MR Uniformity Ratio Estimates to Evaluate Ventricular Mechanical Dyssynchrony and Prognosis After ST-Segment Elevation Myocardial Infarction.

BACKGROUND: The impact of left ventricular mechanical dyssynchrony (LVMD) on the long-term prognosis of ST-segment elevation myocardial infarction (STEMI) is unclear. HYPOTHESIS: MR uniformity ratio estimates (URE) can detect LVMD and assess STEMI prognosis. STUDY TYPE: Retrospective analysis of a prospective multicenter registry (EARLY-MYO trial, NCT03768453). POPULATION: Overall, 450 patients (50 females) with first-time STEMI were analyzed, as well as 40 participants without cardiovascular disease as controls. FIELD STRENGTH/SEQUENCE: 3.0-T, balanced steady-state free precession cine and late gadolinium enhancement imaging. ASSESSMENT: MRI data were acquired within 1 week of symptom onset. Major adverse cardiovascular events (MACEs), including cardiovascular death, nonfatal re-infarction, hospitalization for heart failure, and stroke, were the primary clinical outcomes. LVMD was represented by circumferential URE (CURE) and radial URE (RURE) calculated using strain measurements. The patients were grouped according to clinical outcomes or URE values. Patients' clinical characteristics and MR indicators were compared. STATISTICAL TESTS: The Student's t-test, Mann-Whitney U test, chi-square test, Fisher's exact test, receiver operating characteristic curve analysis with area under the curve, Kaplan-Meier analysis, Cox regression, logistic regression, intraclass correlation coefficient, c-index, and integrated discrimination improvement were used. P < 0.05 was considered statistically significant. RESULTS: CURE and RURE were significantly lower in patients with STEMI than in controls. The median follow-up was 60.5 months. Patients with both lower CURE and RURE values experienced a significantly higher incidence of MACEs by 3.525-fold. Both CURE and RURE were independent risk factors for MACEs. The addition of UREs improved diagnostic efficacy and risk stratification based on infarct size and left ventricular ejection fraction (LVEF). The indicators associated with LVMD included male sex, serum biomarkers (peak creatine phosphokinase and cardiac troponin I), infarct size, and LVEF. DATA CONCLUSION: CURE and RURE may be useful to evaluate long-term prognosis after STEMI. EVIDENCE LEVEL: 4 TECHNICAL EFFICACY: Stage 2.

Peak early diastolic strain rate improves prediction of adverse cardiovascular outcomes in patients with ST-elevation myocardial infarction.

BACKGROUND: The prognostic role of diastolic dysfunction measured by the circumferential peak early diastolic strain rate (PEDSR) on ST-elevation myocardial infarction (STEMI) is not completely established. OBJECTIVES: We aimed to investigate the prognostic value of diastolic function by measuring PEDSR within 1 week after STEMI. METHODS: The cardiac magnetic resonance (CMR) pictures of 420 subjects from a clinical registry study (NCT03768453) were analyzed and the composite major adverse cardiac events (MACEs) were followed up. RESULTS: The PEDSR of patients was significantly lower compared with that of control subjects (P < 0.001). Within the median follow-up period of 52 months, PEDSR of patients who experienced MACEs deceased more significantly than that of patients without MACEs (P < 0.001). After adjusting with clinical or CMR indexes, per 0.1/s reduction of PEDSR increased the risks of MACEs to 1.402 or 1.376 fold and the risk of left ventricular (LV) remodeling to 1.503 or 1.369 fold. When PEDSR divided by best cutoff point, significantly higher risk of MACEs (P < 0.001) and more remarkable LV remodeling (P < 0.001) occurred in patients with PEDSR ≤ 0.485/s. Moreover, when adding the PEDSR to the conventional prognostic factors such as LV ejection fraction and infarction size, better prognostic risk classification models were created. Finally, aging, tobacco use, remarkable LV remodeling, and a low LV ejection fraction were factors related with the reduction of PEDSR. CONCLUSIONS: Diastolic dysfunction has an important prognostic effect on patients with STEMI. Measurement of the PEDSR in the acute phase could serve as an effective index to predict the long-term risk of MACEs and cardiac remodeling.

DCAF13 promotes breast cancer cell proliferation by ubiquitin inhibiting PERP expression.

Evolutionarily conserved DDB1-and CUL4-associated factor 13 (DCAF13) is a recently discovered substrate receptor for the cullin RING-finger ubiquitin ligase 4 (CRL4) E3 ubiquitin ligase that regulates cell cycle progression. DCAF13 is overexpressed in many cancers, although its role in breast cancer is currently elusive. In this study we demonstrate that DCAF13 is overexpressed in human breast cancer and that its overexpression closely correlates with poor prognosis, suggesting that DCAF13 may serve as a diagnostic marker and therapeutic target. We knocked down DCAF13 in breast cancer cell lines using CRISPR/Cas9 and found that DCAF13 deletion markedly reduced breast cancer cell proliferation, clone formation, and migration both in vitro and in vivo. In addition, DCAF13 deletion promoted breast cancer cell apoptosis and senescence, and induced cell cycle arrest in the G1/S phase. Genome-wide RNAseq analysis and western blotting revealed that loss of DCAF13 resulted in both mRNA and protein accumulation of p53 apoptosis effector related to PMP22 (PERP). Knockdown of PERP partially reversed the hampered cell proliferation induced by DCAF13 knockdown. Co-immunoprecipitation assays revealed that DCAF13 and DNA damage-binding protein 1 (DDB1) directly interact with PERP. Overexpression of DDB1 significantly increased PERP polyubiquitination, suggesting that CRL4DCAF13 E3 ligase targets PERP for ubiquitination and proteasomal degradation. In conclusion, DCAF13 and the downstream effector PERP occupy key roles in breast cancer proliferation and potentially serve as prognostics and therapeutic targets.

Phosphorescent Host-Guest Complexes on the Basis of Polyhedral Oligomeric Silsesquioxane-Functionalized Metallotweezers.

Phosphorescent host-guest systems have attracted considerable attention because of their intriguing properties and diverse applications. In this study, a polyhedral oligomeric silsesquioxane-functionalized gold(III) tweezer receptor has been designed and synthesized. It is capable of sandwiching platinum(II) terpyridine compounds into its cavity with a high noncovalent binding affinity (association constants: ∼105 M-1 in chloroform). The resulting heterometallic host-guest complexes exhibit enhanced phosphorescent emission compared with those of the individual species in chloroform, thanks to the prevention of vibration and rotation upon noncovalent complexation. They can further assemble into nanospheres in chloroform/diethyl ether (1:9, v/v) owing to phase segregation between the metallotweezer/guest motif and the peripheral polyhedral oligomeric silsesquioxane unit. When terpyridine platinum(II) chloride serves as the complementary guest, the resulting noncovalent system displays an intraligand emission at the individual host-guest complexed state yet excimeric emission at the supramolecular assembled state, yielding the phosphorescent solvatochromic behaviors. Overall, the polyhedral oligomeric silsesquioxane-functionalized metallotweezer combines guest encapsulation and supramolecular assembly capabilities, which provides new avenues for color-tunable phosphorescent materials.

Taxonomic description of Pseudomonas rhizovicinus sp. nov., isolated from the rhizosphere of a desert shrub Haloxylon ammodendron.

A Gram-negative aerobic bacterium, strain M30-35 T, was isolated from the rhizosphere of Haloxylon ammodendron in Tengger desert, Gansu province, northwest China. Our previous research indicated that strain M30-35 T can promote the growth of ryegrass (Lolium perenne L.). In this study, strain M30-35 T was subjected to a polyphasic taxonomic study. Phylogenetic analysis of the 16S rRNA gene and two other housekeeping genes (gyrB, rpoD) showed that strain M30-35 T is a member of Pseudomonas anguilliseptica group. The average nucleotide identity (ANI) scores for strains KMM 3042 T and FR1439T were 76.5% and 83.7%, respectively, and DNA-DNA hybridization (DDH) were 21.6% and 26.6%, respectively, and the rates were less than the threshold range for species determination. The dominant cellular fatty acids of strain M30-35 T were C16:0 (22.7%), summed feature 3 (C16:1ω7c and/or C16:1ω6c; 18.5%), summed feature 8 (C18:1ω7c and/or C18:1ω6c; 23.1%). The major polar lipids were diphosphatidylglycerol, phosphatidylethanolamine, phosphatidylglycerol, phospholipid and aminophospholipid and the predominant respiratory quinone was ubiquinone (Q9). On the basis of above data, it can be concluded that strain M30-35 T represents a novel species in the genus Pseudomonas, for which the name Pseudomonas rhizovicinus sp. nov. is proposed. The type strain is M30-35 T (= MCCC 1K03247T = KCTC 52664 T).

32A9, a novel human antibody for designing an immunotoxin and CAR-T cells against glypican-3 in hepatocellular carcinoma.

BACKGROUND: Treatment of hepatocellular carcinoma (HCC) using antibody-based targeted therapies, such as antibody conjugates and chimeric antigen receptor T (CAR-T) cell therapy, shows potent antitumor efficacy. Glypican-3 (GPC3) is an emerging HCC therapeutic target; therefore, antibodies against GPC3 would be useful tools for developing immunotherapies for HCC. METHODS: We isolated a novel human monoclonal antibody, 32A9, by phage display technology. We determined specificity, affinity, epitope and anti-tumor activity of 32A9, and developed 32A9-based immunotherapy technologies for evaluating the potency of HCC treatment in vitro or in vivo. RESULTS: 32A9 recognized human GPC3 with potent affinity and specificity. The epitope of 32A9 was located in the region of the GPC3 protein core close to the modification sites of the HS chain and outside of the Wnt-binding site of GPC3. The 32A9 antibody significantly inhibited HCC xenograft tumor growth in vivo. We then pursued two 32A9-based immunotherapeutic strategies by constructing an immunotoxin and CAR-T cells. The 32A9 immunotoxin exhibited specific cytotoxicity to GPC3-positive cancer cells, while 32A9 CAR-T cells efficiently eliminated GPC3-positive HCC cells in vitro and caused HCC xenograft tumor regressions in vivo. CONCLUSIONS: Our study provides a rationale for 32A9 as a promising GPC3-specific antibody candidate for HCC immunotherapy.

Differential motility parameters and identification of proteomic profiles of human sperm cryopreserved with cryostraw and cryovial.

BACKGROUND: Although sperm cryopreservation has been widely used in human reproductive medicine as an integral infertility management in infertility clinics and for banking sperm in sperm banks, the freezing/thawing protocols are not optimal. The freezing and thawing processes result in changes at both structural and molecular levels, some even detrimental, in human sperm when compared with fresh sperm. The change of sperm proteins after cryopreservation may play negative roles for fertilization and early embryo development. Conventionally, cryostraws (CS) and cryovials (CV) are the most widely used cryopreservation carriers (CPCs) for human sperm cryopreservation accompanied with the use of egg yolk free commercial media. However, the influence of cryopreservation on the proteomic profile of human sperm preserved with the two CPCs is unknown. Therefore the purpose of the present study was to compare the frozen-thawed motility, investigate the proteomic profile of human sperm cryopreserved with the two types of CPCs, and identify the susceptible proteins that play key roles for sperm function and fertility. METHODS: The present study compared the cryosurvival of human sperm frozen with the two different CPCs and identified the sperm proteomic changes by using the isobaric tags for relative and absolute quantification labeling technique coupled with 2D LC-MS/MS analysis after freezing and thawing. RESULTS: Our results indicated that sperm cryopreserved with CV showed higher values for percentage of motile sperm and forward activity rate than those with CS. Compared to fresh sperm, 434 and 432 proteins were differentially identified in human sperm cryopreserved with CS and CV, respectively. CONCLUSION: The proteomic profiles of human sperm are greatly affected by cryopreservation with either type of CPC. GO analysis revealed that most of the differentially identified sperm proteins enriched in the extracellular membrane-bounded organelles, cytoplasm and cytosol. In addition, 106 susceptible proteins having known identities related to sperm functions were identified. In general, cryovial seems to be the preferred CPC for human sperm cryopreservation based on the post-thaw motility parameters and the effect on sperm proteomic profiles. These results are beneficial for the insight into the understanding of the cryoinjury mechanism of sperm and the development of human sperm cryopreservation strategies.

Induced Salt Tolerance of Perennial Ryegrass by a Novel Bacterium Strain from the Rhizosphere of a Desert Shrub Haloxylon ammodendron.

Drought and soil salinity reduce agricultural output worldwide. Plant-growth-promoting rhizobacteria (PGPR) can enhance plant growth and augment plant tolerance to biotic and abiotic stresses. Haloxylon ammodendron, a C4 perennial succulent xerohalophyte shrub with excellent drought and salt tolerance, is naturally distributed in the desert area of northwest China. In our previous work, a bacterium strain numbered as M30-35 was isolated from the rhizosphere of H. ammodendron in Tengger desert, Gansu province, northwest China. In current work, the effects of M30-35 inoculation on salt tolerance of perennial ryegrass were evaluated and its genome was sequenced to identify genes associated with plant growth promotion. Results showed that M30-35 significantly enhanced growth and salt tolerance of perennial ryegrass by increasing shoot fresh and dry weights, chlorophyll content, root volume, root activity, leaf catalase activity, soluble sugar and proline contents that contributed to reduced osmotic potential, tissue K⁺ content and K⁺/Na⁺ ratio, while decreasing malondialdehyde (MDA) content and relative electric conductivity (REC), especially under higher salinity. The genome of M30-35 contains 4421 protein encoding genes, 12 rRNA, 63 tRNA-encoding genes and four rRNA operons. M30-35 was initially classified as a new species in Pseudomonas and named as Pseudomonas sp. M30-35. Thirty-four genes showing homology to genes associated with PGPR traits and abiotic stress tolerance were identified in Pseudomonas sp. M30-35 genome, including 12 related to insoluble phosphorus solubilization, four to auxin biosynthesis, four to other process of growth promotion, seven to oxidative stress alleviation, four to salt and drought tolerance and three to cold and heat tolerance. Further study is needed to clarify the correlation between these genes from M30-35 and the salt stress alleviation of inoculated plants under salt stress. Overall, our research indicated that desert shrubs appear rich in PGPRs that can help important crops tolerate abiotic stress.

Altererythrobacter soli sp. nov., isolated from desert sand.

An alkaliphilic strain designed MN-1T was isolated from a desert sand sample collected from Tengger desert, north-western China. To delineate its taxonomic position, this Gram-stain-negative, rod-shaped, strictly aerobic bacterium was subjected to a polyphasic taxonomic study. Growth was observed at temperatures from 4 to 37 °C (optimum 30-32 °C), at salinities from 0 to 2 % (optimum 1 %) and at pH from 6.5 to 12.0 (optimum 7.0-9.0). Phylogenetic analysis based on 16S rRNA gene sequencing showed that strain MN-1T was a member of the genus Altererythrobacterbut could be distinguished from recognized species of this genus. Compared to the reference strains, the novel strain was flagellated and motile by means of polar flagella. The predominant respiratory quinone was ubiquinone-10 and the major polar lipids were diphosphatidylglycerol, phosphatidylethanolamine, sphingoglycolipid, phosphatidylglycerol, phosphatidylcholine, one unidentified glycolipid, one unidentified phospholipid and four unidentified lipids. The predominant fatty acids were C18 : 1ω7c, summed feature 3 (C16 : 1ω7c and/or C16 : 1ω6c) and C16 : 0. These chemotaxonomic traits were in agreement with the characteristics of the genus Altererythrobacter. Strain MN-1T was most closely related to Altererythrobacter xinjiangensis S3-63T (96.9 % 16S rRNA gene sequence similarity), followed by Altererythrobacter dongtanensis JM27T (96.4 %) and Altererythrobacter marinus H32T (96.1 %). The G+C content of the genomic DNA of strain MN-1T was 67.0 mol%. On the basis of data from this polyphasic taxonomic study, strain MN-1T is proposed as the type strain of a novel species of the genus Altererythrobacter, named as Altererythrobacter soli sp. nov. (=KCTC 52135T=MCCC 1K02066T).

Synergistic Effects of Bacillus amyloliquefaciens (GB03) and Water Retaining Agent on Drought Tolerance of Perennial Ryegrass.

Water retaining agent (WRA) is widely used for soil erosion control and agricultural water saving. Here, we evaluated the effects of the combination of beneficial soil bacterium Bacillus amyloliquefaciens strain GB03 and WRA (the compound is super absorbent hydrogels) on drought tolerance of perennial ryegrass (Lolium perenne L.). Seedlings were subjected to natural drought for maximum 20 days by stopping watering and then rewatered for seven days. Plant survival rate, biomass, photosynthesis, water status and leaf cell membrane integrity were measured. The results showed that under severe drought stress (20-day natural drought), compared to control, GB03, WRA and GB03+WRA all significantly improved shoot fresh weight, dry weight, relative water content (RWC) and chlorophyll content and decreased leaf relative electric conductivity (REC) and leaf malondialdehyde (MDA) content; GB03+WRA significantly enhanced chlorophyll content compared to control and other two treatments. Seven days after rewatering, GB03, WRA and GB03+WRA all significantly enhanced plant survival rate, biomass, RWC and maintained chlorophyll content compared to control; GB03+WRA significantly enhanced plant survival rate, biomass and chlorophyll content compared to control and other two treatments. The results established that GB03 together with water retaining agent promotes ryegrass growth under drought conditions by improving survival rate and maintaining chlorophyll content.

[Impacts of different procedures of testicular sperm retrieval on testicular function and antisperm antibodies in azoospermia patients].

OBJECTIVE: To investigate the influence of different procedures of testicular sperm retrieval on the levels of serum inhibin B (INHB), antisperm antibodies (AsAb), follicle-stimulating hormone (FSH), and testosterone (T) in patients with azoospermia. METHODS: We randomly assigned 210 azoospermia patients to receive testicular sperm extraction (TESE, n = 50), testicular sperm aspiration (TESA, n = 56), testicular fine needle aspiration (TEFNA, n = 64), or microscopic TESE (micro-TESE, n = 40). We measured the levels of serum INHB, FSH, and T and the positive rate of AsAb before and at 1 and 3 months after surgery. RESULTS: Compared with the baseline, the levels of serum FSH at 1 and 3 months after surgery showed no statistically significant differences in the TESE (ï¼»8.51 ± 4.34ï¼½ vs ï¼»8.76 ± 3.07ï¼½ and ï¼»7.24 ± 3.32ï¼½ IU/L, P >0.05), TESA (ï¼»7.70 ± 2.72ï¼½ vs ï¼»7.90 ± 4.57ï¼½ and ï¼»8.04 ± 3.65ï¼½ IU/L, P >0.05), TEFNA (ï¼»6.04 ± 3.17ï¼½ vs ï¼»6.08 ± 2.70ï¼½ and ï¼»6.10 ± 3.32ï¼½ IU/L, P >0.05), or micro-TESE group (ï¼»6.59 ± 2.74ï¼½ vs ï¼»6.89 ± 1.78ï¼½ and ï¼»6.75 ± 2.57ï¼½ IU/L, P >0.05); the positive rate of AsAb (IgM) was significantly increased at 1 month in the TESE (0.00 vs 14.00%, P <0.05) and micro-TESE groups (2.50% vs 15.00%, P <0.05), while the serum T level markedly decreased in the two groups (ï¼»16.52 ± 6.25ï¼½ vs ï¼»9.25 ± 5.76ï¼½ nmol/L and ï¼»14.16 ± 5.45ï¼½ vs ï¼»8.23 ± 4.12ï¼½ nmol/L, P <0.05); the levels of serum INHB were remarkably reduced at 1 and 3 months in the TESE (ï¼»70.56 ± 23.17ï¼½ vs ï¼»42.63 ± 15.34ï¼½ and ï¼»44.05 ± 18.47ï¼½ pg/ml, P <0.05), TESA (ï¼»68.71 ± 14.74ï¼½ vs ï¼»40.55 ± 20.51ï¼½ and ï¼»42.11 ± 19.34ï¼½ pg/ml, P <0.05), TEFNA (ï¼»76.81 ± 27.04ï¼½ vs ï¼»46.31 ± 19.28ï¼½ and ï¼»48.32 ± 20.54ï¼½ pg/ml, P <0.05), and micro-TESE groups (ï¼»74.74 ± 28.35ï¼½ vs ï¼»45.27 ± 18.83ï¼½ and ï¼»47.64 ± 28.34ï¼½ pg/ml, P <0.05), but with no statistically significant differences among the four groups (P >0.05). CONCLUSIONS: Different procedures of testicular sperm retrieval have different impacts on the testicular function and AsAb in patients with azoospermia.

BOTDA sensors enhanced using high-efficiency second-order distributed Brillouin amplification.

A novel approach for long-distance sensing through Brillouin optical time-domain analysis (BOTDA) assisted by second-order distributed Brillouin amplification (DBA) was proposed and experimentally demonstrated. To the best of our knowledge, this is the first BOTDA study that used second-order DBA. Compared with BOTDA assisted by first-order DBA, the proposed approach enhanced the signal-to-noise ratio of the Brillouin trace by ~3 dB for a range featuring minimum sensing intensity. Long-distance sensing with ~5 m spatial resolution and ± 1.6°C measurement uncertainty over ~99 km fiber was successfully realized by employing high-efficiency pumping using ~6 dBm second-order and ~1.5 dBm first-order pumps.

[Roles of PIK3R1 gene in development of hepatocellular carcinoma].

OBJECTIVE: To investigate the roles of phosphatidylinositol 3 kinase regulatory subunit alpha (PIK3R1）gene in the development of hepatocellular carcinoma （HCC）. METHODS: Surgical specimens of liver cancer and corresponding pericancerous liver tissue were collected from 20 patients with hepatocellular carcinoma. Expression of p85α, encoded by PIK3R1, in HCC tissue specimens was detected by Western blotting and immunohistochemistry. HCC HepG2 cells were transfected with PIK3R1 siRNA or PIK3R1-cDNA. The expression of PIK3R1 in transfected HepG2 cells or control cells were detected by real-time PCR. Cell proliferation was evaluated by MTT, colony formation assays and flow cytometry respectively. The expression of PI3K/AKT pathway-related proteins were detected by Western blotting. RESULTS: The expression of p85α in liver tissue was higher than that in pericancerous tissues (1.27±0.58 vs 0.99±0.47，t=-3.25，P<0.05）. The expression of PIK3R1 was decreased by 0.19±0.03 fold in PIK3R1siRNA-transfected HepG2 cells(t=46.77，P<0.05)，and increased by 32.36±3.33 fold in PIK3R1 cDNA -transfected cells（t=-16.31， P<0.05）. MTT result showed that PIK3R1 siRNA inhibited growth of HepG2 cells （0.611±0.072 vs 0.807±0.059，t=3.65，P<0.05），while PIK3R1 cDNA increased the cell growth（0.937±0.060 vs 0.693±0.065，t=-4.78，P<0.05）. PIK3R1 siRNA transfected cells presented lower colony-forming efficiency than control group（3.8%±0.84% vs 15.0%±2.3%，t=7.92，P<0.05），while PIK3R1 cDNA transfected cells had higher colony-forming efficiency than control group (23.6%±3.4% vs 12.0%±1.5%，t=-5.40，P<0.05）. PIK3R1 siRNA reduced the ratio of S phase cells（13.9%±0.015% vs 32.9%±0.07%，t=45.97，P<0.01, while PIK3R1 cDNA increased S phase cells（56.33%±0.024% vs 31.94%±0.042%，t=-8.73，P<0.01）. PIK3R1 increased the level of p-AKT and decreased p53 level. CONCLUSION：p85α is highly expressed in HCC，and PIK3R1 gene may promote proliferation of HepG2 cells by activating PI3K/AKT pathway.

Anteromedial Cortical Support in Reduction of Trochanteric Hip Fractures: From Definition to Application.

➤ The concept of anteromedial cortical support (AMCS) serves as valuable guidance for the intraoperative reduction of trochanteric hip fractures.➤ Positive medial cortical support (MCS) and positive or neutral anterior cortical support (ACS) are desirable. Some evidence has suggested that positive MCS is potentially superior to neutral MCS.➤ Experimental studies underscore the vital importance of the anteromedial wall and reveal why positive MCS potentially outperforms neutral MCS.➤ Incorporating the AMCS concept, the Chang reduction quality criteria (CRQC) are a reliable alternative approach to evaluate the reduction quality of trochanteric hip fractures.

A survival nomogram model constructed with common clinical characteristics to assist clinical decisions for diffuse low-grade gliomas: A population analysis based on SEER database.

Background: The prognosis of diffuse low-grade gliomas (DLGGs, WHO grade 2) is highly variable, making it difficult to evaluate individual patient outcomes. In this study, we used common clinical characteristics to construct a predictive model with multiple indicators. Methods: We identified 2459 patients diagnosed with astrocytoma and oligodendroglioma from 2000 to 2018 in the SEER database. After removing invalid information, we randomly divided the cleaned patient data into training and validation groups. We performed univariate and multivariate Cox regression analyses and constructed a nomogram. Receiver operating characteristic (ROC) curve, c-index, calibration curve, and subgroup analyses were used to assess the accuracy of the nomogram by internal and external validation. Results: After univariate and multivariate Cox regression analyses, we identified seven independent prognostic factors, namely, age (P<0.001), sex (P<0.05), histological type (P<0.001), surgery (P<0.01), radiotherapy (P<0.001), chemotherapy (P<0.05) and tumor size (P<0.001). The ROC curve, c-index, calibration curve, and subgroup analyses of the training group and the validation group showed that the model had good predictive value. The nomogram for DLGGs predicted patients' 3-, 5- and 10-year survival rates based on these seven variables. Conclusions: The nomogram constructed with common clinical characteristics has good prognostic value for patients with DLGGs and can help physicians make clinical decisions.

Relative instability ratios of bone wall defects in trochanteric hip fractures: A finite element analysis.

Background: For decades, medial and lateral wall fragments of trochanteric hip fractures were considered two pivotal factors that could influence the stability of postoperative femur-implant complex. However, most studies seemed to misunderstand the concept of the posteromedial fragment and equated it with the medial wall, which overlooked vital roles of the anteromedial wall. Roles of the posterior coronal bone fragment were also highlighted in some research. However, influences of the bone walls above the trochanteric fracture instability are yet to be investigated and quantified by means of finite element analysis. Methods: Eight trochanteric fracture fixation models with different wall defects were constructed. Outcome indicators were the von Mises stress of the implant models, the maximum/minimum principal strain, the risky tensile/compressive volume and the volume ratios of the bone models, the femoral head vertex displacement, and the fracture surface gap. Based on these indicator values, the relative instability ratios were computed. Results: Outcome indicators, absolute values, and nephograms of all models showed the same upward and concentrating trends with exerted hip contact loads shifting from static walking to dynamic climbing. Similarly, these indicators also exhibited the same trends when the eight models were solved in sequence. Moreover, the relative instability ratio of the medial wall (100%), particularly the anteromedial part (78.7%), was higher than the figure for the lateral wall (36.6%). Conclusion: The anteromedial wall played relatively pivotal stabilizing roles in trochanteric hip fractures compared with the posteromedial wall and the lateral wall, which indicated that orthopedic surgeons should attach more importance to the anteromedial cortex support in an operating theatre.

The Impact of Banana-Shaped Fragments on Trochanteric Hip Fractures Treated by PFNA.

Background: Regarding trochanteric hip fractures, one type of posterior coronal fragments was described as the "banana-shaped fragment", while the impact of the banana-shaped fragment on mechanical stability has not been further studied. The current study investigated the association between the banana-shaped fragment and mechanical complications after surgery. Methods: This retrospective cohort study included 273 patients treated by proximal femoral nail antirotation (PFNA) in the full analysis. The age, the sex, the fracture side, the follow-up time, the American Society of Anesthesiologists classification, the operators, the fracture classification, the tip-apex distance, the blade positions, the reduction quality and the bone mineral density were analyzed in relation to mechanical complications, through univariate and multivariate approaches. Results: Mechanical complications happened in 33 patients. The banana-shaped fragment (adjusted odds ratio 5.240, 95% CI 2.172 to 12.641; p < 0.001), the tip-apex distance and the reduction quality showed significant association with mechanical complications in both univariate and multivariate analysis. Moreover, for 118 patients with the banana-shaped fragment, we found that the use of wire cerclage couldn't significantly lower the rates of mechanical complications (p = 0.648). Conclusions: The banana-shaped fragment had a negative impact on mechanical stability of trochanteric hip fractures treated by PFNA. In the perioperative period, the BSF should be carefully evaluated, and its specific handling deserves further study.

Computational evaluation of the axis-blade angle for measurements of implant positions in trochanteric hip fractures: A finite element analysis.

BACKGROUND: Recently, a novel approach axis-blade angle (ABA) was developed to measure implant positions during trochanteric hip fracture surgery. It was defined as the sum of two angles α and ß measured between the femoral neck axis and helical blade axis in anteroposterior and lateral X-ray films, respectively. Although its clinical practicability has been confirmed, the mechanism is yet to be investigated by means of finite element (FE) analysis. METHODS: Computed tomography images of four femurs and dimensions of one implant at three angles were obtained to construct FE models. For each femur, 15 FE models in an arrangement (intramedullary nails at three angles multiplying five blade positions) were established. Under the simulation of normal walking loads, the ABA, von Mises stress (VMS), maximum/minimum principal strain and displacement were analyzed. RESULTS: When the ABA increased, all outcome indicators initially decreased till reaching inferior-middle site and then increased while the blade positions within the femoral head shifted from the superior-anterior quadrant toward the inferior-posterior quadrant, where the ABA were higher. Only the peak VMS of implant models in the inferior-posterior quadrant (particularly the inferior-middle site within) with blades in did not reach the yielding (risky) cut-off. CONCLUSIONS: From the perspective of angles, ABA, this study demonstrated the inferior-posterior quadrant as the relatively stable and safe regions, especially the inferior-middle site within. This was similar but more elaborate compared with previous studies and clinical practice. Therefore, ABA could be employed as a promising approach to anchor the implants into the optimal region.

Prognostic implications of left ventricular torsion measured by feature-tracking cardiac magnetic resonance in patients with ST-elevation myocardial infarction.

AIMS: The prognostic implication of left ventricular (LV) torsion on ST-elevation myocardial infarction (STEMI) is unclear. METHODS AND RESULTS: We analysed cardiovascular magnetic resonance (CMR) findings of 420 patients from a registry study (NCT03768453). These patients received CMR examination within 1 week after timely primary percutaneous coronary intervention. LV torsion and other CMR indexes were measured. Compared with healthy control subjects, STEMI significantly decreased patients' LV torsion (1.04 vs. 1.63°/cm, P < 0.001). During follow-up (median, 52 months), the reduction of LV torsion was greater in patients with than without composite major adverse cardiac and cerebrovascular events (MACCEs, 0.79 vs. 1.08°/cm, P < 0.001). The risk of MACCEs would increase to 1.125- or 1.092-fold, and the risk of 1-year LV remodelling would increase to 1.110- or 1.082-fold for every 0.1°/cm reduction in LV torsion after adjustment for clinical or CMR parameters respectively. When divided dichotomously, patients with LV torsion≤ 0.802°/cm had significantly higher risk of MACCEs (40.2 vs. 12.3%, P < 0.001) and more remarkable LV remodelling (46.1 vs. 11.9%, P < 0.001) than patients with better LV torsion. The addition of LV torsion to conventional prognostic factors such as the LV ejection fraction and infarction size led to a better risk classification model of patients for both MACCEs and LV remodelling. Finally, tobacco use, worse post-PCI flow, and greater microvascular obstruction size were presumptive risk factors for reduced LV torsion. CONCLUSION: LV torsion measured by CMR is closely associated with the prognosis of STEMI and would be a promising indicator to improve patients' risk stratification. CLINICAL TRIAL REGISTRATION: Clinicaltrials.gov, NCT03768453.

S1PR1 regulates ovarian cancer cell senescence through the PDK1-LATS1/2-YAP pathway.

Cell senescence deters the activation of various oncogenes. Induction of senescence is, therefore, a potentially effective strategy to interfere with vital processes in tumor cells. Sphingosine-1-phosphate receptor 1 (S1PR1) has been implicated in various cancer types, including ovarian cancer. The mechanism by which S1PR1 regulates ovarian cancer cell senescence is currently elusive. In this study, we demonstrate that S1PR1 was highly expressed in human ovarian cancer tissues and cell lines. S1PR1 deletion inhibited the proliferation and migration of ovarian cancer cells. S1PR1 deletion promoted ovarian cancer cell senescence and sensitized ovarian cancer cells to cisplatin chemotherapy. Exposure of ovarian cancer cells to sphingosine-1-phosphate (S1P) increased the expression of 3-phosphatidylinositol-dependent protein kinase 1 (PDK1), decreased the expression of large tumor suppressor 1/2 (LATS1/2), and induced phosphorylation of Yes-associated protein (p-YAP). Opposite results were obtained in S1PR1 knockout cells following pharmacological inhibition. After silencing LATS1/2 in S1PR1-deficient ovarian cancer cells, senescence was suppressed and S1PR1 expression was increased concomitantly with YAP expression. Transcriptional regulation of S1PR1 by YAP was confirmed by chromatin immunoprecipitation. Accordingly, the S1PR1-PDK1-LATS1/2-YAP pathway regulates ovarian cancer cell senescence and does so through a YAP-mediated feedback loop. S1PR1 constitutes a druggable target for the induction of senescence in ovarian cancer cells. Pharmacological intervention in the S1PR1-PDK1-LATS1/2-YAP signaling axis may augment the efficacy of standard chemotherapy.