Therapeutic Efficacy of Nasal Corticosteroids in COVID-19-Related Olfactory Dysfunction: A Comprehensive Systematic Review and Meta-analysis.

OBJECTIVE: Olfactory disturbance is one of the main symptoms of coronavirus disease-2019 (COVID-19). Various olfactory disorders caused by viral infections are treated with nasal corticosteroids. This study aimed to evaluate the safety and efficacy of nasal corticosteroids in the treatment of olfactory disorders caused by the severe acute respiratory syndrome coronavirus 2. DATA SOURCES: We searched the Web of Science, Embase, PubMed, and Cochrane Library databases for clinical trials of nasal corticosteroids for treating COVID-19 olfactory dysfunction. REVIEW METHODS: We assessed the effect of nasal corticosteroids on olfactory function in COVID-19-affected individuals using a Meta-analysis of published studies, considering the number of patients who fully recovered from olfactory dysfunction, olfactory scores following treatment, and olfactory recovery time. RESULTS: Seven studies involving 930 patients were analyzed. The Meta-analysis results revealed that the olfactory score of the experimental group was 1.40 points higher than that of the control group (standardized mean difference [MD]: 1.40, 95% confidence interval [95% CI]: 0.34-2.47, P < .00001). However, the differences in the outcomes of cure rate (risk ratio: 1.18, 95% CI: 0.89-1.69, P = .21) and recovery time (MD: -1.78, 95% CI: -7.36 to 3.81, P = .53) were not statistically significant. Only 1 study reported adverse effects of nasal steroid treatment, namely tension, anger, and stomach irritation. CONCLUSION: Although nasal steroid therapy does not result in significant adverse effects, it proves ineffective in the treatment of COVID-19 olfactory dysfunction.

A predictive model for the recurrence of intracranial aneurysms following coil embolization.

Objective: This study aimed to identify risk factors for intracranial aneurysms (IAs) recurrence and establish a predictive model to aid evaluation. Methods: A total of 302 patients with 312 IAs undergoing coil embolization between September 2017 and October 2022 were divided into two groups based on digital subtraction angiography follow-up. Clinical characteristics, operation-related factors, and morphologies were measured. Cox proportional hazard regression was used to identify the risk factors. Hazard ratios (HRs) were used to score points, and a predictive model was established. The test cohorts consisted of 51 IAs. Receiver operating characteristic curves were generated to determine the cutoff values and area under the curves (AUCs). A Delong test was performed to compare the AUCs. Results: Diameter maximum (D max) (p < 0.001, HR = 1.221), Raymond-Roy occlusion classification (RROC) II or III (p = 0.004, HR = 2.852), and ruptured status (p < 0.001, HR = 7.782) were independent risk factors for the recurrence of IAs. A predictive model was established: D max + 2 * RROC (II or III; yes = 1, no = 0) + 6 * ruptured status (yes = 1; no = 0). The AUC of the predictive model (0.818) was significantly higher than those of D max (0.704), RROC (II or III) (0.645), and rupture status (0.683), respectively (Delong test, p < 0.05). The cutoff values of the predictive model and D max were 9.75 points and 6.65 mm, respectively. Conclusion: The D max, RROC (II or III), and ruptured status could independently predict the recurrence of IAs after coil embolization. Our model could aid in practical evaluations.

Comparison of the Effects of Metformin and Thiazolidinediones on Bone Metabolism: A Systematic Review and Meta-Analysis.

OBJECTIVES: Studies have shown that people with diabetes have a high risk of osteoporosis and fractures. The effect of diabetic medications on bone disease cannot be ignored. This meta-analysis aimed to compare the effects of two types of glucose-lowering drugs, metformin and thiazolidinediones (TZD), on bone mineral density and bone metabolism in patients with diabetes mellitus. METHODS: This systematic review and meta-analysis were prospectively registered on PROSPERO, and the registration number is CRD42022320884. Embase, PubMed, and Cochrane Library databases were searched to identify clinical trials comparing the effects of metformin and thiazolidinediones on bone metabolism in patients with diabetes. The literature was screened by inclusion and exclusion criteria. Two assessors independently assessed the quality of the identified studies and extracted relevant data. RESULTS: Seven studies involving 1656 patients were finally included. Our results showed that the metformin group had a 2.77% (SMD = 2.77, 95%CI [2.11, 3.43]; p < 0.00001) higher bone mineral density (BMD) than the thiazolidinedione group until 52 weeks; however, between 52 and 76 weeks, the metformin group had a 0.83% (SMD = -0.83, 95%CI: [-3.56, -0.45]; p = 0.01) lower BMD. The C-terminal telopeptide of type I collagen (CTX) and procollagen type I N-terminal propeptide (PINP) were decreased by 18.46% (MD = -18.46, 95%CI: [-27.98, -8.94], p = 0.0001) and 9.94% (MD = -9.94, 95%CI: [-16.92, -2.96], p = 0.005) in the metformin group compared with the TZD group.

Morphological evaluation of the risk of posterior communicating artery aneurysm rupture: a mirror aneurysm model.

OBJECTIVE: The aim of this study was to use morphological parameters of mirror posterior communicating artery (PCoA) aneurysms to evaluate aneurysm rupture risk. METHODS: The morphological parameters of 45 pairs of ruptured mirror PCoA aneurysms were analyzed. Conditional univariate and multivariate logistic regression of the following paired morphological parameters was performed: aneurysm with a daughter sac, aneurysm height, aneurysm width, neck width, internal carotid artery diameter, PCoA diameter, flow angle, PCoA angle, aspect ratio, bottleneck factor, size ratio, height/width ratio, fetal posterior cerebral artery, and aneurysm with height > width. A scoring system was established according to the odds ratios (ORs). The receiver operating characteristic was used to test the prediction accuracy of this scoring system in the authors' database of 523 PCoA aneurysms and the threshold value was used to define higher risk. RESULTS: Aneurysm width (OR 1.676, p = 0.014), aneurysm with daughter sac (OR 7.775, p = 0.016), and aneurysm with height > width (OR 9.067, p = 0.012) were independent risk factors for rupture. The scoring system consisted of aneurysm width (1 point per mm), aneurysm with a daughter sac (5 points), and aneurysm with height > width (5 points). The area under the curve (AUC) of the scoring system was 0.842, and its threshold value was 7.97. A score ≥ 8 points was defined as higher risk. The AUC using this definition was 0.802. CONCLUSIONS: Aneurysm width, aneurysms with height > width, and aneurysms with a daughter sac were independent risk factors for PCoA aneurysm rupture. The scoring system devised in this study accurately predicts rupture risk.

Corrigendum: Efficacy of umbilical cord mesenchymal stromal cells for COVID-19: a systematic review and meta-analysis.

[This corrects the article DOI: 10.3389/fimmu.2022.923286.].

A predictive model using risk factor categories for hospital-acquired pneumonia in patients with aneurysmal subarachnoid hemorrhage.

Objectives: To identify risk factors for hospital-acquired pneumonia (HAP) in patients with aneurysmal subarachnoid hemorrhage (aSAH) and establish a predictive model to aid evaluation. Methods: The cohorts of 253 aSAH patients were divided into the HAP group (n = 64) and the non-HAP group (n = 189). Univariate and multivariate logistic regression were performed to identify risk factors. A logistic model (Model-Logit) was established based on the independent risk factors. We used risk factor categories to develop a model (Model-Cat). Receiver operating characteristic curves were generated to determine the cutoff values. Areas under the curves (AUCs) were calculated to assess the accuracy of models and single factors. The Delong test was performed to compare the AUCs. Results: The multivariate logistic analysis showed that the age [p = 0.012, odds ratio (OR) = 1.059, confidence interval (CI) = 1.013-1.107], blood glucose (BG; >7.22 mmol/L; p = 0.011, OR = 2.781, CI = 1.263-6.119), red blood distribution width standard deviation (RDW-SD; p = 0.024, OR = 1.118, CI = 1.015-1.231), and Glasgow coma scale (GCS; p < 0.001, OR = 0.710, CI = 0.633-0.798) were independent risk factors. The Model-Logit was as follows: Logit(P) = -5.467 + 0.057 * Age + 1.023 * BG (>7.22 mmol/L, yes = 1, no = 0) + 0.111 * RDW-SD-0.342 * GCS. The AUCs values of the Model-Logit, GCS, age, BG (>7.22 mmol/L), and RDW-SD were 0.865, 0.819, 0.634, 0.698, and 0.625, respectively. For clinical use, the Model-Cat was established. In the Model-Cat, the AUCs for GCS, age, BG, and RDW-SD were 0.850, 0.760, 0.700, 0.641, and 0.564, respectively. The AUCs of the Model-Logit were insignificantly higher than the Model-Cat (Delong test, p = 0.157). The total points from -3 to 4 and 5 to 14 were classified as low- and high-risk levels, respectively. Conclusions: Age, BG (> 7.22 mmol/L), GCS, and RDW-SD were independent risk factors for HAP in aSAH patients. The Model-Cat was convenient for practical evaluation. The aSAH patients with total points from 5 to 14 had a high risk for HAP, suggesting the need for more attention during treatment.

The therapeutic effect of capsaicin on oropharyngeal dysphagia: A systematic review and meta-analysis.

Objectives: Capsaicin is a specific agonist of TRPV1 (multimodal sensory receptor), which improves oropharyngeal dysphagia by increasing sensory input from the oropharynx and hypopharynx and by increasing repetitive stimulation of the cerebral cortex. The aim of this systematic review was to evaluate the therapeutic effect of capsaicin on swallowing disorders in stroke patients and the elderly. Method: We searched Medline, Embase, PubMed, and Cochrane Library databases. We used the Mesh terms search database to screen all clinical trials that complied with the inclusion criteria. Studies were subjected to literature screening, quality assessment, and data extraction to remove studies that did not meet the inclusion criteria. After literature screening, quality assessment, and data extraction, a systematic review and meta-analysis of the included study were performed. Results: This systematic review and meta-analysis were prospectively registered on PROSPERO under registration number CRD42022313958. Five high-quality randomized controlled trials were ultimately included. The results of our meta-analysis showed a more significant reduction in swallowing function score change in the capsaicin group compared to the control group [SMD = -1.30, 95% CI: (-2.35, -0.25), P = 0.01] and on the Water swallowing test the improvement was significantly higher in the capsaicin group [RR = 2.46, 95% CI: (1.73, 3.50), P < 0.0001]. Conclusions: Although the results of our meta-analysis showed that capsaicin improved swallowing function, most studies had an unclear bias and included few studies. More studies are needed to support this in the future. Systematic review registration: www.crd.york.ac.uk/prospero/display_record.php?RecordID=304061, identifier: 304061.

Risk factors for the rupture of mirror middle cerebral artery aneurysm using computer-assisted semiautomated measurement and hemodynamic analysis.

OBJECTIVES: To identify the morphologic and hemodynamic risk factor of mirror middle cerebral artery (MCA) aneurysms. METHODS: We conducted a retrospective analysis of 40 paired mirror MCA aneurysms. Aneurysms were divided into ruptured and unruptured groups. Seventeen morphological and nine hemodynamic parameters were measured using computer-assisted semiautomated measurement (CASAM) and computer flow dynamic (CFD) simulation. We performed a paired t-test (for normally distributed data) or a paired Wilcoxon rank-sum (for non-normally distributed data) to analyze all parameters between the groups. Multivariate conditional logistic regression analysis identified independent risk factors. The receiver operating characteristic curve was analyzed to acquire the area under the curve (AUC) and the cutoff values of the independent risk factors. RESULTS: There were significant differences in morphological and hemodynamic parameters between the ruptured and unruptured mirror aneurysms. The multivariate logistic analysis showed that the greater size (odds ratio [OR] = 9.807, p = 0.003), smaller neck diameter (OR = 0.285, p = 0.018) and maximum oscillatory shear index (OSI) (OR = 0.000001, p = 0.046) were independently correlated with aneurysm rupture. AUCs for size, N. and maximum OSI were 0.794, 0.695, and 0.701, respectively. The cutoff values of the size, neck diameter, and maximum OSI were 6.30, 5.07, and 0.356437, respectively. CONCLUSIONS: Morphology and hemodynamics can help predict aneurysm rupture risks. The more significant size, smaller neck diameter and maximum OSI were independent risk factors for the rupture of MCA aneurysms. The variables could aid practical risk evaluation.

Clip-reinforced wrapping using the Y-shaped temporalis fascia technique for intracranial aneurysms.

Objectives: This study aims to identify the effectiveness of the clip-reinforced wrapping using the Y-shaped temporalis fascia (CRYST) technique for treating intracranial aneurysms (IAs). Methods: We retrospectively reviewed five patients with ruptured IAs treated using the CRYST technique from July 2016 to May 2021. Three patients had blood blister-like aneurysms (BBAs) (one with intraoperative rupture), and two had anterior communicating artery (AcoA) aneurysms (one with intraoperative rupture). All patients had intraoperative indocyanine green angiography, and digital subtraction angiography (DSA) was reviewed 10-14 days after surgery. At 1 year postoperatively, three patients (two BBAs and one AcoA aneurysm) underwent DSA and two patients (one BBA and one AcoA aneurysm) underwent computed tomographic angiography (CTA). Results: Two aneurysms ruptured intraoperatively during the clipping, and no severe complications occurred. No patients had neurological deficits after surgery, and they had good outcomes. Four DSAs showed no aneurysms and no significant stenosis of the parent artery 10-14 days after surgery. One patient had mild stenosis of the parent artery on DSA 10 days after surgery; the stenosis improved on DSA 1 year after surgery. No other aneurysms recurred, and parent arteries were clear on CTA or DSA 1 year after surgery. Conclusions: Combining our accumulated experience in the work and literature, we described the CRYST technique to treat intractable IAs with specific morphologies and irregular wall structures in our patients. All outcomes and follow-up results were favorable.

Efficacy of umbilical cord mesenchymal stromal cells for COVID-19: A systematic review and meta-analysis.

Objectives: A major challenge for COVID-19 therapy is dysregulated immune response associated with the disease. Umbilical cord mesenchymal stromal cells (UC-MSCs) may be a promising candidate for COVID-19 treatment owing to their immunomodulatory and anti-inflammatory functions. Therefore, this study aimed to evaluate the effectiveness of UC-MSCs inpatients with COVID-19. Method: Medline, Embase, PubMed, Cochrane Library, and Web of Science databases were searched to collect clinical trials concerning UC-MSCs for the treatment of COVID-19. After literature screening, quality assessment, and data extraction, a systematic review and meta-analysis of the included study were performed. Results: This systematic review and meta-analysis were prospectively registered on PROSPERO, and the registration number is CRD42022304061. After screening, 10 studies involving 293 patients with COVID-19 were eventually included. Our meta-analysis results showed that UC-MSCs can reduce mortality (relative risk [RR] =0.60, 95% confidence interval [CI]: [0.38, 0.95], P=0.03) in COVID-19 patients. No significant correlation was observed between adverse events and UC-MSC treatment (RR=0.85, 95% CI: [0.65, 1.10], P=0.22; RR=1.00, 95%CI: [0.64, 1.58], P=1.00). In addition, treatment with UC-MSCs was found to suppress inflammation and improve pulmonary symptoms. Conclusions: UC-MSCs hold promise as a safe and effective treatment for COVID-19. Systematic Review Registartion: PROSPERO, identifier CRD42022304061.

A predictive hemodynamic model based on risk factors for ruptured mirror aneurysms.

Objectives: To identify hemodynamic risk factors for intracranial aneurysm rupture and establish a predictive model to aid evaluation. Methods: We analyzed the hemodynamic parameters of 91 pairs of ruptured mirror aneurysms. A conditional univariate analysis was used for the continuous variables. A conditional multivariate logistic regression analysis was performed to identify the independent risk factors. Differences where p < 0.05 were statistically significant. A predictive model was established based on independent risk factors. Odds ratios (ORs) were used to score points. The validation cohort consisted of 189 aneurysms. Receiver operating characteristic curves were generated to determine the cutoff values and area under the curves (AUCs) of the predictive model and independent risk factors. Results: The conditional multivariate logistic analysis showed that the low shear area (LSA) (OR = 70.322, p = 0.044, CI = 1.112-4,445.256), mean combined hemodynamic parameter (CHP) (>0.087) (OR = 3.171, p = 0.034, CI = 1.089-9.236), and wall shear stress gradient (WSSG) ratio (>893.180) (OR = 5.740, p = 0.003, CI = 1.950-16.898) were independent risk factors. A prediction model was established: 23*LSA + 1*CHP mean (>0.087: yes = 1, no = 0) + 2 * WSSG ratio (>893.180: yes = 1, no = 0). The AUC values of the predictive model, LSA, mean CHP (>0.087), and WSSG ratio (>893.180) were 0.748, 0.700, 0.654, and 0.703, respectively. The predictive model and LSA cutoff values were 1.283 and 0.016, respectively. In the validation cohort, the predictive model, LSA, CHP (>0.087), and WSSG ratio (>893.180) were 0.736, 0.702, 0.689, and 0.706, respectively. Conclusions: LSA, CHP (>0.087), and WSSG ratio (>893.180) were independent risk factors for aneurysm rupture. Our predictive model could aid practical evaluation.

Relationship between the mean of 24-h venous blood glucose and in-hospital mortality among patients with subarachnoid hemorrhage: A matched cohort study.

Objective: The aim of this study was to explore the correlation between the mean of 24-h venous blood glucose (BG) and in-hospital mortality and all-cause mortality (ACM) in patients with subarachnoid hemorrhage (SAH). Methods: Detailed clinical information was acquired from the Medical Information Mart for Intensive IV (MIMIC-IV) database. The best cutoff value of mean BG was calculated using the X-tile program. Univariate and multivariate logistic regressive analyses were utilized to analyze the prognosis significance of mean BG, and survival curves were drawn using the Kaplan-Meier (K-M) approach. To improve the reliability of results and balance the impact of underlying confounders, the 1:1 propensity score matching (PSM) approach was utilized. Results: An overall of 1,230 subjects were selected herein. The optimal cutoff value of the mean BG for in-hospital mortality was 152.25. In addition, 367 pairs of score-matched subjects were acquired after PSM analysis, and nearly all variables' differences were balanced. K-M analysis showed that patients with mean BG ≥ 152.25 mg/dl had significantly higher in-hospital, 3-month, and 6-month mortalities compared with patients with mean BG < 152.25 mg/dl (p < 0.001). The multivariable logistic regressive analyses revealed that patients with mean BG ≥ 152.25 mg/dl had significantly increased in-hospital mortality compared with patients with mean BG < 152.25 mg/dl after the adjustment for possible confounders (OR = 1.994, 95% CI: 1.321-3.012, p = 0.001). Similar outcomes were discovered in the PSM cohort. Conclusion: Our data suggested that mean BG was related to ACM of patients with SAH. More studies are needed to further analyze the role of the mean of 24-h venous BG in patients with SAH.

Myoglobin Offers Higher Accuracy Than Other Cardiac-Specific Biomarkers for the Prognosis of COVID-19.

Although sporadic studies have shown that myoglobin may have better prognostic performance than other cardiac markers in COVID-19, a comprehensive comparative study is lacking. Herein, we retrospectively analyzed the clinical and laboratory data of COVID-19 patients admitted to the Guanggu Campus of Wuhan Tongji Hospital from February 9, 2020 to March 30, 2020, intending to compare the prognostic accuracy of three commonly used cardiac markers on COVID-19 mortality. Our results revealed that abnormal increases in myocardial biomarkers were associated with a significantly increased risk of in-hospital mortality with COVID-19. Interestingly, myoglobin, a non-cardiac-specific biomarker, also expressed in skeletal myocytes, had even higher prognostic accuracy than cardiac-specific biomarkers such as high-sensitivity troponin I (hs-TnI) and creatine kinase-MB (CK-MB). More importantly, multivariate Cox analysis showed that myoglobin, rather than hs-TnI or CK-MB, was independently prognostic for in-hospital mortality in COVID-19. These results were further confirmed by subgroup analyses of patients with severe and critical illnesses and those without a history of cardiovascular disease. Our findings suggest that myoglobin may be a reliable marker of illness reflecting general physiological disturbance and help to assess prognosis and treatment response in patients with COVID-19.

Inflammation-associated factors for predicting in-hospital mortality in patients with COVID-19.

The aim is to explore the relation between inflammation-associated factors and in-hospital mortality and investigate which factor is an independent predictor of in-hospital death in patients with coronavirus disease-2019. This study included patients with coronavirus disease-2019, who were hospitalized between February 9, 2020, and March 30, 2020. Univariate Cox regression analysis and least absolute shrinkage and selection operator regression (LASSO) were used to select variables. Multivariate Cox regression analysis was applied to identify independent risk factors in coronavirus disease-2019. A total of 1135 patients were analyzed during the study period. A total of 35 variables were considered to be risk factors after the univariate regression analysis of the clinical characteristics and laboratory parameters (p < .05), and LASSO regression analysis screened out seven risk factors for further study. The six independent risk factors revealed by multivariate Cox regression were myoglobin (HR, 5.353; 95% CI, 2.633-10.882; p < .001), C-reactive protein (HR, 2.063; 95% CI, 1.036-4.109; p = .039), neutrophil count (HR, 2.015; 95% CI, 1.154-3.518; p = .014), interleukin 6 (Il-6; HR, 9.753; 95% CI, 2.952-32.218; p < .001), age (HR, 2.016; 95% CI, 1.077-3.773; p = .028), and international normalized ratio (HR, 2.595; 95% CI, 1.412-4.769; p = .002). Our results suggested that inflammation-associated factors were significantly associated with in-hospital mortality in coronavirus disease-2019 patients. C-reactive protein, neutrophil count, and interleukin 6 were independent factors for predicting in-hospital mortality and had a better independent predictive ability. We believe these findings may allow early identification of the patients at high risk for death, and can also assist in better management of these patients.

Cardiac Biomarker Levels and Their Prognostic Values in COVID-19 Patients With or Without Concomitant Cardiac Disease.

The coronavirus disease 2019 (COVID-19) pandemic has become a global threat. Increases in cardiac biomarkers are common and are associated with adverse outcomes in patients with COVID-19. Although these increases are more likely to occur in cases with concomitant cardiac disease, the differences in cardiac biomarker levels between patients with and without cardiac disease and their associations with in-hospital mortality are largely unknown. A consecutive serial of laboratory-confirmed COVID-19 cases was retrospectively enrolled. Clinical characteristics, laboratory results, and outcome data were collected. The levels of cardiac biomarkers were evaluated and compared by stratifying patients according to concomitant cardiac conditions and clinical classifications. The prognostic efficacy of cardiac biomarker levels on admission was also assessed. Among the overall study population and survived patients, the cardiac biomarker levels at both the early and late stages in cardiac patients were significantly higher than those in non-cardiac patients. However, their concentrations in cardiac patients were comparable to non-cardiac ones among non-survivors. The cardiac biomarker levels at the late stage of the disease were significantly decreased compared to those at the early stage among patients who were alive. Whereas, the late-stage biomarker levels were significantly increased in patients who ultimately died. Subgroup analysis illustrated that increases in cardiac biomarkers were closely related to the severity of the disease, and were prognostic for high risks of in-hospital mortality in non-cardiac, rather than in cardiac patients. Myo and NT-proBNP, rather than Hs-TnI and CK-MB, were independently associated with in-hospital mortality in the overall population and non-cardiac patients. However, these associations were not significant among cardiac patients. In conclusion, our results helped better understand the release pattern and prognostic performance of cardiac biomarkers in patients with COVID-19. Increased levels of Myo and NT-proBNP on admission could be useful markers for early identifying high-risk patients. However, special attention must be paid when implementing the prognostic function for cardiac patients.

Inhibition of the Receptor for Advanced Glycation End-Products (RAGE) Attenuates Neuroinflammation While Sensitizing Cortical Neurons Towards Death in Experimental Subarachnoid Hemorrhage.

Subarachnoid hemorrhage (SAH) is a threatening and devastating neurological insult with high mortality and morbidity rates. Despite considerable efforts, the underlying pathophysiological mechanisms are still poorly understood. The receptor for advanced glycation end products (RAGE) is a multiligand receptor that has been implicated in various pathological conditions. We previously showed that RAGE was upregulated and may be involved in pathophysiology of SAH. In the current study, we investigated its potential role in SAH. We found that the upregulation of RAGE after SAH was NF-κB-dependent positive feedback regulation. Further, pharmacological inhibition of RAGE attenuated neuroinflammation, indicating a possible contributive role of RAGE in inflammation-associated brain injury after SAH. Conversely, however, inhibition of RAGE sensitized neurons, exacerbating cell death, which correlated with augmented apoptosis and diminished autophagy, suggesting that activation of RAGE may protect against SAH-induced neuronal injury. Furthermore, we demonstrate that inhibition of RAGE significantly reduced brain edema and improved neurological function at day 1 but not at day 3 post-SAH. Taken together, these results suggest that RAGE exerts dual role after SAH. Our findings also suggest caution should be exercised in setting RAGE-targeted treatment for SAH.

Effect of RNAi-mediated LRIG3 gene silencing on proliferation of glioma GL15 cells and expression of PCNA and Ki-67.

BACKGROUND AND OBJECTIVE: Leucine-rich repeats and immunoglobin-like domains 3 (LRIG3), a member of LRIG gene family, is down-regulated in various human cancers, but its functions are still unclear. This study was to explore the effect of RNA interference (RNAi)-mediated LRIG3 gene silencing on the proliferation of glioma GL15 cells and the expression of proliferating cell nuclear antigen (PCNA) and Ki-67, and investigate possible mechanisms. METHODS: The plasmids pGenesil2-LRIG3-shRNA1 and pGenesil2-LRIG3-shRNA2 which containing U6 promoter and LRIG3-specific short hairpin RNA (shRNA) and the plasmid pGenesil2-negative-shRNA containing unspecific shRNA were transfected into GL15 cells. Stable cell clones were selected by G418. The mRNA and protein levels of LRIG3 were measured by reverse transcription-polymerase chain reaction (RT-PCR) and Western blot. Cell proliferation was detected by MTT assay. The expression of PCNA and Ki-67 in GL15 cells were examined by SABC immunohistochemistry. RESULTS: Compared with those in control cells, the mRNA levels of LRIG3 transcripts were reduced by 52.4% and 63.8% in shRNA1- and shRNA2-transfected cells, respectively; its protein levels were reduced by 50.9% and 67.4%, respectively. Cell proliferation was enhanced by LRIG3 shRNA transfection. The positive rate of PCNA was significantly higher in shRNA1- and shRNA2-transfected cells than in control cells [(72.13 +/- 5.64)% and (81.93 +/- 5.23)% vs. (35.40 +/- 5.69)%, p < 0.01]. The positive rate of Ki-67 was also significantly higher in shRNA1- and shRNA2-transfected cells than in control cells [(82.27 +/- 5.50)% and (88.67 +/- 3.52)% vs. (49.73 +/- 5.73)%, p < 0.01]. PCNA expression was positively correlated to Ki-67 expression (r =0.932, p < 0.001). CONCLUSION: Down-regulating LRIG3 gene expression can improve the proliferation of glioma GL15 cells.