Regulation of microRNA-126 on the polarization of human macrophages stimulated by Porphyromonas gingivalis lipopolysaccharide / 中华口腔医学杂志

Objective: To study the effect of microRNA-126 (miR-126) on the polarization of human monocyte-derived macrophages stimulated by Porphyromonas gingivalis (Pg) lipopolysaccharide (LPS). Methods: Macrophages derived from human myeloid leukemia mononuclear cells were stimulated by Pg-LPS (5 mg/L) and by Pg-LPS (5 mg/L) after 24 h-transfection of miR-126 mimic or negative control RNA for 48 h, respectively. Real-time quantitative-PCR (qRT-PCR), enzyme-linked immunosorbent assay (ELISA) and Western blotting were conducted to detect the changes in miR-126, pro-inflammatory factor tumor necrosis factor-α (TNF-α), anti-inflammatory factors interleukin-10 (IL-10), inducible nitric oxide synthase (iNOS), arginase-1 (Arg-1) and M1 polarization-related pathways such as nuclear factor kappa-B (NF-κB) and mitogen-activated protein kinase (MAPK) signaling pathways. Results: Compared with non-LPS stimulation group (TNF-α: 1.000±0.020, iNOS: 1.125±0.064, miR-126: 1.004±0.113, IL-10: 1.003±0.053, Arg-1: 1.130±0.061), the mRNA levels of TNF-α (3.105±0.278) and iNOS (4.296±0.003) increased significantly (t=6.53, P=0.003; t=42.63, P<0.001, respectively), while miR-126, IL-10 and Arg-1 expressions (0.451±0.038, 0.545±0.004 and 0.253±0.017) decreased significantly (t=7.95, P=0.001; t=7.36, P=0.002; t=11.94, P<0.001, respectively) after Pg-LPS stimulated by human-derived macrophages for 48 h. The protein expression of iNOS, TNF-α, Arg-1 and IL-10 were consistent at mRNA levels. Meanwhile, the expressions of phospho-NF-κB p65 (p-p65), phospho-extracellular signal-regulated kinase (p-ERK) and phospho-p38 MAPK (p-p38) increased significantly, while the expression of Arg-1 decreased significantly. Compared with the negative controls (scramble RNA) (TNF-α: 1.141±0.197, iNOS: 1.173±0.115, IL-10: 1.032±0.138, Arg-1: 0.933±0.044), the mRNA levels of TNF-α (0.342±0.022) and iNOS (0.588±0.085) expressions significantly decreased (t=5.35, P=0.006; t=5.05, P=0.007), while IL-10 (1.786±0.221) and Arg-1 expressions (2.152±0.229) significantly increased (t=3.71, P=0.021; t=6.21, P=0.003) after Pg-LPS stimulation with miR-126 mimic transfection. The relative protein expressions of iNOS, p-p65, p-ERK and p-p38 significantly decreased (t=13.00, P<0.001; t=6.98, P=0.002; t=10.86, P<0.001; t=8.32, P=0.001), while the protein level of Arg-1 significantly increased (t=12.08, P<0.001). Conclusions: Pg-LPS could promote M1 polarization of macrophages. miR-126 might inhibit the effect of Pg-LPS on the M1 polarization of macrophages through down-regulating NF-κB and MAPK signaling pathways.

The Genotype and Phenotype of Proline-Rich Transmembrane Protein 2 Associated Disorders in Chinese Children.

Objectives: To study the genetic and clinical characteristics of Chinese children with pathogenic proline-rich transmembrane protein 2 (PRRT2) gene-associated disorders. Methods: Targeted next generation sequencing (NGS) was used to identify pathogenic PRRT2 variations in Chinese children with epilepsy and/or kinesigenic dyskinesia. Patients with confirmed PRRT2-associated disorders were monitored and their clinical data were analyzed. Results: Forty-four patients with pathogenic PRRT2 variants were recruited. Thirty-five of them (79.5%) had heterozygous mutations, including 30 frameshifts, three missenses, one nonsense, and one splice site variant. The c.649dupC was the most common variant (56.8%). Eight patients (18.2%) showed whole gene deletions, and one patient (2.3%) had 16p11.2 microdeletion. Thirty-four cases (97.1%) were inherited and one case (2.9%) was de novo. Forty patients were diagnosed with benign familial infantile epilepsy (BFIE), two patients had paroxysmal kinesigenic dyskinesia (PKD) and two had infantile convulsions and choreoathetosis (ICCA). Patients with whole gene deletions had a later remission than patients with heterozygous mutations (13.9 vs. 7.1 months, P = 0.001). Forty-two patients were treated with antiseizure medications (ASMs). At last follow-up, 35 patients, including one who did not receive therapy, were asymptomatic, and one patient without ASMs died of status epilepticus at 12 months of age. One patient developed autism, and one patient showed mild developmental delay/intellectual disability. Conclusion: Our data suggested that patients with whole gene deletions could have more severe manifestations in PRRT2-associated disorders. Conventional ASMs, especially Oxcarbazepine, showed a good treatment response.

Genetic and phenotypic characteristics of SCN1A-related epilepsy in Chinese children.

SCN1A gene mutations are associated with epilepsy and neurodevelopmental disorders. This study aimed to explore the genotype and phenotype spectrum of SCN1A gene related epilepsy. Epileptic patients who were treated in the Children's Hospital of Chongqing Medical University from January 2015 to July 2018 and identified as having SCN1A mutations by targeted next-generation sequencing were included. Clinical manifestations of all patients were analyzed retrospectively. A total of 24 patients with SCN1A mutations were identified. The age of epilepsy onset ranged from 2 months to 2 years and 9 months. Multiple seizure types were observed. A total of 13 (54.2%) patients had three or more types of seizures. Overall, 16 (66.7%) patients had status epilepticus, 11 (45.8%) patients had fever sensitivity, and nine (37.5%) patients had seizures after vaccination. Moreover, 15 (62.5%) patients showed varying degrees of cognitive and motor development retardation. In addition, two patients had mutations inherited from one of their parents and 22 (91.7%) patients had de novo mutations. The following SCN1A mutation types were identified: missense (16 patients, 66.7%), nonsense (four patients, 16.7%), splice site (one patient), frameshift (one patient), and large deletions (two patients). Overall, 23 of the patients received antiepileptic therapy, of which eight (33.3%) patients had no decrease in seizures and 11 (45.8%) patients had more than 50% decrease in seizure frequency. Three patients had poor response to antiepileptic drug therapy before attempting ketogenic diet, after which seizure frequency decreased by 50%. A total of 10 (41.7%) patients had used sodium channel blockers before accurate diagnosis, all of whom showed ineffective or even aggravated seizure response. SCN1A mutations are associated with a spectrum of seizure-related disorders, ranging from a relatively mild form of febrile seizures to a more severe epileptic encephalopathy known as Dravet syndrome. Early diagnosis of SCN1A mutation-associated epilepsy can aid in appropriate choice of antiepileptic drugs for treatment and reducing adverse sequelae.

Different types of intermittent pneumatic compression devices for preventing venous thromboembolism in patients after total hip replacement.

BACKGROUND: Total hip replacement (THR) is an effective treatment for reducing pain and improving function and quality of life in patients with hip disorders. While this operation is very successful, deep vein thrombosis (DVT) and pulmonary embolism (PE) are significant complications after THR. Different types of intermittent pneumatic compression (IPC) devices have been used for thrombosis prophylaxis in patients following THR. Available devices differ in compression garments, location of air bladders, patterns of pump pressure cycles, compression profiles, cycle length, duration of inflation time and deflation time, or cycling mode such as automatic or constant cycling devices. Despite the widely accepted use of IPC for the treatment of arterial and venous diseases, the relative effectiveness of different types of IPC systems as prophylaxis against thrombosis after THR is still unclear. OBJECTIVES: To assess the comparative effectiveness and safety of different IPC devices with respect to the prevention of venous thromboembolism in patients after THR. SEARCH METHODS: For this update the Cochrane Peripheral Vascular Diseases Group Trials Search Coordinator searched the Specialised Register (November 2014), CENTRAL (2014, Issue 10). Clinical trial databases were searched for details of ongoing and unpublished studies. Reference lists of relevant articles were also screened. There were no limits imposed on language or publication status. SELECTION CRITERIA: Randomized and quasi-randomized controlled studies were eligible for inclusion. DATA COLLECTION AND ANALYSIS: Two review authors independently selected trials, assessed trials for eligibility and methodological quality, and extracted data. Disagreement was resolved by discussion or, if necessary, referred to a third review author. MAIN RESULTS: Only one quasi-randomized controlled study with 121 study participants comparing two types of IPC devices met the inclusion criteria. The authors found no cases of symptomatic DVT or PE in either the calf-thigh compression group or the plantar compression group during the first three weeks after the THR. The calf-thigh pneumatic compression was more effective than plantar compression for reducing thigh swelling during the early postoperative stage. The strength of the evidence in this review is weak as only one trial was included and it was classified as having a high risk of bias. AUTHORS' CONCLUSIONS: There is a lack of evidence from randomized controlled trials to make an informed choice of IPC device for preventing venous thromboembolism (VTE) following total hip replacement. More research is urgently required, ideally a multicenter, properly designed RCT including a sufficient number of participants. Clinically relevant outcomes such as mortality, imaging-diagnosed asymptomatic VTE and major complications must be considered.

Continuous passive motion for preventing venous thromboembolism after total knee arthroplasty.

BACKGROUND: Total knee arthroplasty (TKA) is a common form of orthopaedic surgery. Venous thromboembolism (VTE), which consists of deep venous thrombosis (DVT) and pulmonary embolism (PE), is a major and potentially fatal complication after TKA. The incidence of DVT after TKA is 40% to 80% and the incidence of PE is approximately 2%. It is generally agreed that thromboprophylaxis should be used in patients who undergo TKA. Both pharmacological and mechanical methods are used in the prevention of DVT. Pharmacological methods alter the blood coagulation profile and may increase the risk of bleeding complications. When pharmacological methods cannot be used the mechanical methods become crucial for VTE prophylaxis. Continuous passive motion (CPM) is provided through an external motorised device which enables a joint to move passively throughout a preset arc of motion. Despite the theoretical effectiveness and widespread use of CPM, there are still differing views on the effectiveness of CPM as prophylaxis against thrombosis after TKA. This is an update of the review first published in 2012. OBJECTIVES: The aim of this review was to determine the effectiveness of continuous passive motion (CPM) therapy for preventing venous thromboembolism (VTE) in patients after total knee arthroplasty (TKA). SEARCH METHODS: For this update the Cochrane Peripheral Vascular Diseases Group Trials Search Co-ordinator searched the Specialised Register (last searched February 2014), CENTRAL (2014, Issue 1), Ovid MEDLINE (to week 1 February 2014) and EMBASE (to Week 07 2014). SELECTION CRITERIA: Randomised controlled trials (RCTs) comparing the use of CPM with control in preventing DVT or PE after TKA. People aged 18 years and older who had undergone TKA were included in this review. We excluded studies of patients who presented with DVT at baseline. The experimental and control groups received similar postoperative care and therapy other than the CPM. DATA COLLECTION AND ANALYSIS: Two review authors independently assessed the citations retrieved by the search strategies for reports of relevant RCTs. They independently selected trials that satisfied the inclusion criteria, extracted data and undertook quality assessment. Effects were estimated as risk ratios (RRs), mean differences or standardised mean differences with 95% confidence intervals (CIs). Meta-analyses were performed using a fixed-effect model for continuous variables. Where heterogeneity existed (determined by the I(2) statistic) a random-effects model was used. MAIN RESULTS: Eleven RCTs involving 808 participants met the inclusion criteria. The methodological quality of the included studies was variable and most of the predefined outcomes were reported by only one or two studies, therefore the quality of the evidence was low. Five studies with a total of 405 patients reported the incidence of DVT. In the CPM group (205 patients) 36 developed DVT (18%) compared to 29 (15%) in the control group (200 patients). The results of the meta-analysis showed no evidence that CPM had any effect on preventing VTE after TKA (RR 1.22, 95% CI 0.84 to 1.79). One trial (150 participants) did not find PE in any of the patients during hospitalisation or in the subsequent three months. PE was not reported in the other included studies. None of the trials reported deaths among the included participants. AUTHORS' CONCLUSIONS: There is not enough evidence from the available RCTs to conclude that CPM reduces VTE after TKA. We cannot assess the effect of CPM on mortality because no such events occurred amongst the participants of these trials. The quality of the evidence was low. The results are supported by only a small number of studies, most of which are of low to moderate quality.

Different types of intermittent pneumatic compression devices for preventing venous thromboembolism in patients after total hip replacement.

BACKGROUND: Total hip replacement (THR) is an effective treatment for reducing pain and improving function and quality of life in patients with hip disorders. While this operation is very successful, deep vein thrombosis (DVT) and pulmonary embolism (PE) are significant complications after THR. Different types of intermittent pneumatic compression (IPC) devices have been used for thrombosis prophylaxis in patients following THR. Available devices differ in compression garments, location of air bladders, patterns of pump pressure cycles, compression profiles, cycle length, duration of inflation time and deflation time, or cycling mode such as automatic or constant cycling devices. Despite the widely accepted use of IPC for the treatment of arterial and venous diseases, the relative effectiveness of different types of IPC systems as prophylaxis against thrombosis after THR is still unclear. OBJECTIVES: To assess the comparative effectiveness and safety of different IPC devices with respect to the prevention of venous thromboembolism in patients after THR. SEARCH METHODS: The Cochrane Peripheral Vascular Diseases Group Trials Search Coordinator searched the Specialised Register (May 2012), CENTRAL (2012, Issue 4), MEDLINE (April Week 3 2012) and EMBASE (Week 17 2012). Clinical trial databases were searched for details of ongoing and unpublished studies. Reference lists of obtained articles were also screened. There were no limits imposed on language or publication status. SELECTION CRITERIA: Randomized and quasi-randomized controlled studies were eligible for inclusion. DATA COLLECTION AND ANALYSIS: Two review authors independently selected trials, assessed trials for eligibility and methodological quality, and extracted data. Disagreement was resolved by discussion or, if necessary, referred to a third review author. MAIN RESULTS: Only one quasi-randomized controlled study with 121 study participants comparing two types of IPC devices met the inclusion criteria. The authors found no cases of symptomatic DVT or PE in either the calf-thigh compression group or the plantar compression group during the first three weeks after the THR. The calf-thigh pneumatic compression was more effective than plantar compression for reducing thigh swelling during the early postoperative stage. The strength of the evidence in this review is weak as only one trial was included and it was classified as having a high risk of bias. AUTHORS' CONCLUSIONS: There is a lack of evidence from randomized controlled trials to make an informed choice of IPC device for preventing venous thromboembolism (VTE) following total hip replacement. More research is urgently required, ideally a multicenter, properly designed RCT including a sufficient number of participants. Clinically relevant outcomes such as mortality, imaging-diagnosed asymptomatic VTE and major complications must be considered.

Continuous passive motion for preventing venous thromboembolism after total knee arthroplasty.

BACKGROUND: Total knee arthroplasty (TKA) is a common form of orthopedic surgery. Venous thromboembolism (VTE), which consists of deep venous thrombosis (DVT) and pulmonary embolism (PE), is a major and potentially fatal complication after TKA. The incidence of DVT after TKA is 40% to 80% and the incidence of PE is approximately 2%. It is generally agreed that thromboprophylaxis should be used in patients who undergo TKA. Both pharmacological and mechanical methods are used in the prevention of DVT. Pharmacological methods alter the blood coagulation profile and may increase the risk of bleeding complications. When pharmacological methods cannot be used, the mechanical methods become crucial for VTE prophylaxis. Continuous passive motion (CPM) is through an external motorised device which enables a joint to move passively throughout a preset arc of motion. Despite the theoretical effectiveness and widespread use of CPM, there are still differing views on the effectiveness of CPM as prophylaxis against thrombosis after TKA. OBJECTIVES: The aim of this review is to determine the effectiveness of continuous passive motion therapy for preventing thrombosis in patients after total knee arthroplasty (TKA). SEARCH METHODS: The Cochrane Peripheral Vascular Diseases Group searched their Specialised Register (last searched January 2011), CENTRAL (2011, Issue 1), MEDLINE (1948 to Week 2 January 2011) and EMBASE (1980 to Week 3 January 2011). In addition, the authors searched the reference lists of identified trials. SELECTION CRITERIA: Randomised controlled trials (RCTs) comparing the use of CPM with control in preventing DVT or PE after TKA. People aged 18 years and older who have undergone TKA were included in this review. We excluded studies of patients who presented with DVT at baseline. Both the experimental and control groups received similar postoperative care and therapy other than the CPM. DATA COLLECTION AND ANALYSIS: Two review authors independently assessed the citations retrieved by the search strategies for reports of relevant RCTs. They independently selected trials that satisfied the inclusion criteria, extracted data and undertook quality assessment. Effects were estimated as risk ratios (RRs) or mean differences or standardised mean differences with 95% confidence intervals (CI). Meta-analyses were performed using a fixed-effect model for continuous variables. Where heterogeneity existed (determined by the I(2) statistic), a random-effects model was used. MAIN RESULTS: Ten randomised controlled trials involving 764 participants met the inclusion criteria. Four studies with a total of 361 patients reported the incidence of DVT. In the CPM group (182 patients) 36 developed DVT (20%) compared to 28 (16%) the control group of 179 patients. The meta-analysis result showed no evidence that CPM had any effect on preventing VTE after TKA (RR 1.27, 95% CI 0.87 to 1.86). One trial (150 participants) did not find PE in any of the patients during hospitalisation or in the subsequent three months. None of the trials reported any deaths of the included participants. AUTHORS' CONCLUSIONS: There is not enough evidence from the available RCTs to conclude that CPM reduces VTE after TKA. We cannot assess the effect of CPM on death because no such events occurred amongst the participants of these trials.

Posterior screw-plate system for treating old fracture of the odontoid process.

OBJECTIVE: To assess the efficacy of a screw-plate system for the treatment of old fracture of the odontoid process. METHODS: Twenty-six patients with old fracture of the odontoid process were treated by a posterior screw-plate system. There were 17 men and 9 women ranging in age from 17 to 58 years (mean, 32.8 years). According to the Anderson-D'Alonzo classification, 19 patients were classified as type II, and 7 as type III. According to the Frankel classification, there were 3 patients of grade C, 21 of grade D and 2 of grade E. RESULTS: All operations were successfully performed. The operation time was 75-120 min (mean, 90 min) and the intraoperative blood loss 50-200 ml (mean, 125 ml). There were no postoperative complications. All patients were followed up for 24-36 months. At the final follow-up, one patient had improved from grade C to grade D, two from grade C to grade E, and 15 from grade D to grade E. The other cases had remained stable. There was no breakage of nails or failure of internal fixation during follow-up. Stable bone union was observed in all cases, the average healing time being 7.8 months. CONCLUSION: Posterior screw-plate system is a safe and effective method for treating old fracture of the odontoid process.