Pooled ctDNA analysis of MONALEESA phase III advanced breast cancer trials.

BACKGROUND: The phase III MONALEESA trials tested the efficacy and safety of the cyclin-dependent kinase (CDK)4/6 inhibitor ribociclib with different endocrine therapy partners as first- or second-line treatment of hormone receptor-positive/human epidermal growth factor receptor 2-negative advanced breast cancer (ABC). Using the largest pooled biomarker dataset of the CDK4/6 inhibitor ribociclib in ABC to date, we identified potential biomarkers of response to ribociclib. PATIENTS AND METHODS: Baseline circulating tumour DNA from patients in the MONALEESA trials was assessed using next-generation sequencing. An analysis of correlation between gene alteration status and progression-free survival (PFS) was carried out to identify potential biomarkers of response to ribociclib. RESULTS: Multiple frequently altered genes were identified. Alterations in ERBB2, FAT3, FRS2, MDM2, SFRP1, and ZNF217 were associated with a greater PFS benefit with ribociclib versus placebo. Patients with high tumour mutational burden (TMB) and with ANO1, CDKN2A/2B/2C, and RB1 alterations exhibited decreased sensitivity to ribociclib versus placebo. CONCLUSIONS: Although exploratory, these results provide insight into alterations associated with the improved response to ribociclib treatment and may inform treatment sequencing in patients with actionable alterations following progression on CDK4/6 inhibitors. Validation of potential biomarkers identified here and development of prospective trials testing their clinical utility are warranted. GOV IDENTIFIERS: NCT01958021, NCT02422615, NCT02278120.

[Determination of methylmercury in urine by direct mercury analyzer].

Objective: To develop asolvent extraction-direct mercury analyzer method for determination of methylmercury in urine. Methods: After the urinehydrolyzesd by hydrobromic acid, methylmercury was extracted by tolueneand reverse-extracted from L-cysteine solution, it was then detectedbydirect mercuryanalyzer. Results: The linear range was 0.2-50.0 µg/L, and the related coefficient was 0.9999. The relative standard deviations (RSD) within the group were 5.04%-6.64%, and the RSD between the group were 5.65%-8.11 %. The average recovery efficiencies were 85.4%-95.5%. The detection limitation was 0.0482 µg/L and the quantification concentrations was 0.1607 µg/L. Conclusion: The method, which has low detection limit, high sensitivity, easy to operate, is stability for the determination of methylmercury in urine.

Probing Operator Spreading via Floquet Engineering in a Superconducting Circuit.

Operator spreading, often characterized by out-of-time-order correlators (OTOCs), is one of the central concepts in quantum many-body physics. However, measuring OTOCs is experimentally challenging due to the requirement of reversing the time evolution of systems. Here we apply Floquet engineering to investigate operator spreading in a superconducting 10-qubit chain. Floquet engineering provides an effective way to tune the coupling strength between nearby qubits, which is used to demonstrate quantum walks with tunable couplings, reversed time evolution, and the measurement of OTOCs. A clear light-cone-like operator propagation is observed in the system with multiple excitations, and has a nearly equal velocity as the single-particle quantum walk. For the butterfly operator that is nonlocal (local) under the Jordan-Wigner transformation, the OTOCs show distinct behaviors with (without) a signature of information scrambling in the near integrable system.

[Establishment and clinical validation of an artificial intelligence YOLOv51 model for the detection of precancerous lesions and superficial esophageal cancer in endoscopic procedure].

Objective: To construct the diagnostic model of superficial esophageal squamous cell carcinoma (ESCC) and precancerous lesions in endoscopic images based on the YOLOv5l model by using deep learning method of artificial intelligence to improve the diagnosis of early ESCC and precancerous lesions under endoscopy. Methods: 13, 009 endoscopic esophageal images of white light imaging (WLI), narrow band imaging (NBI) and lugol chromoendoscopy (LCE) were collected from June 2019 to July 2021 from 1, 126 patients at the Cancer Hospital, Chinese Academy of Medical Sciences, including low-grade intraepithelial neoplasia, high-grade intraepithelial neoplasia, ESCC limited to the mucosal layer, benign esophageal lesions and normal esophagus. By computerized random function method, the images were divided into a training set (11, 547 images from 1, 025 patients) and a validation set (1, 462 images from 101 patients). The YOLOv5l model was trained and constructed with the training set, and the model was validated with the validation set, while the validation set was diagnosed by two senior and two junior endoscopists, respectively, to compare the diagnostic results of YOLOv5l model and those of the endoscopists. Results: In the validation set, the accuracy, sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV) of the YOLOv5l model in diagnosing early ESCC and precancerous lesions in the WLI, NBI and LCE modes were 96.9%, 87.9%, 98.3%, 88.8%, 98.1%, and 98.6%, 89.3%, 99.5%, 94.4%, 98.2%, and 93.0%, 77.5%, 98.0%, 92.6%, 93.1%, respectively. The accuracy in the NBI model was higher than that in the WLI model (P<0.05) and lower than that in the LCE model (P<0.05). The diagnostic accuracies of YOLOv5l model in the WLI, NBI and LCE modes for the early ESCC and precancerous lesions were similar to those of the 2 senior endoscopists (96.9%, 98.8%, 94.3%, and 97.5%, 99.6%, 91.9%, respectively; P>0.05), but significantly higher than those of the 2 junior endoscopists (84.7%, 92.9%, 81.6% and 88.3%, 91.9%, 81.2%, respectively; P<0.05). Conclusion: The constructed YOLOv5l model has high accuracy in diagnosing early ESCC and precancerous lesions in endoscopic WLI, NBI and LCE modes, which can assist junior endoscopists to improve diagnosis and reduce missed diagnoses.

Microbially induced carbonate precipitation via methanogenesis pathway by a microbial consortium enriched from activated anaerobic sludge.

AIMS: Various applications of microbially induced carbonate precipitation (MICP) has been proposed. However, most studies use cultured pure strains to obtain MICP, ignoring advantages of microbial consortia. The aims of this study were to: (i) test the feasibility of a microbial consortium to produce MICP; (ii) identify functional micro-organisms and their relationship; (iii) explain the MICP mechanism; (iv) propose a way of applying the MICP technique to soil media. METHODS AND RESULTS: Anaerobic sludge was used as the source of the microbial consortium. A laboratory anaerobic sequencing batch reactor and beaker were used to perform precipitation experiment. The microbial consortium produced MICP with an efficiency of 96·6%. XRD and SEM analysis showed that the precipitation composed of different-size calcite crystals. According to high-throughput 16S rRNA gene sequencing, the functional micro-organisms included acetogenic bacteria, acetate-oxidizing bacteria and archaea Methanosaeta and Methanobacterium beijingense. The methanogenesis acetate degradation provides dissolved inorganic carbon and increases pH for MICP. A series of reactions catalysed by many enzymes and cofactors of methanogens and acetate-oxidizers are involved in the acetate degradation. CONCLUSION: This work demonstrates the feasibility of using the microbial consortium to achieve MICP from an experimental and theoretical perspective. SIGNIFICANCE AND IMPACT OF THE STUDY: A method of applying the microbial-consortium MICP to soil media is proposed. It has the advantages of low cost, low environmental impact, treatment uniformity and less limitations from natural soils. This method could be used to improve mechanical properties, plug pores and fix harmful elements of soil media, etc.

[A case report of orbital epithelioid hemangioendothelioma].

A 70-year-old male patient, who had a right upper eyelid tumor excision 4 years ago, complained of eyelid swelling and ptosis for 3 months. Orbital CT and MRI showed an orbital cystic lesion with hemorrhage in the right eye. The tumor was resected under general anesthesia. The pathological diagnosis was epithelioid hemangioendothelioma. (Chin J Ophthalmol, 2021, 57:696-698).

[Association between parental socioeconomic status and preschoolers' consumption of sugar-sweetened beverages].

Objective: To explore the association between parental socioeconomic status (SES) and preschoolers' consumption of sugar-sweetened beverages (SSB). Methods: In June 2018, all preschoolers from 15 kindergartens were selected from the jurisdiction of Education Commission in Dongcheng District of Beijing by using an equal-proportion stratified cluster sampling method in the study. A self-designed questionnaire was used to investigate the parents of preschoolers to obtain the basic information of preschoolers and parents, the consumption situation of preschoolers' sugar-sweetened beverages and the perception of parents to SSB. A tatol of 3 217 preschoolers were finally included in the analysis. A generalized structural equation model was used to analyze the relationship between preschoolers' consumption of sugar-sweetened beverages and their parents' socioeconomic status and the mediating effect of their cognition of sugar-sweetened beverages. The size of mediating effect was estimated by using deviation correction non-parameter percentile Bootstrap method. Results: The age of 3 217 preschoolers was (4.23±0.67) years, of which 52.6% (n=1 692) were boys, and 77.62% (n=2 497) were SSB consumers. Among the parents of 3 217 preschoolers, fathers and mothers accounted for 24.90% (n=801) and 75.10% (n=2 416), and the M (P25, P75) scores of SES were 66.7 (62.5, 69.5) and 69.5 (64.6, 71.4), respectively. The proportion of parents who took the initiative to learn about their children's consumption of SSB, lacked confidence in restricting preschooler's consumption of SSB and read nutrition labels before purchasing food was 74.08% (n=2 383), 82.90% (n=2 667) and 36.24% (n=1 166), respectively. The generalized structural equation model showed that after adjusting for preschoolers' gender, age, body mass index (BMI) of preschoolers and their parents, preschoolers' consumption of SSB was negatively associated with their parents' SES score [path coefficient (95%CI):-4.69×10-2 (-6.56×10-2,-2.69×10-2) ]. The mediating effect of parents' perception of SSB consumption could explain 48.71% of the total effect [path coefficient (95%CI):-2.28×10-2 (-3.54×10-2, -1.10×10-2)]. Conclusion: The consumption of SSB in preschoolers is negatively associated with their parent's SES, and this relationship is partially mediated by parent's perception of SSB consumption.

Impact of haemoglobin A1c trajectories on chronic kidney disease progression in type 2 diabetes.

AIM: To characterize haemoglobin A1c (HbA1c) trajectories and examine their associations with chronic kidney disease (CKD) progression. METHODS: This was a prospective cohort study on 770 patients with type 2 diabetes mellitus (T2DM) attending a diabetes centre in 2002-2017. Group-based trajectory modelling was used to identify HbA1c trajectories. Cox proportional hazards models were used to examine association between the trajectories and CKD progression which was defined as deterioration across the Kidney Disease: Improving Global Outcomes estimated glomerular filtration rate categories with ≥25% drop from baseline. RESULTS: We identified four HbA1c trajectories: 'near-optimal stable' (49.1%), 'moderate stable' (37.9%), 'moderate-increasing' (6.0%) and 'high-decreasing' (7.0%). Over a median follow-up period of 4.6 years (interquartile range 2.5-5.6), CKD progression occurred in 35.6% of patients. The risk of CKD progression was significantly higher in the moderate-increasing with adjusted hazard ratios (HR) 2.23 (95% confidence interval (CI) 1.09-4.57). After additional adjustment for mean HbA1c, the association between the moderate-increasing subgroup and CKD progression remained significant at HR 3.07 (95% CI 1.08-8.77). CONCLUSION: Moderate-increasing HbA1c trajectory is associated with renal disease progression in patients with T2DM, independent of mean HbA1c. The deleterious effects of deteriorating HbA1c trajectory highlight the importance of achieving sustained good glycaemic control in diabetes management.

Particle and vapor emissions from vat polymerization desktop-scale 3-dimensional printers.

Little is known about emissions and exposure potential from vat polymerization additive manufacturing, a process that uses light-activated polymerization of a resin to build an object. Five vat polymerization printers (three stereolithography (SLA) and two digital light processing (DLP) were evaluated individually in a 12.85 m3 chamber. Aerosols (number, size) and total volatile organic compounds (TVOC) were measured using real-time monitors. Carbonyl vapors and particulate matter were collected for offline analysis using impingers and filters, respectively. During printing, particle emission yields (#/g printed) ranged from 1.3 ± 0.3 to 2.8 ± 2.6 x 108 (SLA printers) and from 3.3 ± 1.5 to 9.2 ± 3.0 x 108 (DLP printers). Yields for number of particles with sizes 5.6 to 560 nm (#/g printed) were 0.8 ± 0.1 to 2.1 ± 0.9 x 1010 and from 1.1 ± 0.3 to 4.0 ± 1.2 x 1010 for SLA and DLP printers, respectively. TVOC yield values (µg/g printed) ranged from 161 ± 47 to 322 ± 229 (SLA printers) and from 1281 ± 313 to 1931 ± 234 (DLP printers). Geometric mean mobility particle sizes were 41.1-45.1 nm for SLA printers and 15.3-28.8 nm for DLP printers. Mean particle and TVOC yields were statistically significantly higher and mean particle sizes were significantly smaller for DLP printers compared with SLA printers (p < 0.05). Energy dispersive X-ray analysis of individual particles qualitatively identified potential occupational carcinogens (chromium, nickel) as well as reactive metals implicated in generation of reactive oxygen species (iron, zinc). Lung deposition modeling indicates that about 15-37% of emitted particles would deposit in the pulmonary region (alveoli). Benzaldehyde (1.0-2.3 ppb) and acetone (0.7-18.0 ppb) were quantified in emissions from four of the printers and 4-oxopentanal (0.07 ppb) was detectable in the emissions from one printer. Vat polymerization printers emitted nanoscale particles that contained potential carcinogens, sensitizers, and reactive metals as well as carbonyl compound vapors. Differences in emissions between SLA and DLP printers indicate that the underlying technology is an important factor when considering exposure reduction strategies such as engineering controls.

[Association of platelet/lymphocyte ratio and neutrophil/lymphocyte ratio with protein-energy wasting in maintenance hemodialysis patients].

Objective: To explore the association of platelet/lymphocyte ratio (PLR) and neutrophil/lymphocyte ratio (NLR) with protein energy wasting (PEW) in maintenance hemodialysis (MHD) patients. Methods: A multicenter cross-sectional study was conducted in eleven hemodialysis centers of Guizhou province from June to August, 2017. Clinical data, physical parameters, body composition data and laboratory values of MHD patients were collected. PLR and NLR were calculated according to routine blood test. All patients were divided into four groups (Q1-Q4) according to the median and quartile of PLR and NLR. Multivariate logistic regression models were applied to analyze the relationships between PLR, NLR and PEW. The comparison of predictive power of PLR and NLR for PEW was evaluated by receiver operating characteristic curve (ROC). Results: A total of 936 MHD patients were enrolled (519 males, 417 females), with a mean age of (55.6±15.6) years. The prevalence of PEW was 46.2% (432/936). Multivariate logistic regression analysis showed that patients in group PLR Q3 and Q4 were 2.07 (95%CI: 1.03-4.13, P=0.014) and 2.73 (95%CI: 1.58-4.74, P<0.001) times more likely to have PEW, compared with those in group PLR Q1 in unadjusted models. PLR was significantly associated with the development of PEW after adjusting age, sex, history of hypertension, diabetes and hemoglobin. Patients in Group PLR Q3 and Q4 were 2.82 times (95%CI: 1.42-5.60, P=0.003) and 2.93 times (95%CI: 1.50-5.73, P=0.002) times more likely to have PEW than those in Group PLR Q1. The ROC showed that only PLR can predict the development of PEW with a diagnostic threshold of 144.09 [area under curve (AUC)=0.61, 95%CI: 0.56-0.66, P<0.001], with a sensitivity and specificity of 61% and 58%, respectively, while the AUC of NLR is 0.55 (P=0.091). Conclusion: For MHD patients, only PLR could be a relevent factor of PEW and it showed the predictive power of PEW rather than NLR.

Updated results from MONALEESA-2, a phase III trial of first-line ribociclib plus letrozole versus placebo plus letrozole in hormone receptor-positive, HER2-negative advanced breast cancer.

Background: The phase III MONALEESA-2 study demonstrated significantly prolonged progression-free survival (PFS) and a manageable toxicity profile for first-line ribociclib plus letrozole versus placebo plus letrozole in patients with hormone receptor-positive (HR+), human epidermal growth factor receptor 2-negative (HER2-) advanced breast cancer. Here, we report updated efficacy and safety data, together with exploratory biomarker analyses, from the MONALEESA-2 study. Patients and methods: A total of 668 postmenopausal women with HR+, HER2- recurrent/metastatic breast cancer were randomized (1 : 1; stratified by presence/absence of liver and/or lung metastases) to ribociclib (600 mg/day; 3-weeks-on/1-week-off; 28-day treatment cycles) plus letrozole (2.5 mg/day; continuous) or placebo plus letrozole. The primary end point was locally assessed PFS. The key secondary end point was overall survival (OS). Other secondary end points included overall response rate (ORR) and safety. Biomarker analysis was an exploratory end point. Results: At the time of the second interim analysis, the median duration of follow-up was 26.4 months. Median PFS was 25.3 months [95% confidence interval (CI) 23.0-30.3] for ribociclib plus letrozole and 16.0 months (95% CI 13.4-18.2) for placebo plus letrozole (hazard ratio 0.568; 95% CI 0.457-0.704; log-rank P = 9.63 × 10-8). Ribociclib treatment benefit was maintained irrespective of PIK3CA or TP53 mutation status, total Rb, Ki67, or p16 protein expression, and CDKN2A, CCND1, or ESR1 mRNA levels. Ribociclib benefit was more pronounced in patients with wild-type versus altered receptor tyrosine kinase genes. OS data remain immature, with 116 deaths observed; 50 in the ribociclib arm and 66 in the placebo arm (hazard ratio 0.746; 95% CI 0.517-1.078). The ORR was 42.5% versus 28.7% for all patients treated with ribociclib plus letrozole versus placebo plus letrozole, respectively, and 54.5% versus 38.8%, respectively, for patients with measurable disease. Safety results, after a further 11.1 months of follow-up, were comparable with those reported at the first analysis, with no new or unexpected toxicities observed, and no evidence of cumulative toxicity. Conclusions: The improved efficacy outcomes and manageable tolerability observed with first-line ribociclib plus letrozole are maintained with longer follow-up, relative to letrozole monotherapy. Clinical trials number: NCT01958021.

[Association of low serum parathyroid hormone with protein-energy wasting in maintenance hemodialysis patients].

Objective: To examine the relationship between low serum parathyroid hormone (PTH) and protein-energy wasting (PEW) in patients who underwent maintenance hemodialysis (MHD) treatment. Methods: A cross-sectional study was conducted in MHD patients between June 2015 and August 2017 in 11 MHD centers from Guizhou province. Body composition and physical parameters were measured, clinical data and other related laboratory values were collected according to the medical record system. Participants were assigned to low serum PTH group (PTH<150 ng/L), target PTH group (150 ng/L≤ PTH ≤300 ng/L) and high serum PTH group (PTH>300 ng/L). Multivariate logistic regression analysis was used to analyze the relationship between low serum PTH and risk of PEW, which was diagnosed according to the diagnostic criteria recommened by the International Society of Renal Nutrition and Metabolism (ISRNM). Results: A total of 873 MHD patients (488 males and 385 females) were included in the final analysis, with a mean age of 55.0 (44.0, 67.0) years and a mean hemodialysis duration of 31.0(17.0, 54.0) months. In unadjusted model, low serum PTH group was associated with PEW (OR=2.12, 95% CI: 1.26-3.54, P=0.004), when compared with high serum PTH group. After adjustment for age and sex, low serum PTH group was still significantly associated with PEW (OR=2.09, 95% CI: 1.23-3.52, P=0.006). Further adjustment for diabetes and hypertension, the correlation between low serum PTH group and PEW was still significant (OR=2.02, 95% CI: 1.04-3.90, P=0.037). However, the correlation was not observed in target PTH group and high serum PTH group. Conclusion: Low serum PTH was associated with risk of PEW, regardless of age, sex, history of diabetes and hypertension, and thus it might be a promising indicator of PEW in MHD patients.

Association of betel nut chewing with exercise performance in a military male cohort: the CHIEF study.

INTRODUCTION: Betel nut chewing may cause obesity, neurohormonal activation and inflammation, possibly impairing exercise performances. METHODS: We examined the cross-sectional association in 4388 military male adults aged 18-50 years from the cardiorespiratory fitness in armed forces study in Taiwan between 2013 and 2014. The status of betel nut chewing was classified as current and former/never based on each participant's response to a questionnaire. Physical fitness was evaluated by three basic exercise tests including 3000 m running, 2 min sit-ups and 2 min push-ups. Multiple logistic regression for the best 10% and the worst 10% performers in each exercise, and linear regression were used to determine the relationship. RESULTS: There were 564 current chewers and 3824 non-current chewers for the analysis. The linear regression shows that current betel nut chewing was positively correlated with 3000 m running duration (r=0.37, p=0.042) after adjusting for age, service specialty, body mass index, exercise frequency and alcohol intake. In addition, the logistic regression shows that as compared with non-current chewers, current chewers had lower odds of being the top 10% performers in 2 min push-ups and higher odds of being the bottom 10% performers in 2 min sit-ups (ORs and 95% CIs: 0.71 (0.50 to 0.99) and 1.32 (1.00 to 1.75), respectively). However, the associations between betel nut chewing and physical fitness were all insignificant after further adjusting for current smoking. CONCLUSIONS: Our findings suggest that the impairment of physical fitness associated with betel nut chewing of military young men might be mainly mediated or moderated by the coexisted cigarette smoking.

Video-tactile pneumatic sensor for soft tissue elastic modulus estimation.

BACKGROUND: A new sensor for estimating elasticity of soft tissues such as a liver was developed for minimally invasive surgery application. METHODS: By measuring deformation and adjusting internal pressure of the pneumatic sensor head, the sensor can be used to do palpation (indentation) of tissues with wide range of stiffness. A video camera installed within the sensor shell is used to register the radius of the contact area. Based on finite element model simulations and the measured data, elastic modulus of the indented soft tissue can be calculated. RESULTS AND CONCLUSIONS: Three phantom materials, namely plastic, silicone and gelatin, with varied stiffness were tested. The experimental results demonstrated that the new sensor can obtain highly reliable data with error less than 5%. The new sensor might be served as an instrument in laparoscopic surgery for diagnosis of pathological tissues or internal organs.

Ventilation rates in recently constructed U.S. school classrooms.

Low ventilation rates (VRs) in schools have been associated with absenteeism, poorer academic performance, and teacher dissatisfaction. We measured VRs in 37 recently constructed or renovated and mechanically ventilated U.S. schools, including LEED and EnergyStar-certified buildings, using CO2 and the steady-state, build-up, decay, and transient mass balance methods. The transient mass balance method better matched conditions (specifically, changes in occupancy) and minimized biases seen in the other methods. During the school day, air change rates (ACRs) averaged 2.0±1.3 hour-1 , and only 22% of classrooms met recommended minimum ventilation rates. HVAC systems were shut off at the school day close, and ACRs dropped to 0.21±0.19 hour-1 . VRs did not differ by building type, although cost-cutting and comfort measures resulted in low VRs and potentially impaired IAQ. VRs were lower in schools that used unit ventilators or radiant heating, in smaller schools and in larger classrooms. The steady-state, build-up, and decay methods had significant limitations and biases, showing the need to confirm that these methods are appropriate. Findings highlight the need to increase VRs and to ensure that energy saving and comfort measures do not compromise ventilation and IAQ.

Particulate matter adheres to human hair exposed to severe aerial pollution: consequences for certain hair surface properties.

BACKGROUND: The deposit and adherence of particulate matter (PM) from aerial pollution onto the surface of human hair is a poorly studied phenomenon. OBJECTIVES: (i) To reproduce in vitro the deposit of known PM on standardized hair swatches in a closed box, (ii) to compare in vitro data with those obtained under 'real-life' conditions of severe aerial pollution and (iii) to assess the changes of the hair surface properties, potentially caused by the adherence of airborne PM onto the hair. METHODS: In vitro: a PM was sprayed onto untreated or sebum-coated hair swatches. Real-life conditions: other swatches were exposed to a severely polluted environment, for 24 to 72 h, in Baoding (PR China). In both cases, swatches were examined using scanning electron microscopy. The shine, the frictional properties and the level of metals were measured and compared to those same properties for the unexposed swatches. RESULTS: This work clearly indicates that, under real-life conditions, a large number of PM of various sizes are deposited onto the hair surface. This phenomenon is increased by the presence of sebum and longer exposure times. The in vitro level of PM deposited onto the hair surface is comparable to the in vivo level. The presence of sebum seems to favour the deposit of larger PM. The shine of the exposed swatches is significantly decreased, whereas their respective friction coefficients are significantly increased. Both the presence of sebum and length of exposure time increased the amount of analysed metals present on the exposed hair surface (Al, Fe, Cu, Ba and Zn). CONCLUSION: This work indicates that a very high amount (e.g. billions) of PM can be deposited on a full head of hair for subjects living in a severely aerially polluted environment. This process can be reproduced in vitro. In real-life, pollution has a strong impact on hair surface properties, leading to a modification of the visual aspect (loss of shine) and the alteration of hair surface (increase in friction force). This work may be used to pave the way for prevention and cleansing studies in the field of hair care.

[Preparation of chaperone-antigen peptide vaccine derived from human gastric cancer stem cells and its immune function].

Objective: To explore the method of extracting chaperone antigen peptide complexes from gastric cancer stem cells and its immune function. Methods: Gastric cancer stem cells and gastric cancer cells were screened by low temperature ultrasonic lysis. After salting out and dialysis, the lysate supernatant was processed with SDS-PAGE to analyze the expression of chaperone antigen peptide complexes, and then was separated and purified with CNBr-activated SepharoseTM 4B. Reverse high pressure liquid chromatography (HPLC), SDS-PAGE and Western blotting were used to analyze the purity and nature of the acquired albumen. Lymphocyte proliferation assay and lymphocytotoxicity assay were used to ditermine the immunological activity of the chaperone-antigen peptide complexes. Results: The chaperone antigen peptide complexes of gastric cancer stem cells were prepared and identified successfully, of which the main components were the antigen peptides of HSP60, HSP70, HSP90 and HSP110. 0.75 µg and 1.00 µg HSP70-antigen peptide and 1.00 µg HSP90-antigen peptide activated lymphocytes significantly. Their A(490) values were 0.26±0.03, 0.45±0.05 and 0.32±0.04, respectively, while the corresponding doses of HSP60-antigen peptide and HSP110-antigen peptide did not activate lymphocytes. The killing rates of 1.00 µg HSP70-antigen peptide and 1.00 µg HSP70 were (45.0±2.0)% and (16.0±2.0)%, respectively, showing a significant difference (P=0.012). Similarly, the killing rates of 1.00 µg HSP90-antigen peptide and 1.00 µg HSP90 were (36.0±5.0)% and (13.0±4.0)%, respectively, also showing a significant difference (P=0.048). Conclusions: The amount of chaperone antigen peptide complexes in gastric cancer cells is extremely low, but it is obviously increased in gastric cancer stem cells. After purification, the chaperone antigen peptide complexes with high purity can be prepared. The extracted chaperone antigen peptide complexes have stronger immunogenicity, and can be used to make tumor vaccine in vitro, which may have a good application value in the targeted therapy of gastric cancer.

The association between MR T1ρ and T2 of cartilage and patient-reported outcomes after ACL injury and reconstruction.

OBJECTIVE: To determine if cartilage T1ρ and T2 relaxation time measures after ACL injury and prior to reconstruction (baseline) are associated with patient-reported outcomes at baseline, 6-months, and 1-year after surgery. DESIGN: Fifty-four ACL-injured participants were scanned in both knees at baseline using 3T MR T1ρ and T2 mapping. Participants also completed Knee-injury and Osteoarthritis Outcome Score (KOOS) and Marx activity level questionnaires at baseline, 6-months, and 1-year after reconstruction. The difference between cartilage T1ρ or T2 of the injured and contralateral knee (side-to-side difference, SSD) was calculated to account for physiological variations among patients. Linear regression models were built to evaluate the association between the baseline SSD T1ρ or T2 and KOOS or Marx at all time points. RESULTS: Higher baseline SSD T1ρ posterolateral tibia (pLT) was associated with worse KOOS in all subscales except symptoms at baseline, worse KOOS pain at 6-months, and worse KOOS in all subscales except sports function at 1-year. Higher baseline SSD T2 femoral trochlea (TrF) was associated with worse KOOS activities of daily living (ADL) at 1-year. Higher baseline SSD T1ρ pLT was associated with lower Marx activity level at 1-year. More severe cartilage lesions, as assessed by Whole-Organ MRI Scoring (WORMS), was significantly associated with worse KOOS pain at 6-months and 1-year. CONCLUSION: T1ρ and T2 of cartilage after ACL injury were associated with KOOS after injury and both KOOS and Marx after reconstruction. Such associations may help clinicians stratify outcomes post-injury, and thus, improve patient management.

Identification of altered pathways in Down syndrome-associated congenital heart defects using an individualized pathway aberrance score.

The aim of this study was to identify disrupted pathways related to Down syndrome (DS), and DS-associated congenital heart defects (DS-CHD). The gene expression profile and pathway data of 10 human DS patients and 5 control samples in E-GEOD-1789 were recruited and analyzed by the individualized pathway aberrance score (iPAS) method, consisting of the data processing, gene-level statistics, pathway-level statistics, and significant measurement steps. The pre-processing step identified 12,493 genes and 1022 pathways (4269 genes). The pathway significant analysis identified eight pathways (adjusted P value <0.1) that differed between the disease and control samples. The cross-presentation of particulate exogenous antigen (phagosomes) and methionine salvage pathways showed the most significant differences among these. The gene expression levels of key pathway genes, such as CYBB and ADI1, were higher in disease samples than in normal controls. Based on our results, we predicted that the cross-presentation of particulate exogenous antigens (phagosomes) and the methionine salvage pathway could be good indicators of DS-CHD.

Reversal of cisplatin resistance in non-small cell lung cancer stem cells by Taxus chinensis var.

Drug resistance in cells is a major impedance to successful treatment of lung cancer. Taxus chinensis var. inhibits the growth of tumor cells and promotes the synthesis of interleukins 1 and 2 and tumor necrosis factor, enhancing immune function. In this study, T. chinensis var.-induced cell death was analyzed in lung cancer cells (H460) enriched for stem cell growth in a defined serum-free medium. Taxus-treated stem cells were also analyzed for Rhodamine 123 (Rh-123) expression by flow cytometry, and used as a standard functional indicator of MDR. The molecular basis of T. chinensis var.-mediated drug resistance was established by real-time PCR analysis of ABCC1, ABCB1, and lung resistance-related protein (LRP) mRNA, and western blot analysis of MRP1, MDR1, and LRP. Our results revealed that stem cells treated with higher doses of T. chinensis var. showed significantly lower growth inhibition rates than did H460 cells (P < 0.05). The growth of stem and H460 cells treated with a combination of T. chinensis var. and cisplatin was also significantly inhibited (P < 0.05). Rh-123 was significantly accumulated in the intracellular region and showed delayed efflux in stem cells treated with T. chinensis var. (P < 0.05), compared to those treated with verapamil. T. chinensis var.-treated stem cells showed significant downregulation of the ABCC1, ABCB1, and LRP mRNA and MRP1, MDR1, and LRP (P < 0.05) compared to H460 cells. Thus, T. chinensis var.-mediated downregulation of MRP1, MDR1, and LRP might contribute to the reversal of drug resistance in non-small cell lung cancer stem cells.