant forms (URF) in both HIV-infected intravenous drug users (IDU) and men who have sex with men (MSM) in Guangzhou, China. We further characterized a novel URF strain isolated from an HIV-infected MSM, GD698. Near full-length genome (NFLG) phylogenic analysis showed that this novel URF was composed of CRF07_BC and CRF55_01B, with two recombinant breakpoints (nt 6,003 and 8,251 relative to the HXB2 genome) in the vpu/env and env genes, respectively. Twenty six percent of the genome is classified as CRF55_01B, spanning part of vpu and most of the env gene. The remaining 74% of the genome is classified as CRF07_BC. Both the backbone CRF07_BC sequence and CRF55_01B fragment were clustered with the HIV-1 isolates found in MSM. The emergence of the novel HIV-1 recombinant indicates the ongoing recombinants derived from the CRF07_BC and CRF55_01B isolates, and provides critical insights into our understanding of the dynamics and complexity of the HIV-1 epidemic in China.
Subject(s)
HIV Infections/virology , HIV-1/genetics , Adult , China/epidemiology , Genes, Viral , Genetic Variation , HIV Infections/epidemiology , Homosexuality, Male , Humans , Male , Molecular Typing , Phylogeny , Sequence Analysis, DNAABSTRACT
Coxsackievirus A6 (CV-A6) is an important pathogen causing hand, foot and mouth disease (HFMD). The aim of this study was to develop and evaluate a rapid real-time reverse transcription recombinase polymerase amplification (RT-RPA) assay for detection of CV-A6. The sensitivity of this assay was 202 copies/reaction, with 100 % specificity. Furthermore, this assay yielded consistent results comparable with a commercial qRT-PCR diagnostic kit. This assay is therefore potentially useful for surveillance of CV-A6 infections and outbreak control.