Plasma Methylated SEPT9 as a Novel Biomarker for Predicting Liver Metastasis in Colorectal Cancer.

This study aimed to explore the role of plasma methylated SEPT9 (mSEPT9) in predicting liver metastasis (LM) in colorectal cancer (CRC) patients. The clinicopathological information of 115 consecutive CRC patients were collected. The differences of clinical characteristics and several biomarkers between CRC patients with LM and those with non-liver metastasis (NM) were analyzed. Multivariate logistic regression analysis was used to identify the risk factors for predicting LM in CRC patients. Receiver operating characteristic curve (ROC) analysis was applied to investigate the sensitivity and specificity of potential biomarkers in indicating the presence of LM in CRC. Compared with the CRC without LM, the levels of plasma mSEPT9 and carcinoembryonic antigen (CEA) were significantly increased in CRC with LM. Multivariate logistic regression analysis showed that plasma mSEPT9 was an independent risk factor for predicting LM in CRC. ROC curves showed that mSEPT9 and CEA could efficiently distinguish LM from NM in CRC. The area under the curve (AUC) of mSEPT9 was 0.850, which was slightly higher than that of CEA (0.842). The optimal cut-off value of mSEPT9 was 35.09 with a sensitivity of 81.82% and a specificity of 73.33%, both similar with that of CEA (sensitivity 87.27% and specificity 75.00%). In addition, the combination of mSEPT9 and CEA had a higher specificity than CEA alone (81.70% Vs 75.00%). Our findings suggest, for the first time, that plasma mSEPT9 might serve as a potential biomarker to predict LM in CRC, which deserves further in-depth study.

Consistency of drug-resistant mutations in plasma and peripheral blood mononuclear cells of patients with treatment-naïve and treatment-experienced HIV-1 infection.

Introduction: Genotypic drug resistance testing is cursrently recommended by the World Health Organization for all patients infected with human immunodeficiency virus type 1 (HIV-1) undergoing care or switching regimes due to failure with previous antiretroviral therapy (ART). Patients with human immunodeficiency virus/acquired immunodeficiency syndrome (HIV/AIDS) who meet the criteria for free testing for genotypic drug resistance due to poor adherence in Henan Province may resume their previous regimens before resampling. Therefore, resistance testing based on plasma RNA can fail in a proportion of patients. Resistance testing based on peripheral blood mononuclear cells (PBMCs) is an alternative option. In this study, we investigated the differences in drug-resistant mutations (DRMs) between plasma HIV RNA and proviral DNA in treatment-experienced and treatment-naïve patients. Methods: Matched plasma RNA and proviral DNA samples of 66 HIV-1 infected treatment-naïve and 78 treatment-experienced patients were selected for DRM analysis and comparison. Results: DRMs were detected in 27.3% (18/66) of treatment-naïve and 80.8% (63/78) of treatment-experienced samples. Resistance to at least one drug was detected based on analysis of plasma RNA and proviral DNA in 7.6% (5/66) and 9.1% (6/66) of treatment-naïve patients and in 79.5% (62/78) and 78.2% (61/78) of treatment-experienced patients, respectively. Furthermore, 61/66 (92.4%) of treatment-naïve patients showed concordant RNA and DNA drug resistance. When drug resistance was defined as intermediate and high, the concordance of drug resistance profiles of paired RNA and proviral DNA samples derived from treatment-naïve patients were up to 97.0% compared with only 80.8% (63/78) in treatment-experienced patients. Discussion: Our data indicate that drug resistance testing based on plasma RNA or proviral DNA might be interchangeable in treatment-naïve patients, whereas plasma RNA-based testing remains the best choice for drug resistance analysis in patients with ART failure in clinical practice.

Increased SPHK1 and HAS2 Expressions Correlate to Poor Prognosis in Pancreatic Cancer.

OBJECTIVE: SPHK1 and HAS2 have been reported to play important roles in tumorigenesis and development. However, their expression and prognostic value in pancreatic cancer (PC) remain unclear. This study is aimed at investigating the expression of SPHK1 and HAS2 on the prognosis of pancreatic cancer. MATERIALS AND METHODS: The expression of SPHK1 and HAS2 in pancreatic cancer tissues was analyzed through TCGA and GTEx databases and validated by qRT-PCR and Western blot in pancreatic cancer cell lines. χ 2 test was used to explore the correlation of the SPHK1 and HAS2 expressions with clinical characteristics. Kaplan-Meier survival analysis and ROC curve were used to evaluate the prognostic and diagnostic roles of SPHK1 and HAS2 in pancreatic cancer. Additionally, Spearman correlation analysis was applied to assess the correlation between the SPHK1 and HAS2 in pancreatic cancer. GO analysis and KEGG analysis were applied to explore the possible signaling pathway that SPHK1 and HAS2 coregulated genes mediated. RESULTS: The expression of SPHK1 and HAS2 was markedly upregulated in pancreatic cancer tissue and cell lines, respectively. Furthermore, there was a significant positive correlation between SPHK1 and HAS2 expressions. ROC curves showed that SPHK1 combine with HAS2 has good diagnostic value in pancreatic cancer patients with 85% sensitivity and 99.4% specificity. Kaplan-Meier analysis showed that increased expression of SPHK1 and HAS2 was significantly associated with short overall survival (OS) of pancreatic cancer patients. GO and KEGG results revealed that SPHK1 and HAS2 mainly involved cell proliferation and invasion mediated by extracellular matrix- (ECM-) receptor interaction, focal adhesion, and PI3K-AKT signaling pathways. CONCLUSIONS: Overexpression of SPHK1 and HAS2 could be important markers for the prognosis of pancreatic cancer.

A quantum circuit simulator and its applications on Sunway TaihuLight supercomputer.

Classical simulation of quantum computation is vital for verifying quantum devices and assessing quantum algorithms. We present a new quantum circuit simulator developed on the Sunway TaihuLight supercomputer. Compared with other simulators, the present one is distinguished in two aspects. First, our simulator is more versatile. The simulator consists of three mutually independent parts to compute the full, partial and single amplitudes of a quantum state with different methods. It has the function of emulating the effect of noise and support more kinds of quantum operations. Second, our simulator is of high efficiency. The simulator is designed in a two-level parallel structure to be implemented efficiently on the distributed many-core Sunway TaihuLight supercomputer. Random quantum circuits can be simulated with 40, 75 and 200 qubits on the full, partial and single amplitude, respectively. As illustrative applications of the simulator, we present a quantum fast Poisson solver and an algorithm for quantum arithmetic of evaluating transcendental functions. Our simulator is expected to have broader applications in developing quantum algorithms in various fields.

Fourier transform infrared spectroscopy combined with deep learning and data enhancement for quick diagnosis of abnormal thyroid function.

BACKGROUND: To evaluate the Fourier transform infrared spectroscopy (FT-IR) combined with deep learning models to allow for quick diagnosis of abnormal thyroid function. MATERIALS AND METHODS: Serum samples of 199 patients with abnormal thyroid function and 183 healthy patients were collected by infrared spectroscopy data and combined with different decibel noise for data expansion. The data were directly imported into three deep models: multilayer perceptron (MLP), a long-short-term memory network (LSTM), and a convolutional neural network (CNN), and 10-fold cross-validation was used to evaluate the performance of the model. RESULTS: The accuracy rates of the three models using the original data were 91.3 %, 88.6 % and 89.3 %, and the accuracy rates of the three models after data enhancement were 92.7 %, 93.6 % and 95.1 %. CONCLUSION: The results of this study indicated that the use of large sample serum infrared spectroscopy data combined with deep learning algorithms is a promising method for the diagnosis of abnormal thyroid function.

Serum ProGRP as a novel biomarker of bone metastasis in prostate cancer.

BACKGROUND: The prognosis of prostate cancer (PCa) is related to tumor metastasis, among which 80% were bone metastasis. In this study, we investigated the correlation between diverse clinical factors and bone metastasis in PCa patients and identified potential biomarkers of bone metastasis in PCa patients. METHODS: The clinical data of 150 PCa patients were reviewed consecutively from January 2015 to March 2020 in this study. The relationships between clinical characteristics, serum biomarkers and bone metastasis in PCa patients were analyzed, respectively. Multivariate logistic regression analysis was applied to identify potential markers of bone metastasis in prostate cancer. Receiver operating characteristic (ROC) curve was used to explore the diagnostic values of potential biomarkers. RESULTS: Compared with the PCa patients without bone metastasis, the serum levels of CA-125, T-PSA, F-PSA, CYFRA21-1 and ProGRP were significantly elevated in PCa patients with bone metastasis. Multivariate logistic regression analysis showed that T-PSA (OR 1.014, P = 0.021), F-PSA (OR 1.124, P = 0.016) and Pro-gastrin-releasing peptide (ProGRP) (OR 1.057, P = 0.026) were significantly associated with the bone metastasis of PCa patients. ROC curves indicated that T-PSA, F-PSA and ProGRP could effectively discriminate bone metastasis from non-bone metastasis PCa patients, and the AUCs (area under the curves) were 0.885, 0.919 and 0.752, respectively. According to the Youden index, the cut-off values of T-PSA, F-PSA and ProGRP were defined as 56.50 ng/ml, 6.96 ng/ml and 31.60 pg/ml, respectively. T-PSA, F-PSA and ProGRP produced a sensitivity of 78.30%, 81.70% and 61.70%, a specificity of 93.30%, 88.90% and 82.20%, respectively. The AUC for the combination of T-PSA, F-PSA with ProGRP was 0.941 with 90.00% sensitivity, much better than that of any single biomarker or two biomarkers combinate. CONCLUSIONS: Serum ProGRP might be a potential tumor marker of bone metastasis in prostate cancer, which may contribute to the early diagnosis of bone metastasis when used alone or in combination with other commonly used biomarkers.

Prevalence and genotype distribution of human papillomavirus in Zhengzhou, China, in 2016.

In this study, the prevalence and genotype distribution of human papillomavirus (HPV) in 49,793 women aged 25-64 years were determined by fluorescent real-time polymerase chain reaction (PCR) assay. HPV was detected in 6,020 women, giving a prevalence of 12.09% (6020/49,793). Single and multiple infections accounted for 71.81% (4323/6020) and 28.19% (1697/6020) of total infections, respectively. The most commonly found genotypes were HPV52 (19.90%, 1198/6020) and HPV16 (19.17%, 1154/6020), followed by HPV58 (13.11%, 789/6020), HPV81 (10.10%, 608/6020) and HPV56 (9.00%, 542/6020). The prevalence of HPV increased with age and was highest in the 54- to 64-year-old age group. The genotypes covered by the nonavalent HPV vaccine accounted for 39.32% (2367/6020) and 22.81% (1373/6020) of the total monoinfections and polyinfections, respectively. This study indicates a high HPV infection rate in women in the city of Zhengzhou and a large percentage of women are infected with single or multiple high-risk HPV genotypes that cannot be prevented using the current nonavalent HPV vaccine. Vaccines incorporating more HPV genotypes and extended age coverage for the current nonavalent vaccine might be necessary to better prevent HPV-related cervical cancer.

Mechanical Properties and Corrosion Resistance of NbTiAlSiZrNx High-Entropy Films Prepared by RF Magnetron Sputtering.

In this study, we designed and fabricated NbTiAlSiZrNx high-entropy alloy (HEA) films. The parameters of the radio frequency (RF) pulse magnetron sputtering process were fixed to maintain the N2 flux ratio at 0%, 10%, 20%, 30%, 40%, and 50%. Subsequently, NbTiAlSiZrNx HEA films were deposited on the 304 stainless steel (SS) substrate. With an increasing N2 flow rate, the film deposited at a RN of 50% had the highest hardness (12.4 GPa), the highest modulus (169 GPa), a small roughness, and a beautiful color. The thicknesses of the films were gradually reduced from 298.8 nm to 200 nm, and all the thin films were of amorphous structure. The electrochemical corrosion resistance of the film in a 0.5 mol/L H2SO4 solution at room temperature was studied and the characteristics changed. The HEA films prepared at N2 flow rates of 10% and 30% were more prone to corrosion than 304 SS, but the corrosion rate was lower than that of 304 SS. NbTiAlSiZrNx HEA films prepared at N2 flow rates of 20%, 40%, and 50% were more corrosion-resistant than 304 SS. In addition, the passivation stability of the NbTiAlSiZrNx HEA was worse than that of 304 SS. Altogether, these results show that pitting corrosion occurred on NbTiAlSiZrNx HEA films.

Comparison of three syphilis algorithms in West China.

OBJECTIVE: The study was designed to analyze three different algorithms with the implementation of treponemal tests for detecting suspected syphilis in west China where no syphilis algorithms guideline exists. METHODS: We retrospectively collected data to reanalyze three syphilis testing algorithms: the classical reverse algorithm, and two options of syphilis screening in European syphilis guideline. The kappa (κ) coefficients were used to compare the concordance between algorithms using different syphilis assays during two periods. A receiver operating characteristic curve was used to determine the optimal S/CO ratios of InTec EIA or Lumipulse® G TP-N assay (CLIA) to predict confirmatory TPPA results. RESULTS: The agreements between the reverse algorithm and the EU option 1 algorithms were perfect irrespective of EIA or CLIA used (all κ > 0.9). But the agreements between the EU option 2 algorithms and reverse or EU option 1 were not good (κ < 0.4). >50% cases confirmed syphilis infections by reverse or EU option 1 algorithm were missed by EU option 2. There is no very need for a confirmatory TPPA assay in EU Option 1 when S/CO is above 6.12 for CLIA (3.67 for EIA). The false-positive rate was 0.26% above this cutoff level. CONCLUSIONS: EU Option 1, involving a reactive TT, followed by another TT of a different type and a quantitative NTT if second TT is positive, which is the same as the 2015 UK syphilis algorithm, is recommended. We also propose that when S/CO of the CLIA or EIA is high enough, TPPA confirmation can be omitted from the testing algorithm, and costs would be significantly reduced.

Serum ARCHITECT PIVKA-II reference interval in healthy Chinese adults: Sub-analysis from a prospective multicenter study.

BACKGROUND: Protein induced by vitamin K absence or antagonist-II (PIVKA-II) has been widely used as a biomarker for liver cancer diagnosis in Japan for decades. However, the reference intervals for serum ARCHITECT PIVKA-II have not been established in the Chinese population. Thus, this study aimed to measure serum PIVKA-II levels in healthy Chinese subjects. METHODS: This is a sub-analysis from the prospective, cross-sectional and multicenter study (ClinicalTrials.gov Identifier: NCT03047603). A total of 892 healthy participants (777 Han and 115 Uygur) with complete health checkup results were recruited from 7 regional centers in China. Serum PIVKA-II level was measured by ARCHITECT immunoassay. All 95% reference ranges were estimated by nonparametric method. RESULTS: The distribution of PIVKA-II values showed significant difference with ethnicity and sex, but not age. The 95% reference range of PIVKA-II was 13.62-40.38 mAU/ml in Han Chinese subjects and 15.16-53.74 mAU/ml in Uygur subjects. PIVKA-II level was significantly higher in males than in females (P < 0.001). The 95% reference range of PIVKA-II was 15.39-42.01 mAU/ml in Han males while 11.96-39.13 mAU/ml in Han females. CONCLUSIONS: The reference interval of serum PIVKA-II on the Architect platform was established in healthy Chinese adults. This will be valuable for future clinical and laboratory studies performed using the Architect analyzer. Different ethnic backgrounds and analytical methods underline the need for redefining the reference interval of analytes such as PIVKA-II, in central laboratories in different countries.

Serum Tumor Marker Carbohydrate Antigen 125 Levels and Carotid Atherosclerosis in Patients with Coronary Artery Disease.

OBJECTIVE: We assessed the correlation between serum carbohydrate antigen 125 (CA125) and carotid intima-media thickness (cIMT) in patients with coronary artery disease (CAD). METHODS: We collected 518 CAD patients from the cardiovascular disease center in our hospital, and all cIMT values were measured in patients with CAD. RESULTS: The serum CA125 concentrations were found to be increased in CAD patients with early carotid atherosclerosis compared with patients without early carotid atherosclerosis (20.1±7.72 vs. 17.7±6.41 U/mL, p<0.001). The cIMT values were increased in patients with higher serum CA-125 levels than those with lower serum CA-125 concentrations (1.16±0.32 vs. 0.98±0.29 mm, p<0.001). There was a positive correlation between serum CA125 and cIMT in CAD patients (r=0.262, p<0.001). Moreover, the serum CA125 concentrations also were positively correlated with cIMT in subjects with early carotid atherosclerosis and without early carotid atherosclerosis (r=0.255, p<0.001; r=0.189, p=0.002). We found that serum CA-125 concentrations were independently correlated with cIMT (beta = 0.293, p<0.001) in multiple linear regression analysis. CONCLUSIONS: We found that serum CA125 concentrations were positively correlated with cIMT in CAD patients, serum CA125 might be a potential biochemical marker for the estimation of atherosclerosis in patients with CAD.

64-qubit quantum circuit simulation.

Classical simulations of quantum circuits are limited in both space and time when the qubit count is above 50, the realm where quantum supremacy reigns. However, recently, for the low depth circuit with more than 50 qubits, there are several methods of simulation proposed by teams at Google and IBM. Here, we present a scheme of simulation which can extract a large amount of measurement outcomes within a short time, achieving a 64-qubit simulation of a universal random circuit of depth 22 using a 128-node cluster, and 56- and 42-qubit circuits on a single PC. We also estimate that a 72-qubit circuit of depth 23 can be simulated in about 16 h on a supercomputer identical to that used by the IBM team. Moreover, the simulation processes are exceedingly separable, hence parallelizable, involving just a few inter-process communications. Our work enables simulating more qubits with less hardware burden and provides a new perspective for classical simulations.

Allocation of marine environmental carrying capacity in the Xiamen Bay.

Three optimization methods are employed to allocate Marine Environmental Carrying Capacity (MECC) in the Xiamen Bay. The hydrodynamic and pollutant fields are first simulated by the Princeton Ocean Model. Taking phosphorus as an index of the water quality, the response fields are then calculated. These response fields represent the relationship between the concentration of the sea zone and the pollution sources. Finally, MECC is optimized and distributed in the Xiamen Bay by three optimization methods. The results show classical linear optimization can only maximize the satisfaction level for one of the stake holders', e.g., dischargers or environmental protection bureau, satisfaction level. However, the fuzzy and grey fuzzy optimizations can provide a compromise, and therefore a fairer result, by incorporating the conflicting goals of all of the different stakeholders. Compared with fuzzy optimization, the grey fuzzy optimization provides a more flexible choice for the decision-makers.

[Measurement of the minimum alveolar concentration of sevoflurane during combined anesthesia with sevoflurane, small-dose dexmedetomidine and fentanyl].

OBJECTIVE: To determine the minimum alveolar concentration (EC(50) and EC(95)) of sevoflurane in body movement response to surgical incision during combined anesthesia with dexmedetomidine, sevoflurane and fentanyl. METHODS: Twenty-six ASA class I or II patients (aged 18-60 years) underwent selective surgery for lumbar disc herniation under general anesthesia with the combination of with dexmedetomidine, sevoflurane and fentanyl. All the patients received infusion with 0.5 mg/kg dexmedetomidine for 10 min before anesthesia induction with intravenous injection of 3 µg/kg fentanyl 8% sevoflurane inhalation. Upon loss of consciousness, sevoflurane concentration was reduced to 5% with intravenous injection of 1-2 mg/kg succinylcholine, and intubation was started after muscles relaxation. Anesthesia was maintained by sevoflurane and dexmedetomidine (0.2 µg·kg(-1)·h(-1)). Before the surgery, a steady state end-tidal sevoflurane concentration was maintained for at least 10 min. The first patient of the series was tested with 1.5% sevoflurane, and the concentration was adjusted according to modified Dixons up-and-down method (with a step size of 0.2%). Probit analysis was used for calculating EC(50), EC(95) and the 95% confidence interval (CI). RESULTS: The EC(50) of sevoflurane was 0.94% (95%CI of 0.76%-1.07% ) and EC(95) was 1.23% (95%CI 1.09%-2.05% ). CONCLUSION: The EC(50) and EC(95) of sevoflurane are 0.94% and 1.23%, respectively, for suppressing body movement in response to surgical incision during combined anesthesia with sevoflurane, dexmedetomidine and fentanyl.