Using machine learning to predict the bleeding risk for patients with cardiac valve replacement treated with warfarin in hospitalized.

BACKGROUND: Distinguishing warfarin-related bleeding risk at the bedside remains challenging. Studies indicate that warfarin therapy should be suspended when international normalized ratio (INR) ≥ 4.5, or it may sharply increase the risk of bleeding. We aim to develop and validate a model to predict the high bleeding risk in valve replacement patients during hospitalization. METHOD: Cardiac valve replacement patients from January 2016 to December 2021 across Nanjing First Hospital were collected. Five different machine-learning (ML) models were used to establish the prediction model. High bleeding risk was an INR ≥4.5. The area under the receiver operating characteristic curve (AUC) was used for evaluating the prediction performance of different models. The SHapley Additive exPlanations (SHAP) was used for interpreting the model. We also compared ML with ATRIA score and ORBIT score. RESULTS: A total of 2376 patients were finally enrolled in this model, 131 (5.5%) of whom experienced the high bleeding risk after anticoagulation therapy of warfarin during hospitalization. The extreme gradient boosting (XGBoost) exhibited the best overall prediction performance (AUC: 0.882, confidence interval [CI] 0.817-0.946, Brier score, 0.158) compared to other prediction models. It also shows superior performance compared with ATRIA score and ORBIT score. The top 5 most influential features in XGBoost model were platelet, thyroid stimulation hormone, body surface area, serum creatinine and white blood cell. CONCLUSION: A model for predicting high bleeding risk in valve replacement patients who treated with warfarin during hospitalization was successfully developed by using machine learning, which may well assist clinicians to identify patients at high risk of bleeding and allow timely adjust therapeutic strategies in evaluating individual patient.

Visible-Light-Mediated Oxidative Coupling of Vinylarenes with Bromocarboxylates Leading to γ-Ketoesters.

A photocatalytic strategy for the synthesis of γ-ketoesters was reported. Using DMSO as both the solvent and terminal oxidant, oxidative coupling of vinylarenes with bromocarboxylates proceeded readily, giving a variety of γ-ketoesters in good isolated yields and with a broad functional-group tolerance.

Cellular pharmacokinetics and pharmacodynamics mechanisms of ginkgo diterpene lactone and its modulation of P-glycoprotein expression in human SH-SY5Y cells.

Ginkgo diterpene lactone (GDL) is the raw material for ginkgo diterpene lactone meglumine injection, which is used for treating cerebral ischemia. The aims of this study were to explore the cellular pharmacokinetics of GDL in whole cells and subcellular fractions, and detect cellular pharmacodynamics on the human SH-SY5Y cells induced by oxygen-glucose deprivation and reoxygenation (OGD/R). Firstly, a simple, sensitive and reliable liquid chromatography-tandem mass spectrometry (LC-MS/MS) method was developed and validated for assessing the amount of ginkgolide A (GA), B (GB) and K (GK) in cellular/subcellular samples. Then, phosphatidylserine and mitochondria membrane potential were assayed to evaluate the extent of apoptosis effect. The study showed that the cellular/subcellular accumulation of GA and GB were increased in a concentration-dependent manner; the levels of GA and GB in cytosol were the highest among these subcellular organelles. Meanwhile, GDL also attenuated the OGD/R-induced increases in the percentage of apoptotic and mitochondria membrane potential. In addition, verapamil increased the rate and amount of GA and GB entering cellular/subcellular compartments through inhibition of P-glycoprotein activity, and promoted the protective effect of GDL. The present study reports the cellular pharmacokinetics profiles of GA and GB in normal and OGD/R-induced SH-SY5Y cells in vitro for the first time, which provided valuable information for clinical safety application.

Preparation of oxazolines and oxazoles via a PhI(OAc)2-promoted cyclization of N-propargylamides.

A metal-free cyclization of N-propargylamides for the synthesis of various oxazolines and oxazoles via a 5-exo-dig process is presented. Using (diacetoxyiodo)benzene (PIDA) as a reaction promoter and lithium iodide (LiI) as an iodine source, intramolecular iodooxygenation of N-propargylamides proceeded readily, leading to the corresponding (E)-5-iodomethylene-2-oxazolines in good to excellent isolated yields. In addition, using the PhI(OAc)2/LiI system, N-propargylamides can be converted to the corresponding oxazole-5-carbaldehydes in the presence of oxygen under visible light irradiation. The resulting products can be further converted into various oxazoline and oxazole derivatives after simple derivatizations, and this method ultimately offers an efficient route to a variety of biologically active structures.

Assessing the cost-effectiveness of replacing antimetabolites with mTOR inhibitors in heart transplant immunosuppression in China: a network meta-analysis-based economic evaluation.

BACKGROUND: Although several pharmacoeconomic studies have assessed the cost-effectiveness of maintenance immunosuppressive regimens for heart transplant recipients, economic comparisons between various combination drug therapies remain sparse. AIM: This study used an economic evaluation based on network meta-analysis to assess the cost-effectiveness of four immunosuppressive regimens for adult heart transplant recipients in China. METHOD: We conducted a systematic search for clinical trials in PubMed, Embase, Cochrane Library, Web of Science, China National Knowledge Infrastructure (CNKI), Wanfang Data, and VIP database. A validated Markov model was adapted to reflect the Chinese medical landscape. Four maintenance immunosuppression regimens were considered: tacrolimus/mycophenolate mofetil (TAC/MMF), cyclosporine/mycophenolate mofetil (CSA/MMF), everolimus/cyclosporine (EVL/CSA), and sirolimus/tacrolimus (SRL/TAC). The probabilities of health events were derived from a comprehensive literature review. Direct medical costs, adjusted for 2022 values, were from public documents and websites, while utilities for quality-adjusted life-years (QALYs) were taken from previous studies. Primary outcomes were mean lifetime cost, QALYs, and cost-effectiveness, with a willingness-to-pay (WTP) threshold set at three times China's GDP per capita in 2022. Sensitivity analyses were conducted to test the robustness of the results. RESULTS: The base case analysis identified TAC/MMF as the most cost-effective regimen, producing a mean of 6.31 QALYs per patient at a cost of Chinese Yuan (CNY) 534,182.89. Sensitivity analyses consistently reinforced TAC/MMF as the most cost-effective and robust choice. CONCLUSION: TAC/MMF is the most cost-effective maintenance immunosuppressive regimen for heart transplant recipients within the Chinese health system. The study findings are reinforced by sensitivity analyses, affirming their robustness amid various uncertainties.

[An abnormal characteristic line mining method of celestial spectrum based on attribute weight and w(k)-distance].

Outlier mining is one of the effective methods to find the abnormal celestial spectrum data, and is also one of effective ways to discover the special and unknown celestial bodies. In the present paper, an abnormal characteristic line mining method of celestial spectrum is presented based on the attribute weight and w(k)-distance by using the idea of information entropy. Based on it, an abnormal characteristic line mining system of celestial spectrum was designed and implemented. Firstly, attribute weight of characteristic line was determined by using the idea of information entropy, so that important degree was effectively reflected for each characteristic line. Secondly, massive characteristic line data set of celestial spectrum was reduced by utilizing pruning technique based on neighborhood radius, so that candidate set of abnormal characteristic line was obtained by deleting data objects in which there may not be abnormal characteristic lines. Thirdly, w(k)-distance sum was computed according to the deviation between the data objects in the candidate set, and the objects whose w(k)-distance sum value ranks the first top n were regarded as abnormal characteristic line data objects. In the end, the experimental and the system's running results validated the effectiveness and feasibility of the method by using the SDSS star spectral data set.

Bromodomain and extraterminal (BET) proteins: biological functions, diseases, and targeted therapy.

BET proteins, which influence gene expression and contribute to the development of cancer, are epigenetic interpreters. Thus, BET inhibitors represent a novel form of epigenetic anticancer treatment. Although preliminary clinical trials have shown the anticancer potential of BET inhibitors, it appears that these drugs have limited effectiveness when used alone. Therefore, given the limited monotherapeutic activity of BET inhibitors, their use in combination with other drugs warrants attention, including the meaningful variations in pharmacodynamic activity among chosen drug combinations. In this paper, we review the function of BET proteins, the preclinical justification for BET protein targeting in cancer, recent advances in small-molecule BET inhibitors, and preliminary clinical trial findings. We elucidate BET inhibitor resistance mechanisms, shed light on the associated adverse events, investigate the potential of combining these inhibitors with diverse therapeutic agents, present a comprehensive compilation of synergistic treatments involving BET inhibitors, and provide an outlook on their future prospects as potent antitumor agents. We conclude by suggesting that combining BET inhibitors with other anticancer drugs and innovative next-generation agents holds great potential for advancing the effective targeting of BET proteins as a promising anticancer strategy.

Interpretable Machine Learning Model Predicting Early Neurological Deterioration in Ischemic Stroke Patients Treated with Mechanical Thrombectomy: A Retrospective Study.

Early neurologic deterioration (END) is a common and feared complication for acute ischemic stroke (AIS) patients treated with mechanical thrombectomy (MT). This study aimed to develop an interpretable machine learning (ML) model for individualized prediction to predict END in AIS patients treated with MT. The retrospective cohort of AIS patients who underwent MT was from two hospitals. ML methods applied include logistic regression (LR), random forest (RF), support vector machine (SVM), and extreme gradient boosting (XGBoost). The area under the receiver operating characteristic curve (AUC) was the main evaluation metric used. We also used Shapley Additive Explanation (SHAP) and Local Interpretable Model-Agnostic Explanations (LIME) to interpret the result of the prediction model. A total of 985 patients were enrolled in this study, and the development of END was noted in 157 patients (15.9%). Among the used models, XGBoost had the highest prediction power (AUC = 0.826, 95% CI 0.781-0.871). The Delong test and calibration curve indicated that XGBoost significantly surpassed those of the other models in prediction. In addition, the AUC in the validating set was 0.846, which showed a good performance of the XGBoost. The SHAP method revealed that blood glucose was the most important predictor variable. The constructed interpretable ML model can be used to predict the risk probability of END after MT in AIS patients. It may help clinical decision making in the perioperative period of AIS patients treated with MT.

[Characteristics and Cause of PM2.5 During Haze Pollution in Winter 2022 in Zhoukou, China].

The characteristics and main factors of causes of haze in Zhoukou in January 2022 were analyzed. Six air pollutants, water-soluble ions, elements, OC, EC, and other parameters in fine particulate matter were monitored and analyzed using a set of online high-time-resolution instruments in an urban area. The results showed that the secondary inorganic aerosols(SNA), carbonaceous aerosols(CA, including organic carbon OC and inorganic carbon EC), and reconstructed crustal materials(CM, such as Al2O3, SiO2, CaO, and Fe2O3, etc.) were the three main components, accounting for 61.3%, 24.3%, and 9.72% in PM2.5, respectively. The concentrations of SNA, CA, CM, and SOA were increased, accompanied with higher AQI. The sulfur oxidation rate(SOR) and nitrogen oxidation rate(NOR) in January were 0.53 and 0.46, respectively. The growth rates[µg·(m3·h)] of sulfate and nitrate were 0.027(-5.89-9.47, range) and 0.051(-23.1-12.4), respectively. During the haze period, the growth rates of sulfate and nitrate were 0.13 µg·(m3·h)-1and 0.24 µg·(m3·h)-1, which were 4.8 and 4.7 times higher than the average value of January, respectively. Although the sulfur oxidation rate was greater than the nitrogen oxidation rate, the growth rate of nitrate was approximately 1.8 times that of sulfate owing to the difference in the concentration of gaseous precursors and the influence of relative humidity. The growth rates of nitrate in SNA were significantly higher than those of sulfate on heavily polluted days. The values of SOR, NOR, and concentrations of SNA and SOA during higher AQI and humidity periods were higher than those in lower AQI and humidity periods. The Ox(NO2+O3) decreased with the increase in relative humidity. The SOA was higher at nighttime, increasing faster with the humidity than that in daytime. Under the situation of lower temperature, higher humidity, and lower wind speed, the emission of gaseous precursors of SNA requires further attention in Zhoukou in winter. Advanced control strategies of emissions of SO2 and NO2, such as mobile sources and coal-burning sources, could reduce the peak of haze in winter efficiently.

Metastatic lymph nodes and prognosis assessed by the number of retrieved lymph nodes in gastric cancer.

BACKGROUND: The prognostic value of quantitative assessments of the number of retrieved lymph nodes (RLNs) in gastric cancer (GC) patients needs further study. AIM: To discuss how to obtain a more accurate count of metastatic lymph nodes (MLNs) based on RLNs in different pT stages and then to evaluate patient prognosis. METHODS: This study retrospectively analyzed patients who underwent GC radical surgery and D2/D2+ LN dissection at the Cancer Hospital of Harbin Medical University from January 2011 to May 2017. Locally weighted smoothing was used to analyze the relationship between RLNs and the number of MLNs. Restricted cubic splines were used to analyze the relationship between RLNs and hazard ratios (HRs), and X-tile was used to determine the optimal cutoff value for RLNs. Patient survival was analyzed with the Kaplan-Meier method and log-rank test. Finally, HRs and 95% confidence intervals were calculated using Cox proportional hazards models to analyze independent risk factors associated with patient outcomes. RESULTS: A total of 4968 patients were included in the training cohort, and 11154 patients were included in the validation cohort. The smooth curve showed that the number of MLNs increased with an increasing number of RLNs, and a nonlinear relationship between RLNs and HRs was observed. X-tile analysis showed that the optimal number of RLNs for pT1-pT4 stage GC patients was 26, 31, 39, and 45, respectively. A greater number of RLNs can reduce the risk of death in patients with pT1, pT2, and pT4 stage cancers but may not reduce the risk of death in patients with pT3 stage cancer. Multivariate analysis showed that RLNs were an independent risk factor associated with the prognosis of patients with pT1-pT4 stage cancer (P = 0.044, P = 0.037, P = 0.003, P < 0.001). CONCLUSION: A greater number of RLNs may not benefit the survival of patients with pT3 stage disease but can benefit the survival of patients with pT1, pT2, and pT4 stage disease. For the pT1, pT2, and pT4 stages, it is recommended to retrieve 26, 31 and 45 LNs, respectively.

[Characterization of Volatile Organic Compounds (VOCs) Using Mobile Monitoring Around the Industrial Parks in the Yangzte River Delta Region of China].

Volatile organic compounds (VOCs) play important roles in the formation of ozone and fine particles in the troposphere. Industrial parks emit significant amounts of VOCs in China, while few studies have characterized them. In the present study, a mobile platform was employed to measure the levels and composition VOCs around industrial parks in the Yangzte River Delta region. The average concentration of VOCs ranged from 39 µg·m-3 (5% percentile) to 533 µg·m-3 (95% percentile) with an average of 183 µg·m-3, which was three times that of ambient concentrations. Maximum VOC concentrations ranged from 307 µg·m-3 (5% percentile) to 12006 µg·m-3 (95% percentile) with an average of 2812 µg·m-3. The frequency of abnormal peak values was as high as 64% across all the industrial parks, of which toluene (32%), xylene (18%), benzene (9%), and>C9 aromatics (19%) were the most common species. Differences in VOC characteristics were observed among the different types of industrial parks. Specifically, highest concentrations of VOCs were observed in textile industrial parks followed by chemical, painting, and petrochemical industrial parks, and VOC concentrations in electronics industrial parks were the lowest. Importantly, species measured using the mobile platform only contributed~50% of VOCs present in ambient samples, indicating that the concentrations of VOCs in the industrial parks were underestimated overall. These results can inform measures to control VOC pollution in industrial parks in China.

Measurement of fexofenadine concentration in micro-sample human plasma by a rapid and sensitive LC-MS/MS employing protein precipitation: application to a clinical pharmacokinetic study.

A simple, rapid and sensitive liquid chromatography/positive ion electro-spray tandem mass spectrometry method (LC-MS/MS) was developed and validated for the quantification of fexofenadine with 100 microL human plasma employing glipizide as internal standard (IS). Protein precipitation was used in the sample preparation procedure. Chromatographic separation was achieved on a reversed-phase C(18 )column (5 microm, 100 x 2.1 mm) with methanol : buffer (containing 10 mmol/L ammonium acetate and 0.1% formic acid; 70 : 30, v/v) as mobile phase. The total chromatographic runtime was approximately 3.0 min with retention time for fexofenadine and IS at approximately 1.9 and 2.1 min, respectively. Detection of fexofenadine and IS was achieved by LC-MS/MS in positive ion mode using 502.1 --> 466.2 and 446.0 --> 321.1 transitions, respectively. The method was proved to be accurate and precise at linearity range of 1-600 ng/mL with a correlation coefficient (r) of > or =0.9976. The validated method was applied to a pharmacokinetic study in human volunteers following oral administration of 60 or 120 mg fexofenadine formulations, successfully.

Palladium-Catalyzed Synthesis and Anticancer Activity of Paclitaxel-Dehydroepiandrosterone Hybrids.

According to the activity-structure relationship of the C-13 side chain in paclitaxel or docetaxel, eighteen novel paclitaxel-dehydroepiandrosterone (DHEA) hybrids were designed and synthesized by Pd(II)-catalyzed Suzuki-Miyaura cross-coupling of 17-trifluoromethanesulfonic enolate-DHEA with different aryl boronic acids. The in vitro anticancer activity of the hybrids against a human liver cancer cell line (HepG-2) was evaluated by MTT assay, showing that most of these hybrids possessed moderate antiproliferative activity against the HepG-2 cancer cell line. Among these hybrids, three ones (7b, 7g, and 7i) with ortho-substituents in the phenyl group of the D-ring of DHEA analogues exhibited moderate anticancer activity. The optimal compound 7i showed superior anticancer activity against the HepG-2 cell line with an IC50 value of 26.39 µM.

[Audit Indicators and Suggested Ranges for Data Validation of Chemical Components in Ambient PM2.5: A Case Study of the Yangtze River Delta].

Diagnostic indicators for the validation of PM2.5 compositional data were calculated, based on the monitoring results of approximately 2100 ambient samples collected in the Yangzi River Delta from 2014 to 2017. According to the results of a correlation analysis, we propose that the audit indexes of the monitoring data of PM2.5 components in ambient air should include:equivalent ratios of anion-cation charge balance(A/C), the consistency between sum of all measured components(∑species) and weighed PM2.5, the consistency between mass reconstructed PM2.5(PM2.5, reconstructed) and weighed PM2.5, the chemical consistency between elemental S and water-soluble SO42-, elemental K and water-soluble K+, and the chemical consistency of theoretical and tested NH4+. The double-sided 95% reference ranges of anion-cation equivalent balance (A/C), ∑species/PM2.5, PM2.5, reconstructed/PM2.5, S/SO42-, and K/K+ ratios were determined in terms of P2.5 and P97.5 as follows:(0.82, 1.35), (0.63, 0.94), (0.62, 1.00), (0.28, 0.50), and (0.66, 2.31). These diagnostic indicators were helpful for judging the errors of chemical component analysis and retain seasonal variation stability. In most cases, NH4+ existed in the form of NH4NO3 and (NH4)2SO4 in spring and summer. With the approach of autumn and winter, it transformed to NH4NO3, (NH4)2SO4, and NH4Cl. The results of literature verification showed the pass rate of A/C was 87.1% and the rate of other indexes was 100%, indicating that the above audit indexes we propose could be applied to not only the Yangzi River Delta but the entire country. Furthermore, there were certain conditions in applying the diagnostic indicators. The S/SO42- ratio worked well with PM2.5 ≥ 40 µg·m-3 in summer and with 60 µg·m-3 ≤ PM2.5 ≤ 140 µg·m-3 in spring, autumn, and winter. Other audit indexes were available universally in all weathers under the condition of PM2.5 ≥ 60 µg·m-3.

[Observation of Aerosol Optical Properties and New Particle Formation in the Yangtze River Delta].

In a recent field campaign focused on air quality study, aerosol optical properties, particle number concentration, and PM2.5 components were monitored in Changzhou, Jiangsu Province, from May 27 to June 27, 2019. An array of instruments were deployed that included scanning mobility particle size spectrometer (SMPS), aethalometer (AE33), cavity attenuation phase shift single albedo monitor (CAPS-ALB), monitor for aerosols and gases in ambient air (MARGA) and RT-4 organic carbon/elemental carbon (OC/EC) carbon analyzer to study the ① changes in chemical composition and optical parameters of the new particles generated during the campaign period. ② comparison of the aerosol extinction coefficient recorded by these instruments and measured value in the reconstruction of IMPROVE (interagency monitoring of protected visual environment) and the calculated coefficient using MIE theory model were carried out. During the entire campaign, two new particle generation events were observed and also found that the particle size continued to increase from 4 nm to 64 nm. It was monitored that in the initial stage of new particle generation, sulfate contributed greatly. The measured average aerosol extinction coefficient during the period of particle generation, using these instruments was 95.40 Mm-1, while the average aerosol extinction reconstruction using the IMPROVE model was observed to be 140.20 Mm-1. The theoretical calculations based on Mie theory model yielded an average extinction coefficient of 93.54 Mm-1. It was found that the average aerosol extinction in Changzhou is lower than the average value of the urban aerosol extinction coefficient, which is measured to be 300 Mm-1 in China, during this period. The deployment of multiple instruments in a single campaign is more desirable because the combination of all observations helped in better characterization of the physicochemical properties of ambient aerosols from various aspects, including particle size spectrum and chemical composition.

Changing trends of clinicopathologic features and survival duration after surgery for gastric cancer in Northeast China.

BACKGROUND: Through analyzing the data from a single institution in Northeast China, this study revealed the possible clinicopathologic characteristics that influence the prognosis of patients with gastric cancer (GC). AIM: To evaluate the changing trends of clinicopathologic features and survival duration after surgery in patients with GC in Northeast China, which is a high-prevalence area of GC. METHODS: The study analyzed the difference in clinicopathologic features and survival duration after surgery of 5887 patients who were histologically diagnosed with GC at the Harbin Medical University Cancer Hospital. The study mainly analyzed the data in three periods, 2000 to 2004 (Phase 1), 2005 to 2009 (Phase 2), and 2010 to 2014 (Phase 3). RESULTS: Over time, the postoperative survival rate significantly increased from 2000 to 2014. In the past 15 years, compared with Phases 1 and 2, the tumor size was smaller in Phase 3 (P < 0.001), but the proportion of high-medium differentiated tumors increased (P < 0.001). The proportion of early GC gradually increased from 3.9% to 14.4% (P < 0.001). A surprising improvement was observed in the mean number of retrieved lymph nodes, ranging from 11.4 to 27.5 (P < 0.001). The overall 5-year survival rate increased from 24% in Phase 1 to 43.8% in Phase 3. Through multivariate analysis, it was found that age, tumor size, histologic type, tumor-node-metastasis stage, depth of invasion, lymph node metastasis, surgical approach, local infiltration, radical extent, number of retrieved lymph nodes, and age group were independent risk factors that influenced the prognosis of patients with GC. CONCLUSION: The clinical features of GC in Northeast China changed during the observation period. The increasing detection of early GC and more standardized surgical treatment effectively prolonged lifetimes.

Prognostic significance of Borrmann type combined with vessel invasion status in advanced gastric cancer.

BACKGROUND: Borrmann classification (types I-IV) for the detection of advanced gastric cancer has been accepted worldwide, and lymphatic and/or blood vessel invasion (LBVI) status is related to the poor prognosis after gastric cancer. AIM: To evaluate the significance of Borrmann type combined with LBVI status in predicting the prognosis of advanced gastric cancer. METHODS: We retrospectively studied the clinicopathological characteristics and long-term survival data of 2604 patients who were diagnosed with advanced gastric adenocarcinoma at Harbin Medical University Cancer Hospital from January 2009 to December 2013. Categorical variables were evaluated by the Pearson's χ 2 test, the Kaplan-Meier method was used to identify differences in cumulative survival rates, and the Cox proportional hazards model was used for multivariate prognostic analysis. RESULTS: A total of 2604 patients were included in this study. The presence of LVBI [LBVI (+)] and Borrmann type (P = 0.001), tumor location (P < 0.001), tumor size (P < 0.001), histological type (P < 0.001), tumor invasion depth (P < 0.001), number of metastatic lymph nodes (P < 0.001), and surgical method (P < 0.001) were significantly correlated with survival. When analyzing the combination of the Borrmann classification and LBVI status, we found that patients with Borrmann type III disease and LBVI (+) had a similar 5-year survival rate to those with Borrmann IV + LBVI (-) (16.4% vs 13.1%, P = 0.065) and those with Borrmann IV + LBVI (+) (16.4% vs 11.2%, P = 0.112). Subgroup analysis showed that the above results were true for any pT stage and any tumor location. Multivariate Cox regression analysis showed that Borrmann classification (P = 0.023), vascular infiltration (P < 0.001), tumor size (P = 0.012), pT stage (P < 0.001), pN stage (P < 0.001), and extent of radical surgery (P < 0.001) were independent prognostic factors for survival. CONCLUSION: Since patients with Borrmann III disease and LBVI (+) have the same poor prognosis as those with Borrmann IV disease, more attention should be paid to patients with Borrmann III disease and LBVI (+) during diagnosis and treatment, regardless of the pT stage and tumor location, to obtain better survival results.

A simple and sensitive HPLC-ESI-MS/MS method for the determination of andrographolide in human plasma.

A liquid chromatography-electrospray ionization tandem mass spectrometry (HPLC-ESI-MS/MS) method for the determination of andrographolide in human plasma was established. Dehydroandrographolide was used as the internal standard (I.S.). The plasma samples were deproteinized with methanol and separated on a Hanbon C(18) column with a mobile phase of methanol-water (70:30, v/v). HPLC-ESI-MS/MS was performed in the selected ion monitoring (SIM) mode using target ions at [M-H(2)O-H](-), m/z 331.1 for andrographolide and [M-H](-), m/z 331.1 for the I.S. Calibration curve was linear over the range of 1.0-150.0ng/mL. The chromatographic separation was achieved in less than 6.5min. The lower limits of quantification (LLOQ) was 1.0ng/mL. The intra and inter-run precisions were less than 6.95 and 7.22%, respectively. The method was successfully applied to determine the plasma concentrations of andrographolide in Chinese volunteers.

[Secondary Aerosol Formation in Urban Shanghai: Insights into the Roles of Photochemical Oxidation and Aqueous-Phase Reaction].

Secondary species are one of the most important components of PM1 particles. To investigate the contributions as well as the factors that affect the formation of the secondary aerosols, a high-resolution time-of-flight aerosol mass spectrometer (HR-TOF-AMS, AMS) was employed to characterize sub-micron particles (PM1) during spring and summer in urban Shanghai. Organics were dominant in PM1 particles and comprised around 55% of the total PM1 mass concentration, followed by sulfate (24%) and nitrate (10%). Positive matrix factorization was further applied to explore the sources of the organics. It was found that primary and secondary organic aerosols accounted for around 34% and 66% of the total organics, respectively. Three episodes were observed during the measurements, where secondary species increased substantially. Increases of secondary species were represented by increases of sulfate and LV-OOA1 in spring, especially during the noontime, thus indicating that their formation is promoted by photochemical oxidation; yet in summer, photochemical and aqueous chemistry together accelerate the formation of secondary species, as indicated by the good correlations between nitrate and aerosol liquid water as well as between SOA and Ox. Overall, we found that contributions from secondary organic and inorganic aerosols to total PM1 particles were 35.5% and 43%, respectively. This study highlights that the influence of photochemical and aqueous chemistry is significant in the promotion of secondary species formation in Shanghai.

An ultra-sensitive Abbott ARCHITECT® assay for the detection of hepatitis B virus surface antigen (HBsAg).

BACKGROUND: Critical to the identification of HBV infection and the prevention of transfusion transmitted disease is the sensitive and accurate detection of Hepatitis B virus surface antigen (HBsAg). Improvements in HBsAg assay sensitivity approaching the performance of nucleic acid testing (NAT) are essential to further reduce the detection window for acute HBV infection in regions where NAT is not widely available. OBJECTIVES AND STUDY DESIGN: An improved HBsAg assay on the fully-automated Abbott ARCHITECT® platform was developed to improve sensitivity, mutant and genotype detection. RESULTS: The analytical sensitivity of the improved prototype assay is 5.2 mIU/ml, which is 3.86- to 14.54-fold more sensitive than comparator assays based on the WHO International Reference Standard. The enhanced sensitivity was also demonstrated with 27 HBV seroconversion panels, detecting more panel members (191 of 364) vs. the ARCHITECT® Qual I (144), Qual II (160) and PRISM® (148) HBsAg assays. Further, the assay detected 7 of 12 HBV DNA positive/HBsAg negative samples, and detected all evaluated mutants and genotypes with higher sensitivity than the comparator assays. The improvement in sensitivity did not diminish assay specificity, attaining 100% (95% CI, 99.97-100%) on 10,633 blood donors. CONCLUSIONS: An Abbott ARCHITECT® HBsAg assay with clinical performance approaching that of mini-pool NAT (approximately 100 copies/ml was developed. The assay has superior HBsAg mutant and genotype detection and specificity, all of which are important for the diagnosis and management of HBV infection.