Comparison of the clinical effect of DHS and PFNA on senile osteoporotic fracture and their significance of changes in BALP expression level

Objective:To investigate the clinical effects of dynamic hip screw (DHS) and proximal femoral nail anti-rotation (PFNA) on senile osteoporosis patients and their effects on the expression level of bone-specific alkaline phosphatase (BALP).Methods:116 elderly patients with osteoporotic fracture were divided into DHS group (n=67) and PFNA group (n=49). BALP values were measured by ELISA before operation and 30 days after operation.Results:The operation time, the bleeding volume, and the weight-bearing time of PFNA group was shorter than DHS group (p<0.05); the dominant blood loss and occult blood loss in PFNA group were less than those in DHS group (p<0.05); the healing time and detumescence time, the complications of PFNA group was fewer than the DHS group (p<0.05). The ten-meter walking speed and the five sitting tests in PFNA group were shorter than that in DHS group (p<0.05); the excellent and good rate and Harris score in PFNA group were higher than those in DHS group (p<0.05). The expression of BALP in PFNA group was lower than that in DHS group (p<0.05).Conclusion:PFNA surgery has less trauma, fewer complications, more optimistic postoperative healing and recovery degree, and is more conducive to the reduction of BALP expression level.     

Upregulation of NLRP3 Inflammasome in the Tears and Ocular Surface of Dry Eye Patients

PurposeTo evaluate the mRNA and protein expressions of NLRP3 inflammasome and its downstream inflammatory factors in human dry eye.MethodsWe recruited 54 patients with Sjögren’s syndrome dry eye (SSDE), 50 patients with non-Sjögren’s syndrome dry eye (NSSDE), and 46 healthy controls. Tear film breakup time (TBUT), Schirmer I test, and fluorescein staining (FL) were performed on all subjects. Tear samples were obtained to analyze the inflammatory cytokine levels of IL-1β and IL-18 via enzyme-linked immunosorbent (ELISA). Conjunctival impression cytology (CIC) specimens were collected to detect the mRNA expression of NLRP3, caspase-1, IL-1β, and IL-18 using quantitative RT-PCR, and the protein expression of NLRP3 and caspase-1 by Western blotting.ResultsNLRP3 mRNA expression showed higher levels in both dry eye groups compared with controls, with a comparably significant elevation in the SSDE group (relative 2.47-fold upregulation, p<0.05). NLRP3 protein expression was also increased in SSDE group (relative1.94-fold upregulation) compared with the controls. mRNA expression of caspase-1 was significantly upregulated in both SSDE (relative 1.44-fold upregulation, p<0.05) and NSSDE (relative 1.32-fold upregulation, p<0.05). Procaspase-1 protein level was increased in SSDE (relative 1.84-fold upregulation) and NSSDE (relative 1.12-fold upregulation) versus controls; and caspase-1 protein expression was also increased in SSDE (relative 1.49-fold upregulation) and NSSDE (relative 1.17-fold upregulation) compared with the controls. The patients with SSDE and NSSDE had higher IL-1β and IL-18 mRNA values and protein expressions than the controls did. The relative mRNA expression of IL-1β upregulated 3.59-fold (p<0.001) in SSDE and 2.13-fold (p<0.01) in NSSDE compared with the controls. IL-1β protein level also showed significant upregulation in SSDE (p=0.01; vs. controls groups). IL-18 mRNA expression levels were significantly upregulated in the SSDE (relative 2.97-fold upregulation, p=0.001) and NSSDE (relative 2.05-fold upregulation, p=0.001) groups compared with the controls; tear IL-18 concentrations were also significantly increased in the SSDE (p<0.001) and NSSDE (p<0.05) groups.ConclusionsIn the current study, we found that mRNA and protein expressions of NLRP3 inflammasome were upregulated in human dry eyes, especially in SSDE; the downstream inflammatory factors caspase-1, IL-1β, and IL-18 were also elevated in dry eye patients. These observations suggest the involvement of NLRP3 inflammasome in the onset and development of the inflammation in dry eye.     

单侧与双侧PVP治疗骨质疏松性椎体压缩骨折临床疗效比较及骨水泥渗漏的危险因素分析

摘要 目的：比较单侧与双侧经皮椎体成形术（PVP）治疗骨质疏松性椎体压缩骨折（OVCF）的临床疗效,并分析骨水泥渗漏的危险因素。方法：回顾性分析2019年5月~2020年12月期间本院收治的205例OVCF患者的临床资料,根据入路方式的不同分为单侧组和双侧组,例数分别为104例和101例。对比两组围术期指标、视觉模拟评分（VAS）、Oswestry功能障碍指数（ODI）、Cobb''s角和椎体前缘高度,记录两组骨水泥渗漏及其他并发症发生情况,采用单因素及多因素Logistic回归分析骨水泥渗漏的影响因素。结果：与双侧组相比,单侧组手术时间缩短,骨水泥注入量、术中透视次数减少（P<0.05）。两组术前、术后3个月、末次随访时VAS、ODI评分均呈下降趋势（P<0.05）。与术前相比,两组术后3个月及末次随访时的椎体前缘高度均升高,Cobb''s角均缩小（P<0.05）。两组并发症发生率组间对比无统计学差异（P>0.05）。PVP患者骨水泥渗漏与骨水泥黏度、皮质断裂、骨折严重程度、骨折位置、年龄、CT值、骨水泥注入量有关（P<0.05）。骨水泥渗漏的危险因素主要有骨水泥注入量>6 mL、骨折严重程度为重度、CT值>63HU、骨水泥黏度为低、皮质断裂（P<0.05）。结论：单侧与双侧PVP治疗OVCF效果相当。其中单侧可减少骨水泥注入量,缩短手术时间,减轻术后疼痛,促进术后功能恢复。而PVP手术最常见的并发症为骨水泥渗漏,受到骨折严重程度、皮质断裂、骨水泥黏度等因素的影响。     

Association of vascular endothelial growth factor gene polymorphisms with osteoporotic vertebral compression fractures in postmenopausal women

Vascular endothelial growth factor (VEGF) is involved in bone formation through its role in angiogenesis. VEGF is also known to promote the healing of fractures. Thus, we determined whether or not VEGF ?2578C>A, ?1154G>A, ?634G>C, and 936C>T polymorphisms and haplotypes are associated with osteoporotic vertebral compression fractures (OVCF) in postmenopausal Korean women. The study subjects consisted of 82 patients with osteoporotic vertebral compression fractures and 117 control postmenopausal Korean women. PCR-RFLP and real-time PCR were used to analyze the VEGF polymorphisms. Homocysteine levels were also measured to determine whether or not polymorphisms of the VEGFgene affect homocysteine/folate metabolism. The AA genotype of the ?2578C>A polymorphism was significantly different between the stroke and control groups; no significant differences in the ?1154G>A, ?634G>C, and 936C>T genotype frequencies existed. However, the A-G-G-C haplotype had a tendency to be associated with OVCF in postmenopausal Korean women. Associations between the VEGF ?2578C>A polymorphism and homocysteine levels were also noted. In summary, these results suggest that the VEGF ?2578C>A polymorphisms and VEGF haplotypes may play an important role in the etiology of OVCF in postmenopausal Korean women.     

PVP与PKP治疗骨质疏松脊柱压缩性骨折的临床治疗效果比较

目的:分析PKP(即经皮椎体后凸成形术)和PVP(即经皮椎体成形术)在骨质疏松性椎体压缩骨折治疗中的临床应用效果。方法:回顾并抽取我院骨科诊治的164例骨质疏松脊柱压缩性骨折患者资料,根据术式分为PKP组和PVP组各82例,对比分析不同手术前各组VAS评分(即视觉模拟评分法)、ODI(即Oswestry功能障碍指数)、椎体高度以及Cobb角变化,同时对2种手术的安全性进行客观评价。结果:手术后,两组VAS评分、ODI、椎体高度以及Cobb角度均出现明显恢复(P0.05),在术后相同时间点,PKP组VAS分数、ODI分数、椎体高度、Cobb角度均显著优于PVP组(P0.05);PKP组手术不良事件发生率(17.07%)显著低于PVP组(36.59%),P0.05,组间差异明显。结论:PVP、PKP虽然均能够对骨质疏松脊柱压缩性骨折达到修复椎体高度、止痛的治疗效果,但是PKP治疗后椎体恢复情况、手术安全性显著优于PVP。     

Pathological and immunological evaluation of different regimens of praziquantel treatment in a mouse model of Schistosoma mansoni infection

BackgroundOne of the considerable challenges of schistosomiasis chemotherapy is the inefficacy of praziquantel (PZQ) at the initial phase of the infection. Immature schistosomes are not susceptible to PZQ at the curative dose. Here, we investigated the efficacy of different PZQ regimens administered during the initial stage of Schistosoma mansoni infection in mice.Methodology/Principal findingsTwo months-old mice were individually infected with 80 S. mansoni cercariae and divided into one infected-untreated control group (IC) and four PZQ-treated groups: PZQ at 100 mg/kg/day for five consecutive days (group PZQ1), PZQ at 100 mg/kg/day for 28 days (group PZQ2), PZQ at 18 mg/kg/day for 28 days (group PZQ3) and a single dose of PZQ at 500 mg/kg (group PZQ4). The treatment started on day one post-infection (p.i), and each group of mice was divided into two subgroups euthanized on day 36 or 56 p.i, respectively. We determined the mortality rate, the parasitological burden, the hepatic and intestinal granulomas, the serum levels of Th-1, Th-2, and Th-17 cytokines, and gene expression. The treatment led to a significant (p < 0.001) reduction of worm burden and egg counts in the intestine and liver in groups PZQ2 and PZQ3. On 56^th day p.i, there was a significant reduction (p < 0.001) of the number and volume of the hepatic granulomas in groups PZQ2 and PZQ3 compared to group PZQ1 or PZQ4. Moreover, in group PZQ3, the serum levels of IFN-γ, TNF-α, IL-13, and IL-17 and their liver mRNA expressions were significantly reduced while IL-10 and TGF-β gene expression significantly increased. The highest mortality rate (81.25%) was recorded in group PZQ2.Conclusion/SignificanceThis study revealed that the administration of PZQ at 18 mg/kg/day for 28 consecutive days was the optimal effective posology for treating S. mansoni infection at the initial stage in a murine model.     

Overexpression of microRNA-155 increases IL-21 mediated STAT3 signaling and IL-21 production in systemic lupus erythematosus

IntroductionInterleukin (IL)-21 is a key cytokine in autoimmune diseases such as systemic lupus erythematosus (SLE) by its regulation of autoantibody production and inflammatory responses. The objective of this study is to investigate the signaling capacity of IL-21 in T and B cells and assess its possible regulation by microRNA (miR)-155 and its target gene suppressor of cytokine signaling 1 (SOCS1) in SLE.MethodsThe signaling capacity of IL-21 was quantified by stimulating peripheral blood mononuclear cells (PBMCs) with IL-21 and measuring phosphorylation of STAT3 (pSTAT3) in CD4+ T cells, B cells, and natural killer cells. Induction of miR-155 by IL-21 was investigated by stimulating purified CD4+ T cells with IL-21 and measuring miR-155 expression levels. The functional role of miR-155 was assessed by overexpressing miR-155 in PBMCs from SLE patients and healthy controls (HCs) and measuring its effects on STAT3 and IL-21 production in CD4+ and CD8+ T cells.ResultsInduction of pSTAT3 in CD4+ T cells in response to IL-21 was significantly decreased in SLE patients compared to HCs (p < 0.0001). Further, expression levels of miR-155 were significantly decreased and SOCS1 correspondingly increased in CD4+ T cells from SLE patients. Finally, overexpression of miR-155 in CD4+ T cells increased STAT3 phosphorylation in response to IL-21 treatment (p < 0.01) and differentially increased IL-21 production in SLE patients compared to HCs (p < 0.01).ConclusionWe demonstrate that SLE patients have reduced IL-21 signaling capacity, decreased miR-155 levels, and increased SOCS1 levels compared to HCs. The reduced IL-21 signaling in SLE could be rescued by overexpression of miR-155, suggesting an important role for miR-155 in the reduced IL-21 signaling observed in SLE.

Electronic supplementary material

The online version of this article (doi:10.1186/s13075-015-0660-z) contains supplementary material, which is available to authorized users.     

Renal Transplant Recipients Treated with Calcineurin-Inhibitors Lack Circulating Immature Transitional CD19+CD24hiCD38hi Regulatory B-Lymphocytes

BackgroundCD19⁺CD24^hiCD38^hi transitional immature B-lymphocytes have been demonstrated to play an important role in regulating the alloimmune response in transplant recipients. Here, we analyzed the effect of calcineurin inhibition on these peripherally circulating regulatory B-cells (Breg) in renal transplant recipients receiving cyclosporine A (CsA) or tacrolimus.MethodsPBMCs from healthy subjects (HS) (n = 16) and renal transplant recipients (n = 46) were isolated. Flow cytometry was performed for CD19, CD24, CD38 and IL-10 either after isolation or after 72 hours of co-culture in presence of PMA/Ionomycin and TLR9-ligand in presence or absence of increasing concentrations of tacrolimus or CsA.ResultsThe amount of CD19⁺ B-cells among lymphocytes was ∼9.1% in HS, ∼3.6% in CsA (n = 11, p<0.05) and ∼6.4% in TAC (n = 35, p<0.05) treated patients. Among B-cells, a distinct subset of Breg was found to be 4.7% in HS, 1.4% in tacrolimus treated patients and almost blunted in patients receiving CsA. Similarily, ∼4% of B-cells in HS and even fewer in CsA or tacrolimus treated patients produced IL-10 (0.5% and 1.5%, p<0.05) and this was confirmed both in non-transplanted CsA-treated healthy subjects and in in vitro co-culture experiments. Among 29 patients with <1% of Breg, 9 cases (31%) displayed an allograft rejection in contrast to only one case of rejection (6%) among 17 patients with >1%.ConclusionCalcineurin inhibitors reduce number and IL-10 production of Bregs in the peripheral circulation of both renal transplant recipients and non-transplanted healthy subjects. CNI induced Breg reduction is not restricted to a solid organ transplant setting and is not mediated by co-medication with steroids or MPA. A low proportion of Breg cells is associated with an elevated frequency of allograft rejection events.     

椎体静脉稀疏区注入骨水泥对PVP术中骨水泥渗漏的影响

目的:探讨椎体静脉稀疏区注入骨水泥对骨质疏松椎体压缩性骨折患者行经皮穿刺椎体成形术(percutaneous vertebroplasty,PVP)术中骨水泥渗漏的影响。方法:选择西安交通大学第二附属医院2014年1月至2018年6月收治的61例骨质疏松椎体压缩性骨折患者,根据骨水泥注入区域的不同,将所有患者分为A组(30例)及B组(31例),A组骨水泥注入区域为椎体静脉密集区(椎体中1/3平面处),B组骨水泥注入区域为椎体静脉稀疏区(椎体上1/3及下1/3平面处),对比两组的骨水泥渗漏率,术前、术后6个月时的视觉模拟评分(Visual analogue scale,VAS),治疗中的骨水泥用量、椎体高度恢复率及cobb角恢复度数。结果:B组的骨水泥渗漏率及骨水泥用量均明显低于A组(P0.05)。两组的VAS评分、椎体高度恢复率、cobb角恢复情况对比差异无统计学意义(P0.05)。结论:与椎体静脉密集区相比,在椎体静脉稀疏区注入骨水泥可显著降低骨质疏松椎体压缩性骨折患者PVP术中骨水泥渗漏率,椎体静脉稀疏区可作为PVP术中骨水泥注射的一个相对安全区域。     

Carvedilol Improves Inflammatory Response,Oxidative Stress and Fibrosis in the Alcohol-Induced Liver Injury in Rats by Regulating Kuppfer Cells and Hepatic Stellate Cells

Aim

To evaluate the anti-inflammatory, anti-oxidant and antifibrotic effects of carvedilol (CARV) in rats with ethanol-induced liver injury.

Methods

Liver injury was induced by gavage administration of alcohol (7 g/kg) for 28 consecutive days. Eighty Wistar rats were pretreated with oral CARV at 1, 3, or 5 mg/kg or with saline 1 h before exposure to alcohol. Liver homogenates were assayed for interleukin (IL)-1β, IL-10, and tumor necrosis factor (TNF)-α level as well as for myeloperoxidase (MPO) activity and malonyldialdehyde (MDA) and glutathione (GSH) levels. Serum aspartate aminotransferase (AST) activity and liver triglyceride (TG) levels were also assayed. Immunohistochemical analyses of cyclooxygenase 2 (COX-2), receptor activator of nuclear factor kappa-B/ligand (RANK/RANKL), suppressor of cytokine signalling (SOCS1), the Kupffer cell marker IBA-1 (ionized calcium-binding adaptor molecule 1), intercellular adhesion molecule 1 (ICAM-1), superoxide dismutase (SOD-1), and glutathione peroxidase (GPx-1) expression were performed. Confocal microscopy analysis of IL-1β and NF-κB expression and real-time quantitative PCR analysis for TNFα, PCI, PCIII, and NF-κB were performed.

Results

CARV treatment (5 mg/kg) during the alcohol exposure protocol was associated with reduced steatosis, hepatic cord degeneration, fibrosis and necrosis, as well as reduced levels of AST (p < 0.01), ALT (p < 0.01), TG (p < 0.001), MPO (p < 0.001), MDA (p < 0.05), and proinflammatory cytokines (IL-1β and TNF-α, both p < 0.05), and increased levels of the anti-inflammatory cytokine IL-10 (p < 0.001) and GSH (p < 0.05), compared to the alcohol-only group. Treatment with CARV 5 mg/kg also reduced expression levels of COX-2, RANK, RANKL, IBA-1, and ICAM-1 (all p < 0.05), while increasing expression of SOCS1, SOD-1, and GPx-1 (all p < 0.05) and decreasing expression of IL-1β and NF-κB (both, p < 0.05). Real-time quantitative PCR analysis showed that mRNA production of TNF-α, procollagen type I (PCI), procollagen type III (PCIII), and NF-κB were decreased in the alcohol-CARV 5 mg/kg group relative to the alcohol-only group.

Conclusions

CARV can reduce the stress oxidative, inflammatory response and fibrosis in ethanol-induced liver injury in a rat model by downregulating signalling of Kuppfer cells and hepatic stellate cells (HSCs) through suppression of inflammatory cytokines.     

Serum levels of appetite-regulating hormones and pro-inflammatory cytokines are ameliorated by a CLA diet and endurance exercise in rats fed a high-fat diet

[Purpose]

This study examined whether conjugated linoleic acid (CLA) supplementation and endurance exercise affect appetite-regulating hormones and pro-inflammatory cytokines in rats.

[Methods]

Seven-week-old male Sprague-Dawley rats were divided randomly into the high-fat diet sedentary group (HS, n=8), the 1.0% CLA supplemented high-fat diet sedentary group (CS, n=8), and the 1.0% CLA supplemented high-fat diet exercise group (CE, n=8). Rats in the CE group swam 60 min/day, 5 days/week for 4 weeks.

[Results]

Leptin and insulin levels in the CS and CE groups were significantly lower than those in the HS group (p<0.001), whereas leptin (p<0.01) and insulin (p<0.05) levels decreased significantly in the CE compared to those in the CS group. Interleukin (IL)-1β (p<0.001) and IL-6 (p<0.01) levels in the CS and CE groups decreased significantly compared to those in the HS group. Leptin (IL-1β: r=0.835, p<0.001), IL-6 (r=0.607, p<0.05), insulin (IL-1β: r=0.797, p<0.01), and IL-6 (r=0.827, p<0.01) levels were positively related with pro-inflammatory cytokine levels.

[Conclusion]

Endurance exercise may play an important role during CLA supplementation of rats on a high-fat diet.     

金天格在老年骨质疏松性椎体骨折术后的应用及临床分析

目的:探讨和分析金天格胶囊在老年骨质疏松症导致的椎体骨折术后的作用和临床疗效。方法:将2013.01-2015.01来我院明确诊断为骨质疏松症导致的椎体骨折共计136人经纳入标准和排除标准筛选后,使用随机数字表将其随机分为2组。实验组给予经皮椎体成形术(PVP)+钙剂+维生素D+唑来磷酸+金天格胶囊治疗。对照组则不给予金天格进行治疗。所有患者均至少接受了12个月的系统随访观察。观察和进行比较的指标主要为疼痛(VAS),骨密度,Macnab腰椎功能评分以及血液肝肾功等指标。结果:在术后3月和12个月,两组患者在疼痛、骨密度及腰椎功能评分等方面较术前均有显著改善(P0.05)。两组之间在上述指标中有统计学显著性差异。而在血液肝肾功等指标的比较中,则未发现疼显著统计学差异(P0.05)。结论:金天格胶囊在骨质疏松性椎体骨折术后的应用,能够有效地提高治疗效果,安全程度较高,在临床中可进一步的进行推广应用。     

Sleep Restriction Increases the Risk of Developing Cardiovascular Diseases by Augmenting Proinflammatory Responses through IL-17 and CRP

Background

Sleep restriction, leading to deprivation of sleep, is common in modern 24-h societies and is associated with the development of health problems including cardiovascular diseases. Our objective was to investigate the immunological effects of prolonged sleep restriction and subsequent recovery sleep, by simulating a working week and following recovery weekend in a laboratory environment.

Methods and Findings

After 2 baseline nights of 8 hours time in bed (TIB), 13 healthy young men had only 4 hours TIB per night for 5 nights, followed by 2 recovery nights with 8 hours TIB. 6 control subjects had 8 hours TIB per night throughout the experiment. Heart rate, blood pressure, salivary cortisol and serum C-reactive protein (CRP) were measured after the baseline (BL), sleep restriction (SR) and recovery (REC) period. Peripheral blood mononuclear cells (PBMC) were collected at these time points, counted and stimulated with PHA. Cell proliferation was analyzed by thymidine incorporation and cytokine production by ELISA and RT-PCR. CRP was increased after SR (145% of BL; p<0.05), and continued to increase after REC (231% of BL; p<0.05). Heart rate was increased after REC (108% of BL; p<0.05). The amount of circulating NK-cells decreased (65% of BL; p<0.005) and the amount of B-cells increased (121% of BL; p<0.005) after SR, but these cell numbers recovered almost completely during REC. Proliferation of stimulated PBMC increased after SR (233% of BL; p<0.05), accompanied by increased production of IL-1β (137% of BL; p<0.05), IL-6 (163% of BL; p<0.05) and IL-17 (138% of BL; p<0.05) at mRNA level. After REC, IL-17 was still increased at the protein level (119% of BL; p<0.05).

Conclusions

5 nights of sleep restriction increased lymphocyte activation and the production of proinflammatory cytokines including IL-1β IL-6 and IL-17; they remained elevated after 2 nights of recovery sleep, accompanied by increased heart rate and serum CRP, 2 important risk factors for cardiovascular diseases. Therefore, long-term sleep restriction may lead to persistent changes in the immune system and the increased production of IL-17 together with CRP may increase the risk of developing cardiovascular diseases.     

Bone Marrow Mesenchymal Stem Cells Attenuate Mitochondria Damage Induced by Hypoxia in Mouse Trophoblasts

ObjectiveWe aimed to observe the change of mitochondrial function and structure as well as the cell function induced by hypoxia in mouse trophoblasts, and moreover, to validate the restoration of these changes after co-culture with bone marrow mesenchymal stem cells (hereinafter referred to as “MSCs”). Further, we explored the mechanism of MSCs attenuating the functional damage of trophoblasts caused by hypoxia.MethodsCells were divided into two groups, trophoblasts and MSCs+trophoblasts respectively, and the two groups of cells were incubated with normoxia or hypoxia. Chemiluminescence was used to assay the β-HCG and progesterone in cell culture supernatants quantitatively. Western blotting and PCR were applied to detect the expression of Mfn2, MMP-2, MMP-9 and integrin β1 in the two groups. The mitochondrial membrane potential of each group of cells was detected with JC-1 dye and the ATP content was measured by the phosphomolybdic acid colorimetric method. We utilized transmission electron microscopy for observing the ultrastructure of mitochondria in trophoblasts. Finally, we assessed the cell apoptosis with flow cytometry (FCM) and analyzed the expression of the apoptosis related genes—Bcl-2, Bax, Caspase3 and Caspase9 by western blotting.ResultsThe results showed that the Mfn2 expression was reduced after 4 h in hypoxia compared with that in normoxia, but increased in the co-culture group when compared with that in the separated-culture group (p<0.05). In addition, compared with the separated-culture group, theβ-HCG and progesterone levels in the co-culture group were significantly enhanced (p<0.05), and so were the expressions of MMP-2, MMP-9 and integrin β1 (p<0.05). Moreover, it exhibited significantly higher in ATP levels and intensified about the mitochondrial membrane potential in the co-culture group. TEM revealed disorders of the mitochondrial cristae and presented short rod-like structure and spheroids in hypoxia, however, in the co-culture group, the mitochondrial cristae had a relatively regular arrangement and the mitochondrial ultrastructure showed hyperfusion. The expression of Bax, Caspase3 and Caspase9 was decreased in the co-culture group when compared with that in trophoblast cells cultured alone (p<0.05), while the Bcl-2 levels and the Apoptosis Index (AI) were markedly increased in the co-culture group (p<0.05).ConclusionBone marrow mesenchymal stem cells can attenuate mitochondria damage and cell apoptosis induced by hypoxia; the mechanism could be upregulating the expression of Mfn2 in mouse trophoblasts and changing mitochondrial structure.     

不同粘度骨水泥椎体成形术对骨质疏松椎体压缩性骨折的临床疗效及生活质量的影响

目的:比较不同粘度骨水泥椎体成形术(PVP)治疗骨质疏松椎体压缩性骨折(OVCF)的临床疗效及生活质量的影响。方法:回顾性分析于2016年8月至2018年2月期间我院收治的104例OVCF患者的临床资料。将患者按数字表法分为对照组(n=52)和研究组(n=52),两组患者均给予PVP治疗,对照组选用低粘度骨水泥,研究组选用高粘度骨水泥。比较两组患者术前、术后1周、术后1个月、术后3个月、术后6个月及术后12个月的Oswestry功能障碍指数(ODI)评分、疼痛视觉模拟量表(VAS)评分、健康状况调查问卷(SF-36)评分以及Cobb角,记录两组并发症发生情况。结果:研究组患者手术时间长于对照组(P<0.05),而两组患者骨水泥注入量、住院时间比较差异无统计学意义(P>0.05)。两组患者术后1周、1个月、3个月、6个月、12个月ODI评分、VAS评分、Cobb角均较术前降低(P<0.05);两组患者术后1个月、3个月、6个月、12个月ODI评分、VAS评分、Cobb角均较术后1周降低(P<0.05);研究组术后1周、1个月、3个月、6个月、12个月ODI评分、VAS评分、Cobb角低于对照组(P<0.05)。两组患者术后1周、1个月、3个月、6个月、12个月SF-36评分均升高,且研究组高于对照组(P<0.05)。两组并发症发生率比较无统计学差异(P>0.05)。结论:高粘度骨水泥应用于PVP治疗OVCF患者疗效确切,可有效减轻患者疼痛状况,改善生活质量,促进患者恢复。     

Evaluation of Electrical Impedance as a Biomarker of Myostatin Inhibition in Wild Type and Muscular Dystrophy Mice

ObjectivesNon-invasive and effort independent biomarkers are needed to better assess the effects of drug therapy on healthy muscle and that affected by muscular dystrophy (mdx). Here we evaluated the use of multi-frequency electrical impedance for this purpose with comparison to force and histological parameters.MethodsEight wild-type (wt) and 10 mdx mice were treated weekly with RAP-031 activin type IIB receptor at a dose of 10 mg kg⁻¹ twice weekly for 16 weeks; the investigators were blinded to treatment and disease status. At the completion of treatment, impedance measurements, in situ force measurements, and histology analyses were performed.ResultsAs compared to untreated animals, RAP-031 wt and mdx treated mice had greater body mass (18% and 17%, p < 0.001 respectively) and muscle mass (25% p < 0.05 and 22% p < 0.001, respectively). The Cole impedance parameters in treated wt mice, showed a 24% lower central frequency (p < 0.05) and 19% higher resistance ratio (p < 0.05); no significant differences were observed in the mdx mice. These differences were consistent with those seen in maximum isometric force, which was greater in the wt animals (p < 0.05 at > 70 Hz), but not in the mdx animals. In contrast, maximum force normalized by muscle mass was unchanged in the wt animals and lower in the mdx animals by 21% (p < 0.01). Similarly, myofiber size was only non-significantly higher in treated versus untreated animals (8% p = 0.44 and 12% p = 0.31 for wt and mdx animals, respectively).ConclusionsOur findings demonstrate electrical impedance of muscle reproduce the functional and histological changes associated with myostatin pathway inhibition and do not reflect differences in muscle size or volume. This technique deserves further study in both animal and human therapeutic trials.     

Impaired M. tuberculosis Antigen-Specific IFN-γ Response without IL-17 Enhancement in Patients with Severe Cavitary Pulmonary Tuberculosis

BackgroundTh1 cells play an essential role in immune protection against tuberculosis. Th17 cells might be involved with immune pathology in active human tuberculosis (TB). The balance between Th1 and Th17 cells in patients with cavitary tuberculosis needs to be clarified which might help understanding the immunological basis of pathologic pathogenesis in TB.MethodInitially treated pulmonary TB (PTB) patients with or without cavities were recruited before chemotherapy. We isolated peripheral blood mononuclear cells, stimulated with phytohemagglutinin (PHA), PPD, or ESAT-6 antigens, and assayed supernatant IFN-γ and IL-17 by ELISA after 24 or 72 hours incubation, respectively. Cells were also stained with antibodies to CD3, CD4, CD8, IFN-γ or IL-17 and the proportion of stained cells was measured by flow cytometry.ResultsWe found wide variation of IFN-γ response in active PTB patients, but less subject-to-subject variation of IL-17 was observed as we previously reported. There were no significant differences in IFN-γ and IL-17 between cavitary and non-cavitary PTB; however, we found decreased IFN-γ secretion in severe cavitary PTB compared to mild lesion non-cavitary PTB (p < 0.05). We also found a decrease in the proportion of CD3+CD4+ T cells in the blood of severe cavitary PTB patients (p < 0.05).ConclusionsIL-17 seemed to have no association with the formation of cavities in active PTB from the study of PBMC. Impaired IFN-γ without IL-17 enhancement occurs in peripheral blood during severe cavitary PTB. Our results demonstrate that M. tuberculosis antigen-specific Th1 response is decreased when PTB lesions develop to severe cavities.     

经皮椎体后凸成形术对绝经后女性椎体骨折的疗效分析

目的：分析经皮椎体后凸成形术对绝经后女性椎体骨折的疗效。方法：选取68例绝经后女性椎体骨折患者并随机分为研究组和对照组,每组各34例。研究组采用经皮椎体后凸成形术（PKP）治疗,对照组采用经皮椎体成形术PVP）治疗。分剐在术前、术后1d以及术后1年对患者进行疼痛视觉类比评分WAS）,观察随访期间Cobb角的矫正程度和骨水泥渗漏情况以及相邻椎体的骨折发生率。结果：两组患者在术后各时间点VAS评分和Cobb角的矫正程度均有明显的改善（P〈0．05）,其中研究组术后Cobb角的矫正程度要明显优于对照组（P〈0．05）,同时研究组患者术后骨水泥渗漏的发生率低于对照组（P〈0．05）,在随访期内,对照组相邻椎体骨折的发生率高于研究组（P〈0．05）。结论：PVP和PKP均能显著缓解OVCF疼痛,但是PKP比PVP更有利于矫正脊柱后凸的畸形,同时降低骨水泥渗漏和相邻椎体骨折的发生率。     

Methylenetetrahydrofolate reductase (MTHFR) and thymidylate synthase (TS) polymorphisms with osteoporotic vertebral compression fracture (OVCF) in postmenopausal Korean women

Hyperhomocysteinemia is associated with the risk of skeletal health problems, such as osteoporosis, low body mineral density, and fracture. 5, 10-Methylenetetrahydrofolate reductase (MTHFR) and thymidylate synthase (TS) are involved in homocysteine metabolism. We hypothesized that certain genetic polymorphisms of MTHFR and TS that cause altered enzyme activity may lead to hyperhomocysteinemia and affect bone metabolism. Therefore, we determined whether MTHFR 677C>T, MTHFR 1298A>C, TS enhancer region (TSER), and TS 3??-UTR 6 bp insertion/deletion polymorphisms are associated with osteoporotic vertebral compression fracture (OVCF) in postmenopausal Korean women. A total of 308 postmenopausal Korean women were enrolled as study subjects. Among them, 84 were patients with OVCF and 224 were controls. The polymorphisms were analysed by PCR-RFLP methods. Single mutations of MTHFR or TS were not associated with the occurrence of OVCF. However, the combined genotypes 2R3R+2R2R/0bp6bp+6bp6bp (TSER/TS 3??-UTR) and AC+CC/0bp6bp+6bp6bp (MTHFR 1298A>C/TS 3??-UTR) were associated with decreased risk for OVCF. 2R-0bp and 2R-6bp haplotype frequencies of TS were significantly different between the cases and controls. In the present study, the combined genotype of TSER/TS 3??-UTR and MTHFR 1298A>C/TS 3??-UTR was associated with a decreased risk for OVCF in postmenopausal Korean women. However, due to the several limitations of our study including the moderately small sample size, our findings should be considered with caution and further research is needed to draw more definitive conclusions.     

Clinical associations of serum interleukin-17 in systemic lupus erythematosus

Introduction

Serum interleukin (IL)-17 concentrations have been reported to be increased in systemic lupus erythematosus (SLE), but associations with clinical characteristics are not well understood. We characterized clinical associations of serum IL-17 in SLE.

Methods

We quantified IL-17 in serum samples from 98 SLE patients studied cross-sectionally, and in 246 samples from 75 of these patients followed longitudinally over two years. Disease activity was recorded using the SLE Disease Activity Index (SLEDAI)-2k. Serum IL-6, migration inhibitory factor (MIF), and B cell activating factor of the tumour necrosis factor family (BAFF) were also measured in these samples.

Results

Serum IL-17 levels were significantly higher in SLE patients compared to healthy donors (P <0.0001). No correlation was observed between serum IL-17 and SLEDAI-2k, at baseline or during longitudinal follow-up. However, we observed that SLEDAI-2k was positively correlated with IL-17/IL-6 ratio. Serum IL-17 was significantly increased in SLE patients with central nervous system (CNS) disease (P = 0.0298). A strong correlation was observed between serum IL-17 and IL-6 (r = 0.62, P <0.0001), and this relationship was observed regardless of disease activity and persisted when integrating cytokine levels over the period observed (r = 0.66, P <0.0001). A strong correlation of serum IL-17 was also observed with serum BAFF (r = 0.64, P <0.0001), and MIF (r = 0.36, P = 0.0016).

Conclusions

Serum IL-17 concentration correlates poorly with SLE disease activity but is significantly elevated in patients with CNS disease. IL-17/IL-6 ratio may be more useful than IL-17 or IL-6 alone to characterize Th17-driven disease, such as SLE. The association of other cytokines with serum IL-17 suggests that IL-17 may drive activation of diverse immune pathways in SLE.