Prevalence and determinants of virological failure, genetic diversity and drug resistance among people living with HIV in a minority area in China: a population-based study.

BACKGROUND: Liangshan Yi Autonomous Prefecture is one of the areas that most severely affected by human immunodeficiency virus (HIV) in China, and virological failure on antiretroviral therapy (ART) is serious in this area. Analyses of prevalence and determinants of ART failure, the genetic diversity and drug resistance among people living with HIV (PLWH) helps improve HIV treatment efficiency and prevent HIV transmission. METHODS: A total of 5157 PLWH were recruited from 2016 to 2017. The venous blood samples were subjected to RT-PCR, followed by sequencing of the HIV-1 pol gene, targeting the protease and reverse transcriptase fragments. HIV-1 diversity was analyzed using the DNAStar software and drug resistance mutations were analyzed using the Stanford University HIV Drug Resistance Database. RESULTS: A total of 2156 (41.81%) PLWH showed virological failure on ART. Males (ORm = 1.25), heterosexual behaviors and drug injection (ORm = 1.44) and mother to child transmission routes (ORm = 1.58), the clinical stage of AIDS (ORm = 1.35), having used illicit drugs and shared the needles (1-4 times: ORm = 1.34; more than 5 times: ORm = 1.52), having ever replaced ART regimen (ORm = 1.48) increased the risk of virological failure among PLWH, while higher education lever (ORm = 0.77) and ≥ 12 months on ART (12 ~ 36 months: ORm = 0.72; ≥36 months: ORm = 0.66) was associated with lower likelihood of virological failure. The data revealed that CRF07_BC (1508, 95.62%) were the most common strains, and the drug-resistant rate was 32.10% among PLWH with virological failure in this area. The high frequencies of drug resistance were found in EFV and NVP of NNRTIs, ABC, FTC and 3TC of NRTIs, and TPV/r in PIs. The most common mutations in NNRTIs, NRTIs and PIs were K103N/KN (64.69%), M184V/MV/I (36.29%) and Q58E/QE (4.93%), respectively. CONCLUSION: We concluded that surveillance of virological failure, HIV-1 subtypes, and drug resistance to understand HIV-1 epidemiology and guide modification of ART guidelines, and target prevention and control strategies should be formatted to reduce the virological failure and drug resistance to promote viral suppression and prevent HIV-1 transmission.

Synergistic effects of ascorbic acid and plant-derived ceramide to enhance storability and boost antioxidant systems of postharvest strawberries.

BACKGROUND: Excessive reactive oxygen species (ROS) may attack biological macromolecules and induce oxidative stress. The inhibition by ascorbic acid (AsA) on oxidative damage has been reported in fruits, while the barrier effect of ceramide has also been proven. However, there are few reports about the effects of ceramide-AsA interactions to enhance storability and boost antioxidant systems in fruits during storage. This study was conducted to study the synergistic effects of AsA in combination with ceramide on the quality of postharvest strawberry (Fragaria anannasa cv. Tianbao). RESULTS: Treatment with 100 mg L-1 AsA plus 1.2 mmol L-1 ceramide significantly delayed the rot of strawberries, reduced the water loss and the contents of ROS, malonaldehyde (MDA), and proline, however, increased the contents of total flavonoids, total phenols, and anthocyanins compared with other treatments. Also, treatment with 100 mg L-1 AsA plus 1.2 mmol L-1 ceramide significantly increased the activities of peroxidase (POD) and superoxide dismutase (SOD) but inhibited the activity of polyphenol oxidase (PPO). CONCLUSION: It is suggested that treatment with 100 mg L-1 AsA plus 1.2 mmol L-1 ceramide could significantly reduce the oxidative damage and maintain the storage quality of strawberries during storage by enhancing the antioxidant systems. © 2019 Society of Chemical Industry.

An Assessment of Trends in HIV-1 Prevalence and Incidence and Spatio-Temporal Analyses of HIV-1 Recent Infection Among MSM During the Surveillance Period Between 2018 and 2022 in Sichuan, China.

Background: Men who have sex with men (MSM) is one main type of high-risk activities facilitating HIV-1 transmission in Sichuan province. Previous works on HIV-1 incidence and prevalence among MSM only concentrated before 2018, the situation after that is unknown. In addition, the distribution of hot-spots related to current HIV-1 epidemic is also rarely known among MSM in Sichuan. Objective: To update trends of HIV-1 prevalence and incidence and to visualize hot-spots of ongoing transmission in Sichuan province during surveillance period among MSM between 2018 and 2022. Methods: Limiting Antigen Avidity assay was performed to detect recent infection within new HIV-1 diagnoses founded during surveillance period among MSM. The HIV-1 prevalence and incidence were calculated according to an extrapolation method proposed by publications and guidelines. Trend tests were performed using χ2 tests with linear-by-linear association. The spatial analysis was conducted with ArcGIS 10.7 to figure hot-spots of HIV-1 recent infections among MSM. Results: Between 2018 and 2022, 16,697 individuals participated in HIV-1 MSM sentinel surveillance program, of which 449 samples (98.25%) were tested with LAg-Avidity EIA, and 230 samples were classified as recent infection. Respectively, the overall prevalence and incidence were 2.74% and 3.69% (95% CI: 3.21, 4.16) and both had significant declining trends (p < 0.001). Luzhou city had a highest HIV-1 incidence (10.74%, 95% CI: 8.39, 13.10) over the study period and was recognized as a hot-spot for recent HIV-1 infection among MSM. Conclusion: During the surveillance period, both HIV-1 prevalence and incidence were declining. However, Luzhou city had an unusually high HIV-1 incidence and became an emerging hot-spot of recent HIV-1 infection among MSM. This finding suggested focused attention, cross-regional intervention strategies, and prevention programs are urgently required to curb the spread of ongoing transmission.

Endovascular stenting for atherosclerotic subclavian artery stenosis in patients with other craniocervical artery stenosis.

Atherosclerotic subclavian artery stenosis (SAS) accompanied with other craniocervical artery stenosis (OCAS) is not uncommon in practice. We sought to investigate the safety and efficacy of endovascular stenting for SAS in patients with OCAS. Between January 2004 and February 2012, 71 consecutive atherosclerotic SAS patients who underwent primary stenting in our medical center were included. The enrolled patients were divided into combined-SAS group (n = 51) and solitary-SAS group (n = 20) depending on the presence or absence of OCAS. Data of demographics, procedure, and the followed-up were retrieved and analyzed. The technical success rate was 95.8%; the clinical success rate was 90.1%. There was no catheter-related major stroke or death. The immediate outcomes had no statistical difference between groups. During a mean of 27 ± 20 months (range 2-88 months) followed-up, 7 (10.3%) restenosis and 12 (17.6%) clinical events were identified. The primary patency rate was 95.3, 84.9 and 84.9% at 12, 24 months, and final followed-up respectively, which had no statistical difference between groups (odds ratio (OR), 2.60; 95% confidence interval (CI), 0.54-12.53; P = 0.232). The overall clinical event-free survival rate was 93.5, 86.2 and 54.6%, respectively, where the result of combined-SAS group was inferior to that of the solitary-SAS group (OR, 3.34; 95% CI, 1.02-11.00; P = 0.047). Endovascular stenting was safe and feasible for atherosclerotic SAS in patients with OCAS, although the combined OCAS may have a significant influence on the long-term outcome. Further studies are warrant to investigate the effects of revascularization for multiple craniocervical artery stenoses on the cerebral hemodynamics and long-term outcomes.

Correlation of extracranial internal carotid artery tortuosity index and intraprocedural complications during carotid artery stenting.

BACKGROUND: To investigate the correlation between tortuosity of extracranial internal carotid artery (EICA) and intraprocedural complications in patients undergoing carotid artery stenting (CAS). METHODS: The study included 244 EICA in 223 patients undergoing CAS. Tortuosity in EICA was measured by the tortuosity index (TI). Multivariate logistic regression was performed to assess the independent risk factors of vasospasm during CAS. Receiver operating characteristic curve was performed to identify the cut-off of TI to predict vasospasm. RESULTS: During the 244 CAS, 71 EICA presented vasospasm and 114 CAS presented hypotension. High TI, long procedural duration and female are independent risk factors for vasospasm during CAS. TI of 118 was the optimal cut-off to predict vasospasm during CAS (sensitivity: 85.9%, specificity: 78.6%). Linear regression analysis demonstrated that TI is positively correlated with procedural duration (p < 0.001). There was no significant difference in TI between the hypotension and non-hypotension groups (p = 0.145). CONCLUSION: TI is an independent risk factor for vasospasm during CAS and a TI ≥118 has the high sensitivity and specificity to predict vasospasm. Our results indicate the value of assessing tortuosity of EICA prior to choosing or performing the procedure in patients with carotid stenosis or occlusion.

Stereotactic Aspiration Acts as an Effective Treatment for Malignant Middle Cerebral Artery Infarction.

Objective: This study seeks to explore the efficacy and prognosis of stereotactic aspiration for malignant middle cerebral artery infarction (mMCAI). Methods: A total of 50 mMCAI patients who were diagnosed and treated in our hospital from January 2018 to June 2020 were collected and then randomly divided into control group (decompressive craniectomy, n = 24) and study group (stereotactic aspiration, n = 26). After 1 and 6 months of treatment, the scores of the National Institutes of Health Stroke Scale (NIHSS), Glasgow Coma Scale (GCS), Barthel Index, and modified Rankin Scale (mRS) were used to evaluate the therapeutic effect. Additionally, the mortality and survival rates after treatment were recorded to compare the prognostic effect between the two groups. Results: One month after treatment, the GCS scores and Barthel Index score increased in both the control and study groups and were significantly higher in the study group. The follow-up results at 1 and 6 months after treatment showed that in comparison with the control group, stereotactic aspiration led to a higher survival rate and lower mortality rate; the latter had superior NIHSS score and mRS score and better prognosis. Conclusion: In comparison with decompressive craniectomy, stereotactic aspiration shows outstanding clinical efficacy and more advantages in the treatment of mMCAI. Therefore, stereotactic aspiration is more worthy of clinical application.

Mesenchymal Stem Cell-Derived Exosomes Improved Cerebral Infarction via Transferring miR-23a-3p to Activate Microglia.

Mesenchymal stem cells-derived exosome (MSCs-exo) is a potential method for cerebral infarction (CI) treatment. Here, western blot and qRT-PCR were carried out to measure the expression of proteins and genes, respectively. Modified neurological severity score and TTC staining were used to evaluate the brain injury of middle cerebral artery occlusion (MCAO) rats. Immunohistochemistry was performed to detect the expression of Iba-1, iNOS, and Arg-1 in tissues. Moreover, the rate of M1/M2 microglia was ensured by flow cytometry, and the concentration of pro-inflammatory factors in medium was measured using ELISA. Here, we found that miR-23a-3p is increased in human umbilical cord blood MSCs-exo. Bone marrow MSCs-exo (BMSCs-exo) could improve the injury in neuronal function and reduce the infarct size in vivo. However, the improvement of BMSCs-exo to CI was reversed by miR-23a-3p knockdown. The inhibition of BMSCs-exo to MCAO-induced microglia activation and M1 polarization and the upregulation of pro-inflammatory factors were limited by miR-23a-3p knockdown, which also confirmed in lipopolysaccharide-induced microglia. Overall, our data indicated that MSCs-exo improves CI via transferring miR-23a-3p, thus to induce the deactivation of microglia and M2 polarization. Our study revealed a new regulatory mechanism of CI.

[Plasma homocysteine levels in ischemic stroke patients with obstructive sleep apnea].

OBJECTIVE: To investigate the association of plasma homocysteine and OSA (obstructive sleep apnea) syndrome in ischemic stroke (IS). METHODS: A total of 92 male IS patients were classified by apnea hypopnea index (AHI) into 2 groups: non-OSA group (AHI < 5/h) and OSA group (AHI > or = 5). All patients were tested for plasma homocysteine when polysomnography was finished at (14 +/- 2) d after the onset of IS. RESULTS: The mean level of homocysteine was significantly higher in the OSA group than that in the non-OSA group (17 +/- 5 vs 11 +/- 3 micromol/L, P < 0.01). Pearson correlation analysis revealed a positive correlation between the homocysteine level and the severity of AHI (r = 0.482, P < 0.01). Further multiple linear regression analysis showed that AHI and folate were independent predictors of homocysteine level (R2 = 0.553, P < 0.01, beta for AHI = 0.671, beta for folate = -0.256). CONCLUSION: The severity of OSA is significantly associated with an elevated level of homocysteine in IS patients. And this association is independent of other causative factors of an elevated level of homocysteine.

Prevalence and Molecular Epidemiology of Transmitted Drug Resistance and Genetic Transmission Networks Among Newly Diagnosed People Living With HIV/AIDS in a Minority Area, China.

Introduction: Transmitted drug resistance (TDR) can compromise antiretroviral therapy (ART) efficacy. We aimed to understand the molecular epidemiology of TDR and its genetic transmission networks among newly diagnosed people living with HIV/AIDS (PLWH). Methods: A total of 1,318 newly diagnosed PLWH, identified in all population-based HIV screening in an HIV-affected county of a minority area of China (i.e., Butuo county), were enrolled between January 1, 2018, and November 31, 2018. HIV-1 pol gene sequences were used for phylogenetic and genotypic drug resistance analyses. The genetic transmission networks were identified. Results: The prevalence of TDR among newly diagnosed PLWH was 8.12% (107/1,318). Patients in the stage of AIDS (adjusted odds ratio, OR: 2.32) and who had a history of sharing a needle ≥5 times (adjusted OR: 3.89) were more likely to have an increased risk of TDR. The prevalence of TDR for non-nucleoside reverse transcriptase inhibitors (NNRTIs) is higher than that of other inhibitors, with a relatively high prevalence of three mutations [V179D/E/DE (4.93%), K103N/KN (3.11%), and E138A/G (1.52%)]. A total of 577 (43.78%) pol sequences were involved in the genetic transmission network, with 171 clusters ranging in size from 2 to 91 pol sequences; 37.38% (40/107) of individuals carrying TDR were involved in the network, and individuals with the same TDR-associated mutations were usually cross-linked. Conclusions: Our data suggest a relatively high level of TDR and many transmission clusters among the newly diagnosed PLWH. Targeted intervention, early identification, and monitoring of resistance are warranted to reduce the TDR and prevent HIV-1 transmission in areas with a high rate of HIV-1.

Circular RNA hsa_circ_0002024 suppresses cell proliferation, migration, and invasion in bladder cancer by sponging miR-197-3p.

Circular RNA hsa_circ_0002024 has been reported to be underexpressed in bladder cancer (BC). However, the biological role of hsa_circ_0002024 in BC and its underlying molecular mechanisms remain unclear. In this study, the expression levels of hsa_circ_0002024 and miR-197-3p were examined by quantitative real-time polymerase chain reaction. The proliferation abilities of EJ and T24 cells were assessed by Cell Counting Kit-8 and 5-ethynyl-20-deoxyuridine assays. Cell migration and invasion were evaluated by transwell migration and invasion assays. Luciferase reporter assay and rescue experiments were conducted to elucidate the underlying mechanism of hsa_circ_0002024. We found that the expression of hsa_circ_0002024 was downregulated, but that of miR-197-3p was upregulated in BC tissues and cell lines. Upregulation of hsa_circ_0002024 suppressed the proliferation, migration, and invasion of EJ and T24 cells. Hsa_circ_0002024 was confirmed as a direct target of miR-197-3p. In addition, we found that restoration of miR-197-3p expression could abolish hsa_circ_0002024-mediated inhibition of BC cell proliferation, migration, and invasion. In conclusion, our data demonstrated that hsa_circ_0002024 suppresses cell proliferation, migration, and invasion in BC by sponging miR-197-3p.

Stereotactic Aspiration of Necrotic Brain Tissue for Treating Malignant Middle Cerebral Artery Infarction: A Report of 13 Consecutive Cases.

BACKGROUND: This study aimed to evaluate the efficacy and safety of stereotactic aspiration of necrotic brain tissue for treating malignant middle cerebral artery infarction (MMI) in patients older than 60 years of age. CASE DESCRIPTION: A total of 13 consecutive patients with MMI (mean age, 67 ± 6.62 years) were enrolled in the study. These patients were treated with stereotactic aspiration of necrotic brain tissue within 72 hours from stroke onset between January 2016 and June 2017. The surgical results and clinical outcomes were evaluated in response to stereotactic aspiration of necrotic brain tissue. The mean preoperative infarction volume in the patients was found to be 153.46 ± 9.39 mL according to the latest computed tomography scan. The 30-day mortality was 2 out of 13 patients (15.4%). Patients were followed-up for 6 months to evaluate the efficacy of stereotactic aspiration of necrotic brain tissue using the modified Rankin Scale (mRS). Among the 11 surviving surgical patients, 6 (54.5%) had an mRS score of 3 (defined as moderate disability), 4 (36.4%) had an mRS score of 4 (defined as moderate to severe disability), and 1 (9.1%) had an mRS score of 5 (defined as severe disability). The probability of 6-month unfavorable outcome, defined as an mRS score of 5 or 6 (death), was 3 out of 13 (23.1%). CONCLUSIONS: Our results suggest the stereotactic aspiration of necrotic brain tissue is an effective and safe method in patients with MMI who are over 60 years of age.

Relationship between cerebral microbleeds and cognitive function in lacunar infarct.

OBJECTIVE: Little is known about the impact of cerebral microbleeds on cognitive function. This study investigated the distribution of cerebral microbleeds and their impact on cognitive function, in patients with lacunar infarct. METHODS: Patients with lacunar infarct were enrolled prospectively. Cerebral microbleeds were classified as absent, mild, moderate or severe, based on magnetic resonance imaging findings. Cognitive function was measured using the Montreal Cognitive Assessment (MoCA) questionnaire, with a total score of <26 indicating cognitive impairment. RESULTS: Of the 85 patients included in the study, 35 (41.2%) had cerebral microbleeds. They were more frequently observed in mixed and deep brain regions, but rarely in the cerebral lobes. Multiple logistic regression analysis demonstrated that presence of cerebral microbleeds (odds ratio [OR] 5.320), duration of education (OR 0.938) and age (OR 1.464) were independent predictors of cognitive impairment. There was a significant correlation between cerebral microbleed severity and MoCA score. CONCLUSION: The number and location of cerebral microbleeds were both closely associated with cognitive impairment, in patients with lacunar infarct.

Stereotactic aspiration plus subsequent thrombolysis for moderate thalamic hemorrhage.

OBJECTIVE: This study aimed to evaluate the efficacy and safety of stereotactic aspiration combined with subsequent thrombolysis in treating moderate thalamic hemorrhage (TH). METHODS: A total of 105 patients with TH were nonrandomly assigned to the conservative treatment group (n = 60) or to the aspiration group (n = 45). Patients in the aspiration group were treated with stereotactic aspiration plus subsequent thrombolysis for removal for their hematomas. RESULTS: The 30-day mortality in the conservative group was significantly higher than that in the aspiration group (28.3% (17/60) vs. 11.2% (5/45), P = 0.032). The rank of the 30-day Glasgow outcome scale in the conservative group was significantly lower than that in the aspiration group (P = 0.041), and the mean 30-day National Institutes of Health Stroke Scale score of the survivors in the conservative group was significantly higher than that in the aspiration group (16.5 ± 4. 2 vs. 14.2 ± 3.9, P = 0.012). There were a greater reduction in TH volume in the aspiration group than in the conservative group from day 1 to day 3 (-0.24% and 39.28%, respectively, P < 0.0001) and from day 1 to day 7 (26.58% and 63.26%, respectively, P < 0.0001). The rank of 90-day Glasgow outcome scale was significantly lower in the conservative group than that in the aspiration group (P = 0.015). Eighteen of 60 patients (30.0%) had a favorable outcome in the conservative group, whereas 23 of 45 patients (51.1%) had a favorable outcome in the aspiration group, and this difference was significant (P = 0.028). The 90-day cumulative mortality rate in the conservative group was significantly higher than that in the aspiration group (33.3% (20/60)) vs. 15.6% (7/45), P = 0.039). CONCLUSIONS: Stereotactic aspiration plus subsequent thrombolysis is effective and safe for moderate TH.

Association between plasma homocysteine levels and obstructive sleep apnoea in patients with ischaemic stroke.

We aimed to investigate the association between plasma homocysteine and obstructive sleep apnoea (OSA) syndrome in patients with ischaemic stroke. A total of 102 patients with ischaemic stroke were classified into four OSA groups based on their apnoea-hypopnoea index (AHI): absent (AHI < 5/hour); mild (5-14/hour); moderate (15-30/hour); and severe (> 30/hour). The mean (± standard deviation) homocysteine levels in the four OSA groups were: absent, 8.98 ± 3.74 µmol/L; mild, 11.46 ± 3.31 µmol/L; moderate, 14.18 ± 4.36 µmol/L; and severe, 18.57 ± 4.56 µmol/L; and these differences were statistically significant (p < 0.001). The Pearson correlation analysis revealed a positive correlation between homocysteine levels and the severity of AHI (r = 0.482, p < 0.001). Multiple linear regression analysis showed that AHI and folate were independent predictors of homocysteine levels (R(2) = 0.539, p < 0.001, ß for AHI = 0.259, ß for folate = -0.400). In conclusion, the severity of OSA is significantly associated with elevated homocysteine levels in patients with ischaemic stroke, and this association is independent of other factors that cause elevation in homocysteine.

Neuroprotective effect of ginsenoside Rb1 on glutamate-induced neurotoxicity: with emphasis on autophagy.

Ginsenoside Rb1 has been demonstrated with neuroprotective effects, but the mechanisms remain unclear. This study aimed to probe the effects and mechanisms of ginsenoside Rb1 on activation of autophagy in glutamate-injured neurons. Ginsenoside Rb1 of exponential concentrations (1.2, 12, 120 microM) or autophagy inhibitor 3-methyladenine (5mM) was added to culture medium for cortical neurons after being treated with glutamate. Cell viability was measured by MTT assay. Autophagosomes formation was observed with transmission electron microscope. Autophagy marked protein LC3 was detected with immunofluorescence and visualized under laser confocal microscopy. Changes of autophagy related protein Beclin-1 were measured with Western blot. We found that ginsenoside Rb1 protected cortical neurons from glutamate-induced cell injury. Autophagy was activated after glutamate treatment, with both autophagosomes and punctate LC3 increased significantly compared with control. Beclin-1 was elevated in glutamate-treated cells. Formation of autophagosome and punctate LC3 was attenuated by ginsenoside Rb1. The level of Beclin-1 in ginsenoside Rb1 treated cells was simultaneously decreased compared with glutamate-treated cells. These results suggested that inhibition of autophagy could be responsible for neuroprotective effects of ginsenoside Rb1 in glutamate-induced injury. Down-regulation of Beclin-1 may play an important role in this process.