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Objective The aim of this study was to determine the therapeutic effect of piperlongumine on hypoxic pulmonary hypertension. Methods A hypoxic pulmonary hypertension rat model was constructed, primary rat pulmonary artery smooth muscle cells (PASMCs) were isolated, and the proliferation of PASMCs was measured by Cell Counting Kit‑8 assay. The expression of autophagic proteins microtubule-associated protein 1 light chain 3B (LC3B) and P62 were examined by western blot. Autophagic flux in PASMCs was detected by tandem mRFP-GFP-LC3 fluorescence analysis. Results Hypoxia-induced proliferation of PASMCs was significantly inhibited by piperlongumine exposure. Treatment with piperlongumine elevated LC3B II/LC3B I protein ratio and decreased the expression of P62 protein in both PASMCs and rat lung tissues. Tandem mRFP-GFP-LC3 fluorescence analysis showed that piperlongumine increased autophagic flux in PASMCs. Inhibition of autophagy using 3-methyladenine (3-MA) attenuated the inhibitory effect of piperlongumine on proliferation of PASMCs. Chronic hypoxia exposure led to a significant increase in rat right ventricle systolic pressure, right ventricular hypertrophy, wall thickness and area of pulmonary artery, and muscularization of pulmonary arterioles, which was obviously suppressed by administration of piperlongumine. 3-MA attenuated the alleviating effects of piperlongumine on pulmonary vascular remodeling. Conclusions Piperlongumine attenuates vascular remodeling in hypoxic pulmonary hypertension by regulating autophagy. Piperlongumine treatment may serve as a promising therapy for hypoxic pulmonary hypertension.

Objective: A large maxillary odontogenic cyst could intrude into the maxillary sinus. The traditional approach following surgery for such a cyst is the Caldwell-Luc procedure However the traditional CDL procedure is associated with more complications and damage of the sinus mucosa. The purpose of this study was to assess a new method with easier operation, which not only prevented postoperative infection but also caused less damage to the maxillary sinus mucosa.Methods: A large odontogenic cyst in the maxillary sinus of 40 patients was diagnosed through radiographic imaging and postoperative histopathology. Twenty patients were treated with maxillary sinus saline irrigation after cyst resection surgery, while 20 patients underwent the traditional Caldwell-Luc procedure. The therapeutic efficacy was evaluated by clinical examination and radiographic imaging; the longest follow-up was 36 months.Results: The postoperative recovery of the 20 patients treated with sinus irrigation. Six patients had mild swelling (30%), 12 had moderate swelling (60%), and 2 had severe swelling (10%); 16 had mild pain (80%), 4 had moderate pain (20%), and 0 had severe pain (0%). Among the 20 patients treated by the Caldwell-Luc approach. Immediately postoperatively, 2 patients had mild swelling (10%), 12 had moderate swelling (60%), and 6 had severe swelling (30%); 10 had mild pain (50%); 6 had moderate pain (30%), and 4 had severe pain (20%). On the second day after surgery, a mild temperature elevation (38.0°C-39.0°C) was noted in 8 patients (40%) treated with the Caldwell-Luc procedure and 1 patient (5%) treated with saline irrigation.Conclusion: Sinus irrigation following large odontogenic cyst surgery involving the maxillary sinus can serve as an alternative to standard CDL and has the advantages of fewer complications, reduced trauma, restoration of the mucosa and more satisfactory results.

Background Though BRCA1 mutation is the most susceptible factor of breast cancer, its prognostic value is disputable. Here in this study, we use a novel method which based on whole-genome analysis to evaluate the chromosome instability (CIN) value and identified the potential relationship between CIN and prognosis of breast cancer patients with germline-BRCA1 mutation. Materials and methods Sanger sequencing or a 98-gene panel sequencing assay was used to screen for BRCA1 germline small mutations in 1151 breast cancer patients with high-risk factors. MLPA assay was employed to screen BRCA1 large genomic rearrangements in familial breast cancer patients with BRCA1 negative for small mutations. Thirty-two samples with unique BRCA1 germline mutation patterns were further subjected to CIN evaluation by LPWGS (low-pass whole-genome sequencing) technology. Results Firstly, 113 patients with germline BRCA1 mutations were screened from the cohort. Further CIN analysis by the LPWGS assay indicated that CIN was independent from the mutation location or type of BRCA1. Patients with high CIN status had shorter disease-free survival rates (DFS) (HR = 6.54, 95% CI 1.30–32.98, P = 0.034). The TP53 copy loss was also characterized by LPWGS assay. The rates of TP53 copy loss in CIN high and CIN low groups were 85.71% (12/14) and 16.67% (3/18), respectively. Conclusion CIN-high is a prognostic factor correlated with shorter DFS and was independent with the germline BRCA1 mutation pattern. Higher CIN values were significantly correlated with TP53 copy loss in breast cancer patients with germline BRCA1 mutation. Our results revealed a reliable molecular parameter for distinguishing patients with poor prognosis from the BRCA1-mutated breast cancer patients.

Background Many clinical trials have assessed the effect and safety of monoclonal antibodies (MAbs) in combination with proteasome inhibitors or immunomodulators plus dexamethasone/prednisone for the treatment of multiple myeloma (MM). The treatment outcomes of comparing different MAbs in combination with the above-mentioned agents remained unclear. We performed the meta-analysis to indirectly compare the effect and safety of MAbs targeting CD38, SLAMF7, and PD-1/PD-L1 in combination with bortezomib/immunomodulators plus dexamethasone/prednisone for patients with MM. Methods We searched thoroughly in the databases for randomised controlled trials (RCTs) in which at least one of the three MAbs were included. We included eleven eligible RCTs with 5367 patients in the meta-analysis. Statistical analysis was carried out using StataMP14 and Indirect Treatment Comparisons software. Results We calculated hazard ratios (HRs) for overall survival (OS) and progression-free survival (PFS) and relative risk (RR) for overall response rate, complete response (CR) or better, very good partial response (VGPR) or better, VGPR, partial response, stable disease, and grade 3 or higher adverse events among the three groups. The HRs for PFS of the CD38 group vs SLAMF7 group, CD38 group vs PD-1/PD-L1 group, and SLAMF7 group vs PD-1/PD-L1 group were 0.662 (95%CI 0.543–0.806), 0.317 (95%CI 0.221–0.454), and 0.479 (95%CI 0.328–0.699), respectively. The HR for OS of the CD38 group vs SLAMF7 group was 0.812 (95%CI 0.584–1.127). The RR for CR or better in the CD38 group vs SLAMF7 group was 2.253 (95%CI 1.284–3.955). The RR for neutropenia of the CD38 group vs SLAMF7 group was 1.818 (95%CI 1.41–2.344). Conclusions Treatment with the CD38 group had longer PFS and better treatment response than that with the SLAMF7 or PD-1/PD-L1 group. In addition, the SLAMF7 group prolonged PFS compared with the PD-1/PD-L1 group and was associated with a lower incidence of grade 3 or higher neutropenia than the CD38 and PD-1/PD-L1 group. In conclusion, MAbs targeting CD38 are the best, followed by those targeting SLAMF7; MAbs targeting PD-1/PD-L1 are the worst when in combination with bortezomib/immunomodulators plus dexamethasone/prednisone for the treatment of MM.

Background Previous case reports have shown the promising antitumor activity of everolimus in solid tumors containing molecular aberrations in PI3K/ATK/mTOR pathway, however, whether it is effective in patients with breast cancer remains unknown. Therefore, we conducted this retrospective cohort study to compare the efficacy of molecularly matched targeted therapy with everolimus to conventional therapy in refractory breast cancer patients harboring PI3K/ATK/mTOR pathway activating mutations. Methods Refractory metastatic breast cancer patients who have received molecular screening using next‐generation sequencing (NGS) between September 8, 2015 and October 30, 2017 in two sites were screened for this study. The primary outcome was progression‐free survival (PFS). The secondary outcomes were overall response rate (ORR), disease control rate (DCR), and safety profile. Results A total of 78 patients were screened for analysis, amongst all, 52 (66.7%) had at least one gene mutation in PI3K/AKT/mTOR pathway. The most common mutation fell in PIK3CA (76.9%, 40/52) with a mutational prevalence of 51.3%. Of the 32 patients who were eligible for efficacy analysis, patients in the everolimus group (n = 19) exhibited shorter PFS than those in the conventional group (n = 13) (median, 1.9 vs 6.1 months; HR, 3.6; 95% CI, 1.48‐8.81; P = .0005). ORR was 15.4% (2/13) in the everolimus group and 23.1% (3/13) in the conventional group (P = 1.000), and DCR was 30.8% (4/13) and 100% (13/13) for each group, respectively (P = .000). The incidence of grade 3‐5 adverse events was relatively higher in the conventional group (38.5%, 5/13) than that in the everolimus group (26.3%, 5/19). Conclusions Our findings suggested that everolimus might not be effective for cancer patients harboring mutations in PI3K/ATK/mTOR pathway and physicians should be cautious about its off‐label use in clinical practice., About 66.7% of patients with refractory breast cancer had at least one gene mutation in PI3K/AKT/mTOR pathway. Off‐label use of everolimus might not provide sufficient benefit for refractory breast cancer patients harboring PI3K/AKT/mTOR pathway mutations.

Chromosomal instabilities (CIN) of plasma cell-free DNA (cfDNA) are common in breast cancer. We aimed to investigate the value of cfDNA CIN in monitoring the breast cancer relapse and additionally to compare it with the traditional biomarkers (CA15-3 and CEA). Overall 62 recurrent breast cancer patients and 20 healthy controls were recruited. Low-pass whole-genome sequencing (LPWGS) was performed to detect cfDNA CIN. A CIN score was calculated. The performance of CA15-3, CEA, and CIN score in monitoring the recurrence was investigated with receiver operating characteristic (ROC) curve and the area under curve (AUC). Multivariable Cox proportional hazard model was established to analyze the correlations between copy number gain/loss and disease-free survival (DFS). cfDNA CIN achieved the positive rate of 77.6% [(95% confidence interval (CI) 73.4–95.3%)] among recurrent breast cancer patients, with an AUC value of 0.933, superior to CA15-3 (positive rate: 38.7%; AUC: 0.864) and CEA (positive rate: 41.93%; AUC: 0.878) (P

Objective. Aspirin usage is associated with increased risk of gastrointestinal bleeding. The present study explored the potential of teprenone, an antiulcerative, in preventing aspirin-related gastric mucosal injuries. Methods. 280 patients with coronary diseases, naïve to aspirin medication, were admitted between 2011 and 2013 at the First Affiliated Hospital of Zhejiang Chinese Medical University and randomized into two groups (n=140). The aspirin group received aspirin enteric-coated tablets 100 mg/day, while the aspirin+teprenone group received teprenone 50 mg 3 times/day along with aspirin. The patients were recorded for gastrointestinal symptoms and gastric mucosal injuries during a follow-up period of 12 months with 3-month intervals. Results. During the 3-month follow-up, no significant difference was observed in the incidence rate of gastrointestinal symptoms between the two groups (P=0.498). However, the incidence rate of gastrointestinal symptoms was significantly lower in the aspirin+teprenone group than in the aspirin group during the follow-ups at 6 months (P=0.036) and 12 months (P=0.036). The incidence rate of gastric mucosal injuries in the aspirin group was significantly increased at 12 months compared to that at 3 months (P=0.016). The incidence rates at 12 months and cumulative for the entire follow-up period in the aspirin+teprenone group were both significantly lower than those of the aspirin group (P=0.049 and P=0.001, respectively). Conclusion. Long-term use of low-dose aspirin causes varying degrees of gastric mucosal damages and gastrointestinal symptoms; the severity will increase within a certain range with the extension of medication duration. Teprenone mitigates the gastrointestinal symptoms caused by low-dose aspirin, lowering both the incidence and severity of gastric mucosal injuries and exerting a positive protective effect.

Metastatic breast cancer (MBC) is the most life-threatening disease in women worldwide. HER2-mutated breast carcinoma has been reported to benefit from HER2-targeted tyrosine kinase inhibitors recently. Here, we presented a heavy pretreated and harbored HER2 V777L mutation de novo stage IV Luminal B (HER2 unamplified) breast cancer patient who achieved an unexpected good response to trastuzumab combined with vinorelbine therapy. Although HER2-unamplified MBC patients do not regularly benefit from anti-HER2 target therapy, HER2 V777L mutation detected by next-generation sequencing from ctDNA may present as a predictive biomarker for anti-HER2-based strategy therapy in HER2-negative MBC patients.

We evaluated whether knees and hips are the key regions to anticipate an opponent’s cutting directions by using the kinematics method during different cutting tasks. Eighteen male university divisi...

Background: More and more germline gene mutations have been discovered in hematological malignances with the development of next gene sequencing (NGS). Tet methylcytosine dioxygenase 2 (TET2) is one of the most common mutation genes in hematological neoplasms. We aimed to analyzed whether germline TET2 mutation has a family aggregation or is a tumor predisposition gene. Further we compared its impact with somatic TET2 mutation in hematological diseases.Methods: A total cohort of 103 hematological patients with TET2 mutation were included from December 2016 to December 2019. Data were extracted from hematology department of West China Hospital of Sichuan University. Bone marrow (BM) or peripheral blood (PB) as somatic DNA origin to be detected by next-generation sequencing (NGS), and nails and hairs as germline DNA origin to be detected by Sanger sequencing, respectively. Further, we compared the clinical characteristics between the patients with germline and somatic TET2 mutation.Results: 103 patients were included, including 33 (32.03%) patients with germline TET2 mutation and 70 (67.97%) patients with somatic TET2 mutation. Variant allele frequency (VAF) of germline TET2 mutation was more stable in our study, ranging from 40% to 55% and mutation sites were more concentrated. Patients with germline TET2 mutation were younger with median age 48 (range, 16-82) (P=0.0078). Further, patients with germline TET2 mutation were mainly myelodysplastic syndromes (MDS) (n=13, 39.4%), while patients with somatic TET2 mutation were acute myeloid leukemia (AML) (n=28, 40.0%) (P=0.0003). Germline TET2 mutation affected the distribution of peripheral blood cell count and the proportion in bone marrow (PP=0.0209), but not in multivariate analysis by Cox regression model (P=0.062).Conclusions: Some family members were asymptomatic carriers, which indicated germline TET2 mutation might have a family aggregation. More importantly, TET2 gene may be a predisposition gene of hematological malignant when the other gene mutations as the second hit. The VAF of germline TET2 mutation is more stable. At the same time, the germline TET2 mutation may be an adverse factor for the MDS patients.

Objective We performed a retrospective cohort study to investigate the prevalence of and risk factors for asymptomatic spondylotic cervical spinal stenosis (ASCSS) in the setting of lumbar spinal stenosis (LSS). Methods A total of 114 patients with a diagnosis of LSS without cervical myelopathy and radiculopathy were grouped into ASCSS and non-ASCSS groups. The medical data and radiological parameters, including age, sex, body mass index, Charlson comorbidity index, symptom duration, redundant nerve roots, dural sac cross-sectional area (DCSA), facet joint angle, lumbar lordosis angle (LLA), pelvic incidence (PI), Torg-Pavlov ratio, and lumbosacral transitional vertebrae, were analyzed. The lumbar stenosis index and cervical stenosis index of the 114 patients were also analyzed. Results ASCSS occurred in 70 of the 114 patients with LSS (61.4%). The two groups showed significant differences in symptom duration, redundant nerve roots, LLA, DCSA, and PI. On multivariate logistic regression analysis, an LLA >35.85° (P Conclusions Our findings suggest that an LLA >35.85° and a DCSA

Endocrine treatment plus CDK4/6 inhibitors have become standard of care for estrogen receptor positive (ER+) breast cancer. Although immune checkpoint inhibitors (ICIs) have shown promising antitumor activity in a variety of cancer types, only limited success has been achieved for metastatic breast cancer (mBC) patients, especially the ER+ subtype, which usually exhibit lower tumor mutation burden (TMB) compared with other subtypes and therefore perceived as immunologically quiescent. Here we present a case of an ER+/HER2- but TMB-high mBC patient who had significant response to combination therapy with anti-PD-1 antibody camrelizumab and vinorelbine and obtained partial response (PR) with a progression-free survival (PFS) of 5 months after failure of multiple lines of therapy. Our case indicates that TMB may serve as a potential biomarker in immunotherapy selection for normally immunologically “cold” tumors such as ER+ mBC, also molecular monitoring during the whole treatment course plays an important role in patient management.

In this paper, the day-ahead optimal dispatching model of power system that is combined by wind-photovoltaic-hydropower-thermal-pumped storage is established. Firstly, according to the characteristics of the short-term hydropower system dispatching problem, a new mathematical model of the cascade hydropower group system with pumped storage power stations is proposed. The coordinated optimized dispatching model of the hydropower group system formed by the cascading of pumped storage power plants and conventional hydropower in the power system is studied. Secondly, the opportunity constraint programming model of forecast error reserve is used to deal with the output uncertainty of wind power and photovoltaic. The randomness and intermittency of renewable energy on the stability of the power system are overcame by the combination of wind-photovoltaic-pumped storage. Thirdly, the model for the joint optimal dispatch of short-term wind, photovoltaic, hydropower and thermal power systems with pumped storage is developed with system economics as the goal. Fourthly, the operation volatility coefficient of thermal power units is proposed to study the impact of renewable energy on the operation of thermal power. Finally, an example system is used to verify the correctness of the proposed dispatching optimal scheduling model, and the results prove that the daily dispatch optimization model proposed in this paper can increase the economic efficiency of the power system by 5%, reduce the start-stop times of thermal power units by 36.55%, and reduce the fluctuation coefficient of the unit by 2.8.

Purpose Intestinal microbiota disorders can aggravate pulmonary inflammation during acute lung injury (ALI). Rhubarb, a Chinese herb, can regulated the gut microbiota. Therefore, this study was conducted to test the hypothesis that rhubarb alleviates gut microbiota dysbiosis and inflammation. Methods Feces were collected from patients with ALI to detect the gut microbiota using 16S rDNA sequencing. Subsequently, a mouse model of ALI was established using lipopolysaccharide to investigate changes in the gut microbiota, the periperal blood was attained for detecting the Th17/Treg cell ratio and the serum level of HDAC6 and HDAC9, and the effect of rhubarb treatment on the gut microbiota and Th17/Treg ratio were also evaluated. Results Both the Firmicutes phyla decreased and the Bacteroidetes increased were identified in patients with ALI, which induced the alternation of histone metabolites. The rat models also showed a similar imbalance in the Firmicutes/Bacteroidetes ratio. Rhubarb treatment alleviated the damaged lung tissue, accelerated Alistipes, Clostridiales and Lactobacillus proliferation, increased the level of HDAC6 in both the mice lung tissue and serum, and markedly reduced the Treg cells and increased the Th17 cells in the spleen tissue. Conclusion we determined that both patients and mouse models presented gut microbiota dysbiosis and Th17/Treg cell imbalances. Rhubarb promoted Alistipes, Clostridiales and Lactobacillus proliferation, increased the HDAC6 concentration, restored the Th17/Treg cell balance, and protected against ALI.

This study was to investigate the efficacy and safety of fulvestrant 500 mg for the treatment of hormone receptor positive advanced postmenopausal women, including ovarian ablation and investigated factors associated with prolonged time-to-treatment failure. Data from 60 women with metastatic breast cancer who were treated at Zhejiang Cancer Hospital. Patients received 500 mg (n = 60) between December 2011 and November 2012 were followed until November 2017. Main outcomes were clinical responses to fulvestrant, including best response, progressive disease, partial response, and stable disease lasting 12 months or more. Time to progression and time to progression-free-survival were also analyzed. Among the included 60 patients (mean age 47.18 years), 51 (85.0%) had received prior adjuvant therapy. During follow-up after fulvestrant treatment, the median PFS for the best response was derived as 7.0 months (inter-quartile = 4, 13.8 months). The observed median progression-free-survival time for best response was represented longer when fulvestrant was first-line treatment than when patients received prior endocrine and/or chemotherapy. Univariate analysis revealed that receiving either endocrine therapy only or endocrine therapy plus chemotherapy prior to fulvestrant treatment may be associated with median progression-free survival time to best response (P = .002, .026, .007, respectively). Fulvestrant treatment is safe and well-tolerated in women with hormone-sensitive advanced breast cancer, and first-line fulvestrant therapy increases progression-free-survival time, especially in patients without prior adjuvant treatment.

Background The meta-analysis compared the efficacy and safety of momelotinib, ruxolitinib and pacitinib in patients with myeloproliferative neoplasms(MPN), which includes essential thrombocythemia, polycythemia vera and primary myelofibrosis. Methods We searched multiple databases and collected relevant studies before Dec. 20,2019. According to predefined criteria, we included eight qualified phase 3 randomized controlled trials with 2125 patients in the meta-analysis. Statistical analysis used StataMP14 and Indirect Treatment Comparisons software. The meta-analysis is registered with PROSPERO, number CRD42020164271. Results The relative risk (95%confidence interval) of momelotinib vs ruxolitinib, ruxolitinib vs pacritinib and momelotinib vs pacritinib by indirect-comparison are as follows: The RR(95%CI) for ≥ 35% reduction in spleen volume from baseline at week 24/32 as determined by magnetic resonance imaging or computed tomography were 0.93(95%CI0.69-1.25), 10.87(95%CI2.52-46.79) and 10.09(95%CI2.27- 44.74); The RR(95%CI) for ≥ 50% reduction in total symptom score from baseline at week 24–32 assessed using the modified Myelofibrosis Symptom Assessment Form were 1.61(95%CI0.25-10.15), 4.40(95%CI2.13-9.09) and 7.12 (95%CI0.91-55.41); The RR(95%CI) for the risk of anemia were 0.60(95%CI0.20-1.85), 0.80(95%CI0.56-1.14) and 0.48 (95%CI0.15-1.56); The RR(95%CI) for thrombocytopenia were 0.69(95%CI0.50-0.96), 1.33(95%CI0.77-2.30) and 0.92(95%CI0.48-1.74); The RR (95%CI) for the risk of fatigue were 1.07(95%CI0.71-1.59), 0.82(95%CI0.49-1.37) and 0.88(95%CI0.46-1.68); The RR(95%CI) for the risk of diarrhea were 1.32(95%CI0.58-3.01), 0.11(95%CI0.03-0.46) and 0.39(95%CI0.15-1.02); The RR(95%CI) for abdominal pain were 0.95(95%CI0.61-1.48), 0.83(95%CI0.30-2.25) and 0.78(95%CI0.26-2.35). The RR(95CI) for the improvement of transfusion-independent of pacritinib vs ruxolitinib was 6.36 (95%CI0.79-50.98). Conclusions Excluding the improvement of transfusion-independent and the risk of thrombocytopenia, pacritinib had relatively poorer efficacy and higher risk of adverse events compared with momelotinib or ruxolitinib. Momelotinib had similar or better efficacy and similar or lower risk of adverse events than ruxolitinib while excluding the risk of diarrhea. In general, momelotinib has the best potential therapeutic value in patients with MPN among the three drugs, but further clinical studies are needed to prove it.

Aim: This study aimed to investigate the relationship between clinicopathological characteristics of atypical meningiomas (AM) and its post-operative recurrence. Materials and Methods: The clinicopathological characteristics and findings from follow up were retrospectively reviewed and compared between AM and benign meningioma (BM) patients. Univariate and multivariate analyses were employed to identify the factors related to the post-operative recurrence of AM. Results: More BM patients were females and received complete resection; the recurrence rate was significantly lower in BM patients as compared to AM patients. The progesterone receptor (PR), E-cadherin protein (E-Ca) and β-catenin positive rates and Ki67 labeling index were significantly different between two groups. Univariate analysis showed the age, tumor size, tumor invasiveness, E-Ca expression, and extent of resection were related to the post-operative recurrence of AM. However, multivariate analysis showed only the extent of resection and tumor invasiveness were the independent factors associated with the post-operative recurrence of AM. Conclusions: The extent of resection and tumor invasiveness are related to the post-operative recurrence of AM. To improve the surgical procedures to maximize the tumor resection is important to improve the prognosis of AM patients.

SIGNIFICANCE This study provides a descriptive characterization of higher-order optical aberrations for the eyes of a larger number of Chinese children and adolescents. PURPOSE To determine the distribution of higher-order aberrations (HOAs) of Han Chinese young subjects with normal vision and their relationship to age. METHODS Children and adolescents, aged from 3 to 17 years, with normal visual acuity were enrolled, and their wavefront aberrations for a 6-mm pupil were evaluated by the Zywave II aberrometer. Their correlations with age were analyzed, and the 95% statistical reference ranges were computed for each Zernike term. RESULTS A total of 1634 eyes (287 for preschool-age children, 897 for school-age children, and 450 for adolescents) were analyzed. There was a significant correlation with age and the root mean square (RMS) of total HOAs (r = 0.256, P < .0001), third-order aberrations (r = 0.062, P = .029), fourth-order aberrations (r = 0.197, P < .0001), fifth-order aberrations (r = 0.067, P = .017), and trefoil-like aberrations (r = 0.100, P < .0001) in the myopic group. There were significant differences in RMS values (except coma-like aberrations, χ = 4.179, P = .124) as well as the Zernike coefficients among three different age groups. Therefore, the 95% statistical normal reference values were calculated separately for three age groups. CONCLUSIONS The RMS value of total HOAs, coma-like, trefoil-like, third-order, fourth-order, and fifth-order aberrations are correlated with age, and the RMS values and Zernike coefficients of aberrations were different in different age stages of the subjects. This study described the distribution of HOAs in children and adolescents and established 95% statistical normal values of HOAs for different ages of children and adolescents by analyzing the HOAs in a large number of the Han Chinese clinical population.

Natural language understanding (NLU) aims at identifying user intent and extracting semantic slots. This requires sufficient annotating data to get considerable performance in real-world situations. Active learning (AL) has been well-studied to decrease the needed amount of the annotating data and successfully applied to NLU. However, no research has been done on investigating how the relation information between intents and slots can improve the efficiency of AL algorithms. In this paper, we propose a multitask AL framework for NLU. Our framework enables pool-based AL algorithms to make use of the relation information between sub-tasks provided by a joint model, and we propose an efficient computation for the entropy of a joint model. Experimental results show our framework can achieve competitive performance with less training data than baseline methods on all datasets. We also demonstrate that when using the entropy as the query strategy, the model with complete relation information can perform better than those with partial information. Additionally, we demonstrate that the efficiency of these active learning algorithms in our framework is still effective when incorporate with the Bidirectional Encoder Representations from Transformers (BERT).

e13069 Background: The PI3K/AKT/mTOR pathway is frequently altered in breast cancer. Everolimus is a selective inhibitor of mammalian target of Rapamycin (mTOR).The benefit of everolimus in metastatic breast cancer patients with PI3K/AKT/mTOR mutations remains unclear, especially in TNBC patients. Our study aimed to investigate the efficacy of the everolimus-containing chemotherapy in metastatic breast cancer patients with PI3K/AKT/mTOR mutations. Methods: 13 cases of HER2- metastatic breast cancer with PI3K/AKT/mTOR mutations treated with everolimus-containing chemotherapy were analyzed. The genetic profile in PI3K/AKT/mTOR pathway was studied. Results: Overall, 4 cases were hormone receptor (HR) positive and 9 were TNBC. 7 patients only had PIK3CA mutations, 1 patient had only PIK3R1 mutations, and 5 patients had other mutations in the pathway in addition to PIK3CA, including PTEN, PIK3CB, CTNNB1, FGFR1 and TSC2. 5 cases were treated as first or second line chemotherapy, and 8 were as third line or above. The ORR (CR+PR) was 38.5% (5/13), and DCR (CR+PR+SD) was 84.6% (11/13), including 5 cases of PR, 6 cases of SD, and 2 cases of PD. The median PFS was 5.8 months (95% CI 3.7-9.7), and the median OS was 14.3 months (95% CI 6.47-null). However, the ORR of TNBC patients was higher than that of HR-positive, which were 44.4% (4/9) and 25% (1/4), respectively ( p = 0.070). The mPFS was also longer than that of HR-positive with 5.8 months versus 1.7 months, as well as the mOS with 14.3 versus 3.8 months. We also found that the patients carrying other mutations besides PIK3CA in the PI3K/AKT/mTOR pathway had a longer PFS compared to the patients without other mutations, which was 9.7 months and 4.3 months respectively ( p = 0.272). And the DCR of the two groups were 100% and 75% respectively ( p = 0.451). Conclusions: We found that everolimus-containing chemotherapy was effective in the treatment of HER2- metastatic breast cancer with PI3K/AKT/mTOR pathway activation. TNBC patients had a trend of longer mPFS than HR+ patients. And the patients carrying other mutations besides PIK3CA in the PI3K/AKT/mTOR pathway have a trend of longer PFS and higher DCR compared to the patients without other mutations. However, trails with larger samples are needed for further verification.

BACKGROUND: Palbociclib combined with endocrine therapy has been approved as a front-line treatment for hormone receptor positive (HR+), human epidermal growth factor receptor 2 negative (HER2−) advanced breast cancer (ABC). A key challenge remains to uncover biomarkers to identify those patients who may benefit from palbociclib treatment. METHODS: We retrospectively analyzed the values of Ki67 and progesterone receptor (PR) as detected by immunohistochemistry in 81 ABC patients with palbociclib and hormone therapy treatment, and evaluated the impact on progression-free survival (PFS). RESULTS: In the total population, women with Ki67 ≥14% had marginally significantly shorter PFS than those with Ki67

Background: Endocrine therapy(ET) and Chemotherapy(CT) are used as standard maintenance therapy for HR+ and HER2- metastatic breast cancer(MBC) in clinical practice. There was no prospective study data on which is better. In OVERSTEP, we provide some strong evidence for clinical practice. Methods: OVERSTEP(NCT02597868) is a multicenter, randomized, open-label, prospective clinical trial that enrolled 181 patients in China. patients aged 18-70 years without chemotherapy for ABC/MBC previously, histologically confirmed metastatic HR+ and HER2- breast cancer, and ECOG performance status of 0-1. These patients were received capecitabine plus another chemotherapy drug as 1st-line salvage chemotherapy at least 4 cycles. The patients response are CR, PR and SD carried maintenance treatment next, randomly assigned (1:1) to receive either capecitabine single or endocrine therapy. Randomization was done centrally with stratification by endocrine resistance and visceral metastasis. The primary endpoint was progression-free survival(PFS) and analyses were base on all patients who received at least one dose maintenance therapy. We take superiority test in the 2 groups. Results: 136(75.14%) patients were randomized after combined chemotherapy to capecitabine single or endocrine therapy groups for maintenance treatment. 45(24.86%) patients are progress disease (PD) after combined chemotherapy. After a median follow-up of 24.3 months (IQR 20.46-37.25 ) in the endocrine maintenance therapy group and 24.1 months(IQR 20.67-36.77) in the Capecitabine maintenance therapy group ,the hazard ratio for PFS was 0.625(95%CI 0.429-0.909 P=0.013),Median PFS was 17.5 months(95%CI 11.544-23.856) in endocrine maintenance therapy group and 12,2 months(95%CI 11.170-13.230) in capecitabine maintenance therapy group. In endocrine sensitive group, the hazard ratio for PFS was 0.515(95%CI0.269-0.988 P=0.042), Median PFS was 29.3 months(95%CI 14.605-43.995) in endocrine maintenance therapy group and 14.8 months(95%CI 7.445-22.155) in capecitabine maintenance therapy group. In endocrine resistance group, the hazard ratio for PFS was 0.791(95%CI 0.499-1.253 P=0.314), Median PFS was 13.6 months(95%CI 9.111-18.089) in endocrine maintenance therapy group and 12.0 months(95%CI10.357-13.643) in capecitabine maintenance therapy group. In visceral metastasis group, the hazard ratio for PFS was 0.668(95%CI0.410-1.089 P=0.101), Median PFS was 14.3 months(95%CI 11.113-17.487) in endocrine maintenance therapy group and 11.0 months(95%CI 8.140-13.860) in capecitabine maintenance therapy group. In non-visceral metastasis group, the hazard ratio for PFS was 0.54(95%CI0.300-0.972 P=0.037), Median PFS was 25.3 months(95%CI 15.278-35.322) in endocrine maintenance therapy group and 17.0months(95%CI 10.783-23.217) in capecitabine maintenance therapy group. Conclusions: For HR+ and HER2- MBC, after 1st-line salvage combined chemotherapy, ET maintenance has a better survival benefits than CT,especially for ET-sensitive and non-visceral involved cases. So ET maintenance is the first choice for ABC/MBC after 1st-line combined chemotherapy. Citation Format: Jian Huang, Xiying Shao, Li Cai, Yanxia Shi, Zhanhong Chen, Ping Huang, Yongmei Yin, Lili Zhang, Peng Shen, Wenming Cao, Weiwu Ye, Yuan Huang, Caijin Lou, Lei Lei, Yabin Zheng, Weibin Zou, Junqing Chen, Xiaojia Wang. Primary analysis of OVERSTEP: A multicenter, randomized clinical trial of capecitabine or endocrine therapy as a maintenance therapy after the 1st-line chemotherapy in hormone receptor positive and HER2-negative advanced/metastatic breast cancer [abstract]. In: Proceedings of the 2020 San Antonio Breast Cancer Virtual Symposium; 2020 Dec 8-11; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2021;81(4 Suppl):Abstract nr PS13-01.

Reversion mutations are associated with clinical resistance to poly(ADP-ribose) polymerase inhibitors (PARPi). Here, we describe the detection of a BRCA1 reversion mutation in a 39-year-old woman with metastatic breast cancer harboring a heterozygous germline BRCA1 exons 7–8 deletion who received PARPi olaparib combined with immune checkpoint inhibitor camrelizumab as third-line therapy. During progression from the olaparib and camrelizumab combination therapy, we identified via genomic sequencing a novel 7-base pair somatic deletion in BRCA1 (c.617_623delACAAATC). Sequence analyses indicated that this mutation realigned the reading frame of BRCA1, which potentially led to the reversal of its normal function and conferred resistance to PARPi.

BACKGROUND Pentraxin 3 is an acute inflammatory protein of the long pentraxin subfamily. A meta-analysis was performed to assess diagnostic accuracy of pentraxin 3 for respiratory tract infections. METHODS We identify studies examining diagnostic value of pentraxin 3 for respiratory tract infections by searching Pubmed, Web of Knowledge, and Cochrane Library. The sensitivity, specificity, negative likelihood ratio (LR), positive LR, and diagnostic odds ratio were pooled. The area under the summary receiver operator characteristic (SROC) curve and Q point value (Q*) were calculated. RESULTS A total of 8 studies with 961 individuals were eligible for this meta-analysis. The pooled sensitivity of pentraxin 3 in diagnosis of respiratory tract infections was 0.78, the pooled specificity was 0.73, the area under the SROC curve was 0.84, and the Q* was 0.77. The area under the SROC curve of serum and bronchoalveolar lavage fluid (BALF) pentraxin 3 was 0.85 and 0.89, respectively. Meta-regression analysis revealed that cutoff value was the source of heterogeneity among the included studies. The Deek funnel plot test suggested no evidence of publication bias. Subgroup analyses showed that the area under the SROC curve of pentraxin 3 in diagnosis of ventilator-associated pneumonia (VAP) was 0.89. CONCLUSION Pentraxin 3 has a moderate accuracy for diagnosing respiratory tract infections and VAP. The overall diagnostic value of BALF level of pentraxin 3 is superior to its serum concentration.

To investigate gender differences of the associations between hyperuricemia and diabetic kidney disease (DKD) in elderly patients with type 2 diabetes mellitus (T2DM) based on electronic health records (EHR).A total of 20,207 older diabetic patients (mean age 71±7years) were investigated based on the EHR from 2012 to 2013 in the Minhang District of Shanghai-China. The status of hyperuricemia, albuminuric DKD and the odds ratios of DKD relative to hyperuricemia were analyzed among 8541 men and 11,666 women.The overall rate of hyperuricemia was 20.5% (males: 17.2%, females: 23.0%) and that of albuminuric DKD was 36.2% (males: 32.2%, female: 39.1%) in these diabetic patients. Hyperuricemia was independently associated with increased risk of reduced renal function and albuminuria (p0.001) in both genders. After adjustment of traditional DKD risk factors, hyperuricemia had a stronger association with albuminuric DKD in males (OR 1.67, 95% CI: 1.48-1.88) than in females (OR 1.23, 95% CI: 1.12-1.35).This study showed an independent association of hyperuricemia with albuminuric DKD that was stronger in elderly males for the first time in China based on EHR. The level of uric acid should be monitored and managed in older diabetic patients.

Objectives Endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA) is a minimally invasive technique. A meta-analysis was performed to assess the efficacy and safety of EBUS-TBNA in intrathoracic tuberculosis (TB). Methods We searched PubMed, the Cochrane Library, and the Web of Science for suitable studies. The pooled sensitivity, specificity, likelihood ratios (LRs), and diagnostic odds ratio were calculated. A summary receiver operating characteristic (ROC) curve was constructed to calculate the area under the summary ROC curve and Qpoint value (Q*). Results A total of 8 studies with 809 patients were included. The pooled sensitivity and specificity of EBUS-TBNA for diagnosis of intrathoracic TB were 0.80 (95% confidence interval [CI] 0.74–0.85) and 1.00 (95% CI, 0.99–1.00), respectively. The positive LR was 38.25 (95% CI, 13.59–107.65); the negative LR was 0.24 (95% CI, 0.17–0.33); and the diagnostic odds ratio was 186.35 (95% CI, 63.57–546.28). The area under the summary ROC curve was 0.935, and the Q*was 0.871. The pooled sensitivity of EBUS-TBNA for diagnosis of intrathoracic tuberculous lymphadenopathy was 0.87 (95% CI, 0.80–0.95). Only 1 serious complication was reported. Conclusions Endobronchial US-guided TBNA is an effective and safe diagnostic tool for intrathoracic TB, especially intrathoracic tuberculous lymphadenopathy.

Aircraft environmental control system uses the engine compressor air source in general, through the air compressor air conditioning and pressure regulation, and then sent bleed air into the cockpit and equipment cabin. This kind of system is Known as bleed-air environment control system. The system requires an air bleed from the engine compressor, which can adversely affect the performance of the engine: as the air intake increases, the effective power of the engine decreases and the actual thrust is reduced. To enhance the performance of the engine, should try to reduce the amount of bleed air. Based on Flowmaster, the environmental control system of a certain type of aircraft is simulated and the bleed air volume is reduced through the optimal design, which can provide some reference for the modification of the environmental control system of aircraft.

GPS can provide continuous heading information, but the accuracy is easily affected by the velocity and shelter from buildings or trees. For vehicle systems, we propose a low-cost heading angle update algorithm. Based on the GPS/INS integrated navigation kalman filter, we add the GPS heading angle to the measurement vector, and establish its error model. The experiment results show that this algorithm can effectively improve the accuracy of GPS heading angle.

In this paper, we introduce a web-scale general visual search system deployed in Microsoft Bing. The system accommodates tens of billions of images in the index, with thousands of features for each image, and can respond in less than 200 ms. In order to overcome the challenges in relevance, latency, and scalability in such large scale of data, we employ a cascaded learning-to-rank framework based on various latest deep learning visual features, and deploy in a distributed heterogeneous computing platform. Quantitative and qualitative experiments show that our system is able to support various applications on Bing website and apps.

The human hand gesture can record and reproduce the posture and action information of the hand, which is of great significance to people’s production and life. This paper has improved the existing data gloves based on micro inertial technology, and integrates the magnetic field localization method into finger gesture measurements. The strap down inertial navigation technology and the magnetic localization technology are combined in this paper to make the advantages complement each other, and a low cost and high degree of freedom of data gloves are put forward to realize the way of data gloves in the past.

Tractography based on non-invasive diffusion imaging is central to the study of human brain connectivity. To date, the approach has not been systematically validated in ground truth studies. Based on a simulated human brain data set with ground truth tracts, we organized an open international tractography challenge, which resulted in 96 distinct submissions from 20 research groups. Here, we report the encouraging finding that most state-of-the-art algorithms produce tractograms containing 90% of the ground truth bundles (to at least some extent). However, the same tractograms contain many more invalid than valid bundles, and half of these invalid bundles occur systematically across research groups. Taken together, our results demonstrate and confirm fundamental ambiguities inherent in tract reconstruction based on orientation information alone, which need to be considered when interpreting tractography and connectivity results. Our approach provides a novel framework for estimating reliability of tractography and encourages innovation to address its current limitations., Though tractography is widely used, it has not been systematically validated. Here, authors report results from 20 groups showing that many tractography algorithms produce both valid and invalid bundles.

Observational studies suggest an association between fruit and vegetables intake and risk of bladder cancer, but the results are controversial.We therefore summarized the evidence from observational studies in categorical, linear, and nonlinear, dose-response meta-analysis. Pertinent studies were identified by searching EMBASE and PubMed from their inception to August 2013.Thirty-one observational studies involving 12,610 cases and 1,121,649 participants were included. The combined rate ratio (RR, 95 % CI) of bladder cancer for the highest versus lowest intake was 0.83 (0.69-0.99) for total fruit and vegetables, 0.81 (0.70-0.93) for total vegetables, 0.77 (0.69-0.87) for total fruit, 0.84 (0.77-0.91) for cruciferous vegetables, 0.79 (0.68-0.91) for citrus fruits, and 0.74 (0.66-0.84) for yellow-orange vegetables. Subgroup analysis showed study design and gender as possible sources of heterogeneity. A nonlinear relationship was found of citrus fruits intake with risk of bladder cancer (P for nonlinearity = 0.018), and the RRs (95 % CI) of bladder cancer were 0.87 (0.78-0.96), 0.80 (0.67-0.94), 0.79 (0.66-0.94), 0.79 (0.65-0.96), and 0.79 (0.64-0.99) for 30, 60, 90, 120, and 150 g/day. A nonlinear relationship was also found of yellow-orange vegetable intake with risk of bladder cancer risk (P for nonlinearity = 0.033). Some evidence of publication bias was observed for fruit, citrus fruits, and yellow-orange vegetables.This meta-analysis supports the hypothesis that intakes of fruit and vegetables may reduce the risk of bladder cancer. Future well-designed studies are required to confirm this finding.

This study is aimed at exploring the role of serum fibroblast growth factor-23 (FGF-23), matrix Gla (MGP) and Fetuin-A in the calcium-phosphate metabolism and estimate the value of serum FGF-23, MGP and Fetuin-A levels in predicting osteoporosis in maintenance hemodialysis (MHD) patients. This study included 64 patients who receive hemodialysis in our hospital. The serum FGF-23, MGP and Fetuin-A were analyzed by enzyme-linked immunosorbent assay (ELlSA). Bone mineral density (BMD) at the femoral neck was measured by dual-energy X-ray absorptiometry. The 64 patients (30 males, 34 females, 60.6 ± 11.3 years of age) received an average of 6.88 ± 2.94 years of dialysis. Body mass index (BMI), Kt/V, dialysis vintage, patient age, serum levels of FGF-23, Fetuin-A, bone isoenzyme of alkaline phosphatase (ALP-B), and calcium were different in statistical significance among the three groups of patients in terms of normal bone mass (N = 10), osteopenia (N = 24), or osteoporosis (N = 30). BMI, Kt/V, ALP-B, dialysis vintage and serum Fetuin-A level were identified as independent variables of femoral neck BMD by stepwise multiple regression analysis. The area under ROC curve showed that serum Fetuin-A was useful for identifying osteoporosis in MHD patients. The cutoff value corresponding to the highest Youden's index was serum Fetuin-A ≤ 89 μg/mL, which was defined as the optimal predictor of osteoporosis. Its sensitivity/specificity was 71%/77.8%. The incidence of osteoporosis is high in MHD patients. Serum Fetuin-A level is closely correlated with osteoporosis and it may serve as a predictor of osteoporosis.

The soluble triggering receptor expressed on myeloid cells-1 (sTREM-1) is a promising diagnostic marker for many types of infections. A bivariate meta-analysis was performed to evaluate its diagnostic value for lower respiratory tract infections (LRTI). We searched PubMed, Cochrane Library and Web of Science (from January 1966 to August 2013) for all trials assessing diagnostic value of sTREM-1 for LRTI. The pooled sensitivity, specificity, positive likelihood ratio(PLR), negative likelihood ratio(NLR), diagnostic odds ratio (DOR), the area under summary receiver operator characteristic (SROC) curve and the Q* were calculated. Thirteen studies with 1138 patients were included in our meta-analysis. The pooled sensitivity and specificity of sTREM-1 for diagnosis of LRTI was 0.84 and 0.77. The PLR, NLR and DOR were 3.6, 0.21 and 17. The area under SROC curve was 0.88 and the Q* was 0.82. The univariate meta-regression analysis demonstrated that the assay method for sTREM-1 significantly affected sensitivity for LRTI. The Q* of sTREM-1 for diagnosis of community-acquired LRTI was 0.82, and the area under SROC curve was 0.88. The Q* of sTREM-1 in diagnosis of hospital-acquired LRTI was 0.83, and the area under SROC curve was 0.90. The Q* of sTREM-1 for distinguishing culture-positive LRTI from culture-negative diseases was 0.79, and the area under SROC curve was 0.86. Current evidence suggests that sTREM-1 is an accurate marker of LRTI. The overall diagnostic value of sTREM-1 for LRTI, community-acquired LRTI and hospital-acquired LRTI is similar.

In the period of advocating low-carbon in the global, low-carbon building materials were studied in this paper. Through the analysis of low-carbon materials used during the remarkable World Expo buildings, the sustainability application of low-carbon building materials was analyzed in depth. Moreover, the property of technology innovation and geographical, ethnic, social attributes were analyzed. This paper is aimed to provide some guidance for the application of low-carbon building materials in the future.

The objective was to study the present scenario, challenges, and future anticipation of traditional Mongolian medicine (TMM) in China. The literature was retrieved using various sources of information such as meetings with TMM experts, research and review articles, national health databases, and government websites and authoritative papers. Health care using TMM, TMM education and research, and the pharmaceutical industry of TMM has been improved by implementing TMM growth policies. TMM has been extensively used for health care in Mongolia and in various regions of China including Beijing. The national education system of China contains a stream of TMM education. There is a yearly increase in research productivity in the field of TMM due to extensive research funding by the government. The rapidly growing pharmaceutical industry of TMM has provided more availability of TMM to more patients. The literature search revealed good preservation and development of TMM in China, urging the need to take steps for the promotion of its spread and development in China and worldwide.

e13036Background: CA15-3 and CEA are the commonly used serum tumor biomarkers for monitoring breast cancer relapse. However, it is limited by sensitivity. Here we investigated copy number variation...

Reasonable restoration plans for power systems after large-scale power failures are important in both theory and practice. Based on fuzzy data envelopment analysis (DEA), an algorithm for assessing the black-start schemes of power system is proposed in this paper. Depending on the concepts of L-R fuzzy number and α-cut, this algorithm drew important factors from the process of black start as fuzzy input or output indexes and then established a fuzzy computing model. After the black-start schemes were sorted by the relative efficiency values of decision-making units (DMUs), the best one was recommended to dispatchers. The instance of a real power system proves that it is a feasible method. Copyright © 2008 John Wiley & Sons, Ltd.

Interaction between steel cables and concrete is complicated in prestressed concrete bridges, especially in curved prestressed concrete bridges. The most significant behavior of curved beam bridges under the loads is that, at the same time of vertical flexure, torsion occurs on the cross section, which complicates the mechanical analysis to curved beam bridges. Based on coordinating relations of steel cables and concrete (CRSC), the grillage structure finite-element method was adopted to analyze the spatial effect of curved beam bridges. This way, the effect of all prestressing procedures can be simulated properly, including the prestressing loss due to concrete shrinkage and creep, batch prestressing of the cables, etc. Furthermore, it is effective to analyze the integrated behavior of the combined steel cables space out and concrete. The efficiency and reliability of the CRSC method is demonstrated by our analysis system WXQ2.0 developed for curved-skew bridges.

In IEEE 802.16 based wireless mesh networks (WMNs), TDMA (Time Division Multiple Access) is employed as the channel access method and only TDD (Time Division Duplex) is supported and there are no clearly separate downlink and uplink subframes in the physical frame structure. As the uplink and downlink traffic has different characteristics in that the uplink traffic decentralizes in each MSS (Mesh Subscriber Station) and the downlink traffic centralizes in the MBS (Mesh Base Station), different scheduling methods should be taken in the uplink and downlink. This paper presents a uniform slot allocation algorithm which is suitable for both uplinks and downlinks. To achieve higher spatial reuse and greater throughput and to avoid switching frequently between receiving and transmitting within two adjacent time slots when a relay node forwards traffic, different link selection criteria are taken into account when allocating slots for uplinks and downlinks. A combined uplink and downlink slot allocation algorithm is proposed for further improving the spatial reuse and network throughput. The proposed algorithms are evaluated by extensive simulations and the results show that it has good performance in terms of spatial reuse and network throughput. To the best of the authors' knowledge, this work is the first one that considers combined uplink and downlink slot allocation on the centralized scheduling scheme in IEEE 802.16 based WMNs.

Background Germline mutations in the BRCA1 and BRCA2 genes greatly increase a woman’s risk of developing breast and/or ovarian cancer. The prevalence and distribution of such mutations differ across races/ethnicities. Several studies have investigated Chinese women with high-risk breast cancer, but the full spectrum of the mutations in these two genes remains unclear. Methods In this study, 133 unrelated Chinese women with familial breast/ovarian cancer living in Zhejiang, eastern China, were enrolled between the years 2008 and 2014. The complete coding regions and exon-intron boundaries of BRCA1 and BRCA2 were screened by PCR-sequencing assay. Haplotype analysis was performed to confirm BRCA1 and BRCA2 founder mutations. In silico predictions were performed to identify the non-synonymous amino acid changes that were likely to disrupt the functions of BRCA1 and BRCA2. Results A total of 23 deleterious mutations were detected in the two genes in 31 familial breast/ovarian cancer patients with a total mutation frequency of 23.3 % (31/133). The highest frequency of 50.0 % (8/16) was found in breast cancer patients with a history of ovarian cancer. The frequencies of BRCA1 and BRCA2 mutations were 13.5 % (18/133) and 9.8 % (13/133), respectively. We identified five novel deleterious mutations (c.3295delC, c.3780_3781delAG, c.4063_4066delAATC, c.5161 > T and c.5173insA) in BRCA1 and seven (c.1-40delGA, c.4487delC, c.469_473delAAGTC, c.5495delC, c.6141T > A, c.6359C > G and c.7588C > T) in BRCA2, which accounted for 52.2 % (12/23) of the total mutations. Six recurrent mutations were found, including four (c.3780_3781delAG, c.5154G > A, c.5468-1del8 and c.5470_5477del8) in BRCA1 and two (c.3109C > T and c.5682C > G) in BRCA2. Two recurrent BRCA1 mutations (c.5154G > A and c.5468-1del8) were identified as putative founder mutations. We also found 11 unclassified variants, and nine of these are novel. The possibility was that each of the non-synonymous amino acid changes would disrupt the function of BRCA1 and BRCA2 varied according to the different algorithms used. Conclusions BRCA1 and BRCA2 mutations accounted for a considerable proportion of hereditary breast/ovarian cancer patients from eastern China and the spectrum of the mutations of these two genes exhibited some unique features. The two BRCA1 putative founder mutations may provide a cost-effective option to screen Chinese population, while founder effects of the two mutations should be investigated in a lager sample size of patients.

Lung adenocarcinoma is the leading cause of cancer-related death worldwide. The aim of the present study was to investigate the potential function of endoplasmic reticulum protein 29 (ERp29) in lung adenocarcinoma. We examined the expression of ERp29 in 75 patients with lung adenocarcinoma by immunohistochemical analysis, as well as its association with clinicopathological features. We further tested the effects of inhibiting ERp29 on cell proliferation, migration ability, and chemosensitivity to gemcitabine in human lung adenocarcinoma cell lines. ERp29 was significantly overexpressed in lung adenocarcinoma when compared with matched nontumor tissues. However, we did not observe significant associations of ERp29 with any of the clinicopathologic characteristics, including sex, age, differentiation, tumor, node, and metastasis stage, T stage, and lymph node metastasis. Downregulation of ERp29 by small interfering RNA did not affect cell growth, but impaired cell migration of lung adenocarcinoma cells. Inhibition of ERp29 significantly enhanced the chemosensitivity of lung adenocarcinoma cells to gemcitabine. These results support a probable treatment combination of gemcitabine and inhibition of ERp29 overexpression for lung adenocarcinoma to promote the clinical curative effects.

The buildings of the world expo exhibition witnessed the development of world expo, and architecture bearing the world expo display function at the same time is also showing the unique innovation structure. With the development of the Times, the building is no longer as usual the pursuit of simple large space limit, but from structural expression to decorative expression; The latest led technology of green environmental protection, low carbon ecological building materials will be more widely application and development.

In embedded and portable applications, energy dissipation is a major design constraint. Designers must consider energy consumption. SimplePower evaluates the energy considering the system as a whole rather than just as a sum of parts, and concurrently supports both compiler and architectural experimentation. It includes a transition-sensitive, cycle-accurate datapath energy model that interfaces with analytical and transition-sensitive energy models for the memory, clock and bus subsystems, respectively. We analyzed the energy consumption of 10 codes from the multidimensional array domain, and find datapath energy hotspots, bottlenecks and helpful features. Optimized codes saved 21 percent more energy using the most recently used way-prediction cache scheme as compared to executing unoptimized codes from the multidimensional array domain.

Massive MIMO has been identified as one of the promising disruptive air interface technologies to address the massive capacity requirement demanded by 5G wireless communications. Most of the existing works showed different benefits of massive MIMO system but for the co-located deployment scenario. In this paper, we are interested to find out extra benefits that may be brought by distributing the massive number of antennas to different levels. Specifically, we compare the performance of co-located and distributed deployment scenarios in the framework of area spectrum efficiency (ASE) and area energy efficiency (AEE) tradeoff. Closed-form expressions are derived to help discover important design insights. For instance, it is interesting to see the distribution of the massive antennas always helps to improve ASE, but not the case for AEE. Moreover, with the large number of transmit antennas available and the practical cost of channel estimation considered, collaboration between cells is not always welcomed in each deployment scenario and the positive use cases depend on system parameters such as the number of antennas and the way they are distributed.

Background Epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKI) such as erlotinib and gefitinib are targeted drugs for the kinase domain of EGFR. They are widely used for the treatment of non-small cell lung cancer (NSCLC). The EGFR exon 19 deletion mutation and the L858R mutation in exon 21 comprise approximately 90% of the somatic mutations in NSCLC patients that respond to EGFR TKI. Several recent studies have also reported that small cell lung cancer (SCLC) patients with EGFR mutations responded to gefitinib. Further study, however, has been limited due to the difficulty obtaining tumor specimens from SCLC patients. Objectives The aim of this study was to explore the EGFR mutation status in SCLC patients by plasma analysis. Material and methods Plasma samples from SCLC patients were collected for mutant-enriched liquidchip (MEL) analysis to identify the EGFR mutations in exon 19 and 21. Results The exon 19 deletion mutation was detected in one out of 35 patients (a female non-smoker). No exon 21 mutations were found. Conclusions A prevalence of EGFR mutations in SCLC is rare, and occurs most frequently in females and nonsmokers.

Background Despite advances in chemotherapy and radiotherapy in recent decades, the prognosis for small cell lung cancer (SCLC) patients is still poor. Targeted therapies in SCLC must be applied systemically to target not only the primary tumor but also metastases. The phosphatidylinositol 3-kinase (PI3K)/AKT pathways play a key regulatory function in the survival, proliferation, energy metabolism and cellular architecture advantages of malignant cells. The phosphatidylinositol 3-kinase catalytic α (PIK3CA) gene, which encodes the p110α catalytic subunit, plays a key role in the activation of AKT downstream signaling and mammary tumor progression. More than 75% of PIK3CA mutations are clustered in the helical (exon 9) and catalytic domains (exon 20). There have been very few studies reporting the PIK3CA mutations status of patients with SCLC who have undergone surgical treatment in mainland China. Objectives The aim of the study was to investigate the PIK3CA mutation in SCLC. Material and methods Reverse transcription polymerase chain reaction (RT-PCR) and direct sequencing technology was used to detect the PIK3CA mutation in 14 cases of retrospectively collected SCLC patients who underwent surgical treatment at Zhejiang Cancer Hospital, Hangzhou, PRC, between 2002 and 2010. Results The research revealed no mutations in exons 9 and 20 of the PIK3CA gene. A nucleotide alteration of A1634C (E545A) of exon 9 turned out to be a pseudogene-positive, because the mutation disappeared when near-duplicate detection was employed. Conclusions The incidence of PIK3CA mutation is low in SCLC patients, and the pseudogene-positive alteration of A1634C is prone to occur in exon 9 of PIK3CA mutations in human cancers.

Objective: To identify novel potential biomarkers and evaluate combined biomarkers for diagnosing kidney injury with considerable accuracy in preeclampsia. Methods: The level of serum and urine neutrophil gelatinase-associated lipocalin (NGAL), kidney injury molecule-1 (KIM-1), retinol-binding protein (RBP) and interleukin-18 (IL-18) were measured by enzyme-linked immunosorbent assay. Results: The level of serum cystatin C, urine RBP, urine NGAL and urine KIM-1 in preeclampsia group were higher than that in the normal pregnancy group. When four biomarkers are combined, the sensitivity and specificity are 100%/98.20%. Conclusion: Urine KIM-1 is the most potential biomarker for renal injury in preeclampsia. The more biomarkers combined, the more sensitivity and specificity were increased.