The morphology of osseous structure in subtalar joint with chronic ankle instability.

BACKGROUND: Osseous structures have been demonstrated as risk factors for chronic ankle instability (CAI). Previously, the researchers only focused on the osseous structures of ankle, but ignored the osseous structures of subtalar joint(STJ). Accordingly, the aim of our study was to investigate the morphological characteristics of STJ osseous structures in CAI. METHODS: 52 patients with CAI and 52 sex- and age- matched control subjects were enrolled from The Affiliated Traditional Chinese Medicine Hospital of Southwest Medical University. The lateral radiographs of ankle in weight-bearing were used to compare the diversity of the two groups. Specifically, The Length of calcaneus, Calcaneal facet height and Absolute foot height, Böhler's angle, Gissane's angle, Calcaneal inclination angle, Talocalcaneal angle, Tibiotalar angle, Tibiocalcaneal angle, Talar-horizontal angle, talar declination angle, facet inclination angle were gauged in the two groups. RESULTS: The Böhler's angle, Calcaneal inclination, Talocalcaneal angle, Tibiotalar angle, Talar-horizontal angle, Talar declination angle, Facet inclination angle and Absolute foot height of CAI group were significantly higher than normal control group (P < 0.05). There were no significant differences in Gissane's angle, Tibiocalcaneal angle, Length of calcaneus and Calcaneal facet height between patients with CAI and normal controls (P > 0.05). CONCLUSIONS: The osseous structures of STJ in CAI patients are different from normal people in morphology. Therefore, we should pay more attention to the changes of STJ anatomical parameters in the diagnosis and prevention of CAI. LEVEL OF EVIDENCE: Ⅲ.

Anatomical features of plantar fasciitis in various age cohorts: Based on magnetic resonance imaging.

BACKGROUND: Due to the lack of further studies on the influence of age factors on plantar fasciitis, this study evaluates the characteristic observation points of magnetic resonance imaging in various age cohorts of patients with plantar fasciitis to help diagnosis. METHODS: A retrospective analysis of 160 cases of plantar fasciitis patients and normal subjects (who have the disease unrelated to plantar fasciitis) who have undergone an MRI examination in our institution. The two groups were separately divided into young adult subjects (36 to 44 years old), middle age adult subjects (45 to 59 years old), and older adult subjects (60 to 79 years old). Data was gathered regarding plantar fascia thickness, the coronal length of the plantar fascia at the calcaneal origin, the signal intensity of plantar fascia and surrounding structures, and the presence or absence of plantar calcaneal spurs, all of which were assessed objectively by the investigators. RESULTS: There were statistical differences in the thickness of plantar fascia between two groups of three age cohorts (Older adult patients: 0.59 ± 0.09 cm; Middle age adult patients: 0.49 ± 0.09 cm; Young adult patients: 0.47 ± 0.05 cm) (all p < 0.001). In addition, there were also statistical differences in the high signal intensity changes of the plantar fascia and surrounding soft tissues between two groups of three age cohorts (all p < 0.001). In older adult plantar fasciitis patients, with regard to plantar calcaneal spur discovery, there was a statistical difference between the two groups (Chi-square = 12.799. df = 1. p < 0.001). CONCLUSION: In plantar fasciitis cases where a diagnosis is difficult, abnormalities in the soft tissue surrounding the plantar fascia in patients of low age are noteworthy. In older adult patients, the discovery of plantar calcaneal spurs with abnormal thickening of plantar fascia deserves attention, and abnormal MRI findings are more manifest. But the final diagnosis should be based on the medical history. LEVEL OF EVIDENCE: Level 3.

Epigenetic modulator inhibition overcomes temozolomide chemoresistance and antagonizes tumor recurrence of glioblastoma.

Glioblastoma multiforme (GBM) heterogeneity causes a greater number of deaths than any other brain tumor, despite the availability of alkylating chemotherapy. GBM stem-like cells (GSCs) contribute to GBM complexity and chemoresistance, but it remains challenging to identify and target GSCs or factors that control their activity. Here, we identified a specific GSC subset and show that activity of these cells is positively regulated by stabilization of methyl CpG binding domain 3 (MBD3) protein. MBD3 binds to CK1A and to BTRCP E3 ubiquitin ligase, triggering MBD3 degradation, suggesting that modulating this circuit could antagonize GBM recurrence. Accordingly, xenograft mice treated with the CK1A activator pyrvinium pamoate (Pyr-Pam) showed enhanced MBD3 degradation in cells expressing high levels of O6-methylguanine-DNA methyltransferase (MGMT) and in GSCs, overcoming temozolomide chemoresistance. Pyr-Pam blocked recruitment of MBD3 and the repressive nucleosome remodeling and deacetylase (NuRD) complex to neurogenesis-associated gene loci and increased acetyl-histone H3 activity and GSC differentiation. We conclude that CK1A/BTRCP/MBD3/NuRD signaling modulates GSC activation and malignancy, and that targeting this signaling could suppress GSC proliferation and GBM recurrence.

[Inverse ratio ventilation combined with PEEP in infants undergoing thoracoscopic surgery with one lung ventilation for lung cystadenomas: a randomized control trial of 63 cases].

OBJECTIVE: To investigate the effect of inverse ratio ventilation (IRV) combined with positive end-expiratory pressure (PEEP) in infants undergoing thoracoscopic surgery with single lung ventilation (OLV) for lung cystadenomas. METHODS: A total of 66 infants undergoing thoracoscopic surgery with OLV for lung cystadenomas in our hospital from February, 2018 to February, 2019 were randomized into conventional ventilation groups (group N, n=33) and inverse ventilation group (group R, n=33). Hemodynamics and respiratory parameters of the infants were recorded and arterial blood gas analysis was performed at 15 min after two lung ventilation (TLV) (T1), OLV30 min (T2), OLV60 min (T3), and 15 min after recovery of TLV (T4). Bronchoalveolar lavage fluid was collected before and after surgery to detect the expression level of advanced glycation end product receptor (RAGE). RESULTS: Sixty-three infants were finally included in this study. At T2 and T3, Cdyn, PaO2 and OI in group R were significantly higher (P < 0.05) and Ppeak, PaCO2 and PA-aO2 were significantly lower than those in group N (P < 0.05). There was no significant difference in HR or MAP between the two groups at T2 and T3 (P > 0.05). The level of RAGE significantly increased after the surgery in both groups (P < 0.05), and was significantly lower in R group than in N group (P < 0.05). CONCLUSIONS: In infants undergoing thoracoscopic surgery with OLV for pulmonary cystadenoma, appropriate IRV combined with PEEP does not affect hemodynamic stability and can increases pulmonary compliance, reduce the peak pressure, and improve oxygenation to provide pulmonary protection.

Folding Keratin Gene Clusters during Skin Regional Specification.

Regional specification is critical for skin development, regeneration, and evolution. The contribution of epigenetics in this process remains unknown. Here, using avian epidermis, we find two major strategies regulate ß-keratin gene clusters. (1) Over the body, macro-regional specificities (scales, feathers, claws, etc.) established by typical enhancers control five subclusters located within the epidermal differentiation complex on chromosome 25; (2) within a feather, micro-regional specificities are orchestrated by temporospatial chromatin looping of the feather ß-keratin gene cluster on chromosome 27. Analyses suggest a three-factor model for regional specification: competence factors (e.g., AP1) make chromatin accessible, regional specifiers (e.g., Zic1) target specific genome regions, and chromatin regulators (e.g., CTCF and SATBs) establish looping configurations. Gene perturbations disrupt morphogenesis and histo-differentiation. This chicken skin paradigm advances our understanding of how regulation of big gene clusters can set up a two-dimensional body surface map.

The prostate cancer risk variant rs55958994 regulates multiple gene expression through extreme long-range chromatin interaction to control tumor progression.

Genome-wide association studies identified single-nucleotide polymorphism (SNP) rs55958994 as a significant variant associated with increased susceptibility to prostate cancer. However, the mechanisms by which this SNP mediates increased risk to cancer are still unknown. In this study, we show that this variant is located in an enhancer active in prostate cancer cells. Deletion of this enhancer from prostate tumor cells resulted in decreased tumor initiation, tumor growth, and invasive migration, as well as a loss of stem-like cells. Using a combination of capture chromosome conformation capture (Capture-C) and RNA sequencing, we identified genes on the same and different chromosomes as targets regulated by the enhancer. Furthermore, we show that expression of individual candidate target genes in an enhancer-deleted cell line rescued different aspects of tumorigenesis. Our data suggest that the rs55958994-associated enhancer affects prostate cancer progression by influencing expression of multiple genes via long-range chromatin interactions.

4C-seq revealed long-range interactions of a functional enhancer at the 8q24 prostate cancer risk locus.

Genome-wide association studies (GWAS) have identified >100 independent susceptibility loci for prostate cancer, including the hot spot at 8q24. However, how genetic variants at this locus confer disease risk hasn't been fully characterized. Using circularized chromosome conformation capture (4C) coupled with next-generation sequencing and an enhancer at 8q24 as "bait", we identified genome-wide partners interacting with this enhancer in cell lines LNCaP and C4-2B. These 4C-identified regions are distributed in open nuclear compartments, featuring active histone marks (H3K4me1, H3K4me2 and H3K27Ac). Transcription factors NKX3-1, FOXA1 and AR (androgen receptor) tend to occupy these 4C regions. We identified genes located at the interacting regions, and found them linked to positive regulation of mesenchymal cell proliferation in LNCaP and C4-2B, and several pathways (TGF beta signaling pathway in LNCaP and p53 pathway in C4-2B). Common genes (e.g. MYC and POU5F1B) were identified in both prostate cancer cell lines. However, each cell line also had exclusive genes (e.g. ELAC2 and PTEN in LNCaP and BRCA2 and ZFHX3 in C4-2B). In addition, BCL-2 identified in C4-2B might contribute to the progression of androgen-refractory prostate cancer. Overall, our work reveals key genes and pathways involved in prostate cancer onset and progression.

[Effect of pediatric TCI system for propofol plus remifentanil in pediatric short-duration surgery with laryngeal mask airway anesthesia].

OBJECTIVE: To study the effect of a pediatric TCI patent system for propofol plus remifentanil in pediatric short-duration surgery with laryngeal mask airway (LMA) anesthesia. METHODS: A total of 120 pediatric patients underwent short-duration elective surgery, aged 3 - 9 years old, weighted 13 - 26 kg, ASAI grade, were randomly divided into 3 groups (n = 40 each). The propofol concentrations of effect compartment were set at 2 µg/ml in Group A, 3 µg/ml in Group B and 4 µg/ml in Group C. The remifentanil initial concentration of plasma compartment was 2 ng/ml and increased stepwise by 0.5 ng/ml until a successful insertion of LMA. The remifentanil concentration was recorded when LMA was successfully inserted and the cases were numerated at the each remifentanil concentration. Heart rate (HR), mean arterial pressure (MAP), BIS (bispectral index) values and postoperative adverse events were also recorded at the time points of pre-induction (T0), 2 min post-remifentanil TCI (T1), LMA insertion (T2), skin incision (T3), 5 min post-skin incision (T4), 10 min post-skin incision, (T5) and beginning surgery (T6). RESULTS: The satisfactory ratios of a successful insertion of LMA were highest in remifentanil 3.0 ng/ml (AR subgroup), 2.5 ng/ml (BR subgroup) and 2.0 ng/ml (CR subgroup) respectively. The laryngeal mask satisfactory ratio was high in BR subgroup (P < 0.05). There were significantly differences of T1-T5 values of HR, MAP and BIS in AR and CR subgroups (P < 0.05), but not in BR subgroup. The above-mentioned monitoring indices at T2 in AR subgroup and T3 in CR subgroup were significantly higher than those in BR subgroup. There were more adverse reactions in CR and AR subgroups versus BR subgroup (P < 0.05). CONCLUSION: The patented system for propofol 3 µg/ml effect compartment concentration plus remifentanil 2.5 ng/ml plasma concentration TCI displays stable hemodynamics, less stress, fewer complications and better clinical outcomes in pediatric short-duration surgery with LMA anesthesia.