PRICKLE1 gene methylation and abnormal transcription in Chinese patients with ankylosing spondylitis.

BACKGROUND: Ankylosing spondylitis (AS) is a common inflammatory arthritis without a reliable biomarker. The role of methylation and mRNA expression of PRICKLE1 promoter in the pathogenesis of ankylosing spondylitis remains unclear. METHODS: A two-stage case-control design was used to detect the characteristics of methyl group and transcriptome of PRICKLE1 gene in Ankylosing spondylitis. The methylation degree of PRICKLE1 gene promoter region was tested by phosphate-sequencing, and further analyzed whether there was significant difference in methylation level of PRICKLE1 gene. The expression levels of PRICKLE1 mRNA in 50 AS patients and 50 healthy controls were detected by real-time quantitative PCR (RT-qPCR). RESULTS: Compared with healthy control group, the intensity of methylation in 4 ponds of PRICKLE1 in patients with Ankylosing spondylitis was low, and the mRNA levels were overexpressed (P = 0.017). ROC results showed that the sensitivity of PRICKLE1 was 68.67% and specificity was 71.43%. CONCLUSION: There is a significant change in the concentration of serum PRICKLE1 mRNA​in patients with Ankylosing spondylitis, and the degree of gene methylation is significantly reduced, suggesting that PRICKLE1 gene maybe involved in the pathogenesis of Ankylosing spondylitis, which may be useful for predicting the occurrence of AS and finding new early screening indicators.

Particle sorting to improve the removal of fluoride and aluminum nitride from secondary aluminum dross by roasting.

It is important to remove active substances from secondary aluminum dross (SAD) to meet the reuse of SAD. In this work, the removal of active substances from different particle sizes of SAD was studied using roasting improvement with particle sorting. The results showed that roasting after particle sorting pretreatment can effectively remove fluoride and aluminum nitride (AlN) from SAD, while getting the high-grade alumina (Al2O3) crude materials. The active substances of SAD mainly contribute to AlN, aluminum carbide (Al4C3), and soluble fluoride ions. AlN and Al3C4 mainly exist in particles of 0.05-0.1 mm, while Al and fluoride are mainly in particles of 0.1-0.2 mm. The SAD of particle size ranging 0.1-0.2 mm has high activity and leaching toxicity; the gas emission was reached 50.9 mL/g (limit value of 4 mL/g), and the fluoride ion concentration in the literature was 137.62 mg/L (limit value of 100 mg/L) during the identification for reactivity and leaching toxicity according to GB5085.5-2007 and GB5085.3-2007, respectively. Roasting at 1000 °C for 90 min, the active substances of SAD were converted to Al2O3, N2, and CO2; meanwhile, soluble fluoride converted to stable CaF2. The final gas release was reduced to 2.01 mL/g while soluble fluoride from SAD residues was reduced to 6.16 mg/L, respectively. The Al2O3 content of SAD residues was determined at 91.8% and has been classified as category I solid waste. The results suggested that the roasting improvement with particle sorting of SAD can meet the reuse of valuable materials at full scale.

Development and validation of a risk prediction model for diabetic retinopathy in type 2 diabetic patients.

To establish a risk prediction model and make individualized assessment for the susceptible diabetic retinopathy (DR) population in type 2 diabetic mellitus (T2DM) patients. According to the retrieval strategy, inclusion and exclusion criteria, the relevant meta-analyses on DR risk factors were searched and evaluated. The pooled odds ratio (OR) or relative risk (RR) of each risk factor was obtained and calculated for ß coefficients using logistic regression (LR) model. Besides, an electronic patient-reported outcome questionnaire was developed and 60 cases of DR and non-DR T2DM patients were investigated to validate the developed model. Receiver operating characteristic curve (ROC) was drawn to verify the prediction accuracy of the model. After retrieving, eight meta-analyses with a total of 15,654 cases and 12 risk factors associated with the onset of DR in T2DM, including weight loss surgery, myopia, lipid-lowing drugs, intensive glucose control, course of T2DM, glycated hemoglobin (HbA1c), fasting plasma glucose, hypertension, gender, insulin treatment, residence, and smoking were included for LR modeling. These factors, followed by the respective ß coefficient was bariatric surgery (- 0.942), myopia (- 0.357), lipid-lowering drug follow-up < 3y (- 0.994), lipid-lowering drug follow-up > 3y (- 0.223), course of T2DM (0.174), HbA1c (0.372), fasting plasma glucose (0.223), insulin therapy (0.688), rural residence (0.199), smoking (- 0.083), hypertension (0.405), male (0.548), intensive glycemic control (- 0.400) with constant term α (- 0.949) in the constructed model. The area under receiver operating characteristic curve (AUC) of the model in the external validation was 0.912. An application was presented as an example of use. In conclusion, the risk prediction model of DR is developed, which makes individualized assessment for the susceptible DR population feasible and needs to be further verified with large sample size application.

Effects of STN-DBS on cognition and mood in young-onset Parkinson's disease: a two-year follow-up.

Background: The effects of subthalamic nucleus deep brain stimulation (STN-DBS) on the cognition and mood of patients with PD are still not uniformly concluded, and young-onset Parkinson's disease (YOPD) is even less explored. Objective: To observe the effectiveness of STN-DBS on the cognition and mood of YOPD patients. Methods: A total of 27 subjects, with a mean age at onset of 39.48 ± 6.24 and age at surgery for STN-DBS of 48.44 ± 4.85, were followed up preoperatively and for 2 years postoperatively. Using the Unified Parkinson disease rating scale (UPDRS), H&Y(Hoehn and Yahr stage), 39-Item Parkinson's Disease Questionnaire (PDQ-39), Mini-mental state examination (MMSE), Montreal Cognitive Assessment (MoCA), Hamilton depression scale (HAMD), Hamilton anxiety scale (HAMA) to assess motor, cognition, and mood. Results: At the 2-year follow-up after STN-DBS, YOPD patients showed significant improvements in motor and quality of life (UPDRS III: p < 0.001, PDQ-39: p < 0.001); overall cognition was not significantly different from preoperative (MMSE: p = 0.275, MoCA: p = 0.913), although language function was significantly impaired compared to preoperative (MMSE: p = 0.004, MoCA: p = 0.009); depression and anxiety symptoms also improved significantly (HAMD: p < 0.001, HAMA: p < 0.001) and the depression score correlated significantly with motor (preoperative: r = 0.493, p = 0.009), disease duration (preoperative: r = 0.519, p = 0.006; postoperative: r = 0.406, p = 0.036) and H&Y (preoperative: r = 0.430, p = 0.025; postoperative: r = 0.387, p = 0.046); total anxiety scores were also significantly correlated with motor (preoperative: r = 0.553, p = 0.003; postoperative: r = 0.444, p = 0.020), disease duration (preoperative: r = 0.417, p = 0.031), PDQ-39 (preoperative: r = 0.464, p = 0.015) and H&Y (preoperative: r = 0.440, p = 0.022; postoperative: r = 0.526, p = 0.005). Conclusion: STN-DBS is a safe and effective treatment for YOPD. The mood improved significantly, and overall cognition was not impaired, were only verbal fluency decreased but did not affect the improvement in quality of life.

FOXO3a Alleviates the Inflammation and Oxidative Stress via Regulating TGF-ß and HO-1 in Ankylosing Spondylitis.

This study aimed to investigate whether Forkhead box O3a (FOXO3a) modulates inflammation and oxidative stress in ankylosing spondylitis (AS). We applied bioinformatics analysis, quantitative real-time polymerase chain reaction, immunoblotting, enzyme linked immunosorbent assay, chromatin immunoprecipitation, and dual-luciferase reporter assay. Gene overexpression and knockdown of FOXO3a were conducted via lentivirus and small interfering RNA, respectively. Downregulated FOXO3a expression was first confirmed in AS patients. Interleukin-8 (IL-8) and IL-17A were highly expressed and negatively related with FOXO3a in AS. Total antioxidant capacity (T-AOC) were markedly decreased and positively associated with FOXO3a in AS. Overexpression of FOXO3a inhibited the secretion of inflammatory cytokines and promoted the production of antioxidant enzymes in Jurkat cells. Transforming growth factor-ß (TGF-ß) and heme oxygenase 1 (HO-1), which had binding sites to FOXO3a based on bioinformatics analysis, were abnormally expressed and positively related with FOXO3a. Accordingly, FOXO3a obviously elevated the protein and transcription levels of TGF-ß and HO-1 in Jurkat cells. The above results were verified by silencing FOXO3a. Moreover, FOXO3a directly interacted with and promoted the transcription of TGF-ß and HO-1. In summary, the modulation of cellular inflammation and oxidative stress via FOXO3a-mediated TGF-ß and HO-1 activation is partly involved in the pathogenesis of AS.

Biparametric magnetic resonance imaging assessment for detection of muscle-invasive bladder cancer: a systematic review and meta-analysis.

OBJECTIVES: To investigate if removing DCE from the Vesical Imaging Reporting and Data System (VI-RADS) influences the diagnostic accuracy of muscle-invasive bladder cancer (MIBC). We also explored using different reference standards on the MRI diagnostic performance. METHODS: We searched the Cochrane Library, Embase, and PubMed databases to June 26, 2021. Pooled biparametric MRI (bpMRI, T2WI+DWI) and multiparametric MRI (mpMRI, T2WI+DWI+DCE) sensitivities and specificities and the diagnostic performances of these methods for MIBC were compared using different reference standards. RESULTS: Seventeen studies with 2344 patients were finally included, of which 7 studies, including 1041 patients, reported the diagnostic performance of bpMRI. VI-RADS showed sensitivities and specificities of 0.91 (95% CI 0.87-0.94) and 0.86 (95% CI 0.77-0.91) at cutoff scores of 3, and 0.85 (95% CI 0.77-0.90) and 0.93 (95% CI 0.89-0.96) at cutoff scores of 4. BpMRI showed sensitivities and specificities of 0.90 (95% CI 0.69-0.97) and 0.90 (95% CI 0.81-0.95), and 0.84 (95% CI 0.78-0.88) and 0.97 (95% CI 0.87-0.99), respectively, for cutoff scores of 3 and 4. The sensitivities of bpMRI vs mpMRI for MIBC were not significantly different, but bpMRI was more specific than mpMRI at cutoff scores of 3 (p = 0.02) and 4 (p = 0.02). The VI-RADS studies using primary transurethral resection of bladder tumors (TURBT) as the reference standard had significantly higher sensitivities (p < 0.001) than those using secondary TURBT or radical cystectomy as the reference. DATA CONCLUSION: BpMRI and conventional VI-RADS had similar diagnostic efficacies for MIBC. Since MRI overestimated MIBC diagnoses using primary TURBT as the reference standard, we recommend using secondary TURBT as the reference standard. KEY POINTS: • Biparametric MRI without DCE had similar diagnostic efficacies for MIBC compared with conventional VI-RADS. • The sensitivity of VI-RADS was overestimated when referring to the primary TURBT results. • Biparametric MRI comprised of T2WI and DWI could be used for detecting MIBC in clinical practice.

Hemangioblastoma masquerading as a ring enhancing lesion in the cerebellum: A case report.

RATIONALE: Hemangioblastomas (HGBMs) are very rare, and the cerebellum is usually the most common site of occurrence. HGBMs with ring-enhanced walls are often misdiagnosed as metastases, abscesses, glioblastomas, tuberculomas, and demyelinating diseases. Thus, we present a rare case of HGBM masquerading as a ring-enhancing lesion in the cerebellum. PATIENT CONCERNS: We present a 33-year-old female who was admitted to our department because of headaches, unstable walking, and visual loss in both eyes. Cranial nerve examination revealed deficits in cranial nerve II. DIAGNOSIS: Magnetic resonance imaging revealed 2 cystic lesions in the cerebellum, with irregular ring-enhanced cyst walls composed of smaller nodular parts. Immunohistochemical staining of resected specimens established HGBM. INTERVENTIONS: The lesions were completely resected using a right retrosigmoid approach. OUTCOMES: Two years of follow-up revealed no recurrence of her symptoms or tumor. She is currently well and performs her daily duties. LESSONS: HGBMs with enhanced cysts are often misdiagnosed by radiology because of their ring-enhanced nature. Computed tomography angiography may be the best modality for differentiating cerebellar HGBM from other ring-enhancing lesions. Surgery is the gold standard of treatment for these lesions.

Association of interleukin-6 promoter polymorphism with rheumatoid arthritis: a meta-analysis with trial sequential analysis.

OBJECTIVES: The association of interleukin-6 (IL-6) -174G/C (rs1800795) and IL-6 -572G/C (rs1800796) single-nucleotide polymorphism (SNP) with the risk of acquiring rheumatoid arthritis (RA) was inconsistent among previous studies. This paper aims to investigate the association between IL-6 promoter polymorphism with RA in different ethnics. METHODS: Relevant studies were searched using Medline and Google Search engines; STATA software was used to perform the meta-analysis. Pooled odds ratios (OR) were calculated to estimate the potential genetic associations. Subgroup analysis and sensitivity analysis were applied to explore the sources of heterogeneity. Lastly, we used TSA (trial sequential analysis) software to verify the reliability of meta-analysis results. RESULTS: A total of 18 studies were included, involving 8116 subjects (3820 RA patients and 4296 controls). We found a tendency to associate RA with the IL-6 -174G/C allele in Asians (C vs G: OR = 4.56, 95% CI = 1.85-11.23; P < 0.001); with IL-6 -572G/C genotype or allele frequencies, there was no statistical differences between RA patients and controls (P > 0.05). TSA results indicate that the current meta-analysis can draw conclusions. CONCLUSIONS: IL-6-174G/C gene polymorphism were associated with increased risk of RA in Asians, but not in Caucasians. There was no association between IL-6 -572G/C gene polymorphism and the risk of RA. Key Points • Although the association between interleukin-6 (IL-6) promoter polymorphism and rheumatic arthritis (RA) has been discussed in the previous meta-analysis, their conclusions are inconsistent. • In this study, trial sequential analysis (TSA) was introduced into the meta-analysis, and the following two important conclusions were confirmed: (1) IL-6-174G/C gene polymorphism was associated with increased risk of RA in Asians, but not in Caucasians. (2) There was no association between IL-6 -572G/C gene polymorphism and the risk of RA.

A Novel Parameter for Fatigue Damage Assessment of Laser-Repaired Nickel-Based Alloy.

The fatigue damage assessment of laser-repaired components is critical to their service safety. However, since laser repairing is an advanced green remanufacturing technology, the current research on its fatigue mechanical behavior and fatigue damage evaluation methods is still immature. In addition, the relevant models used for the fatigue damage evaluation can only indicate the fatigue limit of components, which cannot describe the damage accumulation process of the components during the fatigue testing. Therefore, there is an urgent need to develop a fatigue damage evaluation method that can describe the fatigue damage accumulation and evolution to reveal the damage evolution mechanism during the fatigue test. In this study, based on the 3D-DIC technique, new damage parameters, i.e., strain average value and strain standard deviation, are proposed to quantitatively describe the damage status of the nickel-based components during the stress-based fatigue process. Then, based on the new damage parameters, a strain average value/strain standard deviation damage curve method is proposed to describe the damage status evolution of the components during the fatigue testing and evaluate its fatigue damage. For example, in the tensile fatigue test, the strain average value/strain standard deviation damage curves of the substrate component and the laser-repaired component can be divided into two damage stages. In the first damage stage, the damage increases slowly with the increase in the cycle number, whereas in the second damage stage, the damage increases rapidly with the increase in the cycle number. At this time, there is a demarcation point between the first damage stage and second damage stage in the strain average value damage curve and strain standard deviation damage curve. The cycle number of the demarcation point can be used as a reference value for the fatigue failure of the laser-repaired component. In addition, the electron backscatter diffraction (EBSD) technique was used to verify the validity of the evaluation results from the novel damage parameters.

A petroclival glioma mimicking trigeminal schwannoma: A case report.

RATIONALE: Glioma in the petroclival region is very rare. Also, very few cases of primary gliomas have been reported to have radiographic as well as intraoperative features of extra-axial lesions resulting in diagnostic dilemma in the literature. We present a rare case of petroclival glioma mimicking trigeminal schwannoma in a young female. PATIENT CONCERNS: We present a 21-years old female with a 3-month history of pain in the right eye with no visual impairment. Cranial nerves examination revealed mild deficits in the trigeminal nerve, facial nerve, auditory nerve, oculomotor as well as the trochlear nerve. DIAGNOSES: Magnetic resonance imaging detected an extra-axial mass with mixed signal intensities in the right petroclivus area. Immunohistochemical established glioma with world health organization (WHO) grade II. INTERVENTIONS: The lesion was resected via 2 successive operations in 6 months interval. The patient was further treated with radiotherapy and post-radiotherapy temozolamide. OUTCOMES: Two years follow-up revealed no recurrence of the lesions and she is well. Nevertheless, he is still being followed diligently to uncover any recurrence. LESSONS: The extra-axial nature as well as petroclival location of the glioma makes our case very unique and very rare. The imaging characteristics were very extraordinary for a glioma which resulted in diagnostic dilemma. Thus, the definitive diagnosis was based on the histopathological evaluation of the excised tumor.

Immunotherapy and Prevention of Cancer by Nanovaccines Loaded with Whole-Cell Components of Tumor Tissues or Cells.

Tumor tissues/cells are the best sources of antigens to prepare cancer vaccines. However, due to the difficulty of solubilization and delivery of water-insoluble antigens in tumor tissues/cells, including water-insoluble antigens into cancer vaccines and delivering such vaccines efficiently to antigen-presenting cells (APCs) remain challenging. To solve these problems, herein, water-insoluble components of tumor tissues/cells are solubilized by 8 m urea and thus whole components of micrometer-sized tumor cells are reasssembled into nanosized nanovaccines. To induce maximized immunization efficacy, various antigens are loaded both inside and on the surface of nanovaccines. By encapsulating both water-insoluble and water-soluble components of tumor tissues/cells into nanovaccines, the nanovaccines are efficiently phagocytosed by APCs and showed better therapeutic efficacy than the nanovaccine loaded with only water-soluble components in melanoma and breast cancer. Anti-PD-1 antibody and metformin can improve the efficacy of nanovaccines. In addition, the nanovaccines can prevent lung cancer (100%) and melanoma (70%) efficiently in mice. T cell analysis and tumor microenvironment analysis indicate that tumor-specific T cells are induced by nanovaccines and both adaptive and innate immune responses against cancer cells are activated by nanovaccines. Overall, this study demonstrates a universal method to make tumor-cell-based nanovaccines for cancer immunotherapy and prevention.

Association of FOXO3a gene polymorphisms and ankylosing spondylitis susceptibility in Eastern Chinese Han population.

OBJECTIVE: To investigate the association of FOXO3a polymorphisms and ankylosing spondylitis (AS) susceptibility in Eastern Chinese Han population. METHODS: FOXO3a polymorphisms rs12206094, rs12212067, rs2253310, rs3800232, and rs4946933 were genotyped in 650 AS patients and 646 controls by the improved Multiple Ligase Detection Reaction. RESULTS: The distribution of genotype in rs12212067 polymorphism was significantly different between AS patients and controls (P = 0.020), especially in male population (P = 0.009). There was significant difference of the genotype frequency distribution at rs3800232 between patients and controls in male population. The results of binary regression analysis showed that the rs12212067 GG genotype and rs3800232 TT genotype were obviously correlated with elevated AS risk, and the associations were still significant after being adjusted by age and gender (all P < 0.05). Interestingly, rs12212067 and rs3800232 genotypes were associated with disease activity of patients. Additionally, haplotype block rs12212067G- rs3800232T (OR = 1.403, 95%CI = 1.011-1.949) was further shown to confer promoting effect on developing AS. CONCLUSION: Among Eastern Chinese Han population, FOXO3a polymorphism rs12212067 and rs3800232 may contribute to increased risk of developing AS, but well-designed multicenter studies are needed to further confirm these preliminary findings in the future.

Single nucleotide polymorphisms of TRAF2 and TRAF5 gene in ankylosing spondylitis: a case-control study.

Objective To investigate the role of eight locus polymorphisms of tumor necrosis factor receptor-associated factor 2 (TRAF2) and TRAF5 gene and their interaction in the susceptibility to ankylosing spondylitis (AS) in Chinese Han population. Methods Eight single nucleotide polymorphisms (SNPs) of TRAF2 (rs3750511, rs10781522, rs17250673, rs59471504) and TRAF5 (rs6540679, rs12569232, rs4951523, rs7514863) gene were genotyped in 673 AS patients and 687 controls. Results The SNPs of TRAF2 and TRAF5 do not indicate a correlation with the susceptibility of AS in Chinese Han population. Genotype frequencies of rs3750511 were statistically significant in females between patients and controls. The allele frequencies of rs10781522 and genotype frequencies of rs3750511 were statistically significant between groups of different diseases activity. One three-locus model, TRAF2 (rs10781522, rs17250673) and TRAF5 (rs12569232), had a maximum testing accuracy of 52.67% and a maximum cross-validation consistency (10/10) that was significant at the level of P = 0.0001, after determined empirically by permutation testing. As to environmental variables, only marginal association was found between sleep quality and AS susceptibility. Conclusion TRAF2 rs3750511 polymorphism may be associated with the susceptibility and severity of AS. Besides, the interaction of TRAF2 and TRAF5 genes may be associated with AS susceptibility, but many open questions remain.

Treatment of maxillofacial congenital melanocytic nevus with percutaneous radiofrequency thermal ablation: A case series study.

When congenital melanocytic nevus (CMN) is in the maxillofacial region, a safer, more effective and fewer side-effects treatment is needed for patients with high requirement for appearance. The objective of this study was to investigate the effectiveness of radiofrequency thermal ablation (RFA) for CMN in the maxillofacial region. We reviewed 21 patients treated with RFA for CMN followed by a blinded retrospective analysis of serial photographs taken during the course of their therapy. Questionnaires were used to evaluate perceived therapeutic response and complications of this treatment. Most CMNs stopped growing, faded in color and became smaller. Reduction in size of 90% to 100% was obtained in two patients (10%), 75% to 90% in six patients (29%), 50% to 75% in two patients (10%), <50% in eight patients (38%), and three had no reduction (13%). Clear effect of clinical response score was obtained in two patients (10%), excellent in four patients (19%), good in 14 patients (67%), and fair in one patient (4%). No serious complication, severe hypertrophic scarring, and evidence of recurrence was observed in any case. Percutaneous RFA, as a minimally invasive and safe treatment, may provide an alternative treatment for maxillofacial CMN.

Construction of a knowledge graph for diabetes complications from expert-reviewed clinical evidences.

A knowledge graph is a structured representation of data that can express entity and relational knowledge. More attention has been paid to the study of a clinical knowledge graph, especially in the field of chronic diseases. However, knowledge graph construction is based mainly on electronic medical records and other data sources, and the authority of the constructed knowledge graph presents some problems. Therefore, regarding the quality of evidence, this study, in combination with experimental research on system evaluation and meta-analysis presents some new information, On the basis of evidence-based medicine (EBM), the secondary results of systematic evaluation and meta-analyses of social, psychological, and behavioral aspects were extracted as data for the core nodes and edges of a knowledge graph to construct a graph of type 2 diabetes (T2D) and its complications. In this study, relevant life-style evidence that are factors for the risk of diabetic retinopathy (DR), diabetic nephropathy (DN), diabetic foot (DF), and diabetic depression (DD), and the results of several of the relevant clinical test, including bariatric surgery, myopia, lipid-lowering drugs, lipid-lowering drug duration, blood glucose control, disease course, glycosylated hemoglobin, fasting blood glucose, hypertension, sex, smoking and other common lifestyle characteristics were finally extracted. The evidence-based knowledge graph of the DM complications was constructed by extracting relevant disease, risk factors, risk outcomes, and other diabetes entities and the strength of the data for the odds ratio (OR) or relative risk (RR) correlations from clinical evidence. Moreover, the risk prediction models constructed using a logistic model were incorporated into the knowledge graph to visualize the risk score of DM complications for each user. In short, the EBM-powered construction of the knowledge graph could provide high-quality information to support decisions for the prevention and control of diabetes and its complications.

[The Therapeutic Effect and Mechanism of Static Progressive Stretching in Different Durations on Traumatic Knee Contracture in Rats].

OBJECTIVE: To investigate the effect and mechanism of static progressive stretching (SPS) in different durations on traumatic knee contracture in rats. METHODS: Seventy male Wistar rats were randomly divided into three groups, including surgical modeling group ( n=50), control group (CON, no surgery, no treatment, n=10) and trauma without immobilization group (TRA, no treatment, n=10). The knee contracture model was established, and 50 surgical modeling rats were randomly divided into five groups including static progressive stretching treatment for 20 minutes group (S20 min, n=10), treatment for 30 minutes group (S30 min, n=10), treatment for 40 minutes group (S40 min, n=10), untreatment group (UNT, no SPS, n=10) and modeling group (MOD, n=10, euthanized after immobilization for histological staining and Western blot). Individuals in the S20 min, S30 min, and S40 min groups were anesthetized and submitted to SPS. One treatment session took place every other day. A total of 8 sessions were given till the final treatment session on the day 16. On the day 0, 8, and 16 of intervention, the range of joint motion (ROM) and gait analysis were measured and compared. After the ROM measurements and gait analysis, the rats were euthanized on the day 16 and the samples were stained with HE and Masson methods. The changes of pathological organization were observed. Western blot was used to detect the expressions of transforming growth factor-ß1 (TGF-ß1) and interleukin-6 (IL-6). RESULTS: ① ROM：the ROM of S30 min group recovered similar to that of the S20 min and S40 min groups after 8 days of treatment ( P>0.05), and was the best among all the surgical modeling groups after 16 d of treatment ( P<0.05). The ROM of S20 min, S30 min and S40 min groups significantly improved on the day 8 and day 16 comparing with that on day 0 ( P<0.01). ② Gait analysis: the stands in the S30min group improved best on the day 8 and day 16 ( P<0.05) , and better than that on day 0 ( P<0.05). The stride length of the S30 min group progressed similar to that of the S40 min group on the day 8 ( P>0.05), and there was no difference among three groups on the day 16 ( P>0.05). The stride length of the S30 min group appeared to recover more quickly on the day 8 ( P<0.05), and those of S20 min and UNT groups recovered significantly on the day 16 ( P<0.05). In addition, the swings in the S30 min group improved best ( P<0.05), and it appeared to recover better on the day 16 ( P<0.05). There was no statistical difference in terms of the swing speed among the four surgical modeling groups on the day 8 ( P>0.05). The swing speed of the S30min group increased most than those of the other three groups ( P<0.05), and it was much better on the day 8 and day 16 comparing with that on the day 0 ( P<0.05 ). ③ HE and Masson staining: the fibrosis and inflammation of the S30min group were significantly suppressed comparing to the other groups on the day 16. ④ Western blot: The protein expression levels of TGF-ß1 and IL-6 were significantly lower than those in the other intervention groups including the S20 min, S40 min and UNT groups on the day 16 ( P<0.05). CONCLUSION: Static progressive stretching treatment for 30 min could significantly improve the traumatic knee contracture in rats. The mechanism may be that the SPS decreased the expressions of TGF-ß1 and IL-6, reduced the adhesion and inflammation of joint capsule. Therefore it relieved the pain and increased the joint mobility by reconstructing the structure of the capsule and suppressing the fibrotic changes.

TNFR2 knockdown triggers apoptosis-induced proliferation in primarily cultured Schwann cells.

After sciatic nerve injury, Schwann cells in the distal segments of injury site undergo apoptosis and meanwhile proliferation. Although apoptosis-induced proliferation (AiP) has been characterized in various models, whether the proliferation of Schwann cells in the distal segments is triggered by apoptosis remains unelucidated. In this study, we used small interfering RNA to knock down the expression of TNFR1 and TNFR2 in primarily cultured Schwann cells, respectively and observed its effects on apoptosis and proliferation. The downregulation of TNFR1 or TNFR2 resulted in a remarkable decrease of cell viability and dramatically increased the apoptosis of Schwann cells. In contrast, the cell apoptosis induced by the knockdown of TNFR2, but not TNFR1, promoted the Schwann cell proliferation. Together, these observations indicated that Schwann cells can undergo AiP, and TNFR2 knockdown triggers the process. Additionally, we established the sciatic nerve injury model on TNF-α knock-out (KO) mice, and found that the Schwann cells of KO mice occurred significantly less apoptosis and proliferation than that of wild-type mice in the distal segments, which indicated TNF-α and its receptors were essential in the massive apoptosis and the apoptosis-induced proliferation of Schwann cells after sciatic nerve injury. The finding of AiP in Schwann cells may be beneficial to develop new approaches to promote axon regeneration and thereby improve the functional recovery after peripheral nerve injury.

Radiofrequency ablation micro-dissecting of eyelid nevus with XL-RFA device under operating microscope.

AIM: To study the effect of an innovative micro-dissection procedure by radiofrequency ablation (MRA) in removing eyelid nevus. METHODS: Fifty-six consecutive outpatients with eyelid nevus were treated with MRA using a monopolar device. The effect of MRA was determined after following-up for 6mo to 5y. RESULTS: Fifty-two cases (52 eyes, 92.9%) were cured once, and 4 cases (4 eyes, 7.1%) received second treatment for small residual. All cases healed well after surgery, with no pigmentation, no scars, no loss of eyelashes, no deformation of eyelid margin. There was no visual impairment after healing. CONCLUSION: MRA of eyelid nevus using the XL-RFA device is highly efficient without significant complications.

Clinicopathological significance of ribosomal protein S6 kinase A6 in lung squamous cell carcinoma: an immunohistochemical and RNA-seq study.

Ribosomal protein S6 kinase A6 (RPS6KA6) is a downstream factor of the ERK-MAPK pathway and has been extensively studied in various types of cancer. However, the role of RPS6KA6 in lung squamous cell carcinoma (LUSC) remains unclear. This study investigated expression of the RPS6KA6 and its clinicopathological correlation with LUSC and explored genetic alterations in the ribosomal protein S6 kinase (RSK) family in LUSC and their impact on the survival of patients. Expression of the RPS6KA6 protein in 175 LUSC samples and 30 normal lung tissues samples was determined by immunohistochemistry (IHC). RPS6KA6 protein expression in the LUSC tissues was significantly higher compared with that in the normal lung tissues (P=0.017). Overexpression of RPS6KA6 protein correlated with tumor size (r=0.260, P=0.001), lymph node metastasis (r=0.683, P<0.001), and TNM stage (r=0.378, P<0.001). RPS6KA6 RNA-seq data were obtained from the Cancer Genome Atlas (TCGA) and ONCOMINE database. RPS6KA6 mRNA expression in the LUSC tissues was significantly higher than that in paired noncancerous samples (TCGA: P=0.005; ONCOMINE: P=0.018). According to the cBioPortal online software, three detecting methods, including Seqv2, Array and U133, identified that the frequency of the genetic alterations in the RSKs in LUSC were 77%, 44%, and 42%, respectively. However, survival analysis of LUSC patients with or without RSKs genetic alterations reached no statistical significance. This study suggests that RPS6KA6 may be an oncogene in LUSC, and that expression of the RPS6KA6 protein is associated with the progression of LUSC. The RSK genes are frequently altered in LUSC, but the alterations have no significant effect on the survival of patients.

Design of an α-helical antimicrobial peptide with improved cell-selective and potent anti-biofilm activity.

AR-23 is a melittin-related peptide with 23 residues. Like melittin, its high α-helical amphipathic structure results in strong bactericidal activity and cytotoxicity. In this study, a series of AR-23 analogues with low amphipathicity were designed by substitution of Ala1, Ala8 and Ile17 with positively charged residues (Arg or Lys) to study the effect of positively charged residue distribution on the biological viability of the antimicrobial peptide. Substitution of Ile17 on the nonpolar face with positively charged Lys dramatically altered the hydrophobicity, amphipathicity, helicity and the membrane-penetrating activity against human cells as well as the haemolytic activity of the peptide. However, substitution on the polar face only slightly affected the peptide biophysical properties and biological activity. The results indicate that the position rather than the number of positively charged residue affects the biophysical properties and selectivity of the peptide. Of all the analogues, A(A1R, A8R, I17K), a peptide with Ala1-Arg, Ala8-Arg and Ile17-Lys substitutions, exhibited similar bactericidal activity and anti-biofilm activity to AR-23 but had much lower haemolytic activity and cytotoxicity against mammalian cells compared with AR-23. Therefore, the findings reported here provide a rationalization for peptide design and optimization, which will be useful for the future development of antimicrobial agents.