Outcomes and risk factors for infection after endovascular treatment in patients with acute ischemic stroke.

AIMS: Infection is a common complication following acute ischemic stroke (AIS) and significantly contributes to poor functional outcomes after stroke. This study aimed to investigate the effects of infection after endovascular treatment (post-EVT infection) on clinical outcomes and risk factors in patients with AIS. METHODS: We retrospectively analyzed AIS patients treated with endovascular treatment (EVT) between January 2016 and December 2022. A post-EVT infection was defined as any infection diagnosed within 7 days after EVT. The primary outcome was functional independence, defined as a modified Rankin scale (mRS) score of 0-2 at 90 days. A multivariable logistic regression analysis was conducted to determine independent predictors of post-EVT infection and the associations between post-EVT infection and clinical outcomes. RESULTS: A total of 675 patients were included in the analysis; 306 (45.3%) of them had post-EVT infections. Patients with post-EVT infection had a lower rate of functional independence than patients without infection (31% vs 65%, p = 0.006). In addition, patients with post-EVT infection achieved less early neurological improvement (ENI) after EVT (25.8% vs 47.4%, p < 0.001). For safety outcomes, the infection group had a higher incidence of any intracranial hemorrhage (23.9% vs 15.7%, p = 0.01) and symptomatic intracranial hemorrhage (10.1% vs 5.1%, p = 0.01). Unsuccessful recanalization (aOR 1.87, 95% CI 1.11-3.13; p = 0.02) and general anesthesia (aOR 2.22, 95% CI 1.25-3.95; p = 0.01) were identified as independent predictors for post-EVT infection in logistic regression analysis. CONCLUSION: AIS patients who develop post-EVT infections are more likely to experience poor clinical outcomes. Unsuccessful recanalization and general anesthesia were independent risk factors for the development of post-EVT infection.

Low-to-moderate dose statins improve the functional outcome of acute ischemic stroke with conventional medication treatment.

Background: Low-to-moderate dose statins (LMDSs) are more commonly used among Asian acute ischemic stroke (AIS) patients in clinical practice. However, the correlation between the LMDS use and prognosis has not been evaluated in AIS patients with conventional medication treatment alone. This study aimed to investigate the influence of LMDS on the prognosis of AIS patients and how prognosis and potential prognostic factors interact with different statin doses. Methods: This retrospective cohort study included AIS patients who were admitted within 7 days after symptom onset and received conventional medication treatment alone from November 2019 to November 2020 in the Neurology, Department of West China Hospital, Sichuan University. From a total of 782 initial patients, a final cohort of 327 patients was included in the study. These patients were divided into three groups based on statin doses: non-statin (48 patients), LMDS (152 patients), and high-dose statin (HDS) (127 patients). The follow-up period was 3 months after the onset of stroke and the primary outcome was defined as a modified Rankin scale (mRS) score of 0 to 2 at 3 months, secondary outcomes were hemorrhagic transformation (HT) and death within 3 months. Stratified analysis was also conducted to test the robustness of the relationship between the use of different statin doses and functional outcomes in various subgroups. Results: Compared with non-statin therapy, both LMDS therapy and HDS therapy were associated with good functional outcomes [odds ratio (OR) =3.68, 95% confidence interval (CI): 1.13-12.01, P=0.0309; OR =3.45, 95% CI: 1.06-11.26, P=0.0402, respectively] and a lower risk of HT (OR =0.30, 95% CI: 0.11-0.86, P=0.0253; OR =0.36, 95% CI: 0.13-0.99, P=0.0488, respectively). However, there was no significant difference in all-cause death within 3 months among the three groups (OR =0.84, 95% CI: 0.29-2.46, P=0.7468; OR =0.76, 95% CI: 0.26-2.22, P=0.6104). Additionally, no significant differences were observed between LMDS therapy and HDS therapy regarding good functional outcomes at 3 months (OR =0.94, 95% CI: 0.50-1.77, P=0.8411) and the occurrence of HT (OR =1.19, 95% CI: 0.47-3.02, P=0.7093). The results of the relationship between different statin doses and 3-month good functional outcome were consistent after interaction tests. Conclusions: Our findings provide evidence for the benefit and safety of LMDS therapy in AIS patients with medication treatment alone. LMDS therapy is associated with favorable impacts on 3-month functional outcomes and a reduced risk of HT compared to non-statin therapy. There were no significant differences in achieving 3-month good functional outcome, the risk of HT or death within 3 months were observed between LMDS and HDS therapy in our study. Further studies with prospective design and larger sample sizes are necessary to validate our results.

Collateral Status Modification of the Association Between Blood Pressure Variation Within 72 Hours After Endovascular Treatment and Clinical Outcome in Acute Ischemic Stroke: A Retrospective Cohort Study.

Background: Blood pressure variation and collateral status have been reported to be associated with clinical outcome in patients with acute ischemic stroke who received endovascular treatment; however, the relationship between blood pressure variation within 72 hours after EVT and clinical outcome in different collateral status remains unclear. Methods: Acute ischemic stroke patients due to large vessel occlusion with EVT were retrospectively enrolled. We classified participants into poor collateral (ASITN/SIR grade <2) and good collateral subgroups (ASITN/SIR grade ≥2). The primary outcome was unfavorable neurological outcome defined as a 3-month modified Rankin Scale (mRS) score ≥2. The interactive effect was tested to determine the influence of collateral status on the association between BP variation and clinical outcome. Results: A total of 545 patients were included. The poor collateral subgroup was detected in 198 patients with an average age of 70.2 years. The association between BP variation and primary outcome did not differ under different collateral status (P for interaction >0.05). However, the association between the mean and coefficient of variation (CV) values of DBP and 3-month mortality was significantly discrepant under different collateral status (P for interaction <0.05). In the good collateral subgroup, higher mean DBP was associated with a lower risk of 3-month mortality (OR 0.95, 95% CI 0.91-1, P = 0.033) compared with the poor subgroup (OR 1.04, 95% CI 0.97-1.1, P = 0.286). In addition, a higher CV of DBP was associated with a higher risk of 3-month mortality (OR 1.24, 95% CI 1.13-1.36, P < 0.01) compared with poor status (OR 1.08, 95% CI 0.94-1.23, P=0.275). Conclusion: For patients who received EVT with good collateral status, increased CV of DBP was significantly associated with higher 3-month mortality, while higher mean DBP within 72 h after EVT was associated with a decrease in 3-month mortality.

MicroRNA hsa-miR-320a-3p and Its Targeted mRNA FKBP5 Were Differentially Expressed in Patients with HIV/TB Co-Infection.

Among the PLWH (people living with HIV) population, the risk of developing active tuberculosis (TB) is increasing. Active TB also accelerates the deterioration of PLWH's immune function and is one of the leading causes of death in the PLWH population. So far, accurate diagnosis of active TB in the PLWH population remains challenging. Through data analysis of HIV/TB co-infection in the GEO database, the differentially expressed genes as well as their related microRNA (miRNA) were acquired and were further verified through clinical blood samples. Dual-luciferase assay was used to verify the mechanism of miRNA on mRNA. The enrichment of immune cells in database patient samples was analyzed by bioinformatics and finally verified by blood routine data. Our study found that FKBP5 (FK506 binding protein 5) was highly expressed in the HIV/TB co-infection group; hsa-miR-320a-3p was highly expressed in the HIV infection group but decreased in the HIV/TB co-infection group. Dual-luciferase assay results showed that hsa-miR-320a-3p mimics significantly reduced the relative luciferase activity of the WT-FKBP5 group; however, this phenomenon was not observed in the MUT-FKBP5 group. At the same time, as a key molecule of the immune-related pathway, FKBP5 is highly correlated with the amount of neutrophils, which provides a new suggestion for the treatment of the HIV/TB co-infection population. Our study found that hsa-miR-320a-3p can decrease FKBP5 expression, suggesting a potential regulatory role for FKBP5. The involvement of FKBP5 and its related molecule hsa-miR-320a-3p in HIV/TB co-infection proposes them as potential biomarkers for the diagnosis of active TB in the PLWH population.

Abnormal flow pattern of low wall shear stress and high oscillatory shear index in spontaneous vertebral artery dissection with vertebral artery hypoplasia.

Introduction: Spontaneous vertebral artery dissection (sVAD) might tend to develop in vertebral artery hypoplasia (VAH) with hemodynamic dysfunction and it is crucial to assess hemodynamics in sVAD with VAH to investigate this hypothesis. This retrospective study aimed to quantify hemodynamic parameters in patients with sVAD with VAH. Methods: Patients who had suffered ischemic stroke due to an sVAD of VAH were enrolled in this retrospective study. The geometries of 14 patients (28 vessels) were reconstructed using Mimics and Geomagic Studio software from CT angiography (CTA). ANSYS ICEM and ANSYS FLUENT were utilized for mesh generation, set boundary conditions, solve governing equations, and perform numerical simulations. Slices were obtained at the upstream area, dissection or midstream area and downstream area of each VA. The blood flow patterns were visualized through instantaneous streamline and pressure at peak systole and late diastole. The hemodynamic parameters included pressure, velocity, time-averaged blood flow, time-averaged wall shear stress (TAWSS), oscillatory shear index (OSI), endothelial cell action potential (ECAP), relative residence time (RRT) and time-averaged nitric oxide production rate (TARNO). Results: Significant focal increased velocity was present in the dissection area of steno-occlusive sVAD with VAH compared to other nondissected areas (0.910 m/s vs. 0.449 vs. 0.566, p < 0.001), while focal slow flow velocity was observed in the dissection area of aneurysmal dilatative sVAD with VAH according to velocity streamlines. Steno-occlusive sVAD with VAH arteries had a lower time-averaged blood flow (0.499 cm3/s vs. 2.268, p < 0.001), lower TAWSS (1.115 Pa vs. 2.437, p = 0.001), higher OSI (0.248 vs. 0.173, p = 0.006), higher ECAP (0.328 Pa-1 vs. 0.094, p = 0.002), higher RRT (3.519 Pa-1 vs. 1.044, p = 0.001) and deceased TARNO (104.014 nM/s vs. 158.195, p < 0.001) than the contralateral VAs. Conclusion: Steno-occlusive sVAD with VAH patients had abnormal blood flow patterns of focal increased velocity, low time-averaged blood flow, low TAWSS, high OSI, high ECAP, high RRT and decreased TARNO. These results provide a good basis for further investigation of sVAD hemodynamics and support the applicability of the CFD method in testing the hemodynamic hypothesis of sVAD. More detailed hemodynamic conditions with different stages of sVAD are warranted in the future.

Significant elevated CXCL14 and decreased IL-39 levels in patients with tuberculosis.

To explore the serum levels of IL-39, CXCL14, and IL-19 in patients with tuberculosis (TB) along with their clinical significances and their concentration changes in macrophages after Bacille Calmette-Guérin vaccine (BCG) or Mycobacterium tuberculosis (M. tb) H37Rv stimulation in vitro. The serum levels of IL-39, CXCL14, and IL-19 of 38 TB patients, and 20 healthy staff members were measured by enzyme-linked immunosorbent assay. Moreover, the levels of IL-19, CXCL14, and IL-39 in cultured THP-1 macrophages were detected at 12, 24, and 48 h after stimulation with BCG or M. tb H37Rv strains. It was found the serum level of IL-39 was significantly reduced and CXCL14 was remarkably elevated in TB patients. In vitro, at 48 h after stimulation, IL-39 level of cultured THP-1 macrophages in the H37Rv group was significantly lower than that in the BCG and control groups, and the CXCL14 level of cultured THP-1 macrophages in the H37Rv stimulation group was remarkably higher than that in the control group. Therefore, IL-39 and CXCL14 may be involved the pathogenesis of TB, and serum IL-39 and CXCL14 could potentially serve as a new biomarker of TB.

[SigE inhibits DNA damage and participates in the regulation of DNA damage repair in Mycobacterium smegmatis].

Objective To investigate the anti-DNA damage role of Sigma factor E (SigE) and its regulation mechanism of DNA damage repair in Mycobacterium smegmatis(MS). Methods The SigE gene of Mycobacterium smegmatis was cloned into plasmid pMV261 to construct recombinant plasmid pMV261(+)-SigE, and the inserted gene was verified by sequencing. The recombinant plasmid was electrically transformed into Mycobacterium smegmatis to construct SigE over-expression strain, and the expression of SigE was detected by Western blot analysis. The Mycobacterium smegmatis containing pMV261 plasmid was used as the control strain. Growth differences between the two stains were monitored by measuring the 600 nm absorbance (A600) value of the bacterial culture suspension. The survival rate differences between two kinds of strains which were treated with three kinds of DNA damaging agents including ultraviolet ray (UV), cisplatin (DDP), and mitomycin C (MMC) were detected by colony forming unit (CFU) counting assay. DNA damage repair pathways of Mycobacteria were analyzed through bioinformatics and SigE-related genes were screened. The relative expression levels of these genes possibly related to the SigE against DNA damage were detected by real-time fluorescence quantitative PCR. Results SigE over-expression strain pMV261(+)-SigE/MS was constructed and the expression of SigE in Mycobacterium smegmatis was detected. Compared with the control strain, the SigE over-expression strain grew more slowly and entered the growth plateau later; survival rate analysis found that SigE over-expression strain was more resistant to three DNA damaging agents including UV, DDP, and MMC. Bioinformatic analysis indicated that SigE gene was closely related to DNA damage repair genes recA, single-strand DNA binding protein, (ssb), and dnaE2; the expression levels of recA, dnaE2, and ssb in SigE over-expression strain all increased with varying degrees compared with those in the control strain. Conclusion SigE plays an important role in inhibiting the DNA damage of Mycobacterium smegmatis, whose mechanism is closely related to the regulation of DNA damage repair.

Methylprednisolone Promotes Mycobacterium smegmatis Survival in Macrophages through NF-κB/DUSP1 Pathway.

BACKGROUND: Mycobacterium tuberculosis (M. tuberculosis) is the causative agent of tuberculosis. As an important component of host immunity, macrophages are not only the first line of defense against M. tuberculosis but also the parasitic site of M. tuberculosis in the host. Glucocorticoids can cause immunosuppression, which is considered to be one of the major risk factors for active tuberculosis, but the mechanism is unclear. OBJECTIVE: To study the effect of methylprednisolone on the proliferation of mycobacteria in macrophages and try to find key molecules of this phenomenon. METHODS: The macrophage line RAW264.7 infected by M. smegmatis was treated with methylprednisolone, and the intracellular bacterial CFU, Reactive Oxygen Species (ROS), cytokine secretion, autophagy, and apoptosis were measured. After the cells were treated with NF-κB inhibitor BAY 11-7082 and DUSP1 inhibitor BCI, respectively, the intracellular bacterial CFU, ROS, IL-6, and TNF-α secretion were detected. RESULTS: After treatment with methylprednisolone, the CFU of intracellular bacteria increased, the level of ROS decreased, and the secretion of IL-6 and TNF-α decreased in infected macrophages. After BAY 11-7082 treatment, the CFU of M. smegmatis in macrophages increased, and the level of ROS production and the secretion of IL-6 by macrophages decreased. Transcriptome high-throughput sequencing and bioinformatics analysis suggested that DUSP1 was the key molecule in the above phenomenon. Western blot analysis confirmed that the expression level of DUSP1 was increased in the infected macrophages treated with methylprednisolone and BAY 11-7082, respectively. After BCI treatment, the level of ROS produced by infected macrophages increased, and the secretion of IL-6 increased. After the treatment of BCI combined with methylprednisolone or BAY 11-7082, the level of ROS produced and the secretion of IL-6 by macrophages were increased. CONCLUSION: methylprednisolone promotes the proliferation of mycobacteria in macrophages by suppressing cellular ROS production and IL-6 secretion through down-regulating NF-κB and up-regulating DUSP1 expression. BCI, an inhibitor of DUSP1, can reduce the level of DUSP1 in the infected macrophages and inhibit the proliferation of intracellular mycobacteria by promoting cellular ROS production and IL-6 secretion. Therefore, BCI may become a new molecule for host-directed therapy of tuberculosis, as well as a new strategy for the prevention of tuberculosis when treated with glucocorticoids.

Inhibition of mycobacteria proliferation in macrophages by low cisplatin concentration through phosphorylated p53-related apoptosis pathway.

BACKGROUND: Drug resistance is a prominent problem in the treatment of tuberculosis, so it is urgent to develop new anti- tuberculosis drugs. Here, we investigated the effects and mechanisms of cisplatin (DDP) on intracellular Mycobacterium smegmatis to tap the therapeutic potential of DDP in mycobacterial infection. RESULTS: Macrophages infected with Mycobacterium smegmatis were treated with DDP alone or combined with isoniazid or rifampicin. The results showed that the bacterial count in macrophages decreased significantly after DDP (≤ 6 µg/mL) treatment. When isoniazid or rifampicin was combined with DDP, the number of intracellular mycobacteria was also significantly lower than that of isoniazid or rifampicin alone. Apoptosis of infected cells increased after 24 h of DDP treatment, as shown by flow cytometry and transmission electron microscopy detection. Transcriptome sequencing showed that there were 1161 upregulated and 645 downregulated differentially expressed genes (DEGs) between the control group and DDP treatment group. A Trp53-centered protein interaction network was found based on the top 100 significant DEGs through STRING and Cytoscape software. The expression of phosphorylated p53, Bax, JAK, p38 MAPK and PI3K increased after DDP treatment, as shown by Western blot analysis. Inhibitors of JAK, PI3K or p38 MAPK inhibited the increase in cell apoptosis and the reduction in the intracellular bacterial count induced by DDP. The p53 promoter Kevetrin hydrochloride scavenges intracellular mycobacteria. If combined with DDP, Kevetrin hydrochloride could increase the effect of DDP on the elimination of intracellular mycobacteria. In conclusion, DDP at low concentrations could activate the JAK, p38 MAPK and PI3K pathways in infected macrophages, promote the phosphorylation of p53 protein, and increase the ratio of Bax to Bcl-2, leading to cell apoptosis, thus eliminating intracellular bacteria and reducing the spread of mycobacteria. CONCLUSION: DDP may be a new host-directed therapy for tuberculosis treatment, as well as the p53 promoter Kevetrin hydrochloride.

Is endovascular treatment still good for acute ischemic stroke in the elderly? A meta-analysis of observational studies in the last decade.

Background: The lack of randomized evidence makes it difficult to establish reliable treatment recommendations for endovascular treatment (EVT) in elderly patients. This meta-analysis aims to evaluate the therapeutic effects of endovascular treatment for acute ischemic stroke in the elderly compared with younger patients. Methods: Comprehensive literature retrieval was conducted to identify studies that directly compared the outcomes of EVT in elderly patients and those aged <80 years. The primary outcome was functional independence, defined as mRS 0-2 at 90 days after EVT. The secondary outcomes were the rate of successful recanalization, symptomatic intracranial hemorrhage (sICH) and mortality. Odds ratios (ORs) were estimated using a random effects model. Results: In total, twenty-six studies with 9,492 enrolled participants were identified. Our results showed that, compared with patients aged <80 years undergoing EVT, EVT was associated with a lower rate of functional independence at 90 days (OR = 0.38; 95% CI, 0.33-0.45; p < 0.00001) and a higher mortality rate (OR = 2.51; 95% CI, 1.98-3.18; p < 0.00001) in the elderly. Furthermore, even without a significantly observed increase in sICH (OR = 1.19; 95% CI, 0.96-1.47; p = 0.11), EVT appeared to be associated with a lower rate of successful recanalization (OR = 0.81; 95% CI, 0.68-0.96; p = 0.02). Conclusion: Evidence from observational studies revealed that EVT has less functional outcomes in elderly patients with acute ischemic stroke. Further studies are needed to better identify patients aged ≥80 years who could potentially benefit from EVT.

Low-dose statins improve prognosis of patients with ischaemic stroke undergoing intra-arterial thrombectomy: A prospective cohort study.

BACKGROUND: High-dose statins are recommended as preventive drugs in guidelines for patients with ischaemic stroke undergoing thrombectomy. Not only in clinical practice but also based on large-scale studies, low-dose statins have been widely used and demonstrated to be efficient in Asian populations. However, it remains unknown whether a low-dose statin is related to the prognosis of patients with thrombectomy. Can low-dose statins reduce the risk of bleeding at the same time? METHODS: We prospectively collected data from patients with acute ischaemic stroke undergoing intra-arterial thrombectomy. Efficacy outcomes were National Institutes of Health Stroke Scale (NIHSS) score improvement at 7 days after admission and a favourable functional outcome (FFO) at 90 days. Safety outcomes were rates of in-hospital haemorrhage events and death within 2 years. RESULTS: We included 256 patients in this study. Compared with the control group, the low-dose statin group had a higher NIHSS improvement rate at 7 days, a higher FFO rate at 90 days and a lower death rate within 2 years. The low-dose statin group had a lower percentage of gastrointestinal haemorrhage. Statin use was significantly related to an improved NIHSS score (p = 0.028, OR = 1.773) at 7 days and FFO (P < 0.001, OR = 2.962) at 90 days and to lower death rates (P = 0.025, or = 0.554) within 2 years. CONCLUSION: In Asian acute ischaemic stroke patients with intra-arterial thrombectomy, low-dose statin use was significantly related to NIHSS improvement at 7 days, FFO at 90 days and decreased death rates within 2 years.

Development and validation of a prognostic nomogram based on objective nutritional indexes in ischemic stroke patients with large vessel occlusion undergoing endovascular thrombectomy.

BACKGROUND AND AIMS: Preserved nutritional status in acute ischemic stroke patients with large vessel occlusion (LVO) undergoing endovascular thrombectomy (EVT) is important but lacks an effective evaluation method. We aimed to investigate the prognostic value of objective nutritional indexes (ONIs) in LVO patients after EVT that were validated by studies in patients with other vascular diseases receiving intervention therapy and to develop a functional prediction nomogram for better stroke management. METHODS AND RESULTS: LVO patients undergoing EVT from 2016 to 2020 were retrospectively enrolled and randomly classified into training and validation cohorts at a ratio of 7:3. The ONIs, including the Controlling Nutritional Status (CONUT) score, Nutritional Risk Index (NRI), and Prognostic Nutritional Index (PNI), were calculated. A stepwise logistic regression model for 3-month poor functional outcome based on the smallest Akaike information criterion was employed to develop the nomogram, and the nomogram's determination and clinical use were tested by area under the curve (AUC), calibration plots, and decision curve analysis and compared with three earlier prognostic models. A total of 418 patients were enrolled. The CONUT independently related and increased the risk of 3-month poor functional outcome with an OR of 1.387 (95% CI: 1.133-1.698, p = 0.002). A nomogram including CONUT and other seven factors (AIC = 274.568) was developed. The AUC of the nomogram was 0.847 (95% CI: 0.799-0.894) and 0.836 (95% CI: 0.755-0.916) in the training and validation cohort, respectively, with better predictive performance and clinical utility than previous models. CONCLUSION: The CONUT independently related to the poor functional outcome, and the newly established nomogram reliably predicted the functional outcome in LVO patients after EVT.

Relationship Between Body Temperature and Early Neurological Deterioration after Endovascular Thrombectomy for Acute Ischemic Stroke with Large Vessel Occlusion.

BACKGROUND: Early neurological deterioration (END) after endovascular thrombectomy (EVT) is strongly associated with poor prognosis in patients with large vessel occlusion. The relationship between body temperature and END after EVT is unknown, which we aimed to investigate in this study. METHODS: END was defined as an increase of four or more points on the National Institutes of Health Stroke Scale score compared with the baseline assessment within 24 h. Logistic regression and restricted cubic spline models were used to assess the relationship between body temperature and END. RESULTS: Among 7741 consecutive patients with ischemic stroke, 406 patients with large vessel occlusion who underwent EVT were enrolled. In total, 88 (21.7%) patients developed END. Logistic regression showed that the maximum body temperature within 24 h (odds ratio [OR] = 1.97 per °C, 95% confidence interval [CI] 1.17-3.32, p = 0.010) was independently associated with END. This association was nonlinear and J shaped (p for nonlinearity = 0.010), and the risk of END increased when the maximum body temperature within 24 h was lower or higher than 37.0 °C. Fever burden is also independently associated with END (OR = 1.06 per °C × hour, 95% CI 1.01-1.11, p = 0.012). In addition, the timing of fever onset was independently associated with END, and the highest risk of END was associated with fever onset within 6 h after EVT (OR = 3.92, 95% CI 1.25-12.27, p = 0.019). CONCLUSIONS: In summary, there is a J-shaped association between the maximum body temperature within 24 h after EVT and END. Moreover, the risk of END differed according to the timing of fever onset.

High throughput sequencing of whole transcriptome and construct of ceRNA regulatory network in RD cells infected with enterovirus D68.

BACKGROUND: With the advancement of sequencing technologies, a plethora of noncoding RNA (ncRNA) species have been widely discovered, including microRNAs (miRNAs), circular RNAs (circRNAs), and long ncRNAs (lncRNAs). However, the mechanism of these non-coding RNAs in diseases caused by enterovirus d68 (EV-D68) remains unclear. The goal of this research was to identify significantly altered circRNAs, lncRNAs, miRNAs, and mRNAs pathways in RD cells infected with EV-D68, analyze their target relationships, demonstrate the competing endogenous RNA (ceRNA) regulatory network, and evaluate their biological functions. METHODS: The total RNAs were sequenced by high-throughput sequencing technology, and differentially expressed genes between control and infection groups were screened using bioinformatics method. We discovered the targeting relationship between three ncRNAs and mRNA using bioinformatics methods, and then built a ceRNA regulatory network centered on miRNA. The biological functions of differentially expressed mRNAs (DEmRNAs) were discovered through GO and KEGG enrichment analysis. Create a protein interaction network (PPI) to seek for hub mRNAs and learn more about protein-protein interactions. The relative expression was verified using RT-qPCR. The effects of Fos and ARRDC3 on virus replication were confirmed using RT-qPCR, virus titer (TCID50/ml), Western blotting. RESULTS: 375 lncRNAs (154 upregulated and 221 downregulated), 33 circRNAs (32 upregulated and 1 downregulated), 96 miRNAs (49 upregulated and 47 downregulated), and 239 mRNAs (135 upregulated and 104 downregulated) were identified as differently in infected group compare to no-infected group. A single lncRNA or circRNA can be connected with numerous miRNAs, which subsequently coregulate additional mRNAs, according to the ceRNA regulatory network. The majority of DEmRNAs were shown to be connected to DNA binding, transcription regulation by RNA polymerase II, transcription factor, MAPK signaling pathways, Hippo signal pathway, and apoptosis pathway, according to GO and KEGG pathway enrichment analysis. The hub mRNAs with EGR1, Fos and Jun as the core were screened through PPI interaction network. We preliminarily demonstrated that the Fos and ARRDC3 genes can suppress EV-D68 viral replication in order to further verify the results of full transcriptome sequencing. CONCLUSION: The results of whole transcriptome analysis after EV-D68 infection of RD cells were first reported in this study, and for the first time, a ceRNA regulation network containing miRNA at its center was established for the first time. The Fos and ARRDC3 genes were found to hinder viral in RD cells. This study establishes a novel insight host response during EV-D68 infection and further investigated potential drug targets.

Development and external validation of a nomogram for neurosyphilis diagnosis among non-HIV patients: a cross-sectional study.

BACKGROUND: The diagnosis of neurosyphilis is challenging due to the requirement of a lumbar puncture and cerebrospinal fluid (CSF) laboratory tests. Therefore, a convenient diagnostic nomogram for neurosyphilis is warranted. This study aimed to construct diagnostic models for diagnosing neurosyphilis. METHODS: This cross-sectional study included data of two patient cohorts from Western China Hospital of Sichuan University between September 2015 and April 2021 and Shangjin Hospital between September 2019 and April 2021 as the development cohort and the external validation cohort, respectively. A diagnostic model using logistic regression analysis was constructed to readily provide the probability of diagnosis at point of care and presented as a nomogram. The clinical usefulness of the diagnostic models was assessed using a receiver operating characteristic (ROC) and Harrell concordance (Harrell C) index for discrimination and calibration plots for accuracy, which adopted bootstrap resampling 500 times. RESULTS: One hundred forty-eight and 67 patients were included in the development and validation cohorts, respectively. Of those, 131 were diagnosed as having reactive neurosyphilis under the criteria of positive results in both CSF treponemal and non-treponemal tests. In the development cohort, male, psychiatric behaviour disorders, and serum toluidine red unheated serum test were selected as diagnostic indicators applying a stepwise procedure in multivariable logistic model. The model reached 80% specificity, 79% sensitivity, and 0·85 area under the curves (AUC) (95% confidence interval, 0·76-0·91). In the validation cohorts, the Harrell C index for the diagnostic possibility of reactive neurosyphilis was 0·71. CONCLUSIONS: A convenient model using gender, presence of psychiatric behaviour disorders, and serum TRUST titre was developed and validated to indicate diagnostic results in patients suspected of neurosyphilis. Checking the model value of factors on nomogram is a feasible way to assist clinicians and primary health servers in updating patients' medical charts and making a quantitatively informed decision on neurosyphilis diagnosis. TRIAL REGISTRATION: This research was retrospectively registered in the Ethics committee on biomedical research, West China Hospital of Sichuan University. The research registration and committee's reference number was 1163 in 2020 approval.

Statin Treatment in the Acute Phase and the Risk of Post-stroke Pneumonia: A Retrospective Cohort Study.

Background: We aimed to investigate the impact of statin treatment in the acute phase on the risk and severity of post-stroke pneumonia because of the uncertain effects of statins on post-stroke pneumonia. Methods: Consecutive cases of acute ischemic stroke (AIS) between January 2014 and February 2019 were retrospectively analyzed. Additionally, the association of statin treatment in the acute phase with the risk and severity of post-stroke pneumonia was estimated with logistic regression. We registered the present study in the Chinese Clinical Trial Registry (ChiCTR 2000032838). Results: Of the 1,258 enrolled patients, no significant difference was observed in post-stroke pneumonia risk between the two groups (with/without statin treatment in the acute phase) after propensity score matching (35.1 vs. 27.9%, p = 0.155). We did not find statin treatment in the acute phase to significantly increase the risk of post-stroke pneumonia both before and after matched analysis [odds ratio (OR) = 1.51, 95% confidence interval (CI) = 0.85-2.67, p = 0.157; OR = 1.57, 95% CI = 0.77-3.18, p = 0.213, respectively]. In the 271 patients with post-stroke pneumonia, no significant difference was found in its severity between two groups (19.6 vs. 19.4%, p = 0.964). No significant association was found between statin treatment and post-stroke pneumonia severity (OR = 0.95, 95% CI = 0.39-2.31, p = 0.918). Conclusions: There appeared to be no additional benefits of statin treatment in the acute phase for post-stroke pneumonia reduction among AIS patients. Clinical Trial Registration:http://www.chictr.org.cn, identifier: ChiCTR2000032838.

Association of Aortic Stiffness and Cognitive Decline: A Systematic Review and Meta-Analysis.

Background: Increased aortic stiffness has been found to be associated with cognitive function decline, but the evidence is still under debate. It is of great significance to elucidate the evidence in this debate to help make primary prevention decisions to slow cognitive decline in our routine clinical practice. Methods: Electronic databases of PubMed, EMBASE, and Cochrane Library were systematically searched to identify peer-reviewed articles published in English from January 1, 1986, to March 16, 2020, that reported the association between aortic stiffness and cognitive function. Studies that reported the association between aortic pulse wave velocity (PWV) and cognitive function, cognitive impairment, and dementia were included in the analysis. Results: Thirty-nine studies were included in the qualitative analysis, and 29 studies were included in the quantitative analysis. The aortic PWV was inversely associated with memory and processing speed in the cross-sectional analysis. In the longitudinal analysis, the high category of aortic PWV was 44% increased risk of cognitive impairment (OR 1.44; 95% CI 1.24-1.85) compared with low PWV, and the risk of cognitive impairment increased 3.9% (OR 1.039; 95% CI 1.005-1.073) per 1 m/s increase in aortic PWV. Besides, meta-regression analysis showed that age significantly increased the association between high aortic PWV and cognitive impairment risk. Conclusion: Aortic stiffness measured by aortic PWV was inversely associated with memory and processing speed and could be an independent predictor for cognitive impairment, especially for older individuals.

Low dose statins improve prognosis of ischemic stroke patients with intravenous thrombolysis.

BACKGROUND: For acute ischaemic stroke patients, it is uncertain whether intravenous thrombolysis combined with statins might increase the therapeutic effect. Additionally, using high-intensity statins after thrombolysis may increase the risk of bleeding in patients. Asian stroke patients often take low-dose statins. It is speculated that reducing the dose of statins may improve the risk of bleeding. METHODS: Data from consecutive acute ischaemic stroke patients with intravenous thrombolysis were prospectively collected. Efficacy outcomes included NIHSS (National Institutes of Health Stroke Scale) score improvement at 7 days after admission and mRS (Modified Rankin Scale) improvement at 90 days. Safety outcomes included haemorrhage events (intracerebral haemorrhage and gastrointestinal haemorrhage) in the hospital and death events within 2 years. RESULTS: The study finally included 215 patients. The statin group had a higher percentage of NIHSS improvement at 7 days (p < 0.001) and a higher percentage of a favourable functional outcome (FFO, mRS < = 2) (p < 0.001) at 90 days. The statin group had a lower percentage of intracerebral haemorrhage (p < 0.001) and gastrointestinal haemorrhage (p = 0.003) in the hospital and a lower percentage of death events (p < 0.001) within 2 years. Logistic regression indicated that statin use was significantly related to NIHSS improvement (OR = 4.697, p < 0.001), a lower percentage of intracerebral haemorrhage (OR = 0.372, p = 0.049) and gastrointestinal haemorrhage (OR = 0.023, p = 0.016), and a lower percentage of death events (OR = 0.072, p < 0.001). CONCLUSION: For acute ischaemic stroke patients after intravenous thrombolysis, the use of low-dose statins was related to NIHSS improvement at 7 days and inversely related to haemorrhage events in the hospital and death events within 2 years, especially for moderate stroke or noncardioembolic stroke patients.

The impact of COVID-19 pandemic on headache symptoms and drug withdrawal among patients with medication overuse headache: a cross-sectional study.

BACKGROUND: Coronavirus disease 2019 (COVID-19) bring about a range of psychological distress and symptom deterioration to headache patients especially to some migraineurs. Compared to migraineurs or normal control, medication overuse headache (MOH) patients are more likely to experience a worse psychological distress and poorer outcome in non-COVID-19 time. However, in COVID-19 pandemic, whether MOH patients would have greater physical and mental symptom deterioration or worse relief of headache symptoms and medications overuse remained unclear. We aim to investigate the impact of COVID-19 on MOH patients to guide for a better management in this study. METHODS: We enrolled MOH patients who were diagnosed and treated at headache clinic of West China Hospital. Information of the pre-pandemic 3 months period and COVID-19 pandemic period was collected. Univariate and multivariate logistic regression were performed to identify independent factors associated with changes in headache symptoms and drug withdrawal. RESULTS: Seventy-eight MOH patients were enrolled into the study ultimately. In comparison to pre-pandemic period, fewer MOH patients reported decreased headache days, intensity and days with acute medications per month during the pandemic. Available access to regular prophylactic medications was significantly associated with a reduction of at least 50% in headache days and decrease in headache intensity per month with respective odds ratios of 39.19 (95% CI 3.75-409.15, P = 0.002) and 10.13 (95% CI 2.33-44.12, P = 0.002). Following abrupt withdrawal and high educational level were both significant factors in decreasing headache intensity. Male sex was significantly associated with decrease in days with acute medication per month during the pandemic (odds ratios 4.78, 95%CI 1.44-15.87, P = 0.011). CONCLUSIONS: Our findings reflect that MOH patients experienced a worse relief of headache symptoms and drug withdrawal during the pandemic. Available access to regular prophylactic medications was the significant independent factor for improvement of headache symptoms. Male sex was significantly associated with decreased days with acute medications per month.