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Objective@#To understand the survival status and influencing factors of HIV/AIDS patients with highly active antiretroviral therapy ( HAART ) among drug users in Yili Prefecture, Xinjiang from 2005 to 2019, so as to provide references for reducing AIDS mortality. @*Methods @#The demographic information, clinical stage, baseline CD4+T lymphocyte ( CD4 ) level and treatment status of HIV/AIDS patients with HAART in Yili Prefecture from 2005 to 2019 were collected through AIDS Antiretroviral Therapy Information System. The survival rate was calculated by the life table method. The influencing factors for survival time were analyzed by Cox proportional hazard regression model.@*Results@#Totally 1 935 patients were recruited, the median age receiving HAART was 37 years old and the median CD4 counts was 293/μL. The cumulative survival rates at 1, 5, 7 and 10 years were 97%, 78%, 73%, and 66%, respectively. The multivariate Cox proportional hazards regression analysis showed that the patients with body mass index of 18.5-<28.0 kg/m2 ( HR: 0.391-0.656, 95%CI: 0.234-0.958 ), baseline CD4>200/μL ( HR: 0.354-0.667, 95%CI: 0.232-0.841 ) , or missed medication in the last 7 days ( HR=0.009, 95%CI: 0.001-0.061 ) had lower risk of death; the patients with WHO clinical stage of Ⅱ-Ⅳ ( HR: 1.479-2.311, 95%CI: 1.004-3.288 ) or treatment delay ≥1 years ( HR: 1.287-1.388, 95%CI: 1.029-1.826 ) had higher risk of death. @*Conclusions@#The 5-year cumulative survival rate of HIV/AIDS patients with HAART in Yili Prefecture is 78%. Body mass index, baseline CD4 level, WHO clinical stage, treatment delay and missed medication in last 7 days were the influencing factors for survival time.
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This study aimed to construct the dual-gene expression vector pHsa-miR16-siRNA which can express human miR-16 and HBV X siRNA,and examine its regulatory effect on HBV gene expression in the HepG2.2.15 cell line.The expression vectors siR-1583 and pHsa-miR16-siRNA were designed and constructed.HepG2.2.15 cells were transfected with the empty vector,siR-1583,pmiR-16 and pHsa-miR16-siRNA,respectively.ELISA was performed to measure the expression of HBsAg and HBeAg in the culture supematant 48 and72 h post transfection.Fluorescence quantitative PCR was used to measure the HBV mRNA degradation efficiency and HBV DNA copy number.The results showed that the expression of HBV genes was significantly inhibited in HepG2.2.15 cells transfected with siR-1583,pmiR-16 and pHsa-miR16-siRNA,respectively,when compared with that in cells transfected with the empty vectors,with the inhibitory effect of pHsa-miR16-siRNA being the most significant.ELISA showed that the inhibitory rates of HBsAg and HBeAg in pHsa-miR16-siRNA transfected cells were correspondingly 87.3％ and 85.0％ at 48 h,and 88.6％ and 86.5％ at 72 h post transfection (P＜0.01vs.control group).RT-PCR showed that the level of HBV mRNA decreased by 80.2％ (t=-99.22,P＜0.01),the genomic HBV DNA by 92.8％ (t=-73.06,P＜0.01),and the supernatant of HBV DNA copy number by 89.8％ (t=-47.13,P＜0.01) in pHsa-miR16-siRNA transfected group.It was suggested that the dual-gene expression vector pHsa-miR16-siRNA can inhibit the replication of HBV more efficiently than a single-gene expression vector.
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OBJECTIVE To investigate the effects of LW-AFC, a new formula derived from Liuwei Dihuang decoction, on gut microbiota and the behavior of learning and memory of SAMP8 mice, a mouse model of Alzheimer Disease (AD), and identify the specific intestinal microbiota correlating with cognitive ability. METHODS Morris-water maze test, novel object recognition test and shuttle-box test were conducted to observe the ability of learning and memory. 16S rRNA amplicon sequencing (Illumina, San Diego, CA, USA) was employed to investigate gut microbiota. RESULTS The treatment of LW- AFC improved cognitive impairments of SAMP8 mice, including spatial learning and memory ability, active avoidance response, and object recognition memory capability. Our data indicated that there were significantly 8 increased and 12 decreased operational taxonomic units (OTUs) in the gut microbiota of SAMP8 mice compared with senescence accelerated mouse resistant 1 (SAMR1) strains, the control of SAMP8 mice. The treatment of LW- AFC altered 22 (16 increased and 6 decreased) OTUs in SAMP8 mice and among them, 15 OTUs could be reversed by LW-AFC treatment resulting in a microbial composition similar to that of SAMR1 mice. We further showed that there were 7 (3 negative and 4 positive correlation) OTUs significantly correlated with all the three types of cognitive abilities, at the order level, including Bacteroidales, Clostridiales, Desulfovibrionales, CW040, and two unclassified orders. LW-AFC had influences on bacterial taxa correlated with the abilities of learning and memory in SAMP8 mice and restored them to SAMR1 mice. CONCLUSION The effects of LW-AFC on improving cognitive impairments of SAMP8 mice might be via modulating intestinal microbiome and LW-AFC could be used as a potential anti-AD agent.
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Seeding dispersal is an active detachment exhibit in aging Pseudomonas aeruginosa biofilm. Yet, effect factors of this process in the biofilm of clinical isolated mucoid P. aeruginosa strain remain to be better characterized. In our previous work, one mucoid P. earuginosa strain PA17 was isolated from a patient with recurrent pulmonary infection. In this study, confocal scanning laser microscope combined with LIVE/DEAD viability staining revealed that PA17 biofilm exhibited earlier seeding dispersal than non-mucoid PAO1. We further compared the motility and the expression of motility-associated gene during biofilm development between PA17 and PAO1. PA17 was found to be impaired in all three kinds of motility compared to PAO1. Moreover, we investigated the expression of rhamnolipid-associated genes in PA17 and PAO1 biofilm. The expression of these genes was in accordance with the process of seeding dispersal. Our results indicated that rhamnolipid but not motility is associated with the initiation of seeding dispersal of PA17 biofilm.
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PURPOSE: To investigate the effect of primary tumorectomy on angiogenesis and pulmonary metastasis in osteosarcoma-bearing nude mice. METHODS: Osteosarcoma was introduced to nude mice via subcutaneous injection of MG-63 cells. One hundred and eighty osteosarcoma-bearing mice were used equally in 3 parallel experiments. The effect of tumorectomy (TR) on the expression of vascular endothelial growth factor (VEGF) and endostatin was investigated by ELISA. Meanwhile, the effect on angiogenesis was evaluated by Matrigel plug assay, and pulmonary metastasis assessed by calculating the metastatic foci. Sham-operation (SO) and untreated (UT) groups served as controls. RESULTS: The VEGF (TR: 79.55 ± 7.82 pg/mL vs. SO: 110.01 ± 5.69 pg/mL, UT: 123.50 ± 10.41 pg/mL; p < 0.01) and endostatin (TR: 47.09 ± 6.22 ng/mL vs. SO: 117.64 ± 7.39 ng/mL, UT: 126.73 ± 6.55 ng/mL; p<0.01) were down-regulated significantly after tumorectomy, and angiogenesis was significantly promoted simultaneously. The incidence of pulmonary metastatic foci was 80.0% in the TR group, 40.0% in the SO group and 35.0% in the UT group. CONCLUSION: Primary tumorectomy can down-regulate the expression of VEGF and endostatin and promote angiogenesis which leads to the acceleration of pulmonary metastasis. These findings imply that anti-angiogenic treatment can be considered after primary tumorectomy.
Subject(s)
Animals , Mice , Bone Neoplasms/pathology , Bone Neoplasms/surgery , Endostatins/blood , Lung Neoplasms/secondary , Neovascularization, Pathologic/etiology , Osteosarcoma , Vascular Endothelial Growth Factor A/blood , Collagen/administration & dosage , Drug Combinations , Enzyme-Linked Immunosorbent Assay , Hemoglobins/analysis , Laminin/administration & dosage , Mice, Nude , Neovascularization, Pathologic/pathology , Proteoglycans/administration & dosage , Time Factors , Tumor Cells, CulturedABSTRACT
We prepared single-chain immunoglobulin Fv fragments (scFv) SLH10 specific for the HepG2 cell line after biopanning from a large human-naive phage display library (Griffin. 1 Library). The three-dimensional (3D) structure of SLH10 was modelled by the Insight II molecule simulation software.The structure was refined using the molecular dynamics method.The structures with the least steric clashes and lowest energy were determined finally. The optimized structures of heavy (VH) and light (VL) variable chains of SLH10 scFv were obtained.Then SLH10 bivalent single-chain Fv (BsFv) was constructed that would be suitable for high-affinity targeting.SLH10 BsFv was generated by linking scFvs together and identified by sequencing. Its expression products were confirmed by western blot analysis.The relative molecular masses of scFv and BsFv were approximately 30 kDa and 60 kDa,respectively. Flow cytometry revealed that SLH10 BsFv bound the selected cell lines with greater signal intensity than the parental scFv. The improved antigen binding of SLH10 BsFv may be useful for immunodiagnostics or targeted gene therapy for liver cancer.