Effects and clinical significance of NLRP3 inflammasome activated by IL-17A in CRSwNP / 中华耳鼻咽喉头颈外科杂志

Objective: To investigate the effects and clinical significance of NOD-like receptor family pyrin domain containing 3 (NLRP3) inflammasome activated by interleukin (IL)-17A in chronic rhinosinusitis with nasal polyps (CRSwNP). Methods: Patients underwent nasal endoscopic surgery in the Third Affiliated Hospital of Sun Yat-sen University from January 2020 to December 2021 were collected, including 28 CRSwNP (including 19 males and 9 females, aged 19 to 67 years), 22 chronic rhinosinusitis without nasal polyps (CRSsNP) and 22 controls. qRT-PCR was used to detect the expressions of IL-17A, NLRP3, IL-1β and IL-18 in the three groups, and their correlations were analyzed. The positions of IL-17A, NLRP3 and IL-18 in nasal polys were analyzed by immunofluorescence. Western Blotting and ELISA were employed to detect the expression of NLRP3, IL-1β and IL-18 in the human nasal epithelial cells after using IL-17A stimulation or IL-17A receptor inhibitor. Immunofluorescence was used to observe the NLRP3, IL-1β, and IL-18 protein expression after IL-17A stimulating human nasal epithelial cells, and after the use of IL-17A receptor inhibitor and NLRP3 inhibitor MCC950. The correlations between NLRP3, IL-1β, IL-18 and CT scores, nasal endoscopic scores, visual analogue scale (VAS) scores, and sino-nasal outcome test (SNOT) 22 scores of CRSwNP patients were analyzed. SPSS 20.0 software was used for statistical analysis. Results: The expressions of IL-17A, NLRP3, IL-1β and IL-18 in the tissues of CRSwNP patients were significantly higher than those in CRSsNP group(P=0.018,P<0.001,P=0.005, P=0.016) and the control group(all P<0.001). IL-17A was positively correlated with the expression of NLRP3, IL-1β, and IL-18(r ralue was 0.643,0.650,0.629,respectively, all P<0.05). IL-17A, NLRP3, and IL-18 were co-localized in the epithelial propria of polyp tissue. IL-17A stimulated the expressions of NLRP3, IL-1β, and IL-18 in human nasal epithelial cells. After the use of IL-17A receptor inhibitor, the expressions of NLRP3, IL-1β, and IL-18 were significantly down-regulated. After the use of NLRP3 inhibitor MCC950, IL-17A was significantly down-regulated to promote the expression of NLRP3, IL-1β, and IL-18. The expressions of NLRP3, IL-1β and IL-18 were positively correlated with CT, nasal endoscopy, VAS, and SNOT22 scores in patients with CRSwNP. Conclusions: IL-17A promotes the release of IL-1β and IL-18 by activating the NLRP3 inflammasome and aggravates the severity of the disease in CRSwNP.

Origanum vulgare L. leaf extract alleviates finasteride-induced oxidative stress in mouse liver and kidney

Objective: To investigate the hepatorenoprotective effects of Origanum vulgare L. against finasteride-induced oxidative injury in the liver and kidney of mice. Methods: Liquid chromatography-electrospray ionization-tandem mass spectrometry (LC-ESI/MS) analysis was utilized to yield a fingerprint of Origanum vulgare polyphenolic constituents. Thirty BALB/c mice received 0.5 mL/day distilled water, finasteride (25 mg/kg/day for 10 d), and 100, 200, or 400 mg/kg/day finasteride + Origanum vulgare extract with 6 mice per group for five weeks. On day 36, liver and kidney function as well as pro- and anti-inflammatory (IFN-γ, IL-12, IL-6, TNF-α, IL-1β, and IL-10) cytokines were measured. The total antioxidant status, nitric oxide (NO), and malondialdehyde levels as well as the activities of NO synthase and catalase were also evaluated. Histopathological study was conducted to assess the effect of Origanum vulgare extract on finasteride-induced renal and hepatic toxicities. Results: Twenty-five major polyphenolic compounds were identified in the Origanum vulgare extract by LC-ESI/MS. Origanum vulgare extract, especially at 200 and 400 mg/kg/day doses, significantly improved liver and kidney biochemical indices, decreased inflammatory cytokines, increased total antioxidant status and NO synthase and catalase activities, as well as decreased plasma NO and malondialdehyde levels in a dose-dependent manner as compared to the finasteride group. Histopathological results further confirmed the protective effect of Origanum vulgare extract. Conclusions: Origanum vulgare extract ameliorates finasteride-induced hepatic and renal biochemical and histopathological alterations, and restores antioxidant/oxidant balance.

Origanum vulgare L. leaf extract alleviates finasteride-induced oxidative stress in mouse liver and kidney

Objective: To investigate the hepatorenoprotective effects of Origanum vulgare L. against finasteride-induced oxidative injury in the liver and kidney of mice. Methods: Liquid chromatography-electrospray ionization-tandem mass spectrometry (LC-ESI/MS) analysis was utilized to yield a fingerprint of Origanum vulgare polyphenolic constituents. Thirty BALB/c mice received 0.5 mL/day distilled water, finasteride (25 mg/kg/day for 10 d), and 100, 200, or 400 mg/kg/day finasteride + Origanum vulgare extract with 6 mice per group for five weeks. On day 36, liver and kidney function as well as pro-and antiinflammatory (IFN-γ, IL-12, IL-6, TNF-α, IL-1β, and IL-10) cytokines were measured. The total antioxidant status, nitric oxide (NO), and malondialdehyde levels as well as the activities of NO synthase and catalase were also evaluated. Histopathological study was conducted to assess the effect of Origanum vulgare extract on finasteride-induced renal and hepatic toxicities. Results: Twenty-five major polyphenolic compounds were identified in the Origanum vulgare extract by LC-ESI/MS. Origanum vulgare extract, especially at 200 and 400 mg/kg/day doses, significantly improved liver and kidney biochemical indices, decreased inflammatory cytokines, increased total antioxidant status and NO synthase and catalase activities, as well as decreased plasma NO and malondialdehyde levels in a dose-dependent manner as compared to the finasteride group. Histopathological results further confirmed the protective effect of Origanum vulgare extract. Conclusions: Origanum vulgare extract ameliorates finasteride-induced hepatic and renal biochemical and histopathological alterations, and restores antioxidant/oxidant balance.

Origanum vulgare L. leaf extract alleviates finasteride-induced oxidative stress in mouse liver and kidney

Objective: To investigate the hepatorenoprotective effects of Origanum vulgare L. against finasteride-induced oxidative injury in the liver and kidney of mice. Methods: Liquid chromatography-electrospray ionization-tandem mass spectrometry (LC-ESI/MS) analysis was utilized to yield a fingerprint of Origanum vulgare polyphenolic constituents. Thirty BALB/c mice received 0.5 mL/day distilled water, finasteride (25 mg/kg/day for 10 d), and 100, 200, or 400 mg/kg/day finasteride + Origanum vulgare extract with 6 mice per group for five weeks. On day 36, liver and kidney function as well as pro-and antiinflammatory (IFN-γ, IL-12, IL-6, TNF-α, IL-1β, and IL-10) cytokines were measured. The total antioxidant status, nitric oxide (NO), and malondialdehyde levels as well as the activities of NO synthase and catalase were also evaluated. Histopathological study was conducted to assess the effect of Origanum vulgare extract on finasteride-induced renal and hepatic toxicities. Results: Twenty-five major polyphenolic compounds were identified in the Origanum vulgare extract by LC-ESI/MS. Origanum vulgare extract, especially at 200 and 400 mg/kg/day doses, significantly improved liver and kidney biochemical indices, decreased inflammatory cytokines, increased total antioxidant status and NO synthase and catalase activities, as well as decreased plasma NO and malondialdehyde levels in a dose-dependent manner as compared to the finasteride group. Histopathological results further confirmed the protective effect of Origanum vulgare extract. Conclusions: Origanum vulgare extract ameliorates finasteride-induced hepatic and renal biochemical and histopathological alterations, and restores antioxidant/oxidant balance.

Effects of traditional Chinese exercises and general aerobic exercises on older adults with sleep disorders: A systematic review and meta-analysis / 中西医结合学报

BACKGROUND@#Sleep disorders are common in older adults and have a negative influence on their physical and mental health. General aerobic exercises (GAEs) have long been used in the treatment of sleep disorders as a non-pharmacological measure. However, there is no consensus on the efficacy of traditional Chinese exercises (TCEs) for treating sleep disorders in older adults and the difference between TCEs and GAEs.@*OBJECTIVE@#This study assessed the effects of TCEs and GAEs on the sleep quality of older adults and the differences between these two interventions.@*SEARCH STRATEGY@#PubMed, Embase, Cochrane Library, Web of Science, China Biology Medicine disc, China National Knowledge Infrastructure, China Science Journal Database and Wanfang Data were searched from their inception to August 2020.@*INCLUSION CRITERIA@#Randomized controlled trials (RCTs) that evaluated the effects of TCEs and GAEs on older adults with sleep disorders were included.@*DATA EXTRACTION AND ANALYSIS@#Data were extracted by two researchers working independently. The risk bias of included studies was assessed using the Cochrane Handbook for Systematic Reviews of Interventions 5.1.0 and the quality of evidence was assessed using the Grades of Recommendation, Assessment, Development and Evaluation approach. The Pittsburgh Sleep Quality Index (PSQI) was used to estimate sleep quality. Meta-analyses were performed to assess the total PSQI score of the exercise intervention as the primary outcome, and the scores of subjective sleep quality, sleep latency, sleep duration, habitual sleep efficiency, sleep disturbance, use of sleep medication and daytime dysfunction were assessed as secondary outcomes. Subgroup, sensitivity, and meta-regression analyses were conducted to assess the contribution of covariables to heterogeneity.@*RESULTS@#A total of 22 RCTs (including 1747 participants) were included in the meta-analysis. The results indicated that TCEs (weighted mean difference [WMD] = -2.14, 95% confidence interval [CI] [-2.82, -1.46], P < 0.001; heterogeneity: P < 0.001, I@*CONCLUSION@#Current evidence shows that both TCEs and GAEs, as complementary and non-pharmacological approaches, help to improve the sleep quality in older adults with potentially clinical implications; however, there was not enough evidence to conclude the difference between them. More rigorous and high-quality RCTs are needed to arrive at reliable conclusions.

Short-segment decompression/fusion versus long-segment decompression/fusion and osteotomy for Lenke-Silva type VI adult degenerative scoliosis / 中华医学杂志(英文版)

BACKGROUND@#The effect of short-segment decompression/fusion versus long-segment decompression/fusion and osteotomy for Lenke-Silva type VI adult degenerative scoliosis (ADS) has not been clarified. This study aimed to compare the clinical and radiographic results of short-segment fusion vs. long-segment fusion and osteotomy for patients with Lenke-Silva type VI ADS.@*METHODS@#Data of 28 patients who underwent spinal surgery for ADS from January 2012 to January 2014 in the General Hospital of Northern Theater Command were reviewed. Of the 28 patients, 12 received long-segment fusion and osteotomy and 16 received short-segment fusion. Radiographic imaging parameters and clinical outcomes, including the sagittal vertical axis (SVA), lumbar lordosis (LL) angle, pelvic tilt (PT), sacral slope (SS), the visual analog scale (VAS), Japanese Orthopedic Association (JOA), Oswestry disability index (ODI), and lumbar stiffness disability index (LSDI) scores, were recorded. The difference between groups was compared using the dependent t test or Chi-squared test.@*RESULTS@#The Cobb and LL angles and SVA improved in both groups; however, PT and SS angles did not improve following short fusion. There were significant differences in the post-operative SVA (26.8 ± 5.4 mm vs. 47.5 ± 7.6 mm, t = -8.066, P  0.05). The post-operative LSDI score was 3.5 ± 0.5 in the long fusion group, which was significantly higher than that of the short fusion group (1.4 ± 0.7; P < 0.001).@*CONCLUSIONS@#The clinical outcomes of patients with Lenke-Silva type VI ADS who underwent short-segment decompression/fusion were comparable to those of patients who underwent long-segment decompression/fusion and osteotomy despite poor correction of sagittal imbalance. Moreover, short-segment decompression/fusion showed a short operation time and reduced surgical trauma.

Short-segment decompression/fusion versus long-segment decompression/fusion and osteotomy for Lenke-Silva type VI adult degenerative scoliosis / 中华医学杂志(英文版)

Background@#The effect of short-segment decompression/fusion versus long-segment decompression/fusion and osteotomy for Lenke-Silva type VI adult degenerative scoliosis (ADS) has not been clarified. This study aimed to compare the clinical and radiographic results of short-segment fusion vs. long-segment fusion and osteotomy for patients with Lenke-Silva type VI ADS.@*Methods@#Data of 28 patients who underwent spinal surgery for ADS from January 2012 to January 2014 in the General Hospital of Northern Theater Command were reviewed. Of the 28 patients, 12 received long-segment fusion and osteotomy and 16 received short-segment fusion. Radiographic imaging parameters and clinical outcomes, including the sagittal vertical axis (SVA), lumbar lordosis (LL) angle, pelvic tilt (PT), sacral slope (SS), the visual analog scale (VAS), Japanese Orthopedic Association (JOA), Oswestry disability index (ODI), and lumbar stiffness disability index (LSDI) scores, were recorded. The difference between groups was compared using the dependent t test or Chi-squared test.@*Results@#The Cobb and LL angles and SVA improved in both groups; however, PT and SS angles did not improve following short fusion. There were significant differences in the post-operative SVA (26.8 ± 5.4 mm vs. 47.5 ± 7.6 mm, t = -8.066, P < 0.001), PT (14.7 ± 1.8° vs. 29.1 ± 3.4°, t = -13.277, P < 0.001), and SS (39.8 ± 7.2° vs. 26.1 ± 3.3°, t = 6.175, P < 0.001) between the long and short fusion groups. All patients had improved ODI, JOA, and VAS scores post-operatively (all P < 0.001), with no significant difference between the groups (all P > 0.05). The post-operative LSDI score was 3.5 ± 0.5 in the long fusion group, which was significantly higher than that of the short fusion group (1.4 ± 0.7; P < 0.001).@*Conclusions@#The clinical outcomes of patients with Lenke-Silva type VI ADS who underwent short-segment decompression/fusion were comparable to those of patients who underwent long-segment decompression/fusion and osteotomy despite poor correction of sagittal imbalance. Moreover, short-segment decompression/fusion showed a short operation time and reduced surgical trauma.

Clinical curative effect of percutaneous vertebroplasty combined with percutaneous pedicle screw fixation for thoracolumbar fracture / 局解手术学杂志

Objective To discuss the clinical curative effect of percutaneous vertebroplasty(PVP)combined with percutaneous pedicle screw fixation for thoracolumbar fracture.Methods Retrospectively analyzed the clinical data of 43 patients with thoracolumbar fracture who underwent PVP combined with percutaneous pedicle screw fixation in our hospital from November 2015 to June 2017.Those patients included 28 males and 15 females,and the age of patients ranged from 50 to 66 years old,with an average age of(58.26 ±3.67)years old.The func-tional outcome were evaluated by VAS scores and ODI scores before and after the operation.The sagittal Cobb angle was used to evaluate the reduction of fracture.Results All these patients all successfully completed the operation,and there was no complications after operation.The operation time ranged from 60 to 126 min,with an average time of(96.07 ±15.69)min;the blood loss ranged from 60 to 180 min,with an average time of(113.26 ±24.7)min.All the patients were followed up for 4 to 23 months,with an average time of(12.07 ±4.01)months. The VAS score,ODI score and sagittal Cobb angle were significantly decreased in the last follow -up period compared with those before surgery,and the difference was statistically significant(P<0.05).Conclusion PVP combined with percutaneous pedicle screw fixation in the treatment of thoracolumbar fracture has smaller incision,less blood loss,shorter operation time and better improvement of local pain,func-tional movement and kyphosis.

Neutralization of Interleukin-9 Decreasing Mast Cells Infiltration in Experimental Autoimmune Encephalomyelitis / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>Th9 cells are a newly discovered CD4+ T helper cell subtype, characterized by high interleukin (IL)-9 secretion. Growing evidences suggest that Th9 cells are involved in the pathogenic mechanism of multiple sclerosis (MS). Mast cells are multifunctional innate immune cells, which are perhaps best known for their role as dominant effector cells in allergies and asthma. Several lines of evidence point to an important role for mast cells in MS and its animal models. Simultaneously, there is dynamic "cross-talk" between Th9 and mast cells. The aim of the present study was to examine the IL-9-mast cell axis in experimental autoimmune encephalomyelitis (EAE) and determine its interaction after neutralizing anti-IL-9 antibody treatment.</p><p><b>METHODS</b>Female C57BL/6 mice were randomly divided into three groups (n = 5 in each group): mice with myelin oligodendrocyte glycoprotein (MOG)-induced EAE (EAE group), EAE mice treated with anti-IL-9 antibody (anti-IL-9 Abs group), and EAE mice treated with IgG isotype control (IgG group). EAE clinical score was evaluated. Mast cells from central nervous system (CNS) were detected by flow cytometry. The production of chemokine recruiting mast cells in the CNS was explored by reverse transcription-polymerase chain reaction (RT-PCR). In mice with MOG-induced EAE, the expression of IL-9 receptor (IL-9R) complexes in CNS and spleen mast cells was also explored by RT-PCR, and then was repeating validated by immunocytochemistry. In vitro, spleen cells from EAE mice were cultured with anti-IL-9 antibody, and quantity of mast cells was counted by flow cytometry after co-culture.</p><p><b>RESULTS</b>Compared with IgG group, IL-9 blockade delayed clinical disease onset and ameliorated EAE severity (t = -2.217, P = 0.031), accompany with mast cells infiltration decreases (day 5: t = -8.005, P < 0.001; day 15: t = -11.857, P < 0.001; day 20: t = -5.243, P = 0.001) in anti-IL-9 Abs group. The messenger RNA expressions of C-C motif chemokine ligand 5 (t = -5.932, P = 0.003) and vascular cell adhesion molecule-1 (t = -4.029, P = 0.004) were significantly decreased after IL-9 neutralization in anti-IL-9 Abs group, compared with IgG group. In MOG-induced EAE, the IL-9R complexes were expressed in CNS and spleen mast cells. In vitro, splenocytes cultured with anti-IL-9 antibody showed significantly lower levels of mast cells in a dose-dependent manner, compared with splenocytes cultured with anti-mouse IgG (5 μg/ml: t = -0.894, P = 0.397; 10 μg/ml: t = -3.348, P = 0.019; 20 μg/ml: t = -7.639, P < 0.001).</p><p><b>CONCLUSIONS</b>This study revealed that IL-9 neutralization reduced mast cell infiltration in CNS and ameliorated EAE, which might be relate to the interaction between IL-9 and mast cells.</p>