New stilbene metabolites isolated from the tuber of Bletilla striata and their biological assessment.

A phytochemical investigation of the tuber of Bletilla striata afforded eight stilbene derivatives, including a new bibenzyl (1) and two new phenanthrene (2 and 3). The structures of these compounds were elucidated using a combination of spectroscopic analyses. Further, the anti-inflammatory activity of all the compounds was evaluated to assess their capability to inhibit nitric oxide (NO) production by RAW 264.7 macrophages. The bioactive screening revealed that compounds 4 and 7 exhibited moderate inhibitory effects against NO production with the IC50 values 38.7 and 16.7 µM, respectively.

Empirical Analysis of Customer Risk and Corporate Financing Constraints Based on Supply Chain Networks.

A supply chain's risk spillover effect will affect the customer's risk on the financing constraints of suppliers. This paper builds on the evaluation of customer risk by fuzzy mathematics, combines with the A-share listed companies in Shanghai and Shenzhen from 2007 to 2019 as a study sample, and empirically inspects the influence of customer risk on the level of corporate financing constraints. According to the study, it shows that the customer risk is currently at a moderate level, which will notably impair the supplier's external financing ability. This phenomenon is more remarkable when the monetary policy is tightened with fierce competition in the industry. This paper unveils the economic consequences of customer risk spillovers from a supply chain, enriches the study of the generation mechanism of corporate financing constraints, and provides investors and regulators with empirical evidence to appreciate corporate financing constraints.

Wearable Devices in Health Monitoring from the Environmental towards Multiple Domains: A Survey.

The World Health Organization (WHO) recognizes the environmental, behavioral, physiological, and psychological domains that impact adversely human health, well-being, and quality of life (QoL) in general. The environmental domain has significant interaction with the others. With respect to proactive and personalized medicine and the Internet of medical things (IoMT), wearables are most important for continuous health monitoring. In this work, we analyze wearables in healthcare from a perspective of innovation by categorizing them according to the four domains. Furthermore, we consider the mode of wearability, costs, and prolonged monitoring. We identify features and investigate the wearable devices in the terms of sampling rate, resolution, data usage (propagation), and data transmission. We also investigate applications of wearable devices. Web of Science, Scopus, PubMed, IEEE Xplore, and ACM Library delivered wearables that we require to monitor at least one environmental parameter, e.g., a pollutant. According to the number of domains, from which the wearables record data, we identify groups: G1, environmental parameters only; G2, environmental and behavioral parameters; G3, environmental, behavioral, and physiological parameters; and G4 parameters from all domains. In total, we included 53 devices of which 35, 9, 9, and 0 belong to G1, G2, G3, and G4, respectively. Furthermore, 32, 11, 7, and 5 wearables are applied in general health and well-being monitoring, specific diagnostics, disease management, and non-medical. We further propose customized and quantified output for future wearables from both, the perspectives of users, as well as physicians. Our study shows a shift of wearable devices towards disease management and particular applications. It also indicates the significant role of wearables in proactive healthcare, having capability of creating big data and linking to external healthcare systems for real-time monitoring and care delivery at the point of perception.

Unobtrusive Health Monitoring in Private Spaces: The Smart Home.

With the advances in sensor technology, big data, and artificial intelligence, unobtrusive in-home health monitoring has been a research focus for decades. Following up our research on smart vehicles, within the framework of unobtrusive health monitoring in private spaces, this work attempts to provide a guide to current sensor technology for unobtrusive in-home monitoring by a literature review of the state of the art and to answer, in particular, the questions: (1) What types of sensors can be used for unobtrusive in-home health data acquisition? (2) Where should the sensors be placed? (3) What data can be monitored in a smart home? (4) How can the obtained data support the monitoring functions? We conducted a retrospective literature review and summarized the state-of-the-art research on leveraging sensor technology for unobtrusive in-home health monitoring. For structured analysis, we developed a four-category terminology (location, unobtrusive sensor, data, and monitoring functions). We acquired 912 unique articles from four relevant databases (ACM Digital Lib, IEEE Xplore, PubMed, and Scopus) and screened them for relevance, resulting in n=55 papers analyzed in a structured manner using the terminology. The results delivered 25 types of sensors (motion sensor, contact sensor, pressure sensor, electrical current sensor, etc.) that can be deployed within rooms, static facilities, or electric appliances in an ambient way. While behavioral data (e.g., presence (n=38), time spent on activities (n=18)) can be acquired effortlessly, physiological parameters (e.g., heart rate, respiratory rate) are measurable on a limited scale (n=5). Behavioral data contribute to functional monitoring. Emergency monitoring can be built up on behavioral and environmental data. Acquired physiological parameters allow reasonable monitoring of physiological functions to a limited extent. Environmental data and behavioral data also detect safety and security abnormalities. Social interaction monitoring relies mainly on direct monitoring of tools of communication (smartphone; computer). In summary, convincing proof of a clear effect of these monitoring functions on clinical outcome with a large sample size and long-term monitoring is still lacking.

Unobtrusive Health Monitoring in Private Spaces: The Smart Vehicle.

Unobtrusive in-vehicle health monitoring has the potential to use the driving time to perform regular medical check-ups. This work intends to provide a guide to currently proposed sensor systems for in-vehicle monitoring and to answer, in particular, the questions: (1) Which sensors are suitable for in-vehicle data collection? (2) Where should the sensors be placed? (3) Which biosignals or vital signs can be monitored in the vehicle? (4) Which purposes can be supported with the health data? We reviewed retrospective literature systematically and summarized the up-to-date research on leveraging sensor technology for unobtrusive in-vehicle health monitoring. PubMed, IEEE Xplore, and Scopus delivered 959 articles. We firstly screened titles and abstracts for relevance. Thereafter, we assessed the entire articles. Finally, 46 papers were included and analyzed. A guide is provided to the currently proposed sensor systems. Through this guide, potential sensor information can be derived from the biomedical data needed for respective purposes. The suggested locations for the corresponding sensors are also linked. Fifteen types of sensors were found. Driver-centered locations, such as steering wheel, car seat, and windscreen, are frequently used for mounting unobtrusive sensors, through which some typical biosignals like heart rate and respiration rate are measured. To date, most research focuses on sensor technology development, and most application-driven research aims at driving safety. Health-oriented research on the medical use of sensor-derived physiological parameters is still of interest.

Cervical Screening by Pap Test and Visual Inspection Enabling Same-Day Biopsy in Low-Resource, High-Risk Communities.

OBJECTIVE: To develop an effective, low-cost, single-visit cervical screening strategy incorporating a modified Pap test and visual inspection with acetic acid and Lugol's iodine for low-income settings. METHODS: We conducted a prospective cohort trial. Two low-income Muslim Uyghur communities in China's far western Kashi Prefecture served as pilot and validation study sites, respectively, and 4,049 women (aged 30-59 years) were screened. The conventional Pap test was modified using a cotton swab to collect cervical cells without scraping the cervix using an Ayre spatula, allowing visual inspection with acetic acid (and visual inspection with Lugol's iodine if visual inspection with acetic acid was negative) to be performed in a single visit. Results from both tests were available within 1-2 hours. Women positive for either or both underwent same-day biopsy that was shipped by a courier service to a central pathology laboratory. RESULTS: Single-visit screening incorporating both a modified Pap test and visual inspection achieved a sensitivity of 96.0% (95% CI 91.6-100), which was superior to Pap testing (76%, 95% CI 66.3-85.7; P<.001) or visual inspection with acetic acid-visual inspection with Lugol's iodine (48%, 95% CI 36.7-59.3; P<.001) alone in detecting cervical intraepithelial neoplasia (CIN) 2 or worse lesions. Rapid interpretation of both diagnostic procedures facilitated efficient same-day biopsy that achieved a negative predictive value of 98.2% in detecting CIN 2 or worse lesions. The increased sensitivity and minimized loss of follow-up allowed this approach to identify an extremely high prevalence of CIN 1 (2,741/100,000, 95% CI 2,238-3,245/100,000), CIN 2 or 3 (1,457/100,000, 95% CI 1,088-1,826/100,000), and cervical cancer (395/100,000, 95% CI 202-589/100,000) among these underscreened, at-risk women. CONCLUSION: Single-visit cervical screening with both a modified Pap test and visual inspection has greater sensitivity to detect high-grade CINs, reduces loss of follow-up, and could be an efficient low-cost strategy for low-resource settings.

Comparison of the flexible parametric survival model and Cox model in estimating Markov transition probabilities using real-world data.

BACKGROUND AND OBJECTIVE: Markov micro-simulation models are being increasingly used in health economic evaluations. An important feature of the Markov micro-simulation model is its ability to consider transition probabilities of heterogeneous subgroups with different risk profiles. A survival analysis is generally performed to accurately estimate the transition probabilities associated with the risk profiles. This study aimed to apply a flexible parametric survival model (FPSM) to estimate individual transition probabilities. MATERIALS AND METHODS: The data were obtained from a cohort study investigating ischemic stroke outcomes in Western China. In total, 585 subjects were included in the analysis. To explore the goodness of fit of the FPSM, we compared the estimated hazard ratios and baseline cumulative hazards, both of which are necessary to the calculate individual transition probabilities, and the Markov micro-simulation models constructed using the FPSM and Cox model to determine the validity of the two Markov micro-simulation models and cost-effectiveness results. RESULTS: The flexible parametric proportional hazards model produced hazard ratio and baseline cumulative hazard estimates that were similar to those obtained using the Cox proportional hazards model. The simulated cumulative incidence of recurrent ischemic stroke and 5-years cost-effectiveness of Incremental cost-effectiveness Ratios (ICERs) were also similar using the two approaches. A discrepancy in the results was evident between the 5-years cost-effectiveness and the 10-years cost-effectiveness of ICERs, which were approximately 0.9 million (China Yuan) and 0.5 million (China Yuan), respectively. CONCLUSIONS: The flexible parametric survival model represents a good approach for estimating individual transition probabilities for a Markov micro-simulation model.

[Health Utility of Patients with Stroke Measured by EQ-5D and SF-6D].

OBJECTIVE: To compare EQ-5D and SF-6D for measuring health utility of stroke patients in health economic evaluation studies. METHODS: A prospective cohort study was conducted on 596 stroke patients in the West China Hospital of Sichuan University from 2010 to 2016. Data were collected at baseline through face to face interviews and at the follow-up stages through telephone interviews with a three-month interval. EQ-5D and SF-6D were used for measuring health utility scores of the participants. The consistency of the two instruments was assessed using Bland-Altman plot and Intraclass correlation coefficient (ICC) . Logistic regression models were established to identify predictors of health utility. RESULTS: The participants had a mean utility score of 0.78 (95% confidence interval:0.76, 0.80) in EQ-5D,compared with 0.74 (95% confidence interval: 0.73, 0.76) in SF-6D,and a median (interquartile range) of 0.86 (0.68, 1.00) in EQ-5D and 0.73 (0.62, 0.86) in SF-6D. The 95% limits of agreement between the two instruments ranged from -0.28 to 0.35,with an ICC of 0.67 (95% confidence interval: 0.62,0.71). EQ-5D had a higher ceiling effect. The health utility score of stroke patients changed there rapidly in acute phase (less than 3 months) but barely changed there after.Severity of stroke was a major predictor of health utility scores. CONCLUSION: The two instruments generate inconsistent results in health utility. SF-6D is better for measuring health utility in patients with stroke in China.

Toward Reporting Support and Quality Assessment for Learning from Reporting: A Necessary Data Elements Model for Narrative Medication Error Reports.

To understand and prevent medication errors, spontaneous reporting systems are developed and implemented to aggregate medication error reports for root cause analysis (RCA). Despite of the rich relational information in medication error reports, low quality, especially incompleteness, impedes effective utilization of the reports for analyzing and learning. The lack of a completeness evaluation tool for narrative medication error reports is a barrier to improving the quality of reports. Moreover, no effective mechanisms are integrated in reporting systems for knowledge support upon reporting. In this study, we developed a minimal data model which defines necessary elements in narrative medication error reports and utilized it to evaluate patient safety organization (PSO) medication reports. This study holds promise in bridging the gap between the low quality of narrative reports and the needs of analyzing and learning from medication errors.

Hair Mercury Levels and Their Relationship with Seafood Consumption among Preschool Children in Shanghai.

Mercury is a global pollutant. Children are vulnerable to environmental toxicants. Seafood consumption is a major source of methylmercury exposure. In order to ascertain children's mercury exposure levels and study their relationship with seafood consumption, we conducted a cross-sectional study among preschool children in Shanghai. According to our data, the geometric mean of the mercury levels in children's hair was 191.9 (95% CI: 181.8, 202.4) µg/kg. These results indicate that high income may be a predictor of elevated mercury levels in children's hair. Intake of marine fish, especially tuna and pomfret, was documented in our study and found to increase the risk of high mercury levels. Frequency of fish consumption was positively related with hair mercury levels. Our study is the first to provide baseline data for hair mercury concentration among preschool children in Shanghai.

Keratose/poly (vinyl alcohol) blended nanofibers: Fabrication and biocompatibility assessment.

Increasing interest in using keratin-based materials for biomedical application has prompted the development of keratin/PVA nanofibers. To date, several kinds of keratins (including wool, feather, and human hair reductive keratins)/PVA blended nanofibers have been fabricated but limited to the in vitro studies. However, few studies focused on the in vivo biocompatibility test of keratin/PVA nanofibers. Herein, the keratose (oxidative keratin)/PVA nanofiber, a novel type of keratin/PVA nanofiber, was fabricated with an electrospinning technique. The obtained nanofibers possess uniform fibrous structure, suitable hydrophilicity and mechanical properties, which could be affected by the mass ratio of keratose to PVA. Furthermore, the biocompatibility tests of keratose/PVA nanofibers have been performed by subcutaneous implantation into SD rats. H&E staining and Masson's trichrome staining revealed that the implants were highly compatible with body tissue, and no acute toxic effects as well as no tissue damage were observed. The implants were fully degraded within four weeks. Beyond this, the analysis of proinflammatory cytokines in rat serum indicated that the implants induced normal immune response and had no immunogenicity. These results demonstrate that keratose/PVA nanofibers have the potential for biomedical applications due to the favorable biocompatibility and biodegradability.

Assessment of epidermal growth factor receptor mutation/copy number and K-ras mutation in esophageal cancer.

BACKGROUND: The molecular status of epidermal growth factor receptor (EGFR) in esophageal cancer has not been well elucidated. The purpose of the study was to investigate the prevalence of EGFR and K-ras mutation, and EGFR gene copy number status as well as its association with clinicopathologic characteristics, and also to identify the prognostic value of EGFR gene copy number in esophageal cancer. METHODS: EGFR mutation in exon 19/exon 21 and K-ras mutation in codon 12/codon 13 were detected by real-time PCR method, while EGFR gene copy number status was analyzed by fluorescent in situ hybridization (FISH). EGFR gene amplification and high polysomy were defined as high EGFR gene copy number status (FISH-positive), and all else were defined as low EGFR gene copy number status (FISH-negative). The relationship between EGFR gene copy number status and clinicpathologic characteristics was analyzed. Kaplan-Meier method and Cox proportional hazards regression model were employed to evaluate the effects of EGFR gene copy number status on the patients' survival. RESULTS: A total of 57 esophageal squamous cell carcinoma (ESCC) patients and 9 esophageal adenocarcinoma (EADC) patients were enrolled in the study. EGFR mutation was identified in one patient who was diagnosed as ESCC with stage IIIC disease. K-ras mutation was identified in one patient who was diagnosed as EADC. In all, 34 of 66 (51.5%) samples were detected as FISH-positive, which includes 30 ESCC and 4 EADC tumor samples. The correlation analysis showed that FISH-positive was significantly associated with the tumor stage (P=0.019) and lymph node metastasis (P=0.005) in esophageal cancer patients, and FISH-positive was also significantly associated with the tumor stage (P=0.007) and lymph node metastasis (P=0.008) in ESCC patients. Cox regression analysis showed that high EGFR gene copy number was not a significant predictor of a poor outcome for esophageal cancer patients (P=0.251) or for ESCC patients (P=0.092), but esophageal cancer patients or ESCC patients with low EGFR gene copy number may have longer survival than those with high EGFR gene copy number according to the survival curve trends. CONCLUSIONS: The results indicated that EGFR or K-ras mutation was rare in esophageal cancer, but high EGFR gene copy number is frequent, and correlated with advanced pathologic stage and more number of the metastatic regional lymph nodes, especially in ESCC. In addition, high EGFR gene copy number is likely to have a deleterious effect on prognosis of esophageal cancer patients or ESCC patients, although no statistical significance was reached in the study.

Development and assessment of kerateine nanoparticles for use as a hemostatic agent.

Uncontrolled bleeding frequently occurs in some emergencies which can result in severe injury and even death. Keratin hydrogel has been found that it had good ahemostatic efficacy in the previous studies. However, an ideal hemostatic agent should not require mixing or preparation in advance, and hydrogel is not easy to store and carry. In the present study, the kerateine was firstly extracted from human hair, and then was prepared nanoparticles by a modified emulsion diffusion method. The synthesized nanoparticles showed spherical morphology with an average diameter of approximately 200 nm. The results of Fourier transform infrared spectroscopy and X-ray diffraction indicated that the chemical structure of kerateine did not change but the crystal form may be transformed in the nanoparticles. In addition, kerateine nanoparticles displayed a faster clotting time in vitro study than the kerateine extracts. Furthermore, kerateine nanoparticles significantly reduced the blood loss and coagulation time in the liver puncture and tail amputation in rat models. Our results indicated that kerateine nanoparticles could quickly form a high viscosity gel onto the wound and accelerate the blood coagulation based on their high specific surface area. Therefore, kerateine nanoparticles have great potential for hemostatic application.

Determination the active compounds of herbal preparation by UHPLC-MS/MS and its application on the preclinical pharmacokinetics of pure ephedrine, single herbal extract of Ephedra, and a multiple herbal preparation in rats.

The herbal preparation Ma-Xing-Gan-Shi-Tang (MXGST) is a popular traditional Chinese formulation that has been used for the treatment of coughs and fevers. The potential active components of MXGST are ephedrine, amygdalin, and glycyrrhizic acid. The aim of this study was to develop a validated analytical method to measure these analytes in the herbal preparation MXGST using ultra high performance liquid chromatography-tandem mass spectrometry (UHPLC-MS/MS). Multiple reaction monitoring (MRM) was used to monitor m/z 166.1→148.1 for ephedrine ([M+H](+)), 475.2→163.0 for amygdalin ([M+NH4](+)), and 840.6→453.3 ([M+NH4](+)) for glycyrrhizic acid. The analytes were separated by a reverse phase C18 column (100×2.1mm, 2.6µm). The mobile phase consisted of 5mM ammonium acetate (0.1% formic acid) and 100% methanol (0.1% formic acid) with a linear gradient elution. Five brands of commercial pharmaceutical herbal products and a laboratory extract of MXGST were analyzed. Moreover, the modified UHPLC-MS/MS method was applied to the comparative pharmacokinetics of ephedrine in rats from the following three sources: (1) pure ephedrine, (2) an herbal extract of Ephedra, and (3) an herbal preparation of MXGST. Plasma samples from rats were prepared by protein precipitation, evaporation and reconstitution. The pharmacokinetic data showed that pure ephedrine was absorbed significantly faster than ephedrine of the Ephedra extract or the MXGST herbal preparation. However, the elimination half-life of ephedrine administered as the pure compound was 93.9±8.07min, but for ephedrine from the Ephedra extract and the MXGST, the half-lives were 133±17 and 247±57.6min, respectively. The area under the concentration curves (AUC) did not show significant differences among the three groups. These data suggest that the rest of the herbal ingredients in the Ephedra extract and the MXGST may provide a compensation effect that reduces the peak concentration of ephedrine and prolongs the elimination half-life.

[Multi-component quantitative analysis combined with chromatographic fingerprint for quality assessment of Onosma hookeri].

A method for simultaneous determination of the shikonin, acetyl shikonin and ß, ß'-dimethylpropene shikonin in Onosma hookeri and the chromatographic fingerprint was estabished by HPLC-DAD on an Agilent Zorbax SB-column with a gradient elution of acetonitrile and water at 0.8 mL x min(-1), 30 degrees C. The quality assessment was conducted by comparing the content difference of three naphthoquinone constituents, in combination with chromatographic fingerprint analysis and systems cluster analysis among 7 batches of radix O. hookeri. The content of the three naphthoquinone constituents showed wide variations in 7 bathces. The similarity value of the fingerprints of sample 5, 6 and 7 was above 0.99, sample 2 and 3 above 0.97, sample 3 and 4 above 0.90, and other samples larger than 0.8, which was in concert with the content of three naphthoquinone constituents. The 7 samples were roughly divided into 4 categories. The results above indicated that the using of this medicine is complex and rather spotty. The established HPLC fingerprints and the quantitative analysis method can be used efficiently for quality assessment of O. hookeri.

[Study on the mixed testing of serum samples in seroepidemiological survey of parasitic diseases].

OBJECTIVE: In order to accumulate experiences for improving the efficiency in serological tests, the present study on mixed testing of serum samples was performed by taking the serological test of trichinellosis and toxoplasmosis as the examples, and had proved the effects on cost-effectiveness of seroepidemiological survey of parasitic disease with method of mixed-samples test. METHODS: According to the binomial distribution principle, to develop an approach to the feasibility of mixed testing of serum samples, and to work on a cost-effectiveness analysis of one-by-one testing and mixed testing using hygienic economic analysis method was performed. For serological test of trichinellosis and toxoplasmosis, 3 kinds of mixed testing methods, namely 3 serum sample mixture, 5 serum sample mixture and 10 serum sample mixture, were performed. RESULTS: The results showed that all the 3 kinds of mixed tests of trichinellosis and toxoplasmosis showing positive result if only 1 weak positive serum sample were mixed with. When the serum samples being mixed were all negative ones, then among the 24 groups tested with each kind of negative serum sample mixture of trichinellosis (3 serum samples, 5 serum samples and 10 serum samples), they all showed negative. However, among the 12 groups tested with 2 kinds of negative serum mixture of toxoplasmosis (3 serum samples and 5 serum samples), all showed negative while among the 18 groups tested with the 10 serum sample mixture, 16 groups showed negative and 2 were positive. The mixed testing of trichinellosis and toxoplasmosis showed that the efficiency of mixed testing was related to the serological positive rate of the parasitic diseases to be examined. When serological positive rate was 10%, the efficiency of mixed testing was higher in 4 serum sample group. When serological positive rate was 1%, the efficiency of mixed testing was higher in 10 serum sample group and when serological positive rate was 0.1%, the in crease of the size of mixed serum samples could decrease the number of testing, but the prerequisite was that there must be one positive sample, so that the positivity for all the mixed tests could be detected. If mixed testing were performed on all negative samples, no positivity could be detected. CONCLUSION: The result of cost-effectiveness analysis demonstrated that for seroepidemiological survey of parasitic diseases, the cost for mixed testing was low, especially when the serological positive rate was expected low (< or = 1%, thus the mixed testing could save a large amount of the cost.