Purpose The genetic diversity and genetic predisposition for drug resistance mutations are the primary features of human immunodeficiency virus type 1 (HIV-1), which could cause the incidence of failure of antiretroviral therapy (ART). This study investigates the distribution of various HIV-1 genotypes and the incidence of pretreatment drug resistance (PDR) in the antiretroviral-naive HIV-1 infected participants in Xi’an, China. Patients and Methods In this study, a cross-sectional analysis was carried out at the Xi’an Eighth Hospital between January 2020 and December 2021 among newly-diagnosed ART-naive HIV-1 infected participants. A nested PCR technique was used for amplifying the target segment of 1.3 kb present in the pol gene that spanned the reverse transcriptase and the protease regions. HIV-1 genotypes and the PDR-associated mutations were identified using the Stanford HIV Drug Resistance Database. Results A total of 317 pol gene sequences were retrieved, amplified, and sequenced. The circulating recombinant form (CRF), CRF07_BC (51.7%) was seen to be the most prevalent HIV-1 genotype, followed by other genotypes like CRF01_AE (25.9%), B (14.2%), and CRF55_01B (4.7%). PDR was found in 18.3% of the population. The PDR mutation frequency in the non-nucleoside reverse transcriptase inhibitor (NNRTI) (16.1%) was significantly higher compared to that of the nucleoside reverse transcriptase inhibitor (NRTI) (4.4%) and the protease inhibitor (0.9%). V179D/E (both were 4.4%) was seen to be the most predominant type of NNRTI mutation. K65R and M184V (1.3%) were the most frequent NRTI-associated mutations. About half (48.3%) of the sequenced HIV-1 strains that had mutations could show a potential low-level NNRTI resistance owing to V179D/E. Multivariate regression analysis revealed one PDR mutation associated with subtype CRF01_AE (p=0.002) and CRF55_01B (p<0.001) as a higher risk mutation. Conclusion Diverse and complex HIV-1 genotypes are distributed in Xi’an, China. Considering new evidence, it is necessary to screen for baseline HIV-1 drug resistance among the newly-diagnosed HIV-1 individuals.
Objective. To explore the proportion and characteristic of Chinese adults meeting The Systolic Blood Pressure Intervention Trial (SPRINT) eligibility criteria and assess its generalizability. Method. Our study was based on a cross-sectional, population-based survey with a sample of 26,093 participants aged over 20 years. The SPRINT eligibility criteria were age ≥ 50 years, elevated SBP of 130 to 180 mmHg depending on the number of antihypertensive medication classes being taken, and increased cardiovascular disease (CVD) but without diabetes, history of stroke and estimated glomerular filtration rate < 20 ml / min / 1.73 m 2 , or receiving dialysis. Results. Overall, we estimated that 4,036 (15.5%) participants would meet the SPRINT eligibility criteria. They were generally older, likely to be female, lower educational level, tended to be more overweight, and had higher Framingham risk score compared with overall population or subjects aged ≥ 50 years. Of participants eligible for SPRINT, most (56.2%) of them were not treated for hypertension, and 542 (13.4%) were not previously considered to have hypertension or need for antihypertension therapy. Among the 11,637 adults with hypertension, 3,494 (30.0%) would potentially benefit from treatment intensification. The most common antihypertensive medication class being taken was diuretic agents. Conclusion. A substantial percentage of Chinese subjects meet the SPRINT eligibility criteria. Further studies are needed to assess the cost-effectiveness from treatment intensification in Chinese setting.
IntroductionDiabetic nephropathy (DN) is a major reason that could lead to kidney failure. Lysozyme (LYZ) is a part of innate immunity and has been shown to have an antibacterial function. In addition, lysozyme (LYZ) has been reported to be capable of inducing nephropathy, implying a possible association between impaired renal function and lysozyme expression.Material and methodsA mouse model of streptozotocin-induced diabetic nephropathy mice model was used to investigate the correlation between DN and LYZ expression, the function of LYZ was confirmed by knockdown and overexpression of LYZ in vivo, and we used immunohistochemistry (IHC) to assess fibrosis-related marker and fibrosis-related cytokine, Masson staining was used to assess renal fibrosis, CCK-8 was used to assess fibroblast proliferation of fibroblasts, the JAK inhibitor AG490 was used to confirm the role played by JAK in this effect, Western-blot was used to investigate the underlying mechanisms.ResultsMechanistically, 25 nM glucose promotes the expression of LYZ in fibroblastic cells, and LYZ may in turn promote the proliferation of renal interstitial fibroblasts. Western blot shows that glucose can activate STAT3 in an LYZ-dependent manner, and JAK inhibitor AG490 can partially suppress LYZ-induced STAT3 activation. Furthermore, we have observed that overexpression of LYZ is associated with the senescent phenotype of renal tubular epithelial cells (RTECs) in vivo.ConclusionsLysozyme promotes kidney fibrosis via the JAK/STAT3 signaling pathway in diabetic nephropathy, and glucose may promote fibroblast proliferation by promoting LYZ auto-secretion.
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