Anisotropic Magnetic Polymeric Particles with a Controllable Structure via Seeded Emulsion Polymerization.

Magnetic polymer composites have been widely utilized in potential applications in material science, such as reduction of dyes, immunodiagnostics, biomedicals, and magnetically controllable photonic crystals owing to large surface areas, fast separation, and recyclable performance. In this work, anisotropic magnetic particles were prepared by seeded emulsion polymerization, with morphologies of "Fe3O4-shell", "hemisphere-like", "raspberry-like", "multiple lobes-like", and "sandwich-like". Poly(styrene/divinylbenzene/mono-2-(methacryloxy)ethyl succinate)@ Fe3O4 (P(St/DVB/MMES)@Fe3O4) were the seed microspheres, and P(St/DVB/MMES)@Fe3O4@polymer particles are achieved by seeded emulsion polymerizations. The morphology of the particles depends on polymerization conditions (monomer ratios and surfactant), particle properties, and so on. Then, the minimum surface free energy change principles were used to predict the equilibrium morphologies of the magnetic polymer composites. Through theory, the model gives the correct tendency and good agreement with the equilibrium morphology which was in tandem with TEM results. Lastly, after in situ surface deposition of Ag nanoparticles, magnetic composite particles with sandwich-like morphology were applied for the catalytic degradation of 4-nitrophenol (4-NP) reacting with NaBH4. The apparent rate coefficient is 0.0069 s-1, and it can keep mainly about 80% efficiency in catalysis after five cycles.

Baicalein ameliorates chronic itch in ACD mice by suppressing the spinal astrocytic STAT3-LCN2 cascade.

Chronic itch is a maladaptive and debilitating symptom in patients with allergic contact dermatitis (ACD), adversely affecting their quality of life. There is a lack of effective treatments for ACD-associated uncontrollable itch. In this study, we explored the antipruritic effects of baicalein (BE), a bioactive flavonoid extracted from the root of Scutellaria baicalensis Georgi, and the underlying mechanisms in alleviating chronic itch triggered by diphenylcyclopropenone (DCP) in a mouse model of ACD. The ACD mice were intraperitoneally injected with BE (5, 30, and 60 mg·kg-1·d-1) for 7 days during the DCP challenge phase. The results showed that DCP-treated mice exhibited severe spontaneous scratching behaviors that was reduced after BE injections in a dose-dependent manner accompanied by inhibition of spinal astrocyte activation. We observed that the spinal astrocytic STAT3-LCN2 cascade plays a crucial role in controlling the activation of astrocytes in chronic itch. Intrathecal injection of the STAT3 inhibitor AG490 or Lcn2 siRNA significantly reduced scratching behavior and astrocyte activation in ACD mice. Moreover, BE markedly attenuated the increased phosphorylation of STAT3 (p-STAT3) and LCN2 expression in the spinal cords of ACD mice and in lipopolysaccharide-stimulated primary spinal astrocytes. Altogether, BE relieved chronic itch by suppressing the spinal astrocytic STAT3-LCN2 cascade. These findings provide a potential avenue for the management of chronic itch. Schematic summary of the main findings illustrating that BE alleviates chronic itch through suppressing the spinal astrocytic STAT3-LCN2 cascade. Specifically, BE suppresses the expression of p-STAT3 to inhibit the reactive state of astrocytes in spinal dorsal horn, and then decreases the expression of astrocytic LCN2 to alleviate chronic itch in ACD mice.

[Guidelines for post-marketing research on clinical effectiveness of Chinese patent medicines].

Due to the lack of specialized guidance, the post-marketing research on clinical effectiveness of Chinese patent medicines demonstrates varied quality and lacks high-quality evidence, failing to meet the demands of policy-making, clinical decision-making, and industrial decision-making. To address this issue, this project gathered experts in clinical medicine, clinical pharmacy, evidence-based medicine, drug epidemiology, medical ethics, and policy and regulation in China. They referred to the model of international post-marketing research on medicines and developed Guidelines for post-marketing research on clinical effectiveness of Chinese patent medicines under the framework of relevant laws and regulations and technical guidance documents in China. The guidelines were developed with consideration to the characteristics of Chinese patent medicines, China's national conditions, and all the stakeholders including marketing authorization holders, clinical researchers, drug administration, and users. The development of the guidelines followed the requirements for developing group standards set by the China Association of Chinese Medicine. The guidelines fully implement the concept of full life-cycle research, emphasizing the combination of traditional Chinese medicine(TCM) theory, human use experience, and clinical trials and pay attention to the compliance, scientificity, and ethics of research. The guidelines clarify the topic selection and decision-making path of the post-marketing research on effectiveness of Chinese patent medicines through six steps: determining research purpose, analyzing drug characteristics, evaluating research basis, proposing clinical orientation, clarifying research purpose, and implementing classified research. The general principles of research design and implementation were clarified from eight aspects: research type, research objects, sample size, efficacy indicators, bias, missing data, evidence level, and practicality. It focuses on the research on the TCM syndrome-based efficacy evaluation, clinical value-oriented mechanism of action, and the effectiveness of Chinese patent medicines with different routes of administration. The guidelines provide a universal methodological basis for the post-marketing research on clinical effectiveness of Chinese patent medicines.

[Guidelines for economic evaluation of post-marketing Chinese patent medicine].

With the premise of drug safety and effectiveness, pharmacoeconomic evaluation can provide optimal solutions for diversified decision-making application scenarios from different research perspectives while maximizing the rational utilization of existing healthcare resources. Chinese patent medicine is an essential component of pharmaceutical utilization in China and a significant part of healthcare expenditure in China. However, the economic evaluation of post-marketing Chinese patent medicine is lacking. These evaluations often lack standardization, exhibit varying quality, and are unable to effectively support healthcare decisions, indicating a need for improvement in overall quality. Given this situation, this project has gathered leading experts from China and has strictly adhered to the requirements of the group standards set by the China Association of Traditional Chinese Medicine in developing Guidelines for economic evaluation of post-marketing Chinese patent medicine, aiming to provide methodological guidance for the post-market pharmacoeconomic evaluation of Chinese patent medicine, enhancing the standardization of pharmacoeconomic evaluations of Chinese patent medicine and the scientific validity of research results, and thereby elevating the overall quality of pharmacoeconomic evaluations for post-marketing Chinese patent medicine. The guidelines adhere to the framework provided by relevant laws and regulations in China and technical guidance documents. It is based on guidance from traditional Chinese medicine(TCM) theories, focusing on the unique characteristics of TCM. It covers various aspects of pharmacoeconomic evaluation, including fundamental principles, research topic selection, research question definition, study design type selection, cost identification and measurement, health outcomes, and evaluation methods. The guidelines offer methodological recommendations and decision guidance to address common issues and challenges in the pharmacoeconomic evaluation of post-marketing Chinese patent medicine.

[Economic evaluation of Annao Pills combined with antihypertensive drugs in treatment of primary hypertension: a study based on decision tree model].

The purpose of this study was to evaluate the economics of Annao Pills combined with antihypertensive drugs in the treatment of primary hypertension in the Chinese medical setting. TreeAge pro 2018 was used for cost-effect analysis and sensitivity analysis of the two treatment regimens. The intervention time of the simulation model was 2 weeks. The cost parameters were derived from Yaozhi.com, and the effect parameters were based on Meta-analysis of randomized controlled trial(RCT) involving Annao Pills. The experimental group was treated with Annao Pills combined with anti-hypertensive drugs(nifedipine controlled-release tablets + losartan potassium tablets), and the control group was treated with anti-hypertensive drugs(nifedipine controlled-release tablets + losartan potassium tablets). The basic analysis showed that the incremental cost-effect ratio(ICER) of the two groups was 2 678.67 yuan, which was less than 7.26% of the per capita disposable income in 2022. That is, compared with anti-hypertensive drugs alone, Annao Pills combined with antihypertensive drugs cost 2 678.67 yuan more for each additional patient with primary hypertension. The results of sensitivity analysis verified the robustness of the basic analysis results. The probability sensitivity results showed that when the patient's personal willingness to pay the price was higher than 2 650 yuan, the probability of the regimen in the experimental group was higher, which was consistent with the results of the basic analysis. In conclusion, when the price was higher than 2 650 yuan, Annao Pills combined with anti-hypertensive drugs was more economical than anti-hypertensive drugs alone in terms of improving the response rate of the patients with primary hypertension.

[Guidelines for construction of traditional Chinese medicine pharmacovigilance system in medical institutions].

The group standard Guidelines for construction of traditional Chinese medicine(TCM) pharmacovigilance system in medical institutions, managed by Chinese Association of Chinese Medicine and led by the Institute of Basic Research in Clinical Medicine,China Academy of Chinese Medical Sciences and Dongfang Hospital of Beijing University of Chinese Medicine, was announced on National Group Standard Information Platform on January 16, 2024, with the standard number T/CACM 1563. 2-2024. According to EU pharmacovigilance regulations and the second-level guidance principles of International Council for Harmonization of Technical Requirements for Pharmaceuticals for Human Use(ICH), the unique characteristics of TCM were fully considered, and the relevant systems and procedures for constructing TCM pharmacovigilance systems in medical institutions were clearly defined. This included establishing TCM pharmacovigilance information platforms, arranging staff, formulating various regulations, and monitoring adverse reactions of TCM(including TCM decoction pieces, granules, Chinese patent medicines, in-hospital preparations, and pre-marketed Chinese patent medicines). It aimed to develop a TCM pharmacovigilance system in medical institutions that was tailored to the characteristics of TCM. The system could be appropriately adjusted according to the scope of practice and actual circumstances of medical institutions at different levels. This will enhance the implementation of TCM pharmacovigilance work and safeguard medication safety. The group standard underwent multiple rounds of consultations with internal and external experts and has ultimately evolved into a guiding document applicable to medical institutions and related entities engaged in pharmacovigilance activities.

[Pharmacovigilance guidelines for clinical application of oral Chinese patent medicines].

Oral Chinese patent medicine is the essence of effective prescriptions created and summarized by Chinese medical scientists through thousands of years of medical practice. It is portable and convenient, with an obvious curative effect and other characteristics. However, at present, oral Chinese patent medicine is rich in dosage forms, various in types, complex in mechanism of action, and broad in clinical positioning. In clinical application, there are often cases of drug use without reference to instructions,repeated drug use, and prolonged drug use, which highlights safety problems such as adverse reactions and hepatorenal toxicity. Oral Chinese patent medicine pharmacovigilance is facing challenges. World Health Organization(WHO) has issued the WHO guidelines on safety monitoring of herbal medicines in pharmacovigilance systems, and International Council for Harmonisation of Technical Requirements for Pharmaceuticals for Human Use(ICH) has issued the ICH E2 pharmacovigilance guidelines. The United States has issued the Pharmacovigilance management standards and pharmacoepidemiological assessment guidelines, and the European Union has issued the Guidelines on good pharmacovigilance practices. Japan, South Korea, and other countries in the Asia Pacific region have established their own pharmacovigilance systems, but currently, there are no pharmacovigilance guidelines related to oral Chinese patent medicine in China. Therefore, experts from many disciplines and fields in China were invited to jointly develop the Pharmacovigilance guidelines for clinical application of oral Chinese patent medicines, which aims to develop pharmacovigilance guidelines for clinical application that are consistent with China's national conditions and highlight the characteristics of oral Chinese patent medicine, and provide guidance for clinically safe and rational drug application in medical institutions.

[Pharmacovigilance guidelines for clinical application of Chinese patent medicines for external use].

There are many kinds and dosage forms of Chinese patent medicines for external use on the market, which are widely used in clinical departments. The common adverse reactions of Chinese patent medicines for external use are skin reactions, and those for the rare severe diseases include palpitation, chest tightness, dyspnea, and anaphylactic shock. At present, World Health Organization(WHO), International Council for Harmonization of Technical Requirements for Pharmaceuticals for Human Use(ICH),the United States, the European Union, and Asia-Pacific countries(such as Japan and South Korea) have not issued any pharmacovigilance guideline of Chinese patent medicines for external use. China has not issued any pharmacovigilance guideline for these medicines, only releasing the standard Evaluation of skin adverse reactions caused by Chinese patent medicines for external use(T/CACM 005-2017). To standardize the safe and reasonable use of Chinese patent medicines for external use, Pharmacovigilance guidelines for clinical application of Chinese patent medicines for external use was developed with the joint efforts of experts in diverse disciplines. The guideline provides guidance on the monitoring and reporting of adverse reactions/events, identification and assessment of risk signals, and risk control measures in the clinical application of Chinese patent medicines for external use to guide the rational use of these medicines in clinical practice. At the same time, the possible risks and risk control measures in clinical application of Chinese patent medicines for external use are listed for clinical reference. In addition, the guideline provides guidance for risk minimization plans and the standardization of activities related to pharmacovigilance of Chinese patent medicines for external use in China.

[Pharmacovigilance guidelines of Chinese patent medicines].

Drug administration law of the People's Republic of China(2019 revised edition), which came into effect on December 1, 2019, proposed that " the state shall establish a pharmacovigilance system". Pharmacovigilance work of Chinese patent medicines is more difficult, and it is necessary to carry out Pharmacovigilance activities that are in line with the characteristics of Chinese patent medicines. Pharmacovigilance guidelines of Chinese patent medicines(T/CACM 1563. 1-2024), based on the principles of Drug Administration Law of the People's Republic of China(2019 revised edition) and Pharmacovigilance quality management standards(No. 65 of 2021) of the National Medical Products Administration, draws on the EU Pharmacovigilance regulation and the secondary guidelines of International Council for Harmonization of Technical Requirements for Pharmaceuticals for Human Use(ICH), and it is drafted in accordance with the provisions of Guidelines for standardization work part 1: structure and drafting rules of standardization documents(GB/T1. 1-2020) based on the characteristics of Chinese patent medicines. It serves as a general document for a series of pharmacovigilance guidelines of Chinese patent medicines, such as Guidelines for construction of traditional Chinese medicine pharmacovigilance system in medical institutions(T/CACM 1563. 2-2024), Pharmacovigilance guidelines for clinical application of oral Chinese patent medicines(T/CACM 1563. 3-2024), Pharmacovigilance guidelines for clinical application of traditional Chinese medicine injections(T/CACM 1563. 4-2024), Pharmacovigilance guidelines for clinical application of Chinese patent medicines for external use(T/CACM 1563. 5-2024), and Pharmacovigilance guidelines for clinical application of Chinese patent medicines for mucosal administration(T/CACM 1563. 6-2024), including four major elements of pharmacovigilance monitoring and reporting of Chinese patent medicines, signal identification, risk evaluation, and risk control, as well as pharmacovigilance activities for Chinese patent medicines, ensuring the safety of public drug use.

[Pharmacovigilance guidelines for clinical application of Chinese patent medicines for mucosal administration].

The group standard Pharmacovigilance guidelines for clinical application of Chinese patent medicines for mucosal administration was released on January 16, 2024, on the national group standards information platform by the Institute of Basic Research in Clinical Medicine of China Academy of Chinese Medical Sciences and School and Hospital of Stomatology of Peking University, under the centralized management by the China Association of Chinese Medicine. The standard number is T/CACM 1563.6-2024. It aims to propose key elements and specify technical methods for safety monitoring and reporting, signal identification, risk assessment, and risk control based on the Drug administration law of the People's Republic of China(revised in 2019), which establishes normative pharmacovigilance guideline of Chinese patent medicine for mucosal administration that is in line with the characteristics of traditional Chinese Medicine(TCM) based on the pharmacovigilance content for clinical application of Chinese patent medicine for mucosal administration. The group standard has been discussed by internal and external experts through multiple rounds of consultation. It serves as a guiding document for stakeholders involved in pharmacovigilance activities, including pharmaceutical license holders, drug manufacturers, medical institutions, research institutes, and pharmaceutical trading enterprises.

HDAC Inhibitor SAHA Alleviates Pyroptosis by up-regulating miR-340 to Inhibit NEK7 Signaling in Subarachnoid Hemorrhage.

BACKGROUND: Subarachnoid hemorrhage (SAH) is a cerebral hemorrhagic disease with a high disability and fatality rate. Cell pyroptosis is involved in the brain injury following SAH. Here, we explored the effect of HDAC inhibitor SAHA against cell pyroptosis after SAH. METHODS: The rat SAH model was established by endovascular perforation and the rat microglia were treated with 25 µm oxyhemoglobin (OxyHb) for 24 h to mimic SAH model in vitro. Neurological score and brain edema were assessed in rat SAH model. TUNEL staining detected apoptosis. qRT-PCR and western blotting were employed to detect expression levels of miR-340, NEK7 and inflammatory cytokines. ELISA assay determined the secretion of IL-1ß and IL-18 in rat serum and cell supernatant. A lactate dehydrogenase (LDH) kit measured the LDH activity in rat primary microglia. Microglia pyroptosis was detected by flow cytometry. RIP and dual luciferase reporter assays confirmed the binding relationship between miR-340 and NEK7. RESULTS: SAHA alleviated neurological dysfunction, inflammatory injury and microglia pyroptosis in SAH rats. SAHA suppressed LDH release, inflammatory factor expression and pyroptosis in microglia treated with OxyHb. Meanwhile, SAHA increased miR-340 expression and inhibited NEK7 level in vivo and in vitro SAH models. Further, miR-340 directly targeted NEK7 to inhibit the NLRP3 signaling pathway. Knockdown of miR-340 or overexpression of NEK7 reversed the suppressive effects of SAHA on microglia inflammation and pyroptosis. Additionally, knockdown of NEK7 impaired microglia inflammation and pyroptosis induced by miR-340 inhibitor. CONCLUSION: HDAC inhibitor SAHA ameliorates microglia pyroptosis in SAH through triggering miR-340 expression to suppress NEK7 signaling. This novel mechanism provides promise for SAHA in SAH treatment.

[Clinical comprehensive evaluation of Xiangju Capsules in treatment of rhinosinusitis].

The articles involving Xiangju Capsules were retrieved, and qualitative research and quantitative research methods were combined to evaluate the evidence of the safety, effectiveness, economy, innovation, suitability, accessibility, and characteristics of traditional Chinese medicine( "6+1" dimensions) of this drug. Multi-criteria decision analysis(MCDA) model and CSC v2.0 software were used to comprehensively evaluate the clinical value of Xiangju Capsules in the treatment of rhinosinusitis and clarify the precise clinical positioning. The dimensions are graded A, B, C, or D. Multi-source safety evidence showed that the main adverse reactions were gastrointestinal reactions, rash, itching, dizziness, and headache. Based on the available studies, the risk is controllable and the safety is grade A. Meta-analysis showed that Xiangju Capsules + conventional western medicine could recover the Lund-Kennedy score, Lund-Mackay score, and CT score, relieve headache, nasal congestion, olfactory disturbance, and facial pain, with the effectiveness is grade B. The incremental cost-effectiveness ratio of Xiangju Capsules + conventional western medicine compared with conventional western medicine alone in the treatment of chronic rhinosinusitis was 263.71 yuan, about 0.82% of the per capita disposable income. The results of sensitivity analysis showed that the research results were relatively robust. Based on the assumption that the per capita disposable income in 2020 will be the threshold of patients' willingness to pay, it is more economical to use Xiangju Capsules + conventional western medicine. The drug belongs to grade A of the national medical insurance, with an average daily cost of 3.06 yuan, and the economy is grade B. This formula is modified from classic formulas and characteristic empirical formulas, be capable of improving immunity and preventing repeated attacks. It can be used for acute and chronic rhinitis-rhinosinusitis. It had a wide range of applicability, especially for the patients with head and face tenderness. Service innovation was reflected in the measures to guarantee supply, capacity, scalability, and coverage of grass-roots sales channels. The industrial innovation was improved through the management of medicinal resources, pharmaceutical industry, production technology, quality control, scientific research and development, and this formula won three national invention patents. Comprehensively, the innovation of Xiangju Capsules is grade B. According to the survey of 188 medical practitioners and 196 patients in 20 provinces, municipalities, and autonomous regions of China, the drug was characterized by easy preparation and administration, individualized medication, simple technology and management, convenient use, storage, and transport, and controllable adverse reactions, with the suitability is grade B. Xiangju Capsules showed the cost of 45.9 and 275.4 yuan for treatment of acute and chronic rhinitis-rhinosinusitis, respectively, being well affordable. It was sold in 35 000 medical institutions in China. The dosage form was suitable for transportation, storage, and grass-root application. With rich, sustainable, and available medicinal resources, the accessibility of Xiangju Capsules is grade A. This drug can be used for both acute and chronic rhinitis-rhinosinusitis, clearing heat and expelling pus, and strengthening the exterior to prevent relapse. After this drug was available on the market, over 4 000 cases were studied, with rich experience in human use accumulated, and characteristics of traditional Chinese medicine is grade B. Overall, the clinical value of Xiangju Capsules is class B. It is suggested that Xiangju Capsules should be used in accordance with the relevant policies of basic clinical drug administration to play its role.

The Notch signalling pathway and miRNA regulation play important roles in the differentiation of Schwann cells from adipose-derived stem cells.

An exploration of the underlying mechanisms is necessary to improve nerve myelin-forming cell Schwann cell (SC) differentiation from adipose-derived stem cells (ADSCs). Primary rat ADSCs were isolated and characterised for cell surface markers using flow cytometry analysis. After treatment with a mixture of glial growth factors, ADSCs were induced to differentiate and subsequently identified by immunofluorescence staining and western blotting. A miRNA microarray analysis was performed to explore the genes and signalling pathways regulating ADSC differentiation into SCs. ELISAs were conducted to measure the expression of neurotrophic factors and changes in the level of nerve cell adhesion factor. Dual luciferase reporter assays and RIP assays were performed to explore the potential mechanism of miR-21-5p in ADSC differentiation. The isolated ADSCs were positive for CD29 and CD44 but negative for CD49. After induction with specific cytokines, the differentiated ADSCs presented a spindle-like morphology similar to SCs and expressed S100. RNA-sequencing analyses revealed that 9821 mRNAs of protein-coding genes and 175 miRNAs were differentially expressed in differentiated SC-like cells compared to primary cultures of ADSCs. KEGG and Gene Ontology analyses revealed that the involvement of the Notch signalling pathway and miRNA negative regulation may be associated with the differentiation of ADSCs into SCs. Treatment with a Notch inhibitor promoted the differentiation of ADSCs. Furthermore, mechanistic studies showed that Jag1 bound to miR-21-5p and upregulated its target gene Jag1, thus affecting ADSC differentiation. These results revealed the mechanism underlying the important roles of miRNAs and the Notch signalling pathway in the differentiation of SCs from ADSCs, enabling potential therapeutic applications of ADSCs in peripheral nerve regeneration in the future.

[Clinical comprehensive evaluation of Huangkui Capsules in treatment of chronic kidney diseases].

Based on Guidelines for the Management of Clinical Comprehensive Evaluation of Drugs(trial version 2021), this study aims to sort out the clinical evidence of Huangkui Capsules(HC) in the treatment of chronic kidney diseases in aspects of safety, effectiveness, economy, innovation, suitability, accessibility, and characteristics of traditional Chinese medicine( "6+1" dimensions) from real-world data, secondary literature evaluations, questionnaires, and public data, with the methods in evidence-based medicine, epidemiology, pharmacoeconomics, and health technology. Furthermore, with multi-criteria decision analysis(MCDA) model and CSC v2.0, the clinical value of the medicine is comprehensively assessed. All the above are to highlight the advantages and characteristics of HC and lay a basis for scientific decision-making by the medical management department. The dimensions are graded A, B, C, or D. According to the conclusions from phase Ⅳ clinical trial, spontaneous reporting system(SRS), systematic review and Meta-analysis, acute toxicity and long-term toxicity tests, it mainly results in the adverse reactions of nausea, abdominal distension, vomiting, pruritus, rash, and good prognosis in patients. According to the available research, the safety evidence is sufficient and the risk is controllable, so the safety of this medicine is grade B. According to Meta-analysis, HC in combination with conventional drugs in the treatment of chronic kidney disease is superior to conventional drugs alone in reducing urinary protein, serum creatinine concentration, and blood urea nitrogen. In addition, HC combined angiotensin receptor blocker(ARB) or angiotensin converting enzyme inhibitor(ACEI) is outstanding in improving total clinical effective rate, reducing 24 h urinary protein quantity, urinary albumin excretion rate, serum creatinine concentration, triglyceride, and total cholesterol in the treatment of diabetic nephropathy as compared with ARB or ACEI alone. As for chronic nephritis, the application together with ARB or ACEI can raise the total effective rate, reduce 24 h urinary protein content, serum creatinine concentration, and blood urea nitrogen, and delay the progress of the disease. HC boasts high-quality evidence in treating chronic kidney disease, diabetic nephropathy, and chronic nephritis. It has obvious clinical significance in treating chronic kidney disease and thus its efficacy in this aspect is grade B. It has outstanding clinical significance for diabetic nephropathy and chronic nephritis and corresponding and the effectiveness is grade A. As for the pharmacoeconomic value, HC combined with ARB or ACEI is more economical in the treatment of chronic kidney disease than Bailing Capsules combined with ARB or ACEI, with high-quality evidence, and thus the economy of the formula is grade B. HC is a key solution to the high urinary protein in patients with hypotension and chronic kidney disease. The innovation is evidenced by the methods to ensuring drug supply, community-level supply, drug safety, effectiveness, and reasonable price, as wells as the aspects of enterprise philosophy, equipment management, research and development in process and technology, enterprise management and marketing. Thus, the prescription is grade A in innovation. The suitability, as evidenced in drug administration, technical management, drug storage, information service, and medication, is grade B. The course of the medicine is affordable, and it is accessible in a wide range of areas and hospitals. Thus, the accessibility is grade A. HC was developed from an in-hospital preparation, with application in numerous patients and thus large-scale real-world data. As a result, HC is grade B in terms of characteristics of traditional Chinese medicine. After comprehensive evaluation, the clinical value of HC in treating chronic kidney disease is class B, and that for diabetic nephropathy and chronic nephritis is class A. The result is of great reference value for the basic clinical medication management.

[Clinical comprehensive evaluation of Ginkgolide Injection in treatment of cerebral infarction].

This clinical value-oriented comprehensive evaluation of drugs was carried out in accordance with Guidelines for Management of Comprehensive Clinical Evaluation of Drugs(trial version 2021), with the qualitative and quantitative evaluation methods adopted. Based on the evidence-based medicine, epidemiology, clinical medicine, pharmacoeconomics, mathematical statistics, and health technology evaluation(HTA), the clinical value of Ginkgolide Injection was evaluated from the "6+1" dimension by giving weight to the criterion level and index level and calculating with multi-criteria decision analysis(MCDA) model and CSC v2.0. After entering the market, Ginkgolide Injection has been subjected to phase Ⅳ clinical trial, spontaneous reporting system(SRS)-based data monitoring, systematic review and Meta-analysis, acute toxicity and long-term toxicity assays, active monitoring, and RCTs, and the evidence of safety was sufficient. The results of active monitoring showed that the incidence of adverse reactions was 0.09%(rare), mainly manifested as flushing, dizziness, rash, nausea, and vomiting. According to the nested case-control study, the adverse reactions of this drug had nothing to do with the product batch, implying that the drug quality was controllable. The adverse reactions mainly resulted from the pharmacodynamic reactions. Because the drug was effective in resisting platelet aggregation, the resulting adverse reactions such as flushing, dizziness, headache, and phlebitis were caused by vasodilation. Skin rash and gastrointestinal symptoms were mainly attributed to the patients' sensitivity to drugs and their own allergic constitution. According to the sufficiency of evidence and the incidence of adverse reactions in the safety research, the safety of Ginkgolide Injection was grade A. The results of Meta-analysis showed that Ginkgolide Injection combined with conventional western medicine was superior to conventional western medicine in improving the clinical effective rate, neurological function score, and activity of daily living score of patients with cerebral infarction. The validity evidence was evaluated according to the PICO principle to be high. According to the GREAD evaluation principle, the quality of such evidence as clinical effective rate, National Institute of Health stroke scale(NIHSS), and Barthel Index(BI) was evaluated, and the results demonstrated that the evidence quality of clinical effective rate and activity of daily living score was medium. The effectiveness of Ginkgolide Injection was grade A. According to the economic report of Ginkgolide Injection, it had short-term and long-term pharmacoeconomic advantages in the treatment of ischemic stroke, and the economic evidence value was good. According to the CASP economic evaluation checklist, the overall quality evaluation results of the economic report are basically clear. To be specific, the economic evidence quality was high. Based on the comprehensive economic evidence quality and economic value, the economy of this drug was grade A. The innovation of this product was evaluated from three aspects: clinical innovation, enterprise service system innovation, and industrial innovation. Ginkgolide Injection could be used 24 h after intravenous thrombolysis for improving patients' neurological function without increasing bleeding, indicating its important clinical innovation. There were many innovations in ensuring drug supply, especially at the grass roots, drug safety, effectiveness, and reasonable price, which has provided reference for establishing enterprise philosophy, managing drug resources, developing process and technology, and determining enterprise management and marketing. Therefore, its innovation was grade A. The drug had no special medication plan in use, exhibiting good suitability for doctors, nurses, and patients. The suitability was grade B. Compared with similar drugs, its price was at a medium level, meaning good affordability, sufficient production capacity, and easy accessibility. Its accessibility was therefore grade B. This drug belonged to Chinese medicinal injection. The large-sample real-world research revealed rich human use experience, so it was grade C for the traditional Chinese medicine characteristic. According to the comprehensive evaluation, the clinical value of Ginkgolide Injection in the treatment of cerebral infarction fell into class A. It is suggested that it can be transformed into the relevant policy results of basic clinical medication management according to the procedure.

[Cost-effectiveness analysis of Qilong Capsules in treatment of ischemic stroke based on prospective real-world cohort study].

In this study, TreeAge Pro was used to build a decision tree model for Qilong Capsules in the treatment of ischemic stroke. We compared the economy between Qilong Capsules + conventional therapy vs conventional therapy in the treatment of ischemic stroke to guide the rational allocation of health resources in clinical practice. The cost parameters in the study were obtained from Menet and the relevant literature published recently. Meanwhile, the efficacy parameter [mean reduction in National Institute of Health stroke scale(NIHSS) score after treatment] was employed to evaluate the short-term economic performance of the two therapies based on a prospective real-world cohort study. The time span of simulation was 24 weeks, and the robustness of this study was verified by sensitivity analysis. Qilong Capsules + conventional therapy and conventional therapy had the direct medical costs of CNY 22 546.50, 21 160.50 and the effectiveness of 2.08, 1.59 points, respectively. The incremental cost-effectiveness ratio(ICER) of the two groups was CNY 2 811.36. That is, compared with conventional therapy, Qilong Capsules + conventional therapy in the treatment of ischemic stroke costed CNY 2 811.36 for each additional point reduction in NIHSS score. If the patient is willing to pay more than CNY 2 811.36, Qilong Capsules + conventional therapy is more economical. The result of sensitivity analysis verified that the ICER was robust. Thus, on the basis of the assumption that per capita disposable income in 2020 is the threshold of patients' willingness to pay, Qilong Capsules + conventional therapy is more economical than conventional therapy alone in the treatment of ischemic stroke.

[Clinical comprehensive evaluation of Qilong Capsules in treatment of ischemic stroke with Qi deficiency and blood stasis syndrome].

The present study systematically sorted out the existing research on Qilong Capsules in the treatment of ischemic stroke with Qi deficiency and blood stasis syndrome and comprehensively evaluated its clinical evidence and value to highlight the advantages and characteristics of products and provide references for the decision-making of national pharmaceutical management departments. Based on the evidence-based medicine, epidemiology, clinical medicine, evidence-based pharmacy, and pharmacoeconomics, the qualitative and quantitative evaluation of "6+1" dimensions of safety, effectiveness, economy, innovation, suitability, and accessibility, as well as characteristics of traditional Chinese medicine(TCM) was performed with multi-criteria decision analysis(MCDA) mo-del using the information, such as public data, literature data, pharmaceutical research, and questionnaire survey, and CSC v2.0 was used to calculate the clinical value of Qilong Capsules. The evaluation results were grade A, B, C, or D. Spontaneous reporting system(SRS) monitoring data, literature reports, clinical trials, and other multi-source safety evidence showed that the main adverse reactions of this drug included dry mouth, nausea, and rash, and no severe adverse reactions was found. The evidence was sufficient with small and controllable known risks, and the safety was grade A. Meta-analysis showed that Qilong Capsules combined with conventional western medicine in the treatment of acute ischemic stroke was superior to the control group in improving neurological deficits, clinical total response rate, patients' activities of daily living, and hemorheological indexes. The level of evidence was high with manifest clinical significance, and the effectiveness was grade A. The results of pharmacoeconomic research showed that Qilong Capsules combined with conventional western medicine in the treatment of ischemic stroke were advantageous in cost-effectiveness as compared with conventional western medicine alone, but the incremental effect was not significant. The quality evaluation results of the economic report were comparatively clear, and the economy was grade B. Aiming at major cerebrovascular diseases in the society and giving full play to the advantages of TCM, Qilong Capsules focused on the inheritance of classics and scientific and technological innovation, and innovation was grade B. The results of the questionnaire survey showed that the technical characteristics and drug application could meet the medication needs of clinical doctors and patients, and the suitability was grade B. The price level of this drug was comparatively high and the affordability was good since the treatment cost accounted for a small proportion of disposable income. The drug accessibility was good with a wide range of drug sales, sufficient production capacity, and sustainable medicinal materials resources, and was grade B. This drug was derived from the classic prescription Buyang Huanwu Decoction with rich experience of human application, which could regulate Qi and blood circulation, and the section of TCM characteristics was grade B. Based on the evidence evaluation results of "6+1" dimensions of Qilong Capsules, the comprehensive evaluation of clinical value was class A. It is suggested that it can be transformed into relevant policy results of basic clinical medication management according to procedures.

[Clinical comprehensive evaluation of Guanxin Shutong Capsules in treatment of coronary heart disease angina pectoris with heart blood stasis syndrome].

This study aims to comprehensively summarize articles on the treatment of coronary heart disease angina pectoris with heart blood stasis syndrome(CHD-AP-HBSS) by Guanxin Shutong Capsules(GSC), and comprehensively evaluate the evidence and value of the formula in "6+1" dimensions based on multi-criteria decision analysis(MCDA) model and Guidelines for Management of Comprehensive Clinical Evaluation of Drugs(trial version 2021) with quantitative and qualitative methods, which is expected to highlight the clinical characteristics and advantages of the prescription and serve as a reference for medical and health departments. The dimensions are grade A, B, C, or D. In terms of safety, according to the reports from the spontaneous reporting system of National Center for ADR Monitoring, and literature analysis, GSC mainly results in the adverse reactions of mild or moderate nausea, diarrhea, rash, palpitation, and headache, with favorable prognosis in patients. Nevertheless, severe adverse reactions have been reported after marketing. Thus, additional evidence for its safety should be accumulated, and the current safety is grade B. Meta-analysis proves that GSC in combination with conventional treatment is superior to conventional treatment alone in alleviating AP and symptoms indicated by electrocardiogram(ECG). Therefore, the effectiveness of the medicine is grade A. As for the pharmacoeconomic value, based on the assumption that the per capita disposable income in 2020 is the willingness-to-pay threshold, it is more economical for CHD-AP patients to use GSC combined with conventional treatment than conventional treatment alone. However, as the currently available clinical parameters fail to support the difference in indirect cost between the two groups, the accuracy in the cost of intervention plan needs to be further improved. Therefore, the economy of the prescription is grade B. GSC has been awarded 13 national invention patents and 1 utility model patent, and won a lot of national and provincial patent awards, marking the enterprise service awareness and innovativeness. As a result, it is grade A in aspect of innovation. A questionnaire on the suitability of GSC suggests that publicity and promotion influence patients' choice and thus additional efforts should be made in this aspect. The suitability of this formula is grade B. Both rural and urban residents can afford the medicine for the whole course and the price is close to that of similar Chinese patent medicines. In addition, it is accessible regardless of season and place, so accessibility is grade A. As a Mongolian empirical formula destined to treat heart stabbing pain, it has the effects of activating blood and resolving stasis, dredging channels and activating collaterals, and moving Qi to relieve pain, and boasts the empirical evidence of more than 2 000 human cases. With prominent characteristics of traditional Chinese medicine, it is grade B. Based on the MCDA model and CSC v2.0, GSC is comprehensively class A in the treatment of CHD-AP-HBSS. The result can serve as a reference for basic clinical medication management.

[Clinical comprehensive evaluation of Reyanning Mixture in treatment of acute upper respiratory tract infection (heat-toxin attacking lung syndrome)].

This study systematically sorted out the evidence data of the safety, effectiveness, economy, innovation, suitability, accessibility, and characteristics of traditional Chinese medicine(TCM) of Reyanning Mixture in the treatment of acute upper respiratory tract infection(heat-toxin attacking lung syndrome) with the qualitative and quantitative evaluation methods adopted. Based on evidence-based medicine, epidemiology, clinical medicine, evidence-based pharmacy, pharmacoeconomics, and health technology evalua-tion(HTA), the clinical value of Reyanning Mixture was evaluated using multi-criteria decision analysis(MCDA) model, Chinese patent medicine clinical evidence, and value evaluation software(CSC v2.0). The SRS monitoring data, Meta-analysis, and other safety evidence showed that the main adverse reactions of Reyanning Mixture were nausea, diarrhea, and rash, and no serious adverse reactions were found. The pharmacovigilance system was sound, and the system was perfect. There was no recall, notification, or interview for unqualified products. Based on the existing research, the evidence was sufficient, and the risk was controllable. Hence, its safety was grade A. Meta-analysis showed that in the treatment of acute upper respiratory tract infection, Reyanning Mixture combined with Amoxicillin Capsules was better than Amoxicillin Capsules alone in shortening the complete fever relief time and improving the cure rate. Besides, it was superior to Shuanghuanglian Granules in shortening the complete fever relief time, cough relief time, nasal congestion relief time, and pharyngeal congestion relief time. The Meta-analysis was conducted based on AMSTAR standard, and its ove-rall quality was proved good. The evidence quality in GRADE system evaluation was medium and low. The quality of evidence was medium, and the clinical value was obvious. Hence, its effectiveness was grade A. The results of pharmacoeconomic research showed that compared with Amoxicillin Capsules, Reyanning Mixture alone or in combination with Amoxicillin Capsules had cost-effectiveness advantages in the treatment of acute upper respiratory tract infection, and the results were stable in sensitivity analysis. According to the CASP economic evaluation checklist, the research problems were clear and the results were reliable. As revealed by the comprehensive evaluation, the evidence quality was sufficient and the result was clear. Its economy was grade B. Reyanning Mixture had multiple therapeutic targets like anti-virus, anti-bacteria, antipyresis, and anti-cough, with good clinical innovation. There were many innovative initiatives in ensuring drug supply, especially at the grass roots, drug safety, and effectiveness, and also multiple innovative contributions to production technology, quality control, scientific and technological research and development, and enterprise management and marketing. Therefore, its innovation was grade B. The dosage form of Reyanning was mixture, which made it convenient for storage and transportation. The usage was easy to be mastered and accepted by doctors and nurses, exhibiting good suitability for clinicians, nurses, pharmacists, and patients who received this drug and basically meeting the needs of clinical medication. The suitability was grade B. The average daily cost of this drug was 8.082 yuan, and the price was low. The treatment cost accounted for a small proportion of the annual disposable income of urban and rural residents, indicating that it was affordable. Reyanning Mixture was available in 31 provinces, cities and autonomous regions, covering 6 910 hospitals. The allocation of hospitals at all levels was more than 50%. There was no shortage or supply restriction of medicinal material resources. The annual production capacity was sufficient to meet the supply demand, so its accessibility was grade A. Reyanning Mixture, sourced from "pneumonia Ⅲ", has been subjected to a real-world study of its clinical application, with 4 367 cases involved, and the characteristic of TCM was grade B. The comprehensive evaluation results demonstrated that the clinical value score of Reyanning Mixture in the treatment of acute upper respiratory tract infection(heat-toxin attacking lung syndrome) was 0.80, making it rated class A. According to the Guidelines for Management of Comprehensive Clinical Evaluation of Drugs(trial version 2021), it is recommended to convert it into the relevant policy results of basic clinical medication management according to the procedures.

[Clinical comprehensive evaluation of Tianshu Capsules in treatment of migraine (syndrome of blood stasis blocking collaterals and syndrome of ascendant hyperactivity of liver Yang)].

This study systematically sorted out the existing studies about Tianshu Capsules in the treatment of migraine(syndrome of blood stasis blocking collaterals, syndrome of ascendant hyperactivity of liver Yang), and conducted comprehensive clinical evaluation through "6+1" dimensions of safety, effectiveness, economy, innovation, suitability, accessibility, and characteristics of traditional Chinese medicine(TCM) to embody the advantages and characteristics and clarify the precise clinical position of Tianshu Capsules. The value of each dimension was calculated via health technology assessment, the multi-criteria decision analysis(MCDA) mo-del and CSC v2.0 software. The results were graded into four levels of A, B, C, or D from high to low. According to the available studies, Tianshu Capsules had low and controllable risks, with the safety rated as A. The drug has obvious clinical significance in the treatment of migraine(syndrome of blood stasis blocking collaterals, syndrome of ascendant hyperactivity of liver Yang), with the effectiveness rated as A. It has clear economic results, with the economy rated as B. The clinical innovation, service system innovation, and industrial innovation are all good, and thus the innovation of Tianshu Capsules is grade A. The drug can meet clinical medication demand of medical care and patients, and thus its suitability is grade A. In view of the reasonable drug price, affordability, and availability, the accessibility is grade A. The prescription originated from the Daxiong Pills recorded in the classic Comprehensive Recording of Sage-like Benefit. In clinical trials, 4 675 patients have used Tianshu Capsules, which indicates rich experience in human administration, and the characteristics of traditional Chinese medicine is grade B. The statutory drug information complies with national stan-dards, and the non-statutory information is standard and accurate. Based on the comprehensive evaluation results of various dimensions of evidence, the clinical value of Tianshu Capsules in the treatment of migraine(syndrome of blood stasis blocking collaterals and syndrome of ascendant hyperactivity of liver Yang) is class A. According to the Comprehensive Clinical Evaluation Management Guidelines of Drugs(trial version 2021) issued by the National Health Commission of the People's Republic of China, we recommend that Tianshu Capsules treating migraine can be transformed into relevant policy results for clinical medication management according to procedures.