Advances in methods and techniques for the study of polysaccharide in vivo processes and immunomodulatory mechanisms / 药学学报

In recent years, polysaccharides have received much attention because of their high safety and good immunological activity. The study of polysaccharide in vivo process is a key scientific problem that needs to be solved for polysaccharide drug development. Some progress has been made in the field of polysaccharide pharmacokinetics and immunomodulation. However, due to the lack of both chromogenic and light-absorbing groups and the complex molecular structure of polysaccharides, the in vivo processes and immunomodulatory mechanisms of polysaccharides have been slow to be investigated. The effective combination of multiple techniques can break the bottleneck of difficult tracing and unknown immunomodulatory mechanism of polysaccharides in vivo, and promote the development and utilization of polysaccharides. In this paper, we systematically summarize the key techniques in the study of polysaccharide in vivo processes and immunomodulatory mechanisms in order to provide technical references and research ideas for the study of polysaccharide in vivo processes and immunomodulatory mechanisms.

Addressing the problem of hook effect in sandwich lateral flow immunoassay: review and impact on future solutions / 中华检验医学杂志

Lateral flow immunoassay (LFIA) is a rapid detection technique that allows researchers to move the antigen-antibody reaction from a test tube or laboratory vessel to a test strip. Due to the chromatographic effect of the test strip, the solution would move to a specified direction based on the test and complete the whole antigen-antibody specific reaction. A qualitative judgment can be made with the naked eye by observing the color change of the reagent strip at a specific location. Because of its advantages of being fast, simple, specific, inexpensive, and requiring no specialized personnel, LFIA is now widely used in medical testing, food quality monitoring, environmental monitoring, agriculture and animal husbandry. A major bottleneck for the development of LFIA technology is the hook effect. This paper summarizes the current methods, means and research progresses to combat the hook effect, hoping to provide a strong technical reference for researchers to design test strips, select suitable nanoparticles, and achieve quantitative LFIA detection.

Research progress on genome-guided precision oncology and development ideas of antitumor Chinese medicine / 中国中药杂志

Genome-guided oncology refers to a new treatment concept that transcends histological classification and pathological ty-ping and uses drugs according to the genetic characteristics of tumors. New drug development technology and clinical trial design based on this concept provide new ideas for the clinical application of precision oncology. The multi-component and multi-target characteristics of Chinese medicine provide rich resources for the development of tumor-targeting drugs from natural products, and the design of the master protocol trial aiming at the characteristics of precision oncology supports the rapid clinical screening of effective tumor-targeting drugs. The emergence of the synthetic lethality strategy breaks through the bottleneck that the drug can only target the oncogene but cannot do anything to the tumor suppressor gene with the loss-of-function mutation in the past. With the rapid development of high-throughput sequencing technology, the cost of sequencing is also decreasing. For the development of tumor-targeting drugs, how to keep up with the update speed of target information is a difficult problem of concern. Based on the integration of innovative ideas and me-thods of precision oncology, network pharmacology, and synthetic lethality strategy on synthetic lethal interaction network of antitumor Chinese medicine compatibility formula design, and the combination of improvement of innovative clinical trial methods, such as master protocol trial, basket trial, and umbrella trial, unique advantages of Chinese medicine are expected to be exerted beyond the antibody-based drugs and small molecule-based drugs and corresponding targeted drugs are potentially developed for clinical application.

Multi-classification prediction model of lung cancer tumor mutation burden based on residual network / 生物医学工程学杂志

Medical studies have found that tumor mutation burden (TMB) is positively correlated with the efficacy of immunotherapy for non-small cell lung cancer (NSCLC), and TMB value can be used to predict the efficacy of targeted therapy and chemotherapy. However, the calculation of TMB value mainly depends on the whole exon sequencing (WES) technology, which usually costs too much time and expenses. To deal with above problem, this paper studies the correlation between TMB and slice images by taking advantage of digital pathological slices commonly used in clinic and then predicts the patient TMB level accordingly. This paper proposes a deep learning model (RCA-MSAG) based on residual coordinate attention (RCA) structure and combined with multi-scale attention guidance (MSAG) module. The model takes ResNet-50 as the basic model and integrates coordinate attention (CA) into bottleneck module to capture the direction-aware and position-sensitive information, which makes the model able to locate and identify the interesting positions more accurately. And then, MSAG module is embedded into the network, which makes the model able to extract the deep features of lung cancer pathological sections and the interactive information between channels. The cancer genome map (TCGA) open dataset is adopted in the experiment, which consists of 200 pathological sections of lung adenocarcinoma, including 80 data samples with high TMB value, 77 data samples with medium TMB value and 43 data samples with low TMB value. Experimental results demonstrate that the accuracy, precision, recall and F1 score of the proposed model are 96.2%, 96.4%, 96.2% and 96.3%, respectively, which are superior to the existing mainstream deep learning models. The model proposed in this paper can promote clinical auxiliary diagnosis and has certain theoretical guiding significance for TMB prediction.

Application progress on taste evaluation methods for oral preparations / 中国中药杂志

Taste is an important factor affecting the medicinal properties of oral preparations and patient compliance with medication, and also an important evaluation index for oral preparation design and clinical application. How to characterize the taste objectively, accurately, simply, and efficiently is a bottleneck problem that restricts the taste design, development, and utilization of oral preparations. At present, the commonly used taste assessment methods for oral preparations are traditional human taste panel, electronic tongue, animal preference test, in vitro release study, and electrophysiological test. The traditional human taste panel is the first choice for taste evaluation, but it is limited by poor subjectivity and reproducibility. Therefore, despite some limitations, the other four taste assessment methods have been applied in the pharmaceutical industry as auxiliary methods. This study reviewed the detection principles, applicability, advantages, and disadvantages of the above methods to provide references for the taste correction research and taste assessment of oral preparations, improve patient compliance and the competitiveness of oral preparation products in the industry, and promote the development of oral preparation technologies.

Focusing on the frailty of the elderly to promote multi-dimensional management / 中国实用护理杂志

Frailty is a common physiological dysfunction syndrome in the elderly. Aging requires active prevention and treatment of the aging problem. Based on the background of aging problem, this paper introduces the classic and personalized methods for identifying senile frailty and analyzes their applicability. This paper discusses the evolution of the intervention center of senile frailty from the horizontal expansion of the intervention object and the vertical extension of the intervention path, discusses the significance of the comprehensive care model based on the comprehensive assessment of the elderly and the multidisciplinary cooperation in the frailty management, and expounds the bottleneck problems in the frailty management of the elderly.

Research and development strategies of new Chinese medicines based on new regulations / 中国中药杂志

In recent years, only a small number of new Chinese medicines have been approved for marketing, which has embodied the bottleneck in the development of the Chinese medicine industry. To tackle this problem, the National Medical Products Administration has issued a series of regulations and technical requirements. In the context of new regulations, this study deeply explored the research and development strategies of new Chinese medicines under the guidance of the new classification of drug registration, and discussed the key technical issues in the research and development.

Interpretation and Suggestions of Notice on Standardizing the Allocation and Use of Licensed Pharmacists in Drug Retail Enterprises and Related Documents / 中国药房

OBJECTIVE：To unscramble the Notice on Standardizing the Allocation and Use of Licensed Pharmacists in Drug Retail Enterprises （called Notice for short ）and related document ，and to give some suggestions to provide reference for the industry and policy decision departments. METHODS ：The background and content of Notice were described briefly ；the problemsexisting in the corresponding provincial differentiated allocation policy and the difficulties existing in the implementation were analyzed to give some relevant suggestions. RESULTS & CONCLUSIONS ：The main contents of Notice contained adhering to the policy of licensed pharmacists ，steadily improving the allocation level of licensed pharmacists ，refining and implementing the allocation requirements ，and strengthening the implementation of supervision and inspection responsibilities ；giving full play to the role of licensed pharmacists and continuously strengthening the team building. At present ，drug administrations of many provinces in China have issued specific policies on the differentiated allocation of licensed pharmacists and pharmaceutical technicians ，which are mainly divided into four schemes. The author believes that the classification method of drug retail enterprises implemented in Shandong and Guangdong provinces are the most scientific. The implementation of differentiated allocation of pharmacists with health（pharmacy）professional title in drug retail enterprises can alleviate the problem of insufficient licensed pharmacists to a certain extent ，but the disadvantage is that it can not achieve accurate registration and control as well as the management of licensed pharmacists ，which is easy to produce policy gaps ；after the “affiliation licensed pharmacist ’s certificate ”phenomenon， the“certificate affiliation of pharmacist with health （pharmacy）professional title ”phenomenon appeared. It is suggested that the provincial drug supervision and administration departments should try the differentiated allocation scheme of hierarchical management；learn from the management experience of licensed pharmacists and pharmaceutical technicians in Guangdong province， develop relevant platforms to manage the information of pharmaceutical technicians uniformly ； strengthen the communication and interaction with the health and human resource security department as well as the mutual promotion mechanism of personnel information screening ，so as to solve the core bottleneck of licensed pharmacists ’quality.

Identification of quality markers of Qixuehe Capsules based on analytic hierarchy process and entropy weight methods / 中国中药杂志

Qixuehe Capsules is a compound Chinese patent medicine developed for treating the disorder of Qi and blood(a common etiology of gynecological disease), which has remarkable effects on smoothing liver and regulating Qi, activating blood circulation, and relieving pain. However, due to its complex prescriptions(15 herbs) and multiple effects, the quality control of Qixuehe Capsules has always been a bottleneck problem limiting its sustainable development. Therefore, this study adopted the traditional Chinese medicine Q-markers quantitative identification system established previously by our research group based on the combination of analytic hierarchy process and entropy weight methods. With the different effects of Qixuehe Capsules as the entry point, the comprehensive scores of chemical ingre-dients in Qixuehe Capsules under the items of effectiveness(smoothing liver and regulating qi, activating blood circulation, and relieving pain), testability and specificity were calculated and integrated, respectively. Subsequently, through the analysis of compatibility relationship of Qixuehe Capsules, 15 active ingredients with high comprehensive scores were found to be the top Q-mar-kers of Qixuehe Capsules, including ferulic acid, quercetin, caffeic acid, kaempferol, rutin, Z-ligustilide, senkyunolide Ⅰ, vanillic acid, protocatechuic acid, chlorogenic acid, rosmarinic acid, senkyunolide A, gallic acid, tetrahydropalmatine and eugenol. Collectively, this study not only provided scientific evidence for further research on the improvement and standardization of quality standards of Qixuehe Capsules but also provided methodological references for the quantitative identification of Q-markers of multi-effect traditional Chinese medicine formulae.

Incentive problem and countermeasures of telemedicine providers in China / 中华医院管理杂志

Objective:To analyze the actual and expected incentives and key issues of telemedicine providers in China and to provide important references for optimizing telemedicine incentive policies.Methods:The sample data came from a questionnaire survey of 1 084 providers in 7 provinces of Fujian, Hainan, Henan, Hunan, Guizhou, Sichuan and Qinghai in October and November 2019 and a semi-structured interview data at 6 hospitals in Henan province in January 2020. Descriptive analysis was used to sort such data into text data for classified summation.Results:The greatest gaps were found between actual incentives and expected ones in expense subsidies, title promotion and excellence awards, with such gaps as high as 18.65, 28.26, 29.28 percentages among providers of junior, deputy senior and senior academic titles respectively. Hospitals fall short in providing adequate incentives for telemedicine providers, not to mention lack of differentiation and diversification in personnel incentives, and poor implementation of incentive policies.Conclusions:It is suggested to strengthen incentive demand analysis, break the homogenization bottleneck of incentive policies, and consolidate internal publicity and implementation of incentive policies.

Practice of management personnel training in county hospital of West China-Mabian Medical Alliance / 中华医院管理杂志

The construction of hospital administration talent echelon has become a " bottleneck" problem in the core competence construction of county-level public hospitals in ethnic regions. West China-Mabian Medical Alliance has made a preliminary exploration on the cultivation of hospital management talents in county-level public hospitals. The hospital carried out the working principle of " setting up a talent pool by post" , and gradually established a reserve talent pool with suitable scale and dynamic adjustment by providing part-time project management positions for young employees in the hospital. There were three kinds of part-time project management positions: part-time assistant to president, part-time project supervisor and part-time department management assistant. In addition, the hospital strengthened the ideological and political education, medical management theory training and practical training of the reserve talents in a planned way. The practical experience of hospital reserve management personnel training based on West China-Mabian Medical Alliance can be used for reference by other county-level hospitals.

Construction and application of scientific research reagents/consumables purchasing platform in comprehensive tertiary medical institutions: Taking Peking University Third Hospital as an example / 中华医学科研管理杂志

Objective:As the amount of scientific reagents/consumables procurement in tertiary medical institutions increases year by year, it is necessary to seek for a more optimized operation mode for the current management needs to improve the procurement service and management of scientific reagents/consumables.Methods:Focused on the bottleneck problem of scientific research reagents/consumables procurement management, combined with the investigation of management mode in the same field and the review of relevant literature, a scientific research reagents/consumables procurement platform suitable for hospital was established, which was operated in the whole hospital for 2 years and continuingly improved.Results:The application of the scientific reagents/consumables procurement platform is expected to save 7%~8% of the scientific reagents/consumables related expenditure, which can make the scientific research procurement work standardized and simple, the procurement management precise and fast, and also provide favorable support for the prevention and control of epidemic diseases in hospitals.Conclusions:This platform is conducive to improving the service and management level of scientific reagents/consumables procurement in our hospital, and has conditions to expand the scope and increase the depth of management and service.

Methodology and applications for multimodal identification of active constituents of traditional Chinese medicine / 中国中药杂志

The discovery of active constituents of traditional Chinese medicine(TCM) faces multiple challenges, such as limited approaches to evaluate poly-pharmacological effects, and the lack of systematic methods to identify active constituents. Aimed at these bottleneck problems in the field, the present study intensively discussed the key scientific problems in the identification of active constituents of TCM, based on scientific methodologies including systematology, information theory, and synergetics. A comprehensive strategy is herein proposed to investigate the correlations between the chemical composition and biological activities of TCM, from macro-, meso-, and micro-scales. Moreover, in this study, we systematically proposed the methodology of the multimodal identification of TCM active constituents, and thoroughly constructed its core technologies. Its technical framework is suggested to be assessed by multimodal information acquisition, centered on multisource information fusion, and focused on interaction evaluation. Furthermore, the core technologies for the multimodal identification of active constituents of TCM were developed in this study, which is according to the characteristics of the exchanges of between TCM and biological organisms, in the aspects of material, energy and information. Finally, two examples of the application of the proposed method were briefly introduced. The proposed methodology provides a novel way to solve the bottlenecks in the study of active constituents of TCM, and lays the foundation for the multimodal study of TCM.

Overlapping Cervical Cell Image Segmentation Based on Bottleneck Detection and Watershed Algorithm / 中国医疗器械杂志

This study proposes an image segmentation method based on bottleneck detection and watershed algorithm to solve the problem of overlapping cervical cell image. First, we use polygon approximation to get all feature points on the cell contour and then use bottleneck detection and ellipse fitting to obtain the correct split point pairs. Therefore, the approximate range of the overlapping region was determined. The watershed algorithm was used to obtain the internal boundary information for the gradient image of the region. Finally, the segmentation results of the overlapped cells were obtained by superimposing with the outer contour. The experimental results show that this algorithm can segment the contour of a single cell from the overlapping cervical cell images with good accuracy and integrity. The segmentation result is close to that of doctors' manual marking, and the segmentation result is better than other existing algorithms.

Developmental status and prospect of artificial placenta / 中华实用儿科临床杂志

Extremely premature infants (EPI),especially those under 25 weeks of gestational age,are difficult to manage clinically and have high mortality and disability rates.It is difficult to solve the bottleneck problem fundamentally in the treatment of EPI.Artificial placenta is a fascinating alternative therapy for neonatal lung failure and is expected to maintain the normal development of EPI after delivery.This article briefly introduces the research history,current situation,difficulties to be overcome and future prospects of artificial placenta.

Developmental status and prospect of artificial placenta / 中华实用儿科临床杂志

Extremely premature infants(EPI), especially those under 25 weeks of gestational age, are difficult to manage clinically and have high mortality and disability rates.It is difficult to solve the bottleneck problem fundamentally in the treatment of EPI.Artificial placenta is a fascinating alternative therapy for neonatal lung failure and is expected to maintain the normal development of EPI after delivery.This article briefly introduces the research history, current situation, difficulties to be overcome and future prospects of artificial placenta.

Study on mechanism and method of membrane preparation and membrane process optimization based on molecular structure analysis of noneffective common macromolecules / 中国中药杂志

The molecular weight of the effective components of traditional Chinese medicine( TCM) is usually less than 1 000.However, " noneffective common macromolecules"( starch,pectin and other macromolecules commonly present in the water extract of TCM) generally have no physiological activity,which restricts the overall advantages of membrane technology to obtain small molecular pharmacodynamic substances,and such macromolecules are the main influence factor of membrane fouling. Therefore,in order to obtain the total pharmacological efficacy of TCM,based on the molecular structure analysis of noneffective common macromolecules,aimed at the key scientific problems in correlation between the molecular structure of noneffective common macromolecules and the pore structure of membrane material,and by referring to the material science theory and molecular simulation method,the correlations between noneffective common macromolecules' molecular structure-solution environment-membrane antagonism were investigated. Multidisciplinary approaches could be integrated to: ① optimize the spatial form of membrane surface and improve the membrane's antifouling ability; ② accurately control the pore structure and the size distribution of membranes,aimed at the innovative preparation technology of special membrane used for TCM; ③ adjust solution environment based on the analysis of molecular structure,and establish the pretreatment method based on the optimization of solution environment. Furthermore,the technical bottleneck on how to obtain the pharmacodynamic micromolecules effectively might be solved,and the theory and technology about TCM pharmaceutical engineering could be developed based on the concept of multivariate and integration.

Overview and prospects of traditional Chinese medicine blending technology oriented by quality consistency / 中国中药杂志

The consistency of drug quality is related to the clinical efficacy and safety,which is highly valued by the government and relevant industries. Compared with chemical medicine,traditional Chinese medicine originates from the nature,and is greatly influenced by natural factors,such as the place of origin,cultivation and processing technology,climate. The quality consistency of traditional Chinese medicine is poor. The quality consistency has become the pain point and difficulty of the development of the traditional Chinese medicine industry,which seriously affects the stability and controllability of clinical efficacy and the reproducibility or recognition of modern research results. It is also a bottleneck for Chinese patent medicine to enter the international market. Mixed batch blending technology is an effective method for the scientific guarantee of the quality consistency in other industries and disciplines,and widely applied in liquor making industry,tobacco industry and perfume industry. Overseas,mixed batch blending technology has been successfully applied in guaranteeing the quality consistency of Ginkgo biloba preparations Jinnado. It has been used in the production of Chinese formulations in Japan for more than 30 years. In recent years,mixed batch blending technology has been introduced into the pharmaceutical field to ensure the quality consistency of traditional Chinese medicine,and relevant research has gradually increased.This manuscript reviews the application of blending technology in other disciplines,summarizes the algorithm principles and software systems of mixed batch blending in traditional Chinese medicine or natural medicine,explains the specific implementation process of mixed batch blending technology,and looks forward to the application prospects of artificial intelligence and other new technologies,in the hope of providing new ideas and technologies for breaking through the problem of quality consistency,and boosting the high-quality and high-level development of Chinese medicine industry in the new era.

Combat readiness training of mobile medical service forces in military hospitals under information condition: Problem analysis / 第二军医大学学报

Under the information condition, there remain many problems in consciousness, training talents, training contents and training methods in the combat readiness training of mobile medical service forces in military hospitals, which reduces the pertinence and effectiveness of combat readiness training and also affects the effect of combat readiness training. In this review, we systematically analyzed the bottleneck problems of combat readiness training in the above 4 aspects, providing new ideas for effectively solving them, so as to truly implement the combat readiness training and effectively improve the service of military hospital mobile medical service forces.

Recent advances in directed evolution / 生物工程学报

Screening is the bottleneck of directed evolution. In order to address this problem, a series of novel semi-rational designed strategies have been developed based on combinatorial active-site saturation test and iterative saturation mutagenesis, including single code saturation mutagenesis, double code saturation mutagenesis and triple code saturation mutagenesis. By creation of "small and smart" high qualified mutant libraries and combinatorial mutagenesis of specific sites, these new strategies have been successfully applied in multiparameter optimization, e.g. stereo/regioselectivity and activity. This review summarized recent advances in directed evolution and its applications in biocatalysis field.