Gender differences in GRK2 in cardiovascular diseases and its interactions with estrogen.

G protein-coupled receptor kinase 2 (GRK2) is a multifunctional protein involved in regulating G protein-coupled receptor (GPCR) and non-GPCR signaling in the body. In the cardiovascular system, increased expression of GRK2 has been implicated in the occurrence and development of several cardiovascular diseases (CVDs). Recent studies have found gender differences in GRK2 in the cardiovascular system under physiological and pathological conditions, where GRK2's expression and activity are increased in males than in females. The incidence of CVDs in premenopausal women is lower than in men of the same age, which is related to estrogen levels. Given the shared location of GRK2 and estrogen receptors, estrogen may interact with GRK2 by modulating vital molecules such as calmodulin (CaM), caveolin, RhoA, nitrate oxide (NO), and mouse double minute 2 homolog (Mdm2), via signaling pathways mediated by estrogen's genomic (ERα and ERß), and non-genomic (GPER) receptors, conferring cardiovascular protection in females. Highlighting the gender differences in GRK2 and understanding its interaction with estrogen in the cardiovascular system is pertinent in treating gender-related CVDs. As a result, this article explores the gender differences of GRK2 in the cardiovascular system and its relationship with estrogen during disease conditions. Estrogen's protective and therapeutic effects and its mechanism on GRK2-related cardiovascular diseases have also been discussed.

Combined anterior and posterior approach in treatment of ankylosing spondylitis-associated cervical fractures: a systematic review and meta-analysis.

OBJECTIVE: Cervical fractures with ankylosing spondylitis (CAS) are a specific type of spinal fracture with poor stability, low healing rate, and high disability rate. Its treatment is mainly surgical, predominantly through the anterior approach, posterior approach, and the anterior-posterior approach. Although many clinical studies have been conducted on various surgical approaches, controversy still exists concerning the choice of these surgical approaches by surgeons. The authors present here a systematic evaluation and meta-analysis exploring the utility of the anterior-posterior approach versus the anterior approach and the posterior approach. METHODS: After a comprehensive literature search of PubMed, Cochrane, Web of Science, and Embase databases, 12 clinical studies were included in the final qualitative analysis and 8 in the final quantitative analysis. Of these studies, 11 conducted a comparison between the anterior-posterior approach and the anterior approach and posterior approaches, while one examined only the anterior-posterior approach. Where appropriate, statistical advantage ratios and 95% confidence intervals were calculated. RESULTS: The present meta-analysis of postoperative neurological improvement showed no statistical difference in the overall neurological improvement rate between the anterior-posterior approach and anterior approach (OR 1.70, 95% CI 0.61 to 4.75; p = 0.31). However, the mean change in postoperative neurological function was lower in patients who received the anterior approach than in those who received the anterior-posterior approach (MD 0.17, 95% CI -0.02 to 0.36; p = 0.08). There was an identical trend between the anterior-posterior approach and posterior approach, with no statistically significant difference in the overall rate of neurological improvement (OR 1.37, 95% CI 0.70 to 2.56; p = 0.38). Nevertheless, the mean change in neurological function was smaller in patients receiving the anterior-posterior approach compared with the posterior approach, but there was no statistically significant difference between the two (MD 0.17, 95% CI -0.02 to 0.36; p = 0.08). CONCLUSIONS: The results of this review and meta-analysis suggest that the benefits of the anterior-posterior approach are different from those of the anterior and posterior approaches in the treatment of ankylosing spondylitis-related cervical fractures. In a word, there is no significant difference between the cervical surgical approach and the neurological functional improvement. Therefore, surgeons should pay more attention to the type of cervical fracture, the displacement degree of cervical fracture, the spinal cord injury, the balance of cervical spine and other aspects to comprehensively consider the selection of appropriate surgical methods.

Application of Suspension Fixation with Button Plates for Patients with Distal Radioulnar Joint Dislocation: A Case Series.

OBJECTIVE: The aim of the present study was to assess the effect of suspension fixation with button plates on the reconstruction of the distal radioulnar joint dislocation (DRUJ). METHODS: This was a case series of six patients (two men and four women) who underwent suspension fixation with button plates for DRUJ dislocation between January 2015 and May 2017. Physical examination, radiography, MRI, functional activity of the wrist joint, grip strength of the wrist joint, Garland-Werley wrist score, Mayo wrist score, and visual analog scale (VAS) score were used to evaluate the effect of this procedure. All patients were followed up every 3 months. The evaluation time point was 12 months after the operation. Comparisons of the functional indexes of wrist function before and after the operation were performed using paired statistical tests. RESULTS: The mean range of motion of the affected limb was 70° at forearm pronation and 75° at forearm supination. The subjective assessments and tests of the motor function of the wrist showed improvement after surgery. The Garland-Werley wrist score was 13.50 ± 2.66 preoperatively, the Mayo wrist score was 56.67 ± 18.35, and the VAS score was 4.83 ± 1.17. The Garland-Werley wrist score was 2.83 ± 1.33 postoperatively at 12 months, the Mayo wrist score was 87.5 ± 6.89, and the VAS score was 0.50 ± 0.55. At 12 months, the Garland-Werley wrist score, the Mayo wrist score, and the VAS score showed significant improvements when compared with those before surgery (P = 0.000, P = 0.003, and P = 0.000, respectively). Radiographic examination revealed that the internal fixation device was in place, and no dislocation of the DRUJ could be observed. None of the patients had internal fixation device removal or re-dislocation of the DRUJ. None of the patients had re-dislocation of the DRUJ. No secondary ulnar or radial fractures and nerve injury were reported during and after surgery. No tumor recurrence was observed in patients with giant cell tumors of the tendon sheath. No loosening and displacement of screws were reported. CONCLUSION: The new method of suspension fixation with button plates for the surgical reconstruction of a DRUJ dislocation is simple, with minimal trauma, and maintains the stability of the DRUJ without the need for intra-articular or extra-articular reconstruction of the ligament. Furthermore, it allows early functional exercise and achieves satisfactory postoperative functional recovery.

GPER mediates estrogen cardioprotection against epinephrine-induced stress.

Currently, there are no conventional treatments for stress-induced cardiomyopathy (SCM, also known as Takotsubo syndrome), and the existing therapies are not effective. The recently discovered G protein-coupled estrogen receptor (GPER) executes the rapid effects of estrogen (E2). In this study, we investigated the effects and mechanism of GPER on epinephrine (Epi)-induced cardiac stress. SCM was developed with a high dose of Epi in adult rats and human-induced pluripotent stem cells-derived cardiomyocytes (hiPSC-CMs). (1) GPER activation with agonist G1/E2 prevented an increase in left ventricular internal diameter at end-systole, the decrease both in ejection fraction and cardiomyocyte shortening amplitude elicited by Epi. (2) G1/E2 mitigated heart injury induced by Epi, as revealed by reduced plasma brain natriuretic peptide and lactate dehydrogenase release into culture supernatant. (3) G1/E2 prevented the raised phosphorylation and internalization of ß2-adrenergic receptors (ß2AR). (4) Blocking Gαi abolished the cardiomyocyte contractile inhibition by Epi. G1/E2 downregulated Gαi activity of cardiomyocytes and further upregulated cAMP concentration in culture supernatant treated with Epi. (5) G1/E2 rescued decreased Ca2+ amplitude and Ca2+ channel current (ICa-L) in rat cardiomyocytes. Notably, the above effects of E2 were blocked by the GPER antagonist, G15. In hiPSC-CM (which expressed GPER, ß1AR and ß2ARs), knockdown of GPER by siRNA abolished E2 effects on increasing ICa-L and action potential duration in the stress state. In conclusion, GPER played a protective role against SCM. Mechanistically, this effect was mediated by balancing the coupling of ß2AR to the Gαs and Gαi signaling pathways.

Patella alignment abnormality in patients with developmental dysplasia of the hip.

BACKGROUND: The purpose of this study was to assess the influence of developmental dysplasia of the hip (DDH) on patella alignment. METHODS: The radiographic data of all the patients who met the inclusion criteria from January 2015 to July 2017 were reviewed, including the quadriceps angle (QA), patellar lateral tilt (PTA), sulcus angle (SA), lateral shift of patella (LSP), and lower limbs alignment. The patients were divided into three groups in accordance with lateral center-edge angle (LCE) and femoral neck torsion angle (FNTA): group A (LCE > 25° and FNTA < 40°), group B (LCE < 20° and FNTA < 40°), and group C (LCE < 20° and FNTA > 40°). RESULTS: One hundred thirty-eight patients with 230 hips (115 females and 23 males) were recruited with an average age of 22 years. There were significant differences between group A and group C as well as group B and group C in QA, SA, PTA, LSP, and lower limbs alignment (p < 0.01). There were no differences in SA, PTA, LSP, and lower limbs alignment (p >0.05) and significant differences in QA (p < 0.01) between group B and group C. The "Pearson's" correlation analysis of the data in total of group B and group C showed that FNTA and LCE and QA and LCE were negatively correlated, whereas FNTA and QA, PTA, SA, and lower limbs alignment as well as SA, PTA, and lower limbs alignment were positively correlated. CONCLUSION: Patients with DDH not only have hip joint change, but also have the patella alignment abnormality, which may lead to patella instability. In the clinic, we should pay attention to the hip development of the patella instability patients for excluding DDH. Level of Evidence: Prognostic level III.

Effect of simvastatin on expression of VEGF and TGF-ß1 in atherosclerotic animal model of type 2 diabetes mellitus.

Expression of vascular endothelial growth factor (VEGF) and transforming growth factor-ß1 (TGF-ß1) in atherosclerosis animal model of type 2 diabetes mellitus treated with simvastatin was investigated. Clean grade mature Sprague Dawley (SD) rats were divided into three groups: Normal control (n=10), model (n=13) and treatment group (n=13); low-dose simvastatin was administered. The changes of VEGF and TGF-ß1 levels were analyzed by tail vein blood sampling. The relationship between levels of VEGF, TGF-ß1 and treatment time was analyzed. The expression level of VEGF in the treatment group after 4 and 8 weeks of intervention was lower compared with the model group (P<0.05). The expression level of TGF-ß1 in the treatment group after 8 weeks of intervention was higher than that in the model group (P<0.05). The expression level of VEGF in the treatment group after 8 weeks of intervention was lower than that after 1 week of intervention (P<0.05). The expression level of TGF-ß1 was increased in the model group after 8 weeks of intervention compared with 1 week before and after the intervention (P<0.05). The expression level of TGF-ß1 in the treatment group at 2, 4 and 8 weeks after intervention were significantly higher than that before intervention (P<0.05). The expression of TGF-ß1 increased after 4 and 8 weeks after intervention compared with 1 week after intervention (P<0.05). The expression of VEGF was negatively correlated with TGF-ß1 expression in the treatment group; negative correlation was found between VEGF and treatment time. There was a positive correlation between TGF-ß1 and treatment time. VEGF and TGF-ß1 may be involved in the development of type 2 diabetes (T2MD) atherosclerosis (AS). Simvastatin may play a therapeutic role in T2MD AS by downregulating VEGF and upregulating the expression of TGF-ß1.

A case report of distal radioulnar joint dislocation fixed by using mini-plate-button.

INTRODUCTION: Pathological factors may cause significant distal radioulnar joint (DRUJ) dislocation, which is a rare clinical entity in orthopedic literature, and corresponding treatments are not uniform. PRESENTATION OF CASE: We describe the case of a DRUJ dislocation caused by giant cell tumour of tendon sheath (GCTTS) in wrist. At surgery, the stabilization of DRUJ was constructed by using mini-plate-button after removal of intraoperative removal of the tumor. Postoperative plain films showed good position, and no obvious dislocation was found. DISCUSSION: Reduction of DRUJ dislocation was facilitated by mini-plate-button and absorbable suture. The treatment avoided intro-articular or extra-articular ligament construction and damage of adjacent tissue and bone. CONCLUSION: For DRUJ dislocation caused by GCTTS leading to severe tendon and ligament damage, the operative treatment of mini-plate-button may be effective.

Perioperative intravenous glucocorticoids can decrease postoperative nausea and vomiting and pain in total joint arthroplasty: A meta-analysis and trial sequence analysis.

BACKGROUND: This meta-analysis aimed to demonstrate the efficacy and safety of intravenous glucocorticoids for reducing pain intensity and postoperative nausea and vomiting (PONV) in patients undergoing total joint arthroplasty (TJA). METHODS: PubMed, Embase, the Cochrane Central Register of Controlled Trials (CENTRAL), Web of Science, and Google databases were searched for randomized controlled trials (RCTs) comparing intravenous glucocorticoids versus no intravenous glucocorticoids or sham for patients undergoing TJA. Outcomes included visual analogue scale (VAS) pain at 12, 24, and 48 hours; the occurrence of PONV; length of hospital stay; the occurrence of infection; and blood glucose levels after surgery. We calculated risk ratios (RR) with a 95% confidence interval (CI) for dichotomous outcomes and the weighted mean difference (WMD) with a 95% CI for continuous outcomes. Trial sequential analysis was also used to verify the pooled results. RESULTS: Thirteen clinical trials involving 821 patients were ultimately included in this meta-analysis. The pooled results indicated that intravenous steroids can decrease VAS at 12 hours (WMD = -8.54, 95% CI -11.55 to -5.53, P = 0.000; I = 35.1%), 24 hours (WMD = -7.48, 95% CI -13.38 to -1.59, P = 0.013; I = 91.8%), and 48 hours (WMD = -1.90, 95% CI -3.75 to -0.05, P = 0.044; I = 84.5%). Intravenous steroids can decrease the occurrence of PONV (RR = 0.56, 95% CI 0.44-0.73, P = 0.000; I = 33.1%). There was no significant difference in the length of hospital stay, occurrence of infection, and blood glucose levels after surgery. CONCLUSION: Intravenous glucocorticoids not only alleviate early pain intensity but also decrease PONV after TJA. More high-quality RCTs are required to determine the safety of glucocorticoids before making final recommendations.

A Case Report of an Osteoid Osteoma on the Bearing Surface of the Talus Treated with Arthroscopic Resection Associated with Autologous Iliac Crest Graft.

Osteoid osteomas are most likely to occur in the talar neck and can be classified as cortical, cancellous, or subperiosteal according to the position of the tumor nidus. However, cases located on the bearing surface of the talus are rare. Herein, the patient presented with an osteoid osteoma on the bearing surface of the talus and achieved good curative effects with arthroscopic resection associated with autologous iliac crest graft.

Effect of mesenchymal stromal cells for articular cartilage degeneration treatment: a meta-analysis.

BACKGROUND AIMS: Articular cartilage is an avascular tissue that has limited capacity for self-repair. Mesenchymal stromal cells have been considered as potential candidates for cartilage regeneration. However, clinical results of cartilage formation with the use of these cells need evaluation. We aimed to assess the effect of mesenchymal stromal cell treatment on articular cartilage defects. METHODS: We searched PubMed, Embase and the Cochrane Central Register of Controlled Trials with key words including "cartilage," "clinical trial," "mesenchymal," "stromal" and "stem cell" up to December 3, 2014. We selected the controlled trial that used treatment with mesenchymal stromal cells on cartilage injury compared with other treatment. We assessed the results of the meta-analysis by means of the error matrix approach. The outcome measures were ranked as comprehensive evaluation index, highest relevance; unilateral evaluation index, medial relevance; and single evaluation index, lowest relevance. RESULTS: Eleven trials assessing 558 patients were included in the meta-analysis. Stem cell treatment significantly improved the American Orthopedic Foot and Ankle Society Scale (Standard Mean Difference, SMD, 0.91; 95% confidence interval [CI], 0.52 to 1.29). The Osteo-Arthritis Outcome Score was also significantly improved in stem cell treatment (SMD, 2.81; 95% CI, 2.02 to 3.60). Other comprehensive evaluation indexes, such as the American Knee Society Knee Score System (SMD -0.12, 95% CI, -1.02 to 0.78), the Hospital for Special Surgery Knee Rating Scale (SMD, 0.24, 95% CI, -0.56 to 1.05) and the International Knee Documentation Committee (SMD, -0.21; 95% CI, -0.77 to 0.34), appeared to have no significant differences by use of stem cell and other treatments. Overall, there was no obvious advantage regarding the application of stem cells to treat cartilage injury, compared with other treatments. CONCLUSIONS: In conclusion, assessment of the comprehensive evaluation index indicated that there were no significant differences after stem cell treatment. However, assessment of clinical symptoms and cartilage morphology showed significant improvement after stem cell treatment.

Boswellic acid attenuates asthma phenotypes by downregulation of GATA3 via pSTAT6 inhibition in a murine model of asthma.

Asthma is a serious global health problem characterised by airway inflammation, airway epithelial wall shedding, enhanced mucus production, increased IgE levels and airway hyperresponsiveness. The pathophysiology of asthma is mediated by Th2 cells which produce Th2 cytokines like interleukin-4, interleukin-5, interleukin-13 and interleukin-9. The differentiation of Th2 cells is induced by the transcription factor GATA3 which is activated by pSTAT6 via IL-4 signalling. To investigate the anti-asthmatic potential of Boswellic acid, as well as the underlying mechanism involved, we studied its anti-asthmatic potential in a murine model of asthma. In this study, BALB/c mice were systemically sensitized by ovalbumin (OVA) followed by aerosol allergen challenges. We investigated the effect of Boswellic acid on airway hyperresponsiveness, inflammatory cell infiltration, Th2 cytokine and OVA-specific IgE production in a mouse model of asthma. We found that Boswellic acid treated groups suppressed allergic airway inflammation, AHR, OVA-specific IgE and Th2 cytokines secretion. It also suppressed the expression of pSTAT6 and GATA3 in a dose dependent manner. Our data suggest that the mechanism by which Boswellic acid effectively treats asthma is based on reductions of Th2 cytokines via inhibition of pSTAT6 and GATA-3 expression.

[Estrogen reduced myocardial damage by regulating Gαs-cAMP pathway in isoprenaline injured rats].

The aim of the present study is to explore the mechanism of estrogen on regulating cardiac function disorder by adjusting the stimulating adenylate cyclase G α protein (Gαs)-cycle adenosine monophosphate (cAMP) signal pathway. Adult female rats were randomly divided into five groups: sham group, ovariectomized group (OVX), OVX and 17ß-estradiol given group (OVX+E2), OVX and isoprenaline injected group (OVX+ISO), OVX and 17ß-estradiol, isoprenaline injected group (OVX+E2+ISO). Rats were ovariectomized, and two weeks later, OVX+E2group was injected with E2, OVX+ISO group was injected with ISO, OVX+E2+ISO group was injected with E2and ISO. Another four weeks later, the hemodynamic parameters were monitored by carotid artery intubation: left ventricular systolic pressure (LVSP), left ventricular end-diastolic pressure (LVEDP), maximal differentials of left ventricular developed pressure (+dp/dt(max)), and minimal differentials of left ventricular developed pressure (-dp/dt(max)). Brain natriuretic peptide (BNP) and cAMP concentration in plasma were determined; Gα(s) protein expression in myocardium was determined. The results showed that the hemodynamic parameters, the concentration of BNP and cAMP in plasma had no significant changes after ovariectomy compared with sham group. But after isoprenaline injection in ovariectomized rats, LVSP and +dp/dt(max) declined (P < 0.01), LVEDP and -dp/dt(max) elevated (P < 0.01); plasma BNP concentration increased (P < 0.01); plasma cAMP concentration decreased (P < 0.01), compared with OVX group. Further estrogen supplements improved the heart function treated by isoprenaline: LVSP and +dp/dt(max) elevated (P < 0.01), LVEDP and -dp/dtmax declined (P < 0.05, P < 0.01); the plasma BNP concentration decreased (P < 0.01); the plasma cAMP concentration increased (P < 0.01). Estrogen had no significant influence on Gαs protein expression. The results suggest that estrogen can alleviate myocardial injury and regulate cardiac function disorder by increasing cAMP level, finally improved the excessive suppression of myocardium.