SP1 regulates BMSC osteogenic differentiation through the miR-133a-3p/MAPK3 axis : SP1 regulates osteogenic differentiation of BMSCs.

BACKGROUND: The progression of osteoporosis (OP) can dramatically increase the risk of fractures, which seriously disturb the life of elderly individuals. Specific protein 1 (SP1) is involved in OP progression. However, the mechanism by which SP1 regulates OP progression remains unclear. OBJECTIVE: This study investigated the mechanism underlying the function of SP1 in OP. METHODS: SAMP6 mice were used to establish an in vivo model of age-dependent OP, and BALB/c mice were used as controls. BMSCs were extracted from two subtypes of mice. Hematoxylin and eosin staining were performed to mark the intramedullary trabecular bone structure to evaluate histological changes. ChIP assay was used to assess the targeted regulation between SP1 and miR-133a-3p. The binding sites between MAPK3 and miR-133a-3p were verified using a dual-luciferase reporter assay. The mRNA levels of miR-133a-3p and MAPK3 were detected using quantitative reverse transcription polymerase chain reaction (RT-qPCR). The protein expression of SP1, MAPK3, Colla1, OCN, and Runx2 was examined using Western blotting. Alkaline phosphatase (ALP) kit and Alizarin Red S staining were used to investigate ALP activity and mineralized nodules, respectively. RESULTS: The levels of SP1 and miR-133a-3p were upregulated, whereas the expression of MAPK3 was downregulated in BMSCs from SAMP6 mice, and miR-133a-3p inhibitor accelerated osteogenic differentiation in BMSCs. SP1 directly targeted miR-133a-3p, and MAPK3 was the downstream mRNA of miR-133a-3p. Mechanically, SP1 accelerated osteogenic differentiation in BMSCs via transcriptional mediation of the miR-133a-3p/MAPK3 axis. CONCLUSION: SP1 regulates osteogenic differentiation by mediating the miR-133a-3p/MAPK3 axis, which would shed new light on strategies for treating senile OP.

MiR-3646 accelerates inflammatory response of Ang II-induced hVSMCs via CYP2J2/EETs axis in hypertension model.

BACKGROUND: Inflammatory response of human vascular smooth muscle cells (hVSMCs) is a driving factor in hypertension progression. It has been reported that miR-3646 was significantly up-regulated in serum samples from patients with coronary artery disease and acute myocardial infarction mice. However, its role and underlying molecular mechanism related to inflammatory response of angiotensin II (Ang II)-induced hVSMCs remain unclear. OBJECTIVE: We aimed to explore the potential molecular mechanisms related to inflammatory response of angiotensin II (Ang II)-induced hVSMCs. METHODS: Ang II-induced hypertension model was established after hVSMCs treated with 1 µM Ang II at 24 h. The interaction between microRNA 3646 (miR-3646) and cytochrome P450 2J2 (CYP2J2) was assessed by dual-luciferase reporter gene assay. MTS assay, Lipid Peroxidation MDA Assay Kit, ELISA, Western blot, and qRT-PCR were performed to examine viability, malondialdehyde (MDA) level, inflammatory cytokine levels, and the level of genes and proteins. RESULTS: Our findings illustrated that miR-3646 was up-regulated but CYP2J2 was down-regulated in Ang II-induced hVSMCs. Mechanically, miR-3646 negatively targeted to CYP2J2 in Ang II-induced hVSMCs. These findings indicated that miR-3646 regulated inflammatory response of Ang II-induced hVSMCs via targeting CYP2J2. Moreover, functional researches showed that CYP2J2 overexpression alleviated inflammatory response of Ang II-induced hVSMCs via epoxyeicosatrienoic acids/peroxisome proliferator-activated receptor-γ (EETs/PPARγ) axis, and miR-3646 aggravated inflammatory response of Ang II-induced hVSMCs via mediating CYP2J2/EETs axis. CONCLUSION: MiR-3646 accelerated inflammatory response of Ang II-induced hVSMCs via CYP2J2/EETs axis. Our findings illustrated the specific molecular mechanism of miR-3646 regulating hypertension.

The effect of additional facet joint block for analgesia in patients with thoracolumbar compression fracture undergoing percutaneous kyphoplasty surgery: A protocol for systematic review and meta-analysis.

BACKGROUND: There is currently no pooled data in the literature to support whether additional facet joint block results in better clinical analgesia after percutaneous kyphoplasty. We assessed the existing evidence on the safety and efficacy of facet joint block in the treatment of patients with thoracolumbar compression fractures undergoing percutaneous kyphoplasty based on qualified trials. METHODS: We will search PubMed, Springer, ScienceDirect, Wanfang, and Cochrane Library databases through April, 2022. Cohort studies focusing on assessing and comparing the effect of facet joint block and control group will be included. The studies are screened and evaluated by 2 reviewers independently for eligibility. The following outcome measures must be showed: pain scores, Oswestry Disability Index, satisfaction, and complications observed within both groups from baseline to the end of follow-up period. Review Manager software (v 5.3; Cochrane Collaboration) is used for the meta-analysis. A P value of <.05 is considered to be statistically significant. Two independent reviewers will assess the risk of bias of the included studies at study level. RESULTS: It is hypothesized that additional facet joint block is associated with better pain control. CONCLUSIONS: This study expects to provide credible and scientific evidence for the efficacy and safety of facet joint block in the treatment of patients with thoracolumbar compression fractures undergoing percutaneous kyphoplasty. REGISTRATION NUMBER: 10.17605/OSF.IO/ARY3C.

Downregulation of lncRNA SNHG16 inhibits vascular smooth muscle cell proliferation and migration in cerebral atherosclerosis by targeting the miR-30c-5p/SDC2 axis.

Atherosclerosis (AS) is the basic lesion underlying the occurrence and development of cerebrovascular diseases. Abnormal proliferation of vascular smooth muscle cells (VSMCs) plays a crucial role in AS. We aimed to explore the role of SNHG16 in AS and the molecular mechanism of VSMC involvement in the regulation of AS. The expression levels of SNHG16, miR-30c-5p and SDC2 were detected by qRT-PCR. CCK-8, wound healing and Transwell assays were used to assess ox-LDL-induced VSMC proliferation, migration, and invasion, respectively. Western blot analysis was used to detect SDC2 and MEK/ERK pathway-related protein levels. A dual-luciferase reporter assay confirmed the binding of SNHG16 with miR-30c-5p and miR-30c-5p with SDC2. SNHG16 and SDC2 expression was upregulated in patients with AS and ox-LDL-induced VSMCs, while miR-30c-5p was downregulated. Ox-LDL-induced VSMC proliferation and migration were increased, and the MEK/ERK signalling pathway was activated. MiR-30c-5p was targeted to SNHG16 and SDC2. Downregulating SNHG16 or upregulating miR-30c-5p inhibited ox-LDL-induced VSMC proliferation and migration and inhibited MEK/ERK signalling pathway activation. In contrast, downregulating miR-30c-5p or upregulating SDC2 reversed the effects of downregulating SNHG16 or upregulating miR-30c-5p. Furthermore, downregulating SDC2 inhibited ox-LDL-induced proliferation and migration of VSMCs and inhibited activation of the MEK/ERK signalling pathway, while upregulating lncRNA SNHG16 reversed the effects of downregulating SDC2. Downregulation of SNHG16 inhibited VSMC proliferation and migration in AS by targeting the miR-30c-5p/SDC2 axis. This study provides a possible therapeutic approach to AS.

[Heat-sensitive moxibustion combined with western medication for low back pain of osteoporosis with kidney-yang deficiency: a randomized controlled trial].

OBJECTIVE: To compare the clinical therapeutic effect between heat-sensitive moxibustion combined with western medication and simple western medication for low back pain of osteoporosis with kidney-yang deficiency. METHODS: A total of 60 patients with osteoporosis were randomized into an observation group (32 cases, 2 cases dropped off) and a control group (32 cases, 3 cases dropped off). In the control group, alendronate sodium tablet and calcium carbonate and vitamin D3 tablet were taken orally. On the basis of the control group, heat-sensitive moxibustion was applied at Mingmen (GV 4), Yaoyangguan (GV 3), Guanyuan (CV 4), Shenshu (BL 23), Zusanli (ST 36) in the observation group, once a day, 5 times a week for 8 weeks. Before and after treatment，the visual analogue scale (VAS) score, Oswestry disability index (ODI) score, bone mineral density (BMD) and TCM clinical symptom score were compared in the two groups. RESULTS: The VAS scores, ODI scores and TCM clinical symptom scores after treatment were reduced in the two groups (P<0.05, P<0.01), and those in the observation group were lower than the control group (P<0.05, P<0.01). The BMD after treatment was increased in the two groups (P<0.01), and that in the observation group was higher than the control group (P<0.05). CONCLUSION: Heat-sensitive moxibustion combined with western medication could relieve low back pain, improve BMD in patients of osteoporosis with kidney-yang deficiency, and its clinical effect is superior to simple western medication.

[Comparison between pathology and computer for quantitative determination of femoral head necrosis].

OBJECTIVE: To compare computer measurement semi automatic quantitative detection software system with ultra thin layer pathological section to confirm the avascular necrosis percentage of the femoral head, and provide reference for clinical treatment options. METHODS: From June 2012 to December 2013, the X-ray and MRI of 24 patients(24 hips on unilateral) were reviewed, who had avascular necrosis of the femoral head at late stage (stage III and IV) according to the ARCO international staging system, and performed by total hip arthroplasty. There were 15 males and 9 females, with an average age of (65.1±8.8) years old ranging 33 to 74 years old. Based on imaging system combined with computer aided technology(CAD) system and postoperative ultrathin slice, the volume of the area of femoral head necrosis were calculated. Then combining with the total volume of the femoral head was calculated by X-ray, the percentage of each femoral head necrosis area was calculated as a percentage of the whole ball head in both methods. RESULTS: For 24 hips, the normal femoral head volume was (39.58±3.29) cm³ on average of X-ray film, the necrotic volume was (20.00±3.04) cm³ on average of MRI by the calculation of computer. The necrotic volume occupying in the volume of the normal femoral head was (42.92±6.09)% on average ranged. The necrotic lesion size was larger than 40% in 16 hips, 30% to 40% in 8 hips, 1 ess than 30% in 0 hip. Under the pathological section, the necrosis volume was (19.89±3.17) cm³, the necrotic volume occupying in the volume of the normal femoral head was (40.33±6.36)%. The necrotic lesion size was larger than 40% in 12 hips, 30% to 40% in 11 hips, 1 ess than 30% in 1 hip. In computer and general measurement, the two entire femoral head volume difference was (0.113±0.466) cm³, there was no significant difference using these measurements(t=-1.186, P=0.248). After the linear correlation statistics analysis, there was a positive correlation relationship in necrotic volume between computer software and pathology measurement(γ=0.980, P=0.000). CONCLUSIONS: The severity of the necrotic femoral head is closely related to the percentage of necrotic area. When the ratio of necrotic lesions and the whole femoral head is greater than 30%, the patients' clinical symptoms tend to aggravate, the probability of total hip arthroplasty increased significantly. It have great significances in femoral head necrosis installment, judge the prognosis, guide the selection of treatment and monitoring curative effect.

[Association of Toll-like receptor 2 and 4 gene polymorphisms with risk of coronary atherosclerotic artery disease in Hunan Han population].

OBJECTIVE: To explore Toll-like receptor 2 (TLR2) and TLR4 polymorphism in Han people from Hunan region and its association with coronary atherosclerotic heart disease.
 Methods: Sanger sequence and statistical analysis were performed to identify the polymorphism of TLR2 and TLR4 genes in 347 unrelated Hunan Han subjects, including 180 healthy people (control group) and 167 patients with coronary atherosclerotic heart disease (coronary atherosclerotic heart disease group).
 Results: There was no significant difference in the genotype frequency and allelic frequency for TLR2 SNP2258G>A and TLR4 SNP896A>G between the 2 groups (P>0.05), while there was significant difference in the TLR4 SNP1196C>T between the 2 groups (P<0.05).
 Conclusion: TLR4 SNP1196C>T polymorphism is associated with coronary atherosclerotic heart disease in Chinese Han populationin in Hunan region.

Secure multiparty computation of a comparison problem.

Private comparison is fundamental to secure multiparty computation. In this study, we propose novel protocols to privately determine [Formula: see text], or [Formula: see text] in one execution. First, a 0-1-vector encoding method is introduced to encode a number into a vector, and the Goldwasser-Micali encryption scheme is used to compare integers privately. Then, we propose a protocol by using a geometric method to compare rational numbers privately, and the protocol is information-theoretical secure. Using the simulation paradigm, we prove the privacy-preserving property of our protocols in the semi-honest model. The complexity analysis shows that our protocols are more efficient than previous solutions.

[A comparative study on the measurement of femoral head necrosis lesions using ultra-thin layer slicing and computer aided identification].

OBJECTIVE: To compare the differences between computer aided identification and ultra-thin layer slicing in measuring the lesions of femoral head necrosis,and to confirm the accuracy and practicability of computer aided method. METHODS: From June 2012 to December 2013, the X-ray and MRI of 24 patients (24 hips on unilateral) were reviewed, who had avascular necrosis of the femoral head (ANFA) at late stage (stage III and IV) according to the ARCO international staging system. There were 15 males and 9 females, with an average age of (65.1 ± 8.8) years old, ranged 33 to 74 years old. Based on the software system with seeds point identification, the ragional adaptive search method with computer aid was used to calculate the volume of necrotic lesion in femoral on MRI. Then the pathological slices of those intraoperative femoral heads were made to measure the gross volume of necrotic lesion in femoral head,and the values were compared with the data in the computer. RESULTS: For 24 hips, by the calculation of computer, the necrotic volume was (20.00 ± 3.04) cm (ranged, 18.72 to 21.29 cm³). Under the pathological section, the necrotic volume of the femoral head was (19.89 ± 3.17) cm³ (ranged, 18.55 to 21.23 cm³). In computer and pathology two kinds of measurement, the two entire femoral head volume had no significant difference using these two measurements (t = -1.227, P = 0.232). CONCLUSION: Computer aided identification for necrotic area of femoral head adaptive can demonstrate the morphology of femoral head necrosis accurately and reliably, which will help surgeon better understand the morphology and orientation in femoral head.

[Annlication of external fixator combined with damage control treatment for open fracture of the extremities].

OBJECTIVE: To investigate the application and effects of external fixator under the guidance of damage control therapy in limb open fracture. METHODS: From May 2008 to January 2013,72 cases with severe limb open fractures (Unincor- porated shock) were divided into control group and observation group (36 cases in each group). In observation group, 36 patients (including 22 males and 14 females) were treated by external fixator at stage I, as soon as possible after waiting for patients physiology conditions being stable,the stage II fracture operation was performed. In control group, 36 patients (24 males and 12 females) were treated by the first stage open reduction. The hospital admission time, open fracture severity score (OFSS),operation duration,operative blood loss,X-ray expose times, callus appear time, fracture healing time, postoperative infection rate, complications and Johner-Wruhs accceccment were recorded and evaluated. RESULTS: All patients were followed up for 8 to 12 months (10.4 in averaged). The mean operation duration, operative blood loss, callus appear time, fracture healing time the mean operation duration reespectively were (56.79±8.87) min, (216.16±18.21) ml, (5.32±0.71) weeks, (12.79±2.52) weeks in observation group,and (104.53±9.28) min, (439.93±14.65) ml, (4.97±1.26) weeks, (14.81±2.63) weeks in control group. According to Johner-Wruhs acccecement,there were were 33 cases in excellent,2 in good,and 1 in poor in observation group,non-union of fracture in 1 case,local infection occurred in 1 cases; in control group 25 cases in excellent,6 in good, and 5 in poor, non-union of fracture in 1 case,local infection occurred in 8 cases. There were significant differences in operation duration, operative blood loss, callus appear time, fracture healing time, postoperative infection rate, complications (P<0.05). There were no significant differences in hospital admission time, open fracture severity score and X-ray expose times (P>0.05). CONCLUSION: Under the guidance of damage control therapy,using external fixator measures to treat patients with open fractures of limbs is worth popularizing in clinical application because it can shorten the operation time, less blood loss, reduce the infection rate and complications, improve the success rate of surgery and recovery rate.

[Progress on treatment of transverse patella fractures with tension band fixation].

Transverse fracture is the most common in patella fracture and tension band fixation is one of the most effective methods. Surgical wire tension band technique is simple, the use of materials is also simple, but it is not strong and difficult to promote. Kirschner tension band technique can get satisfactory reduction with reliable fixation, but it is easy to complicate with steel wire breakage and Kirschner loosening. Screw tension band technique inherits the traditional advantages of simple manipulation and reliable fixation, also overcomes the disadvantages of early activity limitations caused soft tissue irritation of tension band around knee, the slippage and breakage of internal fixation, and the technique can be popularized generally.

[Progress on peri-operative hidden blood loss after hip fracture].

Hip fracture patients preoperative and postoperative exist hidden blood loss which often affect patients' wound healing, increase the probability of infection, prolong rehabilitation exercise, influence postoperative effect. At the same time, the body's blood loss increase the activation of the blood clotting mechanism, promote the incidence of deep vein thrombosis, bleeding and deep vein thrombosis has become the main causes of high risk in hip operation. It is very important to stop bleeding, anticoagulation should not be ignored, so how to effectively deal with the prominent contradiction between the postoperative anticoagulation and bleeding or looking for a best balance has become a intractable problems in hip fracture treatment.