Search

AbstractObjectives Data on angiotensin receptor-neprilysin inhibitor (ARNI) sacubitril-valsartan (SV) in patients undergoing maintenance dialysis is scarce. Our study aimed to investigate the effect of SV on patients undergoing dialysis.Methods We retrospectively reviewed the data of end-stage kidney disease (ESRD) patients undergoing either peritoneal dialysis (PD) or hemodialysis (HD) in our center. A total of 51 patients receiving SV treatment were enrolled in the SV group. Another 51 age and sex-matched patients on dialysis without SV treatment were selected as the control group. All the patients were regularly followed up in the dialysis clinic. Their clinical, biochemical, and echocardiographic parameters were all recorded at baseline and during follow-up. The effect and safety of SV were further analyzed.Results A total of 102 ESRD patients on dialysis (51 patients in the SV group and 51 patients in the control group) were finally enrolled. The median follow-up time was 349 days (interquartile range [IQR]: 217–535 days). The level of B-type natriuretic peptide (BNP) (median [IQR] before and after SV treatment: 596.35 pg/ml [190.6–1714.85] vs. 188.7 pg/ml [83.34–600.35], p

AIM: To evaluate the diagnostic value of panoramic immersion B-scan ultrasonography (Pano-immersion B-scan, PIB) in complex retinal detachment (RD), persistent hyperplastic primary vitreous (PHPV) and intraocular tumors. METHODS: The clinical data of 44 patients collected from May 2012 to December 2019 in Chinese PLA General Hospital was retrospectively studied. All of these patients underwent PIB of the eye, because it was difficult to diagnose by routine ocular fundus examination, conventional ultrasound or/and ultrasonic biomicroscope (UBM) due to opacity of refractive media, pupillary occlusion, large involvement or special location of the lesion. The imaging features of difficult cases in PIB were analyzed. The diagnosis accuracy rating of PIB were evaluated and contrasted with conventional ultrasound or UBM by the standard of intraoperative diagnosis or/and pathological results. RESULTS: According to intraoperative diagnosis or pathological results as gold standard, among the 44 cases, there were 19 cases missed diagnosis, misdiagnosed or difficult-to-diagnose by conventional ultrasound or UBM, including 4 cases of long-standing RD difficult to diagnose, 4 cases misdiagnosed, and 11 cases incompletely observed or miss diagnosed. The diagnostic accuracy rate of PIB and conventional ultrasound or UBM were 100% (44/44) and 56.82% (25/44), and the sensitivity of them were 100% and 56.82%. All the patients underwent PIB and were diagnosed as RD (15 cases), retinal and choroidal detachment (4 cases), subchoroidal hematocele (1 case), vitreous opacity and/or organic membrane formation (4 cases), PHPV (12 cases), iris and/or ciliary body tumors (3 cases), and choroidal tumors (6 cases). According to the intraoperative diagnosis or pathological results, the diagnostic coincidence rate of PIB was 100%, which was significantly higher than conventional ultrasound and UBM. CONCLUSION: PIB can help to accurately diagnose complex RD, PHPV, and intraocular masses with special location or/and excessive size. It has important diagnostic value for patients with equivocal findings at conventional ultrasound examination.

AIM: To present the clinical manifestations of 5 autosomal dominant cone-rod dystrophy (adCORD) patients from two Chinese families with cone-rod homeobox (CRX) mutation (p.R41W), and to explore the clinical heterogeneity of adCORD with CRX mutation (p.R41W). METHODS: Interrogation and ophthalmological examinations were undertaken in all patients and unaffected members. Analysis of clinical features was performed by visual acuity, slit lamp examination, visual field examination, fundoscopy, autofluorescence and spectral domain optical coherence tomography. Targeted next-generation sequencing was applied as a useful tool to identify the causative mutation of CORD genes. RESULTS: A CRX missense mutation c.121C>T was identified in all patients, resulting in an amino acid change from arginine acid to tryptophan (p.R41W). The patients presented with early onset, progressive and different severities with CORD. CONCLUSION: This is the first report of the clinical phenotype of CRX mutation (p.R41W) in Chinese families, and the mutation can lead to a wide range of various retinal phenotypes.

Based on the 16 scenes GF-1 satellite multi-spectral remote sensing images, through the adoption of data processing methods including orthorectification, geometric rectification, data fusion and image mosaic, integrated with field surveys, the remote sensing interpretation signs for the inland wetland types have been built, and the remote sensing survey of inland wetlands in Yadong region has been initiated, with six types of inland wetlands recognized in Yadong region, namely permanent rivers, seasonal rivers, lakes, salt lakes, alpine meadows, and inundated land. The spatial distribution characteristics and the spreading rules of these wetlands have also been revealed. Based on full understanding of the overall characteristics of the inland wetlands in the Yadong region, using the three phases of TM images acquired in 1989, 2003 and 2008 as well as the PMS2 data gathered by GF-1 in 2014, and the wide-range data (WFV3) gathered by GF-1 in 2020. As to the typical salt lakes, a long- time salt lakes transition study was carried out. The results show that the typical salt lakes in Yadong have been shrinking in the past three decades. The average annual shrinkage of Duoqing Co (Co means lake in Tibetan) was stronger than that of Gala Co, which are respective 87.30 hectares (usually short as ha; 1 ha equals to 0.01 km2) /a and 24.20 ha/a; the shrinkage degree of Gala Co was higher than that of Duoqing Co, shrank by 59.27% and 35.73% respectively. Based on the remote sensing survey results and an integrated analysis of the predecessors’ researchers, the reason for the shrinkage of the salt lakes is more inclined to geological factors. Geological process is manifested by a series of extensional faults at the bottom of the lake basin generated from tectonic activities, providing fluid infiltration channels, and inducing the eventual leakage of lake water to the lower strata. The result provides an important instance for understanding the evolution characteristics of wetlands and salt lakes in specific environment of the Tibetan Plateau.©2022 China Geology Editorial Office.

AIM: To evaluate the accuracy of segmented measurement of axial length (AL) in high myopia filled with silicone oil by immersion B-scan ultrasonography (immersion B-scan). METHODS: From June 2016 to June 2020, a total of 67 ultra-high myopia inpatients (67 eyes) who underwent silicone oil removal combined with cataract extraction and intraocular lens (IOL) implantation were retrospectively enrolled. The preoperative axial length (AL) of 31 patients with severe cataract were segmented measured using immersion B-scan (B-scan group) and another 36 patients with mild or moderate cataract were measured using IOLMaster 500 (IOLMaster group). The post-operative ALs in two groups were both measured using IOLMaster 500. The IOL power was calculated with Haigis formula. The differences in ALs between pre- and post-surgery, as well as the postoperative refractive spherical equivalent, absolute refractive error, the prediction deviation of postoperative refraction and best corrected visual acuity (BCVA) were compared. RESULTS: The pre- and post-operative ALs were 30.46±1.63 mm (range 28.09-33.51 mm) and 30.42±1.70 mm (range 28.03-33.90 mm) in B-scan group (t=0.644, P=0.542) and 30.51±1.21 mm (range 28.03-33.90 mm) and 30.43±1.27mm (range 28.54-33.50 mm) in IOLMaster group (t=1.843, P=0.074), respectively. Three months after surgery, BCVA were 0.45±0.13 (range 0.3-0.9) and 0.44±0.20 (range 0.2-1.0) in B-scan and IOLMaster group respectively (t=0.086, P=0.932). There was no significant difference of the postoperative spherical equivalent (-3.11±0.65 D vs -3.21±0.51 D, t=0.671, P=0.505) and the absolute refractive error (0.589±0.340 vs 0.470±0.245 D, t=1.615, P=0.112) between two groups. In B-scan group, absolute refractive error within ±0.50 D was found in 18 eyes (58.1%), within ±1.00 D in 26 eyes (83.9%), and within ±1.50 D in 31 eyes (100%). In IOLMaster group, absolute refractive error within ±0.50 D was found in 23 eyes (63.9%), within ±1.00 D in 34 eyes (94.4%), and within ±1.50 D in 36 eyes (Z=0.757, P=0.449). CONCLUSION: The segmented measurement of ALs by immersion B-scan shows comparable measurement accuracy with that of IOLMaster 500 in ultra-high myopia patients with severe cataract secondary to silicone oil filling and can obtain an ideal postoperative refractive state.

Compared to other crops, maize production demands relatively high temperatures. However, temperatures exceeding 35°C lead to adverse effects on maize yield. High temperatures (≥ 35°C) are consistently experienced by summer maize during its reproductive growth stage in the North China Plain, which is likely to cause irreversible crop damage. This study investigated the effects of elevating temperature (ET) treatment on the yield component of summer maize, beginning at the 9th unfolding leaf stage and ending at the tasseling stage. Results demonstrated that continuous ET led to a decrease in the elongation rate and activity of silks and an elongated interval between anthesis and silking stages, and eventually decreased grain number at ear tip and reduced yield. Although continuous ET before tasseling damaged the anther structure, reduced pollen activity, delayed the start of the pollen shedding stage, and shortened the pollen shedding time, it was inferred, based on phenotypical and physiological traits, that continuous ET after the 9th unfolding leaf stage influenced ears and therefore may have more significant impacts. Overall, when maize plants were exposed to ET treatment in the ear reproductive development stage, the growth of ears and tassels was blocked, which increased the occurrence of barren ear tips and led to large yield losses.

Easily extractable glomalin-related soil protein (EEG) released from arbuscular mycorrhizal fungi exhibits many roles in soil and plants, while it is not clear whether the biostimulator alone or in combination with agronomic practices can improve soil characteristics and fruit quality in citrus. The objective of this study was to analyze the effects of foliar sprays of EEG, singly or in combination with fruit bagging (FB), reflective film mulching (RF), and grass-proof cloth mulching (GPC) on root mycorrhizal colonization rate, fruit internal and external quality, and soil structure and fertility on an early-ripening Satsuma mandarin “Oita 4” (Citrus unshiu cv. Oita 4). Exogenous EEG application increased root mycorrhizal colonization, while agronomic practices dramatically inhibited root mycorrhizal colonization in EEG-treated trees. Foliar EEG application significantly improved the internal and external quality of fruits, but the combination of three agronomic practices with EEG did not further enlarge the improved effect on the external quality of fruit and even produced an inhibitory effect. Also, the addition of RF further amplified the improved effect of EEG on the contents of fruit vitamin C and soluble solids. EEG application also significantly elevated sucrose in the fruit pith and juice sac, fructose in the fruit peel, fruit pith, segment membrane, and juice sac, and glucose in the fruit pith, segment membrane, and juice sac. Additional RF treatment could increase sucrose in the fruit peel and juice sac as well as glucose in the fruit peel to varying degrees in EEG-treated trees. EEG application also significantly increased soil organic carbon, mean weight diameter, nitrate nitrogen, ammonium nitrogen, available phosphorus, and available potassium levels, with additional agronomic practices almost reducing the promoting effect of EEG on these soil variables. It has been summarized that a single EEG application had positive effects on fruit quality and soil fertility, while the additional agronomic practices resulted in little change or even suppressed the positive effects of EEG.

AIM:To use multifocal electroretinogram(MFERG)to evaluate patients' functional changes of the cone system in the macular center of the retina after taking hydroxychloroquine.METHODS:Retrospective study. Totally 264 eyes of 132 patients with rheumatoid arthritis examined in the Ophthalmology Department of the First Medical Center of the PLA General Hospital from January 2017 to November 2019 were included in the analysis. According to the length of medication period, patients were divided into 6 groups: 38 cases 76 eyes in group A did not take hydroxychloroquine, 38 cases 76 eyes in group B took hydroxychloroquine for 1a, 17 cases 34 eyes in group C took hydroxychloroquine for 2a, 18 cases 36 eyes in group D took hydroxychloroquine for 3a, 13 cases 26 eyes in group E took hydroxychloroquine for 5a, and 8 cases 16 eyes in group F took hydroxychloroquine for 5a or more and stopped for 3a. The changes of the best corrected visual acuity(BCVA)and the P1 wave amplitude density value of the first ring retinal response area in the central MFERG were compared among groups.RESULTS:There was no significant difference in BCVA among groups A to F(F=1.287, P=0.270), BCVA in A-F groups were(0.11±0.11, 0.11±0.10, 0.13±0.10, 0.15±0.10, 0.15±0.11, 0.14±0.10 LogMAR),but the amplitude density of P1 wave in group A(122.68±1.87nV/deg2)was significantly higher than other groups(115.76±1.71, 113.38±1.51, 109.10±2.52, 94.61±0.78, 94.02±0.91nV/deg2, all P

Synonymous codon usage bias (SCUB) analysis is an effective method to explore species specificity, evolutionary relationships and mRNA translation, as well as to discover novel genes, which are important for understanding gene function and molecular phylogeny. Cherries (Prunus subg. Cerasus) are flowering plant germplasm resources for edible and ornamental purposes. In this study, we analyzed the codon usage patterns of the 36 chloroplast genomes to provide a scientific basis for elucidating the evolution of subg. Cerasus. The results showed that the average GC content was 0.377, the average GC3 was 0.298, and the average ENC value was 49.69. Neutral-plot analysis, ENC-plot analysis, and PR2-plot analysis all indicated that natural selection was the main factor of codon usage bias in subg. Cerasus, whereas correlation analysis showed that gene expression level and GC1 also affect the codon usage pattern. The codon usage pattern was consistent across 36 species, and 30 high-frequency codons were identified, with preference for A/T endings; there were 23 optimal codons, and only GAU was identified in all individuals; structural differences existed between the clustering tree based on RSCU values and the phylogenetic tree based on CDS, elucidating the importance of locus mutations and no-preference codons in phylogenetic reconstruction. This study describes for the first time the SCUB pattern and characterization of subg. Cerasus chloroplast genomes and provides a new insight to explore the phylogeny of this subgenus.

Photosynthesis sustains plant life on earth and is indispensable for plant growth and development. Factors such as unfavorable environmental conditions, stress regulatory networks, and plant biochemical processes limits the photosynthetic efficiency of plants and thereby threaten food security worldwide. Although numerous physiological approaches have been used to assess the performance of key photosynthetic components and their stress responses, though, these approaches are not extensive enough and do not favor strategic improvement of photosynthesis under abiotic stresses. The decline in photosynthetic capacity of plants due to these stresses is directly associated with reduction in yield. Therefore, a detailed information of the plant responses and better understanding of the photosynthetic machinery could help in developing new crop plants with higher yield even under stressed environments. Interestingly, cracking of signaling and metabolic pathways, identification of some key regulatory elements, characterization of potential genes, and phytohormone responses to abiotic factors have advanced our knowledge related to photosynthesis. However, our understanding of dynamic modulation of photosynthesis under dramatically fluctuating natural environments remains limited. Here, we provide a detailed overview of the research conducted on photosynthesis to date, and highlight the abiotic stress factors (heat, salinity, drought, high light, and heavy metal) that limit the performance of the photosynthetic machinery. Further, we reviewed the role of transcription factor genes and various enzymes involved in the process of photosynthesis under abiotic stresses. Finally, we discussed the recent progress in the field of biodegradable compounds, such as chitosan and humic acid, and the effect of melatonin (bio-stimulant) on photosynthetic activity. Based on our gathered researched data set, the logical concept of photosynthetic regulation under abiotic stresses along with improvement strategies will expand and surely accelerate the development of stress tolerance mechanisms, wider adaptability, higher survival rate, and yield potential of plant species.

Steep canyons surrounded by high mountains resulting from large-scale landslides characterize the study area located in the southeastern part of the Tibetan Plateau. A total of 1766 large landslides were identified based on integrated remote sensing interpretations utilizing multisource satellite images and topographic data that were dominated by 3 major regional categories, namely, rockslides, rock falls, and flow-like landslides. The geographical detector method was applied to quantitatively unveil the spatial association between the landslides and 12 environmental factors through computation of the q values based on spatially stratified heterogeneity. Meanwhile, a certainty factor (CF) model was used for comparison. The results indicate that the q values of the 12 influencing factors vary obviously, and the dominant factors are also different for the 3 types of landslides, with annual mean precipitation (AMP) being the dominant factor for rockslide distribution, elevation being the dominant factor for rock fall distribution and lithology being the dominant factor for flow-like distribution. Integrating the results of the factor detector and ecological detector, the AMP, annual mean temperature (AMT), elevation, river density, fault distance and lithology have a stronger influence on the spatial distribution of landslides than other factors. Furthermore, the factor interactions can significantly enhance their interpretability of landslides, and the top 3 dominant interactions were revealed. Based on statistics of landslide discrepancies with respect to diverse stratification of each factor, the high-risk zones were identified for 3 types of landslides, and the results were contrasted with the CF model. In conclusion, our method provides an objective framework for landslide prevention and mitigation through quantitative, spatial and statistical analyses in regions with complex terrain.

Purpose: To develop a simple, precise and rapid high-performance liquid chromatographic technique coupled with photodiode array detection (DAD) method for the simultaneous determination of rutin, quercetin, luteolin, genistein, galangin and curcumin in propolis. Ultrasound-assisted extraction was applied to isolate six antioxidant phenolic compounds from propolis samples. Chromatographic separation was performed using an Eclipse XDB-C18 column (150 mm×4.6 mm, 5 μ) bu isocratic elution at 25 °C. The mobile phase consisted of phosphate buffered saline (pH = 4.5) and methanol (40/60, v/v). The flow rate was set at 0.8 ml/min and the effluent was monitored using a DAD set at 260 nm. Results: Excellent linear correlation coefficient was observed in the range of 0.9977 to 0.9997. The reproducibility of the method was 1.58 % (RSD) and accuracy was confirmed with average recovery ranging from 95.71 to 104.26 %. Six antioxidant phenolic compounds in propolis samples were successfully determined within 50 min. Conclusion: The proposed isocratic LC method gave good separation and accurate determination of rutin, quercetin, luteolin, genistein, galangin and curcumin in propolis. The proposed method showed good sensitivity, linearity, repeatability and accuracy. [ABSTRACT FROM AUTHOR]

Background: In many parts of the world, including in China, extreme heat events or heat waves are likely to increase in intensity, frequency, and duration in light of climate change in the next decades. Risk perception and adaptation behaviors are two important components in reducing the health impacts of heat waves, but little is known about their relationships in China. This study aimed to examine the associations between risk perception to heat waves, adaptation behaviors, and heatstroke among the public in Guangdong province, China. Methods: A total of 2,183 adult participants were selected using a four-stage sampling method in Guangdong province. From September to November of 2010 each subject was interviewed at home by a well-trained investigator using a structured questionnaire. The information collected included socio-demographic characteristics, risk perception and spontaneous adaptation behaviors during heat wave periods, and heatstroke experience in the last year. Chi-square tests and unconditional logistic regression models were employed to analyze the data. Results: This study found that 14.8%, 65.3% and 19.9% of participants perceived heat waves as a low, moderate or high health risk, respectively. About 99.1% participants employed at least one spontaneous adaptation behavior, and 26.2%, 51.2% and 22.6% respondents employed <4, 4-7, and >7 adaptation behaviors during heat waves, respectively. Individuals with moderate (OR=2.93, 95% CI: 1.38-6.22) or high (OR=10.58, 95% CI: 4.74-23.63) risk perception experienced more heatstroke in the past year than others. Drinking more water and wearing light clothes in urban areas, while decreasing activity as well as wearing light clothes in rural areas were negatively associated with heatstroke. Individuals with high risk perception and employing <4 adaptation behaviors during heat waves had the highest risks of heatstroke (OR=47.46, 95% CI: 12.82-175.73). Conclusions: There is a large room for improving health risk perception and adaptation capacity to heat waves among the public of Guangdong province. People with higher risk perception and fewer adaptation behaviors during heat waves may be more vulnerable to heat waves. [ABSTRACT FROM AUTHOR]

Soybean mosaic virus (SMV), a member of the genus Potyvirus, is a major pathogen of soybean plants in China, and 16 SMV strains have been identified nationwide based on a former detailed SMV classification system. As the P3 gene is thought to be involved in viral replication, systemic infection, pathogenicity, and overcoming resistance, knowledge of the P3 gene sequences of SMV and other potyviruses would be useful in efforts to know the genetic relationships among them and control the disease. P3 gene sequences were obtained from representative isolates of the above-mentioned 16 SMV strains and were compared with other SMV strains and 16 Potyvirus species from the National Center for Biotechnology GenBank database. The P3 genes from the 16 SMV isolates are composed of 1 041 nucleotides, encoding 347 amino acids, and share 90.7-100% nucleotide (NT) sequence identities and 95.1-100% amino acid (AA) sequence identities. The P3 coding regions of the 16 SMV isolates share high identities (92.4-98.9% NT and 96.0-100% AA) with the reported Korean isolates, followed by the USA isolates (88.5-97.9% NT and 91.4-98.6% AA), and share low identities (80.5-85.2% NT and 82.1-84.7% AA) with the reported HZ1 and P isolates from Pinellia ternata. The sequence identities of the P3 genes between SMV and the 16 potyviruses varied from 44.4 to 81.9% in the NT sequences and from 21.4 to 85.3% in the AA sequences, respectively. Among them, SMV was closely related to Watermelon mosaic virus (WMV), with 76.0-81.9% NT and 77.5-85.3% AA identities. In addition, the SMV isolates and potyvirus species were clustered into six distinct groups. All the SMV strains isolated from soybean were clustered in Group I, and the remaining species were clustered in other groups. A multiple sequence alignment analysis of the C-terminal regions indicated that the P3 genes within a species were highly conserved, whereas those among species were relatively variable.

AIM:To evaluate the accuracy of 20 MHz immersion B-scan ultrasonography in observing lens and to investigate the value of this noninvasive preoperative diagnosis method in alkali burn eyes.METHODS: It was a comparative study. Fifty-six cases (56 eyes) of alkali burn eyes were examined by ultrasound biomicroscopy (UBM) and immersion 20 MHz B-scan ultrasonography from June 2011 to April 2013, the images were analyzed, and the ultrasonographic diagnosis compared with the operation results.RESULTS: In 56 alkali burn eyes examined by UBM, the lens were not detected in 16 eyes; the IOL could be detected in 2 eyes; the anterior lens capsule surface or/and the front lens could be detected in 18 eyes, and lens opacification in 3 eyes of them; suspected abnormal lens were detected in the other 20 eyes. In all the same eyes examined by immersion 20 MHz B-scan ultrasonography, the lens were not detected in 16 eyes; the IOL could be detected in 2 eyes; 24 abnormal lens (opacity, lens expansion, shrinkage) and 14 normal lens were found. Compared with the intraoperative findings, the diagnostic accordance rate of the immersion 20 MHz B-scan appearance of lens was 100% (56/56), which was significantly higher than examined by UBM 57.14% (32/56) (χ2=30.55, P=0.0000).CONCLUSION:Immersion 20 MHz B-scan ultrasonography can observe the lens accurately in alkali burn eyes. It has important clinical value to combine with UBM in eyes of alkali burn.

AIM:To evaluate the accuracy of axial length (AL) measurements obtained from immersion B-scan ultrasonography (immersion B-scan) for intraocular lens (IOL) power calculation in patients with high myopia and cataracts.METHODS:Immersion B-scan, contact A-scan ultrasonography (contact A-scan), and the IOLMaster were used to preoperatively measure the AL in 102 eyes from 102 patients who underwent phacoemulsification and IOL implantation. Patients were divided into two groups according to the AL:one containing patients with 22 mm≤ALRESULTS:In group A, ALs measured by immersion B-scan (23.48±1.15) didn’t differ significantly from those measured by the IOLMaster (23.52±1.17) or from those by contact A-scan (23.38±1.20). In the same group, the standard deviation (SD) of the mean error (ME) of immersion B-scan (-0.090±0.397 D) didn’t differ significantly from those of IOLMaster (-0.095±0.411 D) and contact A-scan (-0.099±0.425 D). In group B, ALs measured by immersion B-scan (27.97±2.21 mm) didn’t differ significantly from those of the IOLMaster (27.86±2.18 mm), but longer than those measured by Contact A-scan (27.75±2.23 mm, P=0.009). In the same group, the standard deviation (SD) of the mean error (ME) of immersion B-scan (-0.635±0.157 D) didn’t differ significantly from those of the IOLMaster (-0.679±0.359 D), but differed significantly from those of contact A-scan (-0.953±1.713 D, P=0.028).CONCLUSION:Immersion B-scan exhibits measurement accuracy comparable to that of the IOLMaster, and is thus a good alternative in measuring AL in eyes with high myopia when the IOLMaster can’t be used, and it is more accurate than the contact A-scan.

Azvudine is a novel nucleoside reverse transcriptase inhibitor with antiviral activity on human immunodeficiency virus, hepatitis B virus and hepatitis C virus. Here we reported the in vitro activity of azvudine against HIV-1 and HIV-2 when used alone or in combination with other antiretroviral drugs and its drug resistance features. Azvudine exerted highly potent inhibition on HIV-1 (EC(50)s ranging from 0.03 to 6.92 nM) and HIV-2 (EC(50)s ranging from 0.018 to 0.025 nM). It also showed synergism in combination with six approved anti-HIV drugs on both C8166 and PBMC. In combination assay, the concentrations of azvudine used were 1000 or 500 fold lower than other drugs. Azvudine also showed potent inhibition on NRTI-resistant strains (L74V and T69N). Although M184V caused 250 fold reduction in susceptibility, azvudine remained active at nanomolar range. In in vitro induced resistant assay, the frequency of M184I mutation increased with induction time which suggests M184I as the key mutation in azvudine treatment. As control, lamivudine treatment resulted in a higher frequency of M184I/V given the same induction time and higher occurrence of M184V was found. Molecular modeling analysis suggests that steric hindrance is more pronounced in mutant M184I than M184V due to the azido group of azvudine. The present data demonstrates the potential of azvudine as a complementary drug to current anti-HIV drugs. M184I should be the key mutation, however, azvudine still remains active on HIV-1LAI-M184V at nanomolar range.