Paxillin phase separation promotes focal adhesion assembly and integrin signaling.

Focal adhesions (FAs) are transmembrane protein assemblies mediating cell-matrix connection. Although protein liquid-liquid phase separation (LLPS) has been tied to the organization and dynamics of FAs, the underlying mechanisms remain unclear. Here, we experimentally tune the LLPS of PXN/Paxillin, an essential scaffold protein of FAs, by utilizing a light-inducible Cry2 system in different cell types. In addition to nucleating FA components, light-triggered PXN LLPS potently activates integrin signaling and subsequently accelerates cell spreading. In contrast to the homotypic interaction-driven LLPS of PXN in vitro, PXN condensates in cells are associated with the plasma membrane and modulated by actomyosin contraction and client proteins of FAs. Interestingly, non-specific weak intermolecular interactions synergize with specific molecular interactions to mediate the multicomponent condensation of PXN and are efficient in promoting FA assembly and integrin signaling. Thus, our data establish an active role of the PXN phase transition into a condensed membrane-associated compartment in promoting the assembly/maturation of FAs.

Detection and analysis of potential landslides based on SBAS-InSAR technology in alpine canyon region.

The Lancang River flows through the alpine canyon region of southwest China, an area that has experienced frequent geological disasters over the years. Early monitoring of geological hazards is essential for disaster prevention and mitigation. However, traditional ground monitoring techniques are limited by the complex terrain conditions in high-altitude valley regions. In contrast, interferometric synthetic aperture radar (InSAR) technology can provide a high-precision, wide-range monitoring of slow rock-slope deformation, making it an effective tool for studying geological hazards. Within the study area, multiple synthetic aperture radar (SAR) images from the Sentinel-1A satellite were collected, and surface deformation was obtained using the small baseline subset InSAR (SBAS-InSAR). The results demonstrate that combining ascending and descending orbit images can be successfully applied to landslide monitoring in complex mountainous areas. Over 30 potential landslides were identified by combining InSAR results with optical images. The Line-Of-Sight (LOS) direction deformation features and their relationship with precipitation were analyzed based on two typical landslides, and two-dimensional/three-dimensional (2D/3D) deformation decomposition was carried out to reveal its motion characteristics. It was found that the cumulative deformation fluctuation amplitude was higher during the rainy season, and the main movement direction of the landslide was east-west. In addition, based on the spatial distribution and statistical analysis of deformation points along with meteorological data, geological elements, human activities, and topographic conditions, it is inferred that factors such as low vegetation coverage, tectonic movements, human activities, and high-altitude glacier thawing may contribute to the occurrence of disasters. And it was found that areas with high vegetation cover, high rainfall, and snow cover exhibit lower coherence coefficients. This study offers valuable insights for investigating large-scale geological in alpine canyon regions.

An ULK1/2-PXN mechanotransduction pathway suppresses breast cancer cell migration.

The remodeling and stiffening of the extracellular matrix (ECM) is a well-recognized modulator of breast cancer progression. How changes in the mechanical properties of the ECM are converted into biochemical signals that direct tumor cell migration and metastasis remain poorly characterized. Here, we describe a new role for the autophagy-inducing serine/threonine kinases ULK1 and ULK2 in mechanotransduction. We show that ULK1/2 activity inhibits the assembly of actin stress fibers and focal adhesions (FAs) and as a consequence impedes cell contraction and migration, independent of its role in autophagy. Mechanistically, we identify PXN/paxillin, a key component of the mechanotransducing machinery, as a direct binding partner and substrate of ULK1/2. ULK-mediated phosphorylation of PXN at S32 and S119 weakens homotypic interactions and liquid-liquid phase separation of PXN, impairing FA assembly, which in turn alters the mechanical properties of breast cancer cells and their response to mechanical stimuli. ULK1/2 and the well-characterized PXN regulator, FAK/Src, have opposing functions on mechanotransduction and compete for phosphorylation of adjacent serine and tyrosine residues. Taken together, our study reveals ULK1/2 as important regulator of PXN-dependent mechanotransduction.

Spatio-temporal evolution and prediction of carbon storage in Kunming based on PLUS and InVEST models.

Carbon storage is a critical ecosystem service provided by terrestrial environmental systems that can effectively reduce regional carbon emissions and is critical for achieving carbon neutrality and carbon peak. We conducted a study in Kunming and analyzed the land utilization data for 2000, 2010, and 2020. We assessed the features of land utilization conversion and forecasted land utilization under three development patterns in 2030 on the basis of the Patch-generating Land Use Simulation (PLUS) model. We used the Integrated Valuation of Ecosystem Services and Trade-offs (InVEST) model to estimate changes in carbon storage trends under three development scenarios in 2000, 2010, 2020, and 2030 and the impact of socioeconomic and natural factors on carbon storage. The results of the study indicated that (1) carbon storage is intimately associated with land utilization practices. Carbon storage in Kunming in 2000, 2010, and 2020 was 1.146 × 108 t, 1.139 × 108 t, and 1.120 × 108 t, respectively. During the 20 years, forest land decreased by 142.28 km2, and the decrease in forest land area caused a loss of carbon storage. (2) Carbon storage in 2030 was predicted to be 1.102 × 108 t, 1.136 × 108 t, and 1.105 × 108 t, respectively, under the trend continuation scenario, eco-friendly scenario, and comprehensive development scenario, indicating that implementing ecological protection and cultivated land protection measures can facilitate regional ecosystem carbon storage restoration. (3) Impervious surfaces and vegetation have the greatest influence on carbon storage for the study area. A spatial global and local negative correlation was found between impervious surface coverage and ecosystem carbon storage. A spatial global and local positive correlation was found between NDVI and ecosystem carbon storage. Therefore, ecological and farmland protection policies need to be strengthened, the expansion of impervious surfaces should be strictly controlled, and vegetation coverage should be improved.

Impact of different dietary fibre sources on production performance, bacterial composition and metabolites in the caecal contents of rabbits.

This study was conducted to investigate the effects of different dietary fibre sources on growth performance, gastrointestinal tract development, caecal fermentation and bacterial composition in the caecal contents of rabbits. A total of 120 35-day-old weaned Minxinan black rabbits were divided into three groups and fed a diet composed of peanut straw powder (Group A), alfalfa powder (Group B) and soybean straw powder (Group C) as the main fibre source. The final body weight and average daily gain in Group B were higher than those in Group C, and the average daily feed intake and feed conversion ratio in Group A were lower than those in Group C (p < 0.05). The relative weights of the stomach, small intestine and caecum of rabbits in Group C were higher than those in Groups of B and A, and the relative weights of the caecal contents in Group C were lower than those in Groups A or B (p < 0.05). The pH value and propionic acid, butyric acid and valeric acid concentrations in the caecum of Group C were lower than those in the caecum of Groups A or B, and the concentration of acetic acid in the caecum was lower (p < 0.05). The dominant microbes in the caecal contents of Minxinan black rabbits were Firmicutes, Bacteroidetes and Proteobacteria at the phylum level, and the number of species, Chao1 index and ACE index measured was different between the B-C and A-C groups (p < 0.05). Different dietary fibre sources could affect the growth performance, gastrointestinal tract development and intestinal microbiota of rabbits, and the nutritional value of alfalfa powder was better than that of peanut straw and soybean straw.

Investigation of Catalytic Co-Pyrolysis Characteristics and Synergistic Effect of Oily Sludge and Walnut Shell.

The co-pyrolysis of oily sludge and walnut shell is a reliable method for solid waste treatment and waste recycling. In this paper, a thermogravimetric analysis was used to study the thermodynamics and synergy effect of oily sludge (OS) and walnut shell (WS) at four heating rates (10, 20, 30, and 40 °C/min) in the temperature range from 50-850 °C. Two model-free methods (FWO and KAS) were used to calculate the activation energy. The results showed that the heating rate had no significant effect on the pyrolysis process. The addition of walnut shell improved the pyrolysis process of the samples. Mixture 1OS3WS had a synergy effect, while other blends showed an inhibitory effect. The synergy effect of co-pyrolysis was strongest when the mass ratio of oily sludge was 25%. The activation energy of the Zn-ZSM-5/25 catalyst was the lowest, and the residual substances were the least, indicating that the Zn-ZSM-5/25 was beneficial to the co-pyrolysis of oily sludge and walnut shell. The analysis of catalytic pyrolysis products by Py-GC/MS found that co-pyrolysis was beneficial to the generation of aromatic hydrocarbons. This study provided a method for the resource utilization of hazardous waste and biomass waste, which was conducive to the production of aromatic chemicals with added value while reducing environmental pollution.

Perioperative safety assessment of patients undergoing unilateral or bilateral hip replacements.

Introduction: Due to the aging of the world population and the increase of obesity rate, it is expected that the number of joint replacement surgery will continue to increase in the next few years. This study evaluated the safety differences between unilateral and bilateral hip replacement surgeries. Methods: The data for patients who underwent hip arthroplasty in 2021 and 2022 were examined. The data set included 68 patients who were grouped according to the type of hip replacement needed, sex, age, and body mass index. Total blood loss and operative time were the safety-related indicators used to compare the groups. Results: Regardless of whether the unilateral replacement group was compared with the overall bilateral replacement group or separately with the staged and simultaneous bilateral replacement groups, simultaneous bilateral replacement surgeries were equally safe as the other types of hip replacements. The total blood loss and operative time for the simultaneous bilateral replacement group were not significantly different from those in the unilateral and staged bilateral replacement groups. For overweight patients, the operative time for simultaneous bilateral replacements was significantly shorter than that for unilateral replacements. Conclusions: These findings suggest that for patients requiring bilateral hip replacements, the blood loss risk for patients undergoing simultaneous bilateral hip replacements was similar to that for patients undergoing either unilateral or staged bilateral hip replacements. Thus, simultaneous bilateral total hip replacement (THR) are safe and should be considered for candidate patients.

Structural basis of bacterial effector protein azurin targeting tumor suppressor p53 and inhibiting its ubiquitination.

Tumor suppressor p53 prevents tumorigenesis by promoting cell cycle arrest and apoptosis through transcriptional regulation. Dysfunction of p53 occurs frequently in human cancers. Thus, p53 becomes one of the most promising targets for anticancer treatment. A bacterial effector protein azurin triggers tumor suppression by stabilizing p53 and elevating its basal level. However, the structural and mechanistic basis of azurin-mediated tumor suppression remains elusive. Here we report the atomic details of azurin-mediated p53 stabilization by combining X-ray crystallography with nuclear magnetic resonance. Structural and mutagenic analysis reveals that the p28 region of azurin, which corresponds to a therapeutic peptide, significantly contributes to p53 binding. This binding stabilizes p53 by disrupting COP1-mediated p53 ubiquitination and degradation. Using the structure-based design, we obtain several affinity-enhancing mutants that enable amplifying the effect of azurin-induced apoptosis. Our findings highlight how the structure of the azurin-p53 complex can be leveraged to design azurin derivatives for cancer therapy.

Diagnostic value of exosomes in patients with liver cancer: a systematic review

Background Liver cancer is a disease with high morbidity and mortality. More and more studies have shown that exosomes can be used as biomarkers for the diagnosis of liver cancer, but their diagnostic accuracy is still unclear. Therefore, this meta-analysis summarizes various studies on the diagnostic value of exosomes for liver cancer. Method A comprehensive search was carried out based on the set search terms in PubMed, Web of Science and Wiley until April 1, 2022. All statistical analyses were performed by STATA 17 statistical software and Review Manager 5.4. Quality Assessment for Studies of Diagnostic Accuracy 2 tool was applied to evaluate the quality of included articles. Random effects model was used to calculate various diagnostic indicators. Result A total of 47 studies were included in this meta-analysis. The number of participants was 3196. The combined sensitivity, specificity and the area under the curve with 95% confidence intervals (95% CI) were, respectively 0.80 (0.75–0.84), 0.83 (0.79–0.87), 0.89 (0.85–0.91). Conclusions This meta-analysis shows that exosomes have good diagnostic accuracy for liver cancer and can be used as an effective biomarker for the diagnosis of liver cancer (AU)

Evaluation of Landslide Susceptibility Based on CF-SVM in Nujiang Prefecture.

At present, landslide susceptibility assessment (LSA) based on landslide characteristics in different areas is an effective measure for landslide management. Nujiang Prefecture in China has steep mountain slopes, a large amount of water and loose soil, and frequent landslide disasters, which have caused a large number of casualties and economic losses. This paper aims to understand the characteristics and formation mechanism of regional landslides through the evaluation of landslide susceptibility so as to provide relevant references and suggestions for spatial planning and disaster prevention and mitigation in Nujiang Prefecture. Based on the grid cell, this study selected 10 parameters, namely elevation, slope, aspect, lithology, proximity to faults, proximity to road, proximity to rivers, normalized difference vegetation index (NDVI), land-use type, and precipitation. Support vector machine (SVM), certainty factor method (CF), and deterministic coefficient method-support vector machine (CF-SVM) were used to evaluate the landslide susceptibility in Nujiang Prefecture. According to these three models, the study area was divided into five landslide susceptibility grades, including extremely high susceptibility, high susceptibility, moderate susceptibility, low susceptibility, and very low susceptibility. Receiver operating characteristic curve (ROC) was applied to verify the accuracy of the model. The results showed that CF model (ROC = 0.865), SVM model (ROC = 0.892), CF-SVM model (ROC = 0.925), and CF-SVM model showed better performance. Therefore, CF-SVM model results were selected for analysis. The study found that the characteristics of high and extremely high landslide-prone areas in Nujiang Prefecture have the following characteristics: intense human activities, large density of buildings and arable land, rich water resources, good economic development, perfect transportation facilities, and complex topography and landform. In addition, there is a finding inconsistent with our common sense that the distribution of landslide disasters in the study area does not decrease with the increase of NDVI value. This is because the Nujiang River basin is a high mountain canyon area with low rock strength, barren soil, and underdeveloped vegetation and root system. In an area with large slope, the probability of landslide disaster will increase with the increase of NDVI. The CF-SVM coupling model adopted in this study is a good first attempt in the study of landslide hazard susceptibility in Nujiang Prefecture.

New Technique for Enhancing Residual Oil Recovery from Low-Permeability Reservoirs: The Cooperation of Petroleum Hydrocarbon-Degrading Bacteria and SiO2 Nanoparticles.

Residual crude oil production from low-permeability reservoirs has become a huge challenge because conventional recovery techniques are inefficient. Nanofluids as a new type of oil-displacement agent have become a hot topic in recent years to enhance oil recovery (EOR) in reservoirs. However, the imperfection of agglomeration, dissolution, and instability of nanofluids in reservoir environments limit their ability to drive oil. Here, a novel "microbial-nanofluid" composed of petroleum hydrocarbon-degrading bacteria (PHDB, namely Bacillus cereus) and SiO2 nanoparticles was proposed as a potential new technology for enhancing residual oil recovery. The micromodel displacement test results showed that the optimum composite concentration of "microbial-nanofluids" were PHDB (7.0%, v/v) and SiO2 nanoparticles (100 mg/L), and the residual oil recovery was increased by 30.1% compared with waterflooding (68.8%). Moreover, the morphological characteristics of residual oil mobilization after "microbial-nanofluid" flooding were mainly small and dispersed oil droplets in the excessive areas, and the dead-end areas were almost clean with mobilization. Furthermore, the cooperation mechanism of four kinds of "microbial-nanofluids" to enhance the residual oil recovery in low-permeability reservoirs was preliminarily clarified, namely the co-emulsification of oil, working together to unclog oil clog, microbial-nanofluid self-assembly, and structural disjoining pressure. This study demonstrated that PHDB-SiO2 nanoparticle composite flooding technology provided a significant potential for the EOR from low-permeability reservoirs.

Short-term Effectiveness of a Modified Osteotomy for Total Elbow Joint Replacement in Patients of Hemophilic Elbow Arthritis with Severe Flexion Contracture Deformity: A Three-Cases Series Report.

OBJECTIVE: To report the modified osteotomy and the short-term effectiveness of the total elbow joint replacement in patients of hemophilic elbow arthritis with severe flexion contracture deformity. METHODS: This study introduced the therapeutic approach of the total elbow joint replacement in patients of hemophilic elbow arthritis with severe flexion contracture deformity, and assessed the short-term effectiveness in three cases (three elbows) of end-stage hemophilic elbow arthritis admitted from October 2020 to December 2020. The included patients were all diagnosed with hemophilia A (factor VII deficiency), accompanied by severe bilateral elbow joint flexion contracture, which seriously affects daily life and requires surgical intervention. Clinical data and follow-up results were analyzed before total elbow arthroplasty and 1, 3, and 6 months postoperatively. Pre- and postoperative range of motion, pain score, and function score were compared, and intraoperative and postoperative complications are reported. RESULTS: All three patients were male, with an average age of 31 years. The main clinical manifestations were bilateral elbow arthritis with flexion contracture. Two of the patients underwent right elbow replacement, and one patient underwent left elbow replacement. All cases were followed up for 6 months postoperatively. No incision infection or ulnar nerve injury occurred. Postoperative triceps brachii muscle strength was slightly weakened compared with preoperative muscle strength. Average elbow flexion and extension range of motion was 60° (30°-100°) preoperatively and increased to 127° (110°-140°) postoperatively; rotational range of motion of the affected forearm was 47° (10°-85°) preoperatively and increased to 117° postoperatively. The mean visual analogue scale (VAS) was 6 (5-8) preoperatively and decreased to 3 (2-4) postoperatively. The mean MEPS score was 62 (55-75) and increased to 87 (80-95) postoperatively. During the follow-up, anteroposterior and lateral radiographs showed no signs of prosthesis loosening in the elbow. CONCLUSIONS: For severe hemophilic elbow arthritis patients, the short-term treatment effect of total elbow replacement is good, following the strict adherence to the surgical indications and proper preparation for the perioperative period. The modified osteotomy can fully expose the visual field and reduce complications of ulnar nerve injury. The long-term effects need to be study future.

Diagnostic value of exosomes in patients with liver cancer: a systematic review.

BACKGROUND: Liver cancer is a disease with high morbidity and mortality. More and more studies have shown that exosomes can be used as biomarkers for the diagnosis of liver cancer, but their diagnostic accuracy is still unclear. Therefore, this meta-analysis summarizes various studies on the diagnostic value of exosomes for liver cancer. METHODS: A comprehensive search was carried out based on the set search terms in PubMed, Web of Science and Wiley until April 1, 2022. All statistical analyses were performed by STATA 17 statistical software and Review Manager 5.4. Quality Assessment for Studies of Diagnostic Accuracy 2 tool was applied to evaluate the quality of included articles. Random effects model was used to calculate various diagnostic indicators. RESULTS: A total of 47 studies were included in this meta-analysis. The number of participants was 3196. The combined sensitivity, specificity and the area under the curve with 95% confidence intervals (95% CI) were, respectively 0.80 (0.75-0.84), 0.83 (0.79-0.87), 0.89 (0.85-0.91). CONCLUSIONS: This meta-analysis shows that exosomes have good diagnostic accuracy for liver cancer and can be used as an effective biomarker for the diagnosis of liver cancer.

Perioperative blood loss during joint replacement: comparison between patients with and without hemophilia.

BACKGROUND: Although arthroplasty provides satisfactory pain relief, functional improvement, and reduced flexion contracture in patients with hemophilia arthropathy, bleeding remains the primary problem associated with hemophilic arthropathy joint replacement. We aimed to explore the differences in perioperative blood loss (PBL) associated with joint replacement surgery in patients with and without hemophilia. METHODS: This study retrospectively analyzed 61 cases of PBL in patients undergoing joint replacement surgery, including 37 patients with hemophilia and 24 patients without hemophilia. All patients demonstrated severe joint flexion contractures that seriously affected their daily lives and required surgical intervention. PBL was compared between the two groups. RESULTS: In univariate analysis, the overall (p < 0.001) and hidden (p < 0.001) blood losses were significantly higher for patients with hemophilia than those for patients without hemophilia. However, after adjustment for multiple factors, there was no significant difference in overall blood loss between the two groups (p = 0.731). In addition, sex, age group, and surgical site did not affect blood loss in patients with hemophilia. CONCLUSION: Overt bleeding did not increase significantly in patients with hemophilia, compared with that in patients without hemophilia. In terms of blood loss, joint replacement surgery for patients with hemophilia is relatively safe. The results of this study must be verified by a prospective follow-up study with larger sample size. Trial registration Retrospectively registered.

HIV infection is not associated with perioperative blood loss in patients undergoing total hip arthroplasty.

BACKGROUND: Patients with HIV have a higher prevalence of thrombocytopenia than those without HIV infection, increasing their risk of substantial perioperative blood loss (PBL) during total hip arthroplasty (THA). This study aimed to evaluate PBL risk factors in HIV-infected patients undergoing THA. METHODS: Eighteen HIV+ patients (21 hip joints) and 33 HIV- patients (36 joints) undergoing THA were enrolled in this study. PBL was calculated using the Gross equation, which comprises total blood loss (TBL), dominant blood loss (DBL), and hidden blood loss (HBL). Risk factors for post-THA PBL in both patient populations was evaluated using multivariable linear regression. RESULTS: At baseline, the HIV+ patients were younger, more likely to be male and to have elevated hemoglobin and albumin levels, and lower erythrocyte sedimentation rates than HIV- patients. There were no differences in the T-lymphocyte subsets or coagulation function between the two groups. Age and albumin level were identified as potential HBL risk factors after THA, and albumin level was associated with higher TBL. The unadjusted linear regression analysis showed that the HBL and TBL were significantly higher in HIV+ patients than in HIV- patients. However, after adjusting for other factors, no differences in DBL, HBL, or TBL were observed between HIV- and HIV+ patients. CONCLUSION: PBL was similar in both groups undergoing THA, regardless of their HIV-infection status. THA surgery is a safe and effective procedure in HIV+ patients.

Efficacy and safety of a single intra-articular injection of 6 ml Hylan G-F 20 compared to placebo in Chinese patients with symptomatic knee osteoarthritis : C-SOUND study, a 26-week multicenter double-blind randomized placebo-controlled trial in China.

BACKGROUND: Single 6 ml Hylan G-F 20 injection, is indicated for knee osteoarthritis patients who have failed to respond to non-pharmacologic therapy and/or simple analgesics. To obtain more thorough understanding of the clinical efficacy and safety, a randomized clinical trial was conducted comparing intra-articular (IA) administration of single 6 ml Hylan G-F 20 injection versus placebo in knee OA patients of Chinese ethnicity. METHODS: This was a randomized, multi-center, double-blind, placebo-controlled clinical trial conducted in 21 centers across China. Four hundred forty adults with knee OA received a single 6 ml Hylan G-F 20 or placebo injection and were evaluated for clinical efficacy and safety outcomes over 26 weeks. Western Ontario and McMaster Universities OA (WOMAC) A1 index, treatment-emergent adverse events (TEAEs) and standard safety parameters were measured at pre-injection, and at weeks 1, 4, 8, 12, 16, 20 and 26 post-injection. RESULTS: Four hundred forty patients (male: 98 [22.3%]; female: 342 [77.7%]) were randomized. The mean age [standard deviation (SD)] was 61.5 (7.9) years. All patients were of East Asian ethnicity. Mean WOMAC A1 score at baseline was 5.3 (1.2) and 5.2 (1.3) in single 6 ml Hylan G-F 20 injection and placebo groups, respectively. Significant reductions of WOMAC A1 score were observed in both treatment groups when compared to baseline at 26 weeks post-injection, with the mean reduction of [standard error (SE)/percentage] -2.146 (0.108)/- 40.5% and - 2.271 (0.110) /- 43.7% in the single 6 ml Hylan G-F 20 injection and the placebo groups, respectively. Additionally, clinically important reductions in pain at 26 weeks was reported in 67.0 and 68.2% in single 6 ml Hylan G-F 20 injection and placebo groups (p = 0.36). Regarding safety, TEAEs were similar between the two treatment groups (hylan G-F 20 single: 61.5%; placebo: 64.5%). CONCLUSIONS: While the magnitude of the effect of a single 6 ml Hylan G-F 20 injection in this study is consistent with previously published literature with respect to the efficacy and safety of the drug, the current study shows a strong IA placebo effect and did not established superiority of single 6 ml Hylan G-F 20 injection over IA placebo in Chinese knee OA patients. TRIAL REGISTRATION: Prospectively registered Jun 16, 2017 at www.clinicaltrials.gov ( NCT03190369 ).

Molecular characteristics of drug-resistance Mycobacterium tuberculosis strains isolated from extra pulmonary tuberculosis sites / Características moleculares de cepas de Mycobacterium tuberculosis farmacorresistentes aisladas de los sitios de tuberculosis extrapulmonar

Objectives: China is the second high tuberculosis (TB) burden country in the world. This article was to determinate the molecular characteristic of drug resistance Mycobacterium tuberculosis (DRTB) strains from extra pulmonary tuberculosis (EPTB). Methods: The medical records of patients with EPTB were reviewed and collected from 2006 to 2016. The drug sensitivity of all samples was studied. All multiple drug resistance (MDR) and extensive drug resistance (XDR) strains were included. The detection of the deletion of region of difference 105 (RD105) and mycobacterial interspersed repetitive-unit variable-number tandem-repeat (MIRU-VNTR) were used to discriminate the molecular type of EPTB strains. Results: 162 DRTB isolates were from patients with EPTB including 104 male and 58 female. Beijing genotype had a significant correlation with the patterns of DR (P<0.05), re-treatment patients (P<0.05) and gender (P<0.05). The history of treatment had a statistically significant correlation with patterns of DR (P<0.05) and gender (P<0.05). Patterns of DR had no correlation with gender (P>0.05). Of 162 strains Beijing family strains represented 91.4%. The cluster rate was 17.9% and clustering ratio was 11.1%. Beijing family genotype is predominant in the patients with EPTB. The cluster rate and clustering ratio was low. Conclusions: Beijing family genotype is predominant and highly epidemic in the patients with drug resistance extra pulmonary tuberculosis (DR-EPTB). The cluster rate and clustering ratio was low. Genotype of re-treatment male patient with DR-EPTB is more likely Beijing family genotype.(AU)

Objetivos: China es el país con la segunda mayor carga de tuberculosis (TB) del mundo. Este artículo pretende determinar las características moleculares de cepas de Mycobacterium tuberculosis farmacorresistentes (MBFR) en la tuberculosis extrapulmonar (TBEP). Métodos: Se revisaron y recopilaron los registros médicos de pacientes con TBEP entre 2006 y 2016. Se estudió la sensibilidad farmacológica de todas las muestras. Se incluyeron todas las cepas con farmacorresistencia múltiple (FRM) y farmacorresistencia extensiva (FRE). Para discriminar el tipo molecular de las cepas de TBEP se utilizó la detección de la eliminación de la región de diferencia 105 (RD105) y las repeticiones en tándem con número variable de unidades repetitivas interespaciadas de micobacterias (MIRU-VNTR). Resultados: Ciento sesenta y dos aislados de pacientes con TBEP, de los cuales 104 eran varones y 58 mujeres. El genotipo de Beijing tuvo una correlación significativa con los patrones de FR (p<0,05), pacientes con retratamiento (p<0,05) y sexo (p<0,05). Los antecedentes de tratamiento tuvieron una correlación estadísticamente significativa con los patrones de FR (p<0,05) y sexo (p<0,05). Los patrones de FR no tuvieron correlación con el sexo (p<0,05). Del total de las 162 cepas, las cepas de Beijing representaron el 91,4%. La tasa de agrupamiento fue del 17,9% y la proporción de agrupamiento del 11,1%. El genotipo de Beijing es predominante en los pacientes con TBEP. La tasa de agrupamiento y la proporción de agrupamiento fueron bajas. Conclusiones: El genotipo de Beijing es predominante y altamente epidémico en los pacientes con tuberculosis extrapulmonar farmacorresistente (TBEP-FR). La tasa de agrupamiento y la proporción de agrupamiento fueron bajas. El genotipo de paciente varón con TBEP-FR retratado es más probable en el genotipo de la familia de Beijing.(AU)

DNA methylation and histone acetylation are involved in Wnt10b expression during the secondary hair follicle cycle in Angora rabbits.

Secondary hair follicles (SHFs) in the Angora rabbit exhibit classic cyclic hair development, but the multiple molecular signals involved in hair cycling are yet to be explored in detail. In the present study, we investigated the expression pattern, methylation and histone H3 acetylation status of Wnt10b, as a molecular signal participating in hair cycling, during the SHF cycle in the Angora rabbit. Expression of Wnt10b at the anagen phase was significantly higher than that at both the telogen and catagen phases, suggesting that Wnt10b might serve as a critical activator during cyclic transition of SHFs. Methylation frequency of the fifth CpG site (CpG5-175 bp) in CpG islands at the anagen phase was lower than that at both the catagen and telogen phases. The methylation status of the CpG5 site was negatively correlated with Wnt10b expression. This indicated that the methylation of CpG5 might participate in Wnt10b transcriptional suppression in SHFs. Furthermore, histone H3 acetylation status in the regions-256~-11 bp and 98 ~ 361 bp were significantly lower at both the catagen and telogen phases than at the anagen phase. The histone H3 acetylation level was significantly positively correlated with Wnt10b expression. This confirmed that histone acetylation was likely involved in upregulating Wnt10b transcription in SHFs. Additionally, potential binding to the transcription factors ZF57 and HDBP was predicted within the CpG5 site. In conclusion, our findings reveal the epigenetic mechanism of Wnt10b transcription and provide a new insight into epigenetic regulation during the SHF cycle in the Angora rabbit.

Establishment and validation of nomogram model for survival predicting in patients with spinal metastases secondary to lung cancer.

OBJECTIVES: To evaluate the prognostic effect of pre-treatment factors in patients with spinal metastases secondary to lung cancer, and establish a novel predicting nomogram for predicting the survival probability. METHODS: A total of 209 patients operated for spinal metastases from lung cancer were consecutively enrolled, and divided into the training and validation samples with a ratio of 7:3, for model establishing and validating, respectively. Basing on the training sample, univariate and multivariate COX proportional hazard models were used for identifying the prognostic effect of pre-treatment factors, following which significant prognostic factors would be listed as items in nomogram to calculate the survival probabilities at 3, 6, 12 and 18 months. Then, the C-indexes and the calibration curves would be figured out to evaluate the discrimination ability and accuracy of the model both for the training and validation samples. RESULTS: In the multivariate COX analysis, the gender, smoking history, location of spinal metastasis, visceral metastasis, Karnofsky performance status (KPS), adjuvant therapy, lymphocyte percentage and globulin were found to be significantly associated with the overall survival, and a novel nomogram was generated basing on these independent predictors. The C-indexes for the training and validation samples were 0.761 and 0.732, respectively. Favorable consistencies between the predicted and actual survival rates were demonstrated both in the internal and external validations. DISCUSSION: Pre-treatment characteristics, including gender, smoking history, location of spinal metastasis, visceral metastasis, KPS, adjuvant therapy, percentage of lymphocyte, and serum globulin level, were identified to be significantly associated with overall survival of patients living with spinal metastases derived from lung cancer, and a user-friendly nomogram was established using these independent predictors.

Neuroprotective effect of neuregulin-1ß on spinal cord ischemia reperfusion injury.

Objective: This study was designed to see if neuregulin-1ß (NRG-1ß) plays a protective role in spinal cord ischemia and reperfusion injury (SCII).Design: Animal research.Setting: China.Participants: NA.Interventions: Forty-eight SD rats were randomly divided into control group (n = 16), SCII model group (n = 16) and NRG-1ß-treated group (n = 16). In control group, the abdominal aorta was isolated but not clipped. The rats in NRG-1ß-treated group were treated with 10µg/kg NRG-1ß during developing SCII model.Outcome Measures: Neurological scores were evaluated. At 3, 6, 12 and 24 h after the reperfusion, rats were killed. Pathological changes of spinal cord were assessed with HE staining, and immunohistochemical staining of matrix metalloproteinases-9 (MMP-9) and tissue inhibitor of metalloproteinase-1 (TIMP-1). MMP-9 and TIMP-1 mRNA levels were assessed using real-time PCR.Results: NRG-1ß reduced the damage of SCII in the rats. The expression of MMP-9 protein and mRNA in NRG-1ß treatment group was significantly lower than the model group (P < 0.05) at 6 h, 12 h and 24 h after the perfusion. The expression of TIMP-1 protein and mRNA in the treatment group was significantly higher than the model group at 12 h and 24 h after the perfusion.Conclusion: NRG-1ß reduced the reperfusion damage in rat model of SCII, in which process MMP-9 and TIMP-1 were probably involved.