To interpret the evidence-to-decision （EtD） framework and to illustrate its application in traditional Chinese medicine （TCM） guideline development using the example of the Pharmacovigilance Guideline of Chinese Patent Medicine， thereby providing methodological references for TCM guideline standardization. Based on the core three stages of the EtD framework （formulating the question， making an assessment of the evidence， and drawing conclusions）， critical decision points and evaluation evidence within the evidence-translation process were systematically addressed， aligning with the purpose， scope， and key questions of the guideline. Qualitative research methods， such as the nominal group technique， were employed to formulate recommendations. The analysis was conducted based on the EtD framework. During question formulation， the specific characteristics and practical needs of pharmacovigilance for Chinese patent medicines were clarified， focusing on the core objective of safety assurance throughout the product lifecycle. In the evidence assessment， multi-source evidence was integrated， including policy documents， literature research， and expert consensus， completing the evidence evaluation. Finally， in recommendation-forming， dispersed research evidence and expert experience were synthesized into consensus， culminating in the guideline's completion through solicitation of opinions and peer review. The EtD framework provides a structured tool for evidence-to-decision translation in TCM guideline development， effectively enhancing the transparency and scientific rigor of the process. Therefore， it is recommended that TCM guideline development adopt the EtD framework to improve the evidence-to-decision process with TCM characteristics.

To develop the Pharmacovigilance Guidelines for Clinical Application of Chinese Patent Medicines for Mucosal Administration in response to common problems， including insufficient safety information in package inserts， amplified medication risks in special populations， and non-standard clinical practices， thus establishing a risk management system tailored to the characteristics of Chinese patent medicines for mucosal administration. An approach combining qualitative and quantitative methods was adopted. In accordance with the Drug Administration Law of the People's Republic of China （2019 revision） and the GB/T 1.1—2020 standard， a systematic search was performed in the Chinese Pharmacopoeia （2020 edition）， the Catalog of Medicines Covered by Medical Insurance （2022 edition）， Chinese databases ［China Network of Knowledge Infrastructure （CNKI）， Wanfang Data （Wanfang）， and VIP journal resource integration service platform （VIP）］， and international databases （Cochrane Library， PubMed， and EMbase）. Guideline outlines were developed through questionnaire surveys， expert interviews， and the nominal group technique. The content of each item was formulated with full consideration of traditional Chinese medicine （TCM） incompatibility， as well as the conceptual connotations and extensions of pharmacovigilance. The results included 54 Chinese patent medicines for mucosal administration from the Chinese Pharmacopoeia （2020 edition） and 58 from the Catalog of Medicines Covered by Medical Insurance （2022 edition）. Safety-related items in the corresponding package inserts were collected， and 27 relevant publications were retrieved. Thirty experts from 24 institutions were mobilized for the drafting， and opinions from 61 external experts were solicited. A pharmacovigilance framework was established， covering the full chain of "monitoring， identification， assessment， and control". Based on seven anatomical sites， including nasal， ocular， and oral mucosa， a stratified monitoring system was constructed. The guideline proposed key recommendations on improving package insert sections such as "Adverse Reactions"， "Contraindications"， and "Precautions"， clinical procedure standardization in healthcare institutions， risk control， and dynamic pharmacovigilance. The Guideline provides evidence-based support tailored to the risk profile of Chinese patent medicines for mucosal administration， filling the current gap in international pharmacovigilance standards in this field， while offering technical support for safety management across the full life cycle of medicines for mucosal administration.

To interpret the evidence-to-decision （EtD） framework and to illustrate its application in traditional Chinese medicine （TCM） guideline development using the example of the Pharmacovigilance Guideline of Chinese Patent Medicine， thereby providing methodological references for TCM guideline standardization. Based on the core three stages of the EtD framework （formulating the question， making an assessment of the evidence， and drawing conclusions）， critical decision points and evaluation evidence within the evidence-translation process were systematically addressed， aligning with the purpose， scope， and key questions of the guideline. Qualitative research methods， such as the nominal group technique， were employed to formulate recommendations. The analysis was conducted based on the EtD framework. During question formulation， the specific characteristics and practical needs of pharmacovigilance for Chinese patent medicines were clarified， focusing on the core objective of safety assurance throughout the product lifecycle. In the evidence assessment， multi-source evidence was integrated， including policy documents， literature research， and expert consensus， completing the evidence evaluation. Finally， in recommendation-forming， dispersed research evidence and expert experience were synthesized into consensus， culminating in the guideline's completion through solicitation of opinions and peer review. The EtD framework provides a structured tool for evidence-to-decision translation in TCM guideline development， effectively enhancing the transparency and scientific rigor of the process. Therefore， it is recommended that TCM guideline development adopt the EtD framework to improve the evidence-to-decision process with TCM characteristics.

To develop the Pharmacovigilance Guidelines for Clinical Application of Chinese Patent Medicines for Mucosal Administration in response to common problems， including insufficient safety information in package inserts， amplified medication risks in special populations， and non-standard clinical practices， thus establishing a risk management system tailored to the characteristics of Chinese patent medicines for mucosal administration. An approach combining qualitative and quantitative methods was adopted. In accordance with the Drug Administration Law of the People's Republic of China （2019 revision） and the GB/T 1.1—2020 standard， a systematic search was performed in the Chinese Pharmacopoeia （2020 edition）， the Catalog of Medicines Covered by Medical Insurance （2022 edition）， Chinese databases ［China Network of Knowledge Infrastructure （CNKI）， Wanfang Data （Wanfang）， and VIP journal resource integration service platform （VIP）］， and international databases （Cochrane Library， PubMed， and EMbase）. Guideline outlines were developed through questionnaire surveys， expert interviews， and the nominal group technique. The content of each item was formulated with full consideration of traditional Chinese medicine （TCM） incompatibility， as well as the conceptual connotations and extensions of pharmacovigilance. The results included 54 Chinese patent medicines for mucosal administration from the Chinese Pharmacopoeia （2020 edition） and 58 from the Catalog of Medicines Covered by Medical Insurance （2022 edition）. Safety-related items in the corresponding package inserts were collected， and 27 relevant publications were retrieved. Thirty experts from 24 institutions were mobilized for the drafting， and opinions from 61 external experts were solicited. A pharmacovigilance framework was established， covering the full chain of "monitoring， identification， assessment， and control". Based on seven anatomical sites， including nasal， ocular， and oral mucosa， a stratified monitoring system was constructed. The guideline proposed key recommendations on improving package insert sections such as "Adverse Reactions"， "Contraindications"， and "Precautions"， clinical procedure standardization in healthcare institutions， risk control， and dynamic pharmacovigilance. The Guideline provides evidence-based support tailored to the risk profile of Chinese patent medicines for mucosal administration， filling the current gap in international pharmacovigilance standards in this field， while offering technical support for safety management across the full life cycle of medicines for mucosal administration.

ObjectiveTo investigate the protective effect and mechanism of verbenalin on mouse mononuclear macrophage leukemia cells （RAW264.7） damaged by human coronavirus （HCoV）-229E infection， thereby providing experimental evidence for its development and application. MethodsRAW264.7 macrophages were infected with different concentrations of HCoV-229E to establish a coronavirus-induced macrophage injury model using the cell counting kit-8 （CCK-8） assay for assessing cell proliferation and viability. Cells were randomly divided into four groups： normal control， verbenalin group （125 μmol·L^-1）， model group （HCoV-229E）， and HCoV-229E + verbenalin group （HCoV-229E + 125 μmol·L^-1 verbenalin）. Cell viability was measured using the CCK-8 assay， and the maximum non-toxic concentration （CC₀）， half-maximal cytotoxic concentration （CC₅₀）， half-maximal effective concentration （EC₅₀）， and selectivity index （SI） of verbenalin were calculated. Calcein/PI double staining was used to assess cell viability and cytotoxicity， and JC-1 staining was applied to evaluate changes in mitochondrial membrane potential （MMP）. mito-Keima adenovirus labeling was used to assess mitophagy levels in each group. ResultsA macrophage infection model was successfully established by infecting RAW264.7 cells with the original concentration of HCoV-229E for 36 h. The CC₀ of verbenalin was 125 μmol·L^-1. The CC₅₀ was 448.25 μmol·L^-1. The EC₅₀ against HCoV-229E-infected cells was 46.28 μmol·L^-1， and the SI was 9.68. Compared with the normal group， the model group showed significantly reduced cell survival rate （P<0.01）， increased cell death rate （P<0.01）， decreased MMP （P<0.01）， and suppressed mitophagy （P<0.01）. In contrast， verbenalin treatment significantly improved cell survival rate （P<0.01）， reduced cell death rate （P<0.01）， alleviated MMP loss （P<0.01）， and enhanced mitophagy levels （P<0.01） compared with the model group. ConclusionVerbenalin can enhance the survival rate of macrophages following HCoV-229E infection. The underlying mechanism may be associated with the activation of mitophagy， maintenance of MMP stability， and alleviation of mitochondrial damage.

ObjectiveThis paper aims to investigate the therapeutic effects of Jidesheng Sheyao tablets on varicella-zoster virus （VZV） and its associated postherpetic neuralgia （PHN） to provide experimental evidence for the clinical application and secondary development of Jidesheng Sheyao tablets. MethodsFifty-six guinea pigs were randomly divided into seven groups according to their body weight， namely the normal group， the model group， the positive control group， the high-dose group， medium-dose group， and low-dose group of Jidesheng Sheyao tablets （1.92， 0.96， 0.48 g·d^-1）， and the group treated with oral administration combined with topical application of Jidesheng Sheyao tablets （0.96 g·d^-1 + 1.2 g·kg^-1·d^-1）. The skin on the back of the guinea pigs in each group was depilated and then abraded with sandpaper. Except for the normal group， 200 μL of VZV solution was dropped on the damaged parts of the back of the guinea pigs in the other groups， and the infection lasted for 2 consecutive days. The drug administration started 2 hours after the infection on the first day and lasted for 7 days. The pathological changes of the back of the guinea pigs in each group were observed every day starting from the second day after the infection. On the 7^th day， the guinea pigs were sacrificed by CO₂ anesthesia. The locally infected skin was taken， and the viral DNA nucleic acid load was detected by real-time polymerase chain reaction （Real-time PCR）. The pathological histology examination was carried out after hematoxylin-eosin （HE） staining. Seventy rats were randomly divided into seven groups according to their body weight， namely the normal group， the model group， the positive control group， the high-dose group， medium-dose group， and low-dose group of Jidesheng Sheyao tablets （1.08， 0.54， 0.27 g·d^-1）， and the group treated with oral administration combined with topical application of Jidesheng Sheyao tablets （0.54 g·d^-1 + 1.2 g·kg^-1·d^-1）. The rats in each group （except the normal group） were subcutaneously inoculated with 50 μL of VZV suspension between the web of the first and second fingers of the left forelimb. The skin on the back of the rats was depilated， and the drug administration started 2 hours after the infection and lasted for 10 days. The mechanical withdrawal threshold of the paws of the rats was detected by a Von Frey filament algometer before inoculation and on the 1^st， 3^rd， 6^th， 8^th， and 10^th days after inoculation， and the thermal withdrawal reflex latency of the paws of the rats was detected by a hot and cold plate algometer. On the 10^th day after the virus inoculation， the rats were anesthetized after the behavioral examination， and the dorsal root ganglia of the spinal cord and spinal cord segments were taken. The contents of substance P （SP）， neurokinin （NK）， tumor necrosis factor-α （TNF-α）， and interleukin-1β （IL-1β） in the dorsal root ganglia of the spinal cord and spinal cord were detected by enzyme-linked immunosorbent assay （ELISA）. ResultsCompared with those in the normal group， the guinea pigs in the model group had obvious skin herpes lesions （P<0.01）. The viral nucleic acid load was high （P<0.01）， and there were disorganized subcutaneous cellular structures and obvious infiltration of inflammatory cells and cell necrosis （P<0.01）. The mechanical withdrawal threshold of the paws and the thermal withdrawal reflex latency of the paws of the rats were significantly decreased （P<0.05）， and the contents of NK， SP， TNF-α， and IL-1β in the dorsal root ganglia of the spinal cord and spinal cord of the rats were significantly increased （P<0.01）. Compared with the model group， the high-dose and medium-dose groups of topical administration of Jidesheng Sheyao tablets and the group of oral administration combined with topical application could significantly improve the lesions such as skin redness and herpes of the guinea pigs caused by VZV infection （P<0.01）， reduce the VZV viral nucleic acid load in the skin tissues of the guinea pigs （P<0.01）， alleviate the degree of inflammatory cell infiltration and skin cell necrosis in the skin tissue （P<0.05）， significantly increase the mechanical withdrawal threshold of the paws and the thermal withdrawal reflex latency of the paws of the rats （P<0.05）， and decrease the contents of NK， SP， TNF-α， and IL-1β in the dorsal root ganglia of the spinal cord and spinal cord of the rats （P<0.01）. ConclusionJidesheng Sheyao tablets demonstrated significant therapeutic effects on VZV-induced skin infections and postherpetic neuralgia （PHN）， providing a promising candidate for the prevention and treatment of VZV infections.

ObjectiveTo investigate the protective effect and mechanism of verbenalin on mouse mononuclear macrophage leukemia cells （RAW264.7） damaged by human coronavirus （HCoV）-229E infection， thereby providing experimental evidence for its development and application. MethodsRAW264.7 macrophages were infected with different concentrations of HCoV-229E to establish a coronavirus-induced macrophage injury model using the cell counting kit-8 （CCK-8） assay for assessing cell proliferation and viability. Cells were randomly divided into four groups： normal control， verbenalin group （125 μmol·L^-1）， model group （HCoV-229E）， and HCoV-229E + verbenalin group （HCoV-229E + 125 μmol·L^-1 verbenalin）. Cell viability was measured using the CCK-8 assay， and the maximum non-toxic concentration （CC₀）， half-maximal cytotoxic concentration （CC₅₀）， half-maximal effective concentration （EC₅₀）， and selectivity index （SI） of verbenalin were calculated. Calcein/PI double staining was used to assess cell viability and cytotoxicity， and JC-1 staining was applied to evaluate changes in mitochondrial membrane potential （MMP）. mito-Keima adenovirus labeling was used to assess mitophagy levels in each group. ResultsA macrophage infection model was successfully established by infecting RAW264.7 cells with the original concentration of HCoV-229E for 36 h. The CC₀ of verbenalin was 125 μmol·L^-1. The CC₅₀ was 448.25 μmol·L^-1. The EC₅₀ against HCoV-229E-infected cells was 46.28 μmol·L^-1， and the SI was 9.68. Compared with the normal group， the model group showed significantly reduced cell survival rate （P<0.01）， increased cell death rate （P<0.01）， decreased MMP （P<0.01）， and suppressed mitophagy （P<0.01）. In contrast， verbenalin treatment significantly improved cell survival rate （P<0.01）， reduced cell death rate （P<0.01）， alleviated MMP loss （P<0.01）， and enhanced mitophagy levels （P<0.01） compared with the model group. ConclusionVerbenalin can enhance the survival rate of macrophages following HCoV-229E infection. The underlying mechanism may be associated with the activation of mitophagy， maintenance of MMP stability， and alleviation of mitochondrial damage.

ObjectiveThis paper aims to investigate the therapeutic effects of Jidesheng Sheyao tablets on varicella-zoster virus （VZV） and its associated postherpetic neuralgia （PHN） to provide experimental evidence for the clinical application and secondary development of Jidesheng Sheyao tablets. MethodsFifty-six guinea pigs were randomly divided into seven groups according to their body weight， namely the normal group， the model group， the positive control group， the high-dose group， medium-dose group， and low-dose group of Jidesheng Sheyao tablets （1.92， 0.96， 0.48 g·d^-1）， and the group treated with oral administration combined with topical application of Jidesheng Sheyao tablets （0.96 g·d^-1 + 1.2 g·kg^-1·d^-1）. The skin on the back of the guinea pigs in each group was depilated and then abraded with sandpaper. Except for the normal group， 200 μL of VZV solution was dropped on the damaged parts of the back of the guinea pigs in the other groups， and the infection lasted for 2 consecutive days. The drug administration started 2 hours after the infection on the first day and lasted for 7 days. The pathological changes of the back of the guinea pigs in each group were observed every day starting from the second day after the infection. On the 7^th day， the guinea pigs were sacrificed by CO₂ anesthesia. The locally infected skin was taken， and the viral DNA nucleic acid load was detected by real-time polymerase chain reaction （Real-time PCR）. The pathological histology examination was carried out after hematoxylin-eosin （HE） staining. Seventy rats were randomly divided into seven groups according to their body weight， namely the normal group， the model group， the positive control group， the high-dose group， medium-dose group， and low-dose group of Jidesheng Sheyao tablets （1.08， 0.54， 0.27 g·d^-1）， and the group treated with oral administration combined with topical application of Jidesheng Sheyao tablets （0.54 g·d^-1 + 1.2 g·kg^-1·d^-1）. The rats in each group （except the normal group） were subcutaneously inoculated with 50 μL of VZV suspension between the web of the first and second fingers of the left forelimb. The skin on the back of the rats was depilated， and the drug administration started 2 hours after the infection and lasted for 10 days. The mechanical withdrawal threshold of the paws of the rats was detected by a Von Frey filament algometer before inoculation and on the 1^st， 3^rd， 6^th， 8^th， and 10^th days after inoculation， and the thermal withdrawal reflex latency of the paws of the rats was detected by a hot and cold plate algometer. On the 10^th day after the virus inoculation， the rats were anesthetized after the behavioral examination， and the dorsal root ganglia of the spinal cord and spinal cord segments were taken. The contents of substance P （SP）， neurokinin （NK）， tumor necrosis factor-α （TNF-α）， and interleukin-1β （IL-1β） in the dorsal root ganglia of the spinal cord and spinal cord were detected by enzyme-linked immunosorbent assay （ELISA）. ResultsCompared with those in the normal group， the guinea pigs in the model group had obvious skin herpes lesions （P<0.01）. The viral nucleic acid load was high （P<0.01）， and there were disorganized subcutaneous cellular structures and obvious infiltration of inflammatory cells and cell necrosis （P<0.01）. The mechanical withdrawal threshold of the paws and the thermal withdrawal reflex latency of the paws of the rats were significantly decreased （P<0.05）， and the contents of NK， SP， TNF-α， and IL-1β in the dorsal root ganglia of the spinal cord and spinal cord of the rats were significantly increased （P<0.01）. Compared with the model group， the high-dose and medium-dose groups of topical administration of Jidesheng Sheyao tablets and the group of oral administration combined with topical application could significantly improve the lesions such as skin redness and herpes of the guinea pigs caused by VZV infection （P<0.01）， reduce the VZV viral nucleic acid load in the skin tissues of the guinea pigs （P<0.01）， alleviate the degree of inflammatory cell infiltration and skin cell necrosis in the skin tissue （P<0.05）， significantly increase the mechanical withdrawal threshold of the paws and the thermal withdrawal reflex latency of the paws of the rats （P<0.05）， and decrease the contents of NK， SP， TNF-α， and IL-1β in the dorsal root ganglia of the spinal cord and spinal cord of the rats （P<0.01）. ConclusionJidesheng Sheyao tablets demonstrated significant therapeutic effects on VZV-induced skin infections and postherpetic neuralgia （PHN）， providing a promising candidate for the prevention and treatment of VZV infections.

ObjectiveTo evaluate the pharmacological effects of verbenalin on both in vitro and in vivo infection models of human coronavirus 229E （HCoV-229E） and to preliminarily explore the antiviral mechanism of verbenalin through proteomic analysis. MethodsIn vitro， the cell counting kit-8 （CCK-8） for cell proliferation and viability assessment was used to establish a model of HCoV-229E-induced injury in human lung adenocarcinoma cells（A549）. A549 cells were divided into five groups： normal group， model group， and three verbenalin treatment groups （125， 62.5， and 31.25 μmol·L^-1）. The cell protective activity of verbenalin was evaluated through cell viability assay and immunofluorescence staining. In vivo， 30 BALB/c mice were randomly divided into normal group， model group， chloroquine group， and high-dose， low-dose verbenalin groups （40 and 20 mg·kg^-1）， with six mice per group. An HCoV-229E-induced mouse lung injury model was established to evaluate the therapeutic effects of verbenalin. Lung injury was assessed by detecting the lung index and lung inhibition rate. The severity of pulmonary inflammation cytokines was measured by enzyme-linked immunosorbent assay （ELISA）， while the lung morphology and structure were analyzed by micro-computed tomography （Micro-CT）. Hematoxylin and eosin （HE） staining was used to assess histopathological changes in lung tissue. Additionally， four-dimensional data-independent acquisition （4D-DIA） proteomics was employed to preliminarily explore the potential mechanisms of verbenalin in treating HCoV-229E-induced lung injury in mice， through differential protein expression screening， functional annotation， enrichment analysis， and protein-protein interaction network analysis. ResultsThe A549 cells were infected with HCoV-229E at the original viral titer for 36 hours to establish an in vitro infection model. The maximum non-toxic concentration of verbenalin was 125 μmol·L^-1， and the half-maximal cytotoxic concentration （CC₅₀） was 288.8 μmol·L^-1. Compared with the normal group， the model group showed a significant decrease in cell viability （P<0.01）， a significant increase in the proportion of dead cells （P<0.01）， mitochondrial damage， and a significant reduction in mitochondrial membrane potential （P<0.01）. After treatment with different concentrations of verbenalin （125， 62.5， and 31.25 μmol·L^-1）， cell viability was significantly increased （P<0.01）， and the proportion of dead cells was reduced （P<0.01）， with mitochondrial membrane potential restored （P<0.01）. In vivo experiments further confirmed the therapeutic effect of verbenalin on HCoV-229E-infected mice. Compared to the normal group， the model group showed a significant increase in the lung index （P<0.01）， severe lung tissue injury， lung volume enlargement， and a significant increase in the expression of inflammatory cytokines， including interleukin-6 （IL-6） and tumor necrosis factor-α （TNF-α） （P<0.01）. In contrast， in the verbenalin treatment groups， these pathological changes were significantly improved， with a reduction in the lung index （P<0.01）， alleviation of lung tissue injury， reduced lung volume enlargement， and a significant decrease in inflammatory cytokine expression （P<0.01）. Proteomics analysis revealed that， compared to the normal group， the model group showed enrichment in several antiviral immune-related signaling pathways， including the nuclear factor-κB （NF-κB） signaling pathway （P<0.05）. Compared to the model group， the verbenalin treatment group showed enrichment in several signaling pathways related to inflammatory response and autophagy （P<0.05）， suggesting that verbenalin may exert its antiviral and anti-inflammatory effects by regulating these pathways. ConclusionVerbenalin demonstrates significant therapeutic effects in both in vitro and in vivo HCoV-229E infection models， with its mechanism likely related to the NOD-like receptor protein 3 （NLRP3） inflammasome pathway and mitochondrial autophagy.