Effectiveness and Safety of Lianhua Qingwen Capsules for COVID-19: A Propensity-Score Matched Cohort Study.

As a traditional Chinese medicine, Lianhua Qingwen capsules have been widely used to treat Coronavirus Disease 2019 (COVID-19). This study was aimed to demonstrate the association between treatment with Lianhua Qingwen capsules and the clinical outcomes of hospitalized patients with COVID-19. This retrospective study was conducted at four hospitals in Central China. Data of hospitalized COVID-19 patients were collected between December 19, 2019 and April 26, 2020. Based on whether Lianhua Qingwen capsules were used, patients were classified into Lianhua Qingwen and non-Lianhua Qingwen (control) groups. To control for confounding factors, we used conditional logistic regression in a propensity-score matched (PSM) cohort (1 : 1 balanced), as well as logistic regression without matching as sensitivity analysis. A total of 4918 patients were included, 2760 of whom received Lianhua Qingwen capsules and 2158 of whom did not. In the PSM model, after adjusting for confounders, the in-hospital mortality was similar between the Lianhua Qingwen group and the control group (6.8% vs. 3.3%, adjusted OR, 0.66 [95% CI, 0.38-1.15], p = 0.138). The negative conversion rate of Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2) infection was higher in the Lianhua Qingwen group (88.3% vs. 96.1%, adjusted OR, 4.02 [95% CI, 2.58-6.25], p < 0.001). The incidence of acute liver injury was comparable between the two groups (14.0% vs. 11.5%, adjusted OR: 0.85 [95% CI, 0.71-1.02], p = 0.083), and the incidence of acute kidney injury was lower in the Lianhua Qingwen group (5.3% vs. 3.0%, adjusted OR: 0.71 [95% CI, 0.50-1.00], p = 0.048). Treatment with Lianhua Qingwen capsules was not significantly associated with in-hospital mortality in COVID-19 patients. In the Lianhua Qingwen group, the negative conversion rate of SARS-CoV-2 infection was higher and the incidence of acute kidney injury was lower than in the control group.

[Systematic review and pharmacoeconomic evaluation of Qizhi Weitong Granules in treatment of functional dyspepsia].

This study aims to investigate the efficacy, safety, and cost-effecctiveness of Qizhi Weitong Granules in the treatment of functional dyspepsia. Specifically, two commonly used clinical protocols for the treatment of functional dyspepsia were selected: Qizhi Weitong Granules+Mosapride vs Mosapride alone(control). Meta-analysis of previous clinical studies was performed to examine the efficacy and safety, and pharmacoeconomic evaluation was carried out according to the results of the Meta-analysis. The cost-effectiveness analysis was carried out to elucidated the incremental cost-effectiveness ratio(ICER), and the sensitivity was analyzed with tornado dia-gram and Monte Carlo simulation. The willingness-to-pay threshold of patients for functional dyspepsia was investigated and compared with the ICER to evaluate whether Qizhi Weitong Granules was cost-effective. The result showed that the effective rate of Qizhi Weitong Granules combined with Mosapride in the treatment of functional dyspepsia was 95.49%, which was higher than that of Mosapride alone(73.30%)(OR=8.52, 95%CI[4.36, 16.64])(P<0.000 1). The two groups showed no significant difference in safety. The price of Qizhi Weitong Granules+Mosapride was higher than that of Mosapride alone. The ICER was 640.29 CNY, 1 506.67 CNY lower than the willingness-to-pay threshold. The sensitivity analysis showed that the analysis results were relatively stable. Thus, Qizhi Weitong Granules+Mosapride is safe, effective, and economical in the treatment of functional dyspepsia, which should be further promoted in clinical settings.

Antidelaminating, Thermally Stable, and Cost-Effective Flexible Kapton Platforms for Nitrate Sensors, Mercury Aptasensors, Protein Sensors, and p-Type Organic Thin-Film Transistors.

The inkjet printing of metal electrodes on polymer films is a desirable manufacturing process due to its simplicity but is limited by the lack of thermal stability and serious delaminating flaws in various aqueous and organic solutions. Kapton, adopted worldwide due to its superior thermal durability, allows the high-temperature sintering of nanoparticle-based metal inks. By carefully selecting inks (Ag and Au) and Kapton substrates (Kapton HN films with a thickness of 135 µm and a thermal resistance of up to 400 °C) with optimal printing parameters and simplified post-treatments (sintering), outstanding film integrity, thermal stability, and antidelaminating features were obtained in both aqueous and organic solutions without any pretreatment strategy (surface modification). These films were applied in four novel devices: a solid-state ion-selective (IS) nitrate (NO3-) sensor, a single-stranded DNA (ssDNA)-based mercury (Hg2+) aptasensor, a low-cost protein printed circuit board (PCB) sensor, and a long-lasting organic thin-film transistor (OTFT). The IS NO3- sensor displayed a linear sensitivity range between 10-4.5 and 10-1 M (r2 = 0.9912), with a limit of detection of 2 ppm for NO3-. The Hg2+ sensor exhibited a linear correlation (r2 = 0.8806) between the change in the transfer resistance (RCT) and the increasing concentration of Hg2+. The protein PCB sensor provided a label-free method for protein detection. Finally, the OTFT demonstrated stable performance, with mobility values in the linear (µlin) and saturation (µsat) regimes of 0.0083 ± 0.0026 and 0.0237 ± 0.0079 cm2 V-1 S-1, respectively, and a threshold voltage (Vth) of -6.75 ± 3.89 V.

Two C-terminal sequence variations determine differential neurotoxicity between human and mouse α-synuclein.

BACKGROUND: α-Synuclein (aSyn) aggregation is thought to play a central role in neurodegenerative disorders termed synucleinopathies, including Parkinson's disease (PD). Mouse aSyn contains a threonine residue at position 53 that mimics the human familial PD substitution A53T, yet in contrast to A53T patients, mice show no evidence of aSyn neuropathology even after aging. Here, we studied the neurotoxicity of human A53T, mouse aSyn, and various human-mouse chimeras in cellular and in vivo models, as well as their biochemical properties relevant to aSyn pathobiology. METHODS: Primary midbrain cultures transduced with aSyn-encoding adenoviruses were analyzed immunocytochemically to determine relative dopaminergic neuron viability. Brain sections prepared from rats injected intranigrally with aSyn-encoding adeno-associated viruses were analyzed immunohistochemically to determine nigral dopaminergic neuron viability and striatal dopaminergic terminal density. Recombinant aSyn variants were characterized in terms of fibrillization rates by measuring thioflavin T fluorescence, fibril morphologies via electron microscopy and atomic force microscopy, and protein-lipid interactions by monitoring membrane-induced aSyn aggregation and aSyn-mediated vesicle disruption. Statistical tests consisted of ANOVA followed by Tukey's multiple comparisons post hoc test and the Kruskal-Wallis test followed by a Dunn's multiple comparisons test or a two-tailed Mann-Whitney test. RESULTS: Mouse aSyn was less neurotoxic than human aSyn A53T in cell culture and in rat midbrain, and data obtained for the chimeric variants indicated that the human-to-mouse substitutions D121G and N122S were at least partially responsible for this decrease in neurotoxicity. Human aSyn A53T and a chimeric variant with the human residues D and N at positions 121 and 122 (respectively) showed a greater propensity to undergo membrane-induced aggregation and to elicit vesicle disruption. Differences in neurotoxicity among the human, mouse, and chimeric aSyn variants correlated weakly with differences in fibrillization rate or fibril morphology. CONCLUSIONS: Mouse aSyn is less neurotoxic than the human A53T variant as a result of inhibitory effects of two C-terminal amino acid substitutions on membrane-induced aSyn aggregation and aSyn-mediated vesicle permeabilization. Our findings highlight the importance of membrane-induced self-assembly in aSyn neurotoxicity and suggest that inhibiting this process by targeting the C-terminal domain could slow neurodegeneration in PD and other synucleinopathy disorders.

Updated diagnosis, treatment and prevention of COVID-19 in children: experts' consensus statement (condensed version of the second edition).

In the early February, 2020, we called up an experts' committee with more than 30 Chinese experts from 11 national medical academic organizations to formulate the first edition of consensus statement on diagnosis, treatment and prevention of coronavirus disease 2019 (COVID-19) in children, which has been published in this journal. With accumulated experiences in the diagnosis and treatment of COVID-19 in children, we have updated the consensus statement and released the second edition recently. The current version in English is a condensed version of the second edition of consensus statement on diagnosis, treatment and prevention of COVID-19 in children. In the current version, diagnosis and treatement criteria have been optimized, and early identification of severe and critical cases is highlighted. The early warning indicators for severe pediatric cases have been summarized which is utmost important for clinical practice. This version of experts consensus will be valuable for better prevention, diagnosis and treatment of COVID-19 in children worldwide.

A national survey on fungal infection diagnostic capacity in the clinical mycology laboratories of tertiary care hospitals in China.

BACKGROUND/PURPOSE: As the incidence of fungal infections in China increases, the demand for rapid and accurate diagnosis of mycoses is growing. Yet, information on current diagnostic capacity is scarce. METHODS: An online survey was conducted in February 2018 to collect information on mycology testing from tertiary care hospitals across China. Responses from 348 hospitals were analyzed, and a scoring system was designed and employed to assess the overall diagnostic capacity. RESULTS: Most of the surveyed hospitals did not have separate laboratory space, manpower, or equipment dedicated for fungal testing. Conventional staining methods were widely available (>70%), whereas GMS and fluorescent staining were less common. Fungal identification services were offered mostly with chromogenic medium, morphological characterization or automated identification systems, other than more advanced methods such as MALDI-TOF MS and DNA sequencing. Fungal serology testing was available in 81.1%, with G test being the most often used. Though 91.8% of the respondents had the ability to perform antifungal susceptibility testing for yeasts, less than 13% conducted such testing for molds. The percentage of laboratories participating in External Quality Assessment programs and research was 57.5% and 32.5%, respectively. The average score for the 348 surveyed hospitals was 37.2 (out of a maximum of 89 points), with only 15 hospitals scoring >60, suggesting a general lack of high-quality mycology laboratories. CONCLUSIONS: The overall clinical testing capacity for fungal infection in China is insufficient. More investment and training efforts are warranted to establish centers of excellence and promote access to high-quality diagnostic services.

A rapid advice guideline for the diagnosis and treatment of 2019 novel coronavirus (2019-nCoV) infected pneumonia (standard version).

In December 2019, a new type viral pneumonia cases occurred in Wuhan, Hubei Province; and then named "2019 novel coronavirus (2019-nCoV)" by the World Health Organization (WHO) on 12 January 2020. For it is a never been experienced respiratory disease before and with infection ability widely and quickly, it attracted the world's attention but without treatment and control manual. For the request from frontline clinicians and public health professionals of 2019-nCoV infected pneumonia management, an evidence-based guideline urgently needs to be developed. Therefore, we drafted this guideline according to the rapid advice guidelines methodology and general rules of WHO guideline development; we also added the first-hand management data of Zhongnan Hospital of Wuhan University. This guideline includes the guideline methodology, epidemiological characteristics, disease screening and population prevention, diagnosis, treatment and control (including traditional Chinese Medicine), nosocomial infection prevention and control, and disease nursing of the 2019-nCoV. Moreover, we also provide a whole process of a successful treatment case of the severe 2019-nCoV infected pneumonia and experience and lessons of hospital rescue for 2019-nCoV infections. This rapid advice guideline is suitable for the first frontline doctors and nurses, managers of hospitals and healthcare sections, community residents, public health persons, relevant researchers, and all person who are interested in the 2019-nCoV.

Efficient Clinical Data Sharing Framework Based on Blockchain Technology.

BACKGROUND: While electronic health records have been collected for many years in Taiwan, their interoperability across different health care providers has not been entirely achieved yet. The exchange of clinical data is still inefficient and time consuming. OBJECTIVES: This study proposes an efficient patient-centric framework based on the blockchain technology that makes clinical data accessible to patients and enable transparent, traceable, secure, and effective data sharing between physicians and other health care providers. METHODS: Health care experts were interviewed for the study, and medical data were collected in collaboration with Ministry of Health and Welfare (MOHW) Chang-Hua hospital. The proposed framework was designed based on the detailed analysis of this information. The framework includes smart contracts in an Ethereum-based permissioned blockchain to secure and facilitate clinical data exchange among different parties such as hospitals, clinics, patients, and other stakeholders. In addition, the framework employs the Logical Observation Identifiers Names and Codes (LOINC) standard to ensure the interoperability and reuse of clinical data. RESULTS: The prototype of the proposed framework was deployed in Chang-Hua hospital to demonstrate the sharing of health examination reports with many other clinics in suburban areas. The framework was found to reduce the average access time to patient health reports from the existing next-day service to a few seconds. CONCLUSION: The proposed framework can be adopted to achieve health record sharing among health care providers with higher efficiency and protected privacy compared to the system currently used in Taiwan based on the client-server architecture.

Versatile printed microheaters to enable low-power thermal control in paper diagnostics.

As the capabilities of low-resource field testing have begun to expand to incorporate more complex diagnostic technologies, many of these devices remain tethered to large heaters requiring relatively high-power inputs. Highly efficient microheaters would enable miniaturization of devices for more economic and effective heating with high temperatures and sustained incubation. This work reports the development and application of resistive microheaters printed with nanosilver ink for improved methods of automated sample heating in paper-based point-of-care (POC) and in-field diagnostics. Resistance is easily predicted, and shapes can be altered to fit space and heat-transfer needs, sustained and discrete heating of precise regions are possible. Here, we demonstrate both isothermal nucleic acid amplification at 65 °C and bacterial culture at 37 °C using our microheaters. Printed nanosilver microheaters are easily integrated into reactions that require low-power battery heating, can sustain heating for 16-hour incubations, and cost between 0.17 and 0.58 US dollars each. Further, the microheaters are reusable, stable over 6 months, and can be wetted without degradation or reduction in conductivity. These versatile printed microheaters enable thermal control for a variety of low power heating applications.

Microfluidic rapid and autonomous analytical device (microRAAD) to detect HIV from whole blood samples.

While identifying acute HIV infection is critical to providing prompt treatment to HIV-positive individuals and preventing transmission, existing laboratory-based testing methods are too complex to perform at the point of care. Specifically, molecular techniques can detect HIV RNA within 8-10 days of transmission but require laboratory infrastructure for cold-chain reagent storage and extensive sample preparation performed by trained personnel. Here, we demonstrate our point-of-care microfluidic rapid and autonomous analysis device (microRAAD) that automatically detects HIV RNA from whole blood. Inside microRAAD, we incorporate vitrified amplification reagents, thermally-actuated valves for fluidic control, and a temperature control circuit for low-power heating. Reverse transcription loop-mediated isothermal amplification (RT-LAMP) products are visualized using a lateral flow immunoassay (LFIA), resulting in an assay limit of detection of 100 HIV-1 RNA copies when performed as a standard tube reaction. Even after three weeks of room-temperature reagent storage, microRAAD automatically isolates the virus from whole blood, amplifies HIV-1 RNA, and transports amplification products to the internal LFIA, detecting as few as 3 × 105 HIV-1 viral particles, or 2.3 × 107 virus copies per mL of whole blood, within 90 minutes. This integrated microRAAD is a low-cost and portable platform to enable automated detection of HIV and other pathogens at the point of care.

Aptamer-based SERS biosensor for whole cell analytical detection of E. coli O157:H7.

Infectious outbreaks caused by foodborne pathogens such as E. coli O157:H7 are still imposing a heavy burden for global food safety, causing acute illnesses and significant industrial impact worldwide. Despite the growth of biosensors as a research field, continuous innovation on detection strategies, novel materials and enhanced limits of detection, most of the platforms developed at the laboratory scale never will get to meet the market. The use of aptamers as capture biomolecules has been proposed as a promising alternative to overcome the harsh environmental conditions of industrial manufacturing processes, and to enhance the performance under real, complex, conditions. In this work, we present the feasibility of using aptameric DNA sequences, covalently conjugated to 4-aminothiophenol-gold nanoparticle complexes for the sensitive and highly specific detection of E. coli O157:H7 via surface enhanced Raman spectroscopy (SERS) analysis. Low concentrations of E. coli O157:H7 were detected and quantified within 20 min in both pure culture (∼101 CFU mL-1) and ground beef samples (∼102 CFU mL-1). The SERS intensity response showed a strong negative linear correlation (r2 = 0.995) with increasing concentrations of E. coli O157:H7 (ranging from 102 to 106 CFU mL-1). High specificity was achieved at genus (L. monocytogenes, S. aureus S. typhimurium) species (E. coli B1201) and serotype (E. coli O55:H7) level, demonstrating with 95% of confidence that the interferent microorganisms tested generated a Raman signal response not significantly different from the background (p = 0.786). This work evaluates the incorporation of aptameric DNA sequences as bio capture molecules exclusively. The successful performance presented using non-modified citrate reduced GNPs, is promising for potential low-cost, high-throughput applications. The findings might be applied simultaneously to the detection of a wide variety of foodborne pathogens in a multiplexed fashion employing unique Raman probes and strain-specific aptamer sequences.

Inkjet Printed Nanopatterned Aptamer-Based Sensors for Improved Optical Detection of Foodborne Pathogens.

The increasing incidence of infectious outbreaks from contaminated food and water supply continues imposing a global burden for food safety, creating a market demand for on-site, disposable, easy-to-use, and cost-efficient devices. Despite of the rapid growth of biosensors field and the generation of breakthrough technologies, more than 80% of the platforms developed at lab-scale never will get to meet the market. This work aims to provide a cost-efficient, reliable, and repeatable approach for the detection of foodborne pathogens in real samples. For the first time an optimized inkjet printing platform is proposed taking advantage of a carefully controlled nanopatterning of novel carboxyl-functionalized aptameric ink on a nitrocellulose substrate for the highly efficient detection of E. coli O157:H7 (25 colony forming units (CFU) mL-1 in pure culture and 233 CFU mL-1 in ground beef) demonstrating the ability to control the variation within ±1 SD for at least 75% of the data collected even at very low concentrations. From the best of the knowledge this work reports the lowest limit of detection of the state of the art for paper-based optical detection of E. coli O157:H7, with enough evidence (p > 0.05) to prove its high specificity at genus, species, strain, and serotype level.

Aminolated and Thiolated PEG-Covered Gold Nanoparticles with High Stability and Antiaggregation for Lateral Flow Detection of Bisphenol A.

The few lateral flow assays (LFAs) established for detecting the endocrine disrupting chemical bisphenol A (BPA) have employed citrate-stabilized gold nanoparticles (GNPs), which have inevitable limitations and instability issues. To address these limitations, a more stable and more sensitive biosensor is developed by designing strategies for modifying the surfaces of GNPs with polyethylene glycol and then testing their effectiveness and sensitivity toward BPA in an LFA. Without the application of any enhancement strategy, this modified BPA LFA can achieve a naked-eye limit of detection (LOD) of 0.8 ng mL-1 , which is 12.5 times better than the LOD of regular BPA LFAs, and a quantitative LOD of 0.472 ng mL-1 . This modified LFA has the potential to be applied to the detection of various antigens.

[Strategy of constructing post-market integral evaluation system of traditional Chinese medicine injection].

As an important representative of modern Chinese medicine, traditional Chinese medicine (TCM) injzection has become an indispensable part of the Chinese medicine industry. However, its development is now restricted by the bottleneck of insufficient core competitiveness, low-level research and production, even injection quality and the safe use are not guaranteed. Thus, it is urgent to reevaluate post-marketing TCM injection generally and to make secondary development. Under current circumstances, taking major brands which have good clinical and market foundation, as well as research value, as the main subject of cultivation and evaluation is an important approach to innovative development of TCM injection industry. Unlike oral proprietary Chinese medicine, the cultivatation of major brands of TCM injection needs higher technical support, quality standards and more timely feedback. Therefore, a post-market integral evaluation system adaptive to TCM injection is required. This article discussed some key points on the construction of a post-market integral evaluation system of TCM injection in three levels： optimizing evaluation methods, building synergistic innovation platforms which combine the medical research institutions and pharmaceutical enterprises, and finally constructing the integral evaluation system. A "five to one" structure has been proposed to enhance TCM injection effectiveness, safety and adaptability on the whole, which are from the following aspects： mechanism research, clinical evidence validation, literature information mining, sustainable development of resources and industrialization operation.

Fabrication of nano-indented cavities on Au for the detection of chemically-adsorbed DTNB molecular probes through SERS effect.

Micro/nano-lithographic techniques are usually employed as a straightforward process for roughening a thin-film Au surface for surface-enhanced Raman scattering (SERS). However, a topographical pattern with deepened edges is difficult to control in a rapid and environmental-friendly way. In this study, a simple physical procedure is proposed for tailoring a thin-film Au surface with triangular nanostructures using nano-indentation technique. The as-fabricated nano-indented cavities on Au (nAu) were structured as a characterization substrate for SERS. By calculating the geometries of nAu and the increase of surface area as a function of the concentration of chemically adsorbed 2-nitro-5-thiobenzoic acid (NTB), a combined chemical and electromagnetic effect was estimated. Particularly-made nAu was adjusted for examining chemically adsorbed NTB molecules with differently intensified Raman-active groups by tuning the indentation depth and the tip-to-tip displacement. SERS enhancement factor on a specific NTB/nAu could be increased to 2.1×10(6).

Particulate matter characteristics during agricultural waste burning in Taichung City, Taiwan.

Agricultural waste burning is performed after harvest periods in June and November in Taiwan. Typically, farmers use open burning to dispose of excess rice straw. PM(2.5) and PM(2.5-10) measurements were conducted at National Chung Hsing University in Taichung City using a dichotomous sampler. The sampling times were during straw burning periods after rice harvest during 2002-2005. Ionic species including SO(4)(2-), NO(3)(-), NH(4)(+), K(+), Ca(2+), Cl(-) and Na(+) and carbonaceous species (EC and OC) in PM(2.5) and PM(2.5-10) were analyzed. The results showed that the average PM(2.5) and PM(2.5-10) concentrations were 123.6 and 31.5 microg m(-3) during agricultural waste burning periods and 32.6 and 21.4 microg m(-3) during non-waste burning periods, respectively. The fine aerosol ionic species including Cl(-), K(+) and NO(3)(-) increased 11.0, 6.7 and 5.5 times during agricultural burning periods compared with periods when agricultural waste burning is not performed. K(+) was found mainly in the fine mode during agricultural burning. High nitrogen oxidation ratio was found during agricultural waste burning periods which might be caused by the conversion of Nitrogen dioxide (NO(2)) to NO(3)(-). It is concluded that agricultural waste burning with low dispersion often causes high PM(2.5) and gases pollutant events.