ObjectiveTo evaluate the clinical efficacy of Huayu Tongluo Formula （化瘀通络方， HTF） in patients with mid-stage diabetic kidney disease of blood stasis syndrome and explore its potential mechanisms. MethodsA multi-center， randomized， double-blind， placebo-controlled clinical trial was conducted. Ninety patients of mid-stage diabetic kidney disease of blood stasis syndrome were divided into a control group of 46 cases and a treatment group of 44 cases. Both groups received conventional western medicine treatment， the treatment group additionally taking HTF， while the control group taking a placebo of the formula. The treatment was administered once daily for 24 weeks. The primary outcomes included 24-hour urine total protein （24 h-UTP）， serum albumin （Alb）， glycated hemoglobin （HbA1c）， and serum creatinine （Scr）.The secondary outcomes included changes in levels of endothelin-1 （ET-1）， nitric oxide （NO）， vascular endothelial growth factor （VEGF）， and traditional Chinese medicine （TCM） syndrome scores before and after treatment. Clinical efficacy was evaluated based on TCM syndrome scores and overall disease outcomes. Adverse reactions and endpoint events were recorded. ResultsIn the treatment group after treatment， 24 h-UTP， ET-1， and VEGF levels significantly decreased （P＜0.05）， Alb and NO levels significantly increased （P＜0.05）； while the TCM syndrome scores for edema， lumbar pain， numbness of limbs， dark purple lips， dark purple tongue or purpura， and thin， rough pulse all significantly decreased （P＜0.05）. In the control group， no significant changes were observed in any of the indicators after treatment （P＞0.05）.Compared with the control group， the treatment group showed significant reductions in 24 h-UTP， ET-1， and VEGF levels， and increases in Alb and NO levels （P＜0.05）. The TCM syndrome scores for edema， lumbar pain， dark purple tongue or purpura， and thin， rough pulse were all lower in the treatment group than in the control group （P＜0.05）. The total effective rate of TCM syndrome in the treatment group was 59.09% （26/44）， and the overall clinical effective rate was 45.45% （20/44）. In the control group， these rates were 15.22% （7/46） and 8.7% （4/46）， respectively， with the treatment group showing significantly better outcomes （P＜0.05）. A total of 7 adverse events occurred across both groups， with no significant difference （P＞0.05）. No endpoint events occurred during the study. ConclusionOn the basis of conventional treatment of Western medicine， HTF can further reduce urinary protein levels and improve clinical symptoms in patients with mid-stage diabetic kidney disease of blood stasis syndrome. The mechanism may be related to its effects on endothelial function.

ObjectiveIn order to provide a reference for the optimization of preparation process of stir-fried Glycyrrhizae Radix et Rhizoma（sf-GRR）， the quality changes during the processing was studied. MethodsGlycyrrhizae Radix et Rhizoma was processed by stir-frying for 17 min， and samples were collected every 1 min during the processing. The appearance color of the samples was determined by visual analysis technology， the moisture and extract of the process samples were detected by the drying method and the hot extraction method of alcohol-soluble extract in the general rules of the 2020 edition of Chinese Pharmacopoeia（part Ⅳ）， and the contents of liquiritin apioside， liquiritin， isoliquiritin apioside， isoliquiritin， licoricesaponin G₂ and glycyrrhizic acid in the process samples were determined by high performance liquid chromatography（HPLC）. Then principal component analysis（PCA）， partial least squares-discriminant analysis（PLS-DA） and Spearman correlation analysis were used for clustering， discrimination and correlation analysis of the appearance color， moisture， extract and the contents of six internal components. Based on artificial neural network and random forest algorithm， the prediction model of processing degree of sf-GRR was established. On this basis， based on the five principles of quality marker（Q-Maker）， explore the monitoring Q-Maker of sf-GRR. ResultsThe color of Glycyrrhizae Radix et Rhizoma deepened after stir-frying， and the appearance color of the sample changed from light yellow to dark yellow during processing. During the stir-frying process， the moisture content showed a decreasing trend with the extension of processing time， while the extract content showed an increasing trend with the extension of processing time. After stir-frying， the contents of liquiritin apioside， liquiritin and licoricesaponin G₂ showed an overall decreasing trend， while the contents of isoliquiritin apioside and isoliquiritin increased， and the content of glycyrrhizic acid increased slightly. The correlation analysis showed that moisture was positively correlated with brightness（L^*） and red/green value（a^*）， and negatively correlated with yellow/blue value（b^*） and total color difference（E^*ab）. Isoliquiritin apioside and isoliquiritin had negative correlation with L^* and a^*， and positive correlation with b^* and E^*ab. The processing process of sf-GRR could be divided into two stages of the early stage（0-14 min） and the late stage（15-17 min）， and could be divided into three stages of the early stage（0-6 min）， the middle stage（7-14 min） and the late stage（15-17 min） by combining the moisture， extract， the contents of 6 components and color values. Based on artificial neural network analysis and random forest algorithm， isoliquiritin apioside， isoliquiritin， liquiritin and glycyrrhizic acid were selected as monitoring markers for sf-GRR. ConclusionBased on the analysis of the exterior-interior indicators of process samples of sf-GRR， this paper ultimately identifies four processing monitoring markers， which can provide a basis for optimizing the processing technology of sf-GRR.

Clinical practice guidelines represent the best recommendations for patient care. They are developed through systematically reviewing currently available clinical evidence and weighing the relative benefits and risks of various interventions. However, clinical practice guidelines have to go through a long translation cycle from development and revision to clinical promotion and application, facing problems such as scattered distribution, high duplication rate, and low actual utilization. At present, the clinical practice guideline information platform can directly or indirectly solve the problems related to the lengthy revision cycles, decentralized dissemination and limited application of clinical practice guidelines. Therefore, this paper systematically examines different types of clinical practice guideline information platforms and investigates their corresponding challenges and emerging trends in platform design, data integration, and practical implementation, with the aim of clarifying the current status of this field and providing valuable reference for future research on clinical practice guideline information platforms.

ObjectiveTo investigate the mechanism by which 2，3，5，4'-tetrahydroxyldiphenylethylene-2-O-glucoside （THSG） mitigates cerebral ischemia/reperfusion （CI/R） injury by regulating mitochondrial calcium overload and promoting mitophagy. MethodsSixty male SD rats were randomized into sham， model， SAS （40 mg·kg^-1）， and low-， medium- and high-dose （10， 20， 40 mg·kg^-1， respectively） THSG groups， with 10 rats in each group. The middle cerebral artery occlusion/reperfusion （MCAO/R） model was established by the modified Longa suture method. An oxygen-glucose deprivation/reoxygenation （OGD/R） model was constructed in PC12 cells. Neurological deficits were assessed via Zea Longa scoring， and cerebral infarct volume was measured by 2，3，5-triphenyltetrazolium chloride （TTC） staining. Structural and functional changes of cortical neurons in MCAO/R rats were assessed by hematoxylin-eosin and Nissl staining. PC12 cell viability was detected by cell counting kit-8 （CCK-8） assay， and mitochondrial calcium levels were quantified by Rhod-2 AM. Immunofluorescence was used to detect co-localization of PTEN-induced kinase 1 （PINK1） and leucine zipper/EF-hand-containing transmembrane protein 1 （LETM1） in neurons. Transmission electron microscopy （TEM） was employed to observe mitochondrial morphology in neurons. Western blot was employed to analyze the expression of translocase of outer mitochondrial membrane 20 （TOMM20）， autophagy-associated protein p62， microtubule-associated protein light chain 3 （LC3）， cysteinyl aspartate-specific proteinase-9 （Caspase-9）， B-cell lymphoma 2-associated protein X （Bax）， and cytochrome C （Cyt C）. ResultsCompared with the sham group， the model group exhibited increased infarct volume （P<0.01） and neurological deficit scores （P<0.01）， neuronal structure was disrupted with reduced Nissl bodies. （P<0.01）， mitochondrial swelling/fragmentation， decreased PINK1/LETM1 co-localization （P<0.01）， upregulated protein levels of LC3Ⅱ/LC3Ⅰ， TOMM20， Caspase-9， Bax， and Cyt C （P<0.01）， downregulated protein level of p62 （P<0.05）， weakened PC12 viability （P<0.01）， and elevated mitochondrial calcium level （P<0.01）. Compared with the model group， THSG and SAS groups showed reduced infarct volumes （P<0.05，P<0.01） and neurological deficit scores （P<0.05，P<0.01）， mitigated mitochondrial damage， and increased PINK1/LETM1 co-localization （P<0.01）. Medium/high-dose THSG and SAS alleviated the neurological damage， increased Nissl bodies （P<0.05，P<0.01）， downregulated the protein levels of p62， TOMM20， Caspase-9， Bax， and Cyt C （P<0.05，P<0.01）， and elevated the LC3Ⅱ/LC3Ⅰ level （P<0.05，P<0.01）. High-dose THSG enhanced PC12 cell viability （P<0.01）， increased PINK1/LETM1 co-localization （P<0.01）， and reduced mitochondrial calcium （P<0.01）. ConclusionTHSG may exert the neuroprotective effect on CI/R injury by activating the PINK1-LETM1 signaling pathway， reducing the mitochondrial calcium overload， and promoting mitophagy.

ObjectiveTo investigate the mechanism by which 2，3，5，4'-tetrahydroxyldiphenylethylene-2-O-glucoside （THSG） mitigates cerebral ischemia/reperfusion （CI/R） injury by regulating mitochondrial calcium overload and promoting mitophagy. MethodsSixty male SD rats were randomized into sham， model， SAS （40 mg·kg^-1）， and low-， medium- and high-dose （10， 20， 40 mg·kg^-1， respectively） THSG groups， with 10 rats in each group. The middle cerebral artery occlusion/reperfusion （MCAO/R） model was established by the modified Longa suture method. An oxygen-glucose deprivation/reoxygenation （OGD/R） model was constructed in PC12 cells. Neurological deficits were assessed via Zea Longa scoring， and cerebral infarct volume was measured by 2，3，5-triphenyltetrazolium chloride （TTC） staining. Structural and functional changes of cortical neurons in MCAO/R rats were assessed by hematoxylin-eosin and Nissl staining. PC12 cell viability was detected by cell counting kit-8 （CCK-8） assay， and mitochondrial calcium levels were quantified by Rhod-2 AM. Immunofluorescence was used to detect co-localization of PTEN-induced kinase 1 （PINK1） and leucine zipper/EF-hand-containing transmembrane protein 1 （LETM1） in neurons. Transmission electron microscopy （TEM） was employed to observe mitochondrial morphology in neurons. Western blot was employed to analyze the expression of translocase of outer mitochondrial membrane 20 （TOMM20）， autophagy-associated protein p62， microtubule-associated protein light chain 3 （LC3）， cysteinyl aspartate-specific proteinase-9 （Caspase-9）， B-cell lymphoma 2-associated protein X （Bax）， and cytochrome C （Cyt C）. ResultsCompared with the sham group， the model group exhibited increased infarct volume （P<0.01） and neurological deficit scores （P<0.01）， neuronal structure was disrupted with reduced Nissl bodies. （P<0.01）， mitochondrial swelling/fragmentation， decreased PINK1/LETM1 co-localization （P<0.01）， upregulated protein levels of LC3Ⅱ/LC3Ⅰ， TOMM20， Caspase-9， Bax， and Cyt C （P<0.01）， downregulated protein level of p62 （P<0.05）， weakened PC12 viability （P<0.01）， and elevated mitochondrial calcium level （P<0.01）. Compared with the model group， THSG and SAS groups showed reduced infarct volumes （P<0.05，P<0.01） and neurological deficit scores （P<0.05，P<0.01）， mitigated mitochondrial damage， and increased PINK1/LETM1 co-localization （P<0.01）. Medium/high-dose THSG and SAS alleviated the neurological damage， increased Nissl bodies （P<0.05，P<0.01）， downregulated the protein levels of p62， TOMM20， Caspase-9， Bax， and Cyt C （P<0.05，P<0.01）， and elevated the LC3Ⅱ/LC3Ⅰ level （P<0.05，P<0.01）. High-dose THSG enhanced PC12 cell viability （P<0.01）， increased PINK1/LETM1 co-localization （P<0.01）， and reduced mitochondrial calcium （P<0.01）. ConclusionTHSG may exert the neuroprotective effect on CI/R injury by activating the PINK1-LETM1 signaling pathway， reducing the mitochondrial calcium overload， and promoting mitophagy.

ObjectiveBased on ultra performance liquid chromatography-quadrupole-time-of-flight mass spectrometry（UPLC-Q-TOF-MS）， network pharmacology， molecular docking and cell experiments， the active ingredients， possible targets and molecular mechanisms of Baoxin granules（BXG） regulating ferroptosis in the treatment of heart failure（HF） were explored. MethodsBXG intestinal absorption fluid was prepared by everted gut sac and the chemical composition contained therein were identified by UPLC-Q-TOF-MS. According to the obtained components， the potential targets of BXG were predicted， and the HF-related targets and related genes of ferroptosis were retrieved at the same time， and the intersecting targets were obtained by Venn diagram. In addition， the protein-protein interaction（PPI） network and the component-target network were constructed， and the core components and core targets were obtained by topological analysis. Then Gene Ontology（GO） function and Kyoto Encyclopedia of Genes and Genomes（KEGG） enrichment analysis were performed on the core targets， and molecular docking validation of the key targets and main components was carried out by AutoDockTools 1.5.7. H9c2 cells were used to establish a oxygen-glucose deprivation model， and the protective effect of BXG on cells was investigated by detecting cell viability， cell survival rate and reactive oxygen species（ROS） level. The protein expression levels of signal transducer and activator of transcription 3（STAT3）， phosphorylation（p）-STAT3 and glutathione peroxidase 4（GPX4） were detected by Western blot to clarify the regulatory effect of BXG on ferroptosis. ResultsA total of 61 chemical components in BXG intestinal absorption fluid were identified， and network pharmacology obtained 27 potential targets of BXG for the treatment of HF， as well as 139 signaling pathways. BXG may act on core targets such as STAT3， tumor protein p53（TP53）， epidermal growth factor receptor（EGFR）， JUN and prostaglandin-endoperoxide synthase 2（PTGS2） through core components such as glabrolide and limonin， which in turn intervene in lipid and atherosclerosis， phosphatidylinositol 3-kinase/protein kinase B（PI3K/Akt）， endocrine resistance and other signaling pathways to exert therapeutic effects on HF. Molecular docking showed that the docking results of multiple groups of targets and compounds were good. In vitro cell experiments showed that compared with the blank group， the cell viability and survival rate of the model group were significantly decreased， the level of ROS was significantly increased（P<0.01）， the expression levels of STAT3， p-STAT3， p-STAT3/STAT3 and GPX4 proteins were significantly decreased（P<0.05， P<0.01）. Compared with the model group， the cell viability and survival rate of the BXG group were significantly increased， the ROS level was significantly decreased（P<0.01）， the STAT3， p-STAT3， p-STAT3/STAT3 and GPX4 protein levels were significantly increased（P<0.05， P<0.01）. ConclusionBXG may inhibit the occurrence of ferroptosis by up-regulating the expression of STAT3 and GPX4， thus exerting a therapeutic effect on HF， and flavonoids may be the key components of this role.

ObjectiveBased on ultra performance liquid chromatography-quadrupole-time-of-flight mass spectrometry（UPLC-Q-TOF-MS）， network pharmacology， molecular docking and cell experiments， the active ingredients， possible targets and molecular mechanisms of Baoxin granules（BXG） regulating ferroptosis in the treatment of heart failure（HF） were explored. MethodsBXG intestinal absorption fluid was prepared by everted gut sac and the chemical composition contained therein were identified by UPLC-Q-TOF-MS. According to the obtained components， the potential targets of BXG were predicted， and the HF-related targets and related genes of ferroptosis were retrieved at the same time， and the intersecting targets were obtained by Venn diagram. In addition， the protein-protein interaction（PPI） network and the component-target network were constructed， and the core components and core targets were obtained by topological analysis. Then Gene Ontology（GO） function and Kyoto Encyclopedia of Genes and Genomes（KEGG） enrichment analysis were performed on the core targets， and molecular docking validation of the key targets and main components was carried out by AutoDockTools 1.5.7. H9c2 cells were used to establish a oxygen-glucose deprivation model， and the protective effect of BXG on cells was investigated by detecting cell viability， cell survival rate and reactive oxygen species（ROS） level. The protein expression levels of signal transducer and activator of transcription 3（STAT3）， phosphorylation（p）-STAT3 and glutathione peroxidase 4（GPX4） were detected by Western blot to clarify the regulatory effect of BXG on ferroptosis. ResultsA total of 61 chemical components in BXG intestinal absorption fluid were identified， and network pharmacology obtained 27 potential targets of BXG for the treatment of HF， as well as 139 signaling pathways. BXG may act on core targets such as STAT3， tumor protein p53（TP53）， epidermal growth factor receptor（EGFR）， JUN and prostaglandin-endoperoxide synthase 2（PTGS2） through core components such as glabrolide and limonin， which in turn intervene in lipid and atherosclerosis， phosphatidylinositol 3-kinase/protein kinase B（PI3K/Akt）， endocrine resistance and other signaling pathways to exert therapeutic effects on HF. Molecular docking showed that the docking results of multiple groups of targets and compounds were good. In vitro cell experiments showed that compared with the blank group， the cell viability and survival rate of the model group were significantly decreased， the level of ROS was significantly increased（P<0.01）， the expression levels of STAT3， p-STAT3， p-STAT3/STAT3 and GPX4 proteins were significantly decreased（P<0.05， P<0.01）. Compared with the model group， the cell viability and survival rate of the BXG group were significantly increased， the ROS level was significantly decreased（P<0.01）， the STAT3， p-STAT3， p-STAT3/STAT3 and GPX4 protein levels were significantly increased（P<0.05， P<0.01）. ConclusionBXG may inhibit the occurrence of ferroptosis by up-regulating the expression of STAT3 and GPX4， thus exerting a therapeutic effect on HF， and flavonoids may be the key components of this role.

This paper interprets the disease name related to bi （痹） disease in traditional Chinese medicine （TCM） from the perspective of micropathological phenotypes in knee osteoarthritis （KOA）. By systematically reviewing classical TCM literature on the pathogenesis and clinical features of different subtypes such as damp-retention bi， bone bi， and tendon bi， and integrating these with current research on pathological subtypes of KOA including the synovitis type， cartilage-meniscus type， and subchondral bone type， the study explores the correlation between traditional disease terms and modern micropathological phenotypes. The author proposes subtype classifications of damp-retention bi corresponding to synovial inflammation， bone bi related to abnormal subchondral bone remodeling， and tendon bi representing cartilage and meniscus degeneration. This approach provides a microscopic biological explanation for TCM syndrome differentiation and offers new perspectives for advancing integrative diagnostic and therapeutic strategies in both Chinese and western medicine.

It is believed that wind pathogen lingering in the lungs is the key factor in the pathogenesis of cough variant asthma. Among these， external wind-induced cough is the main trigger， while internal wind hidden in the lung plays an important role in promoting the disease. Weakness of the zang-fu organs is the fundamental cause of recurrent attacks， especially closely related to deficiencies in the lungs， spleen and kidneys. The primary treatment principles proposed are dispelling wind and relieving cough， as well as tonifying deficiency and supporting the upright qi. Clinical practice should integrate differentiation of the root and branch as well as excess and deficiency， applying staged treatment. During the acute attack phase， the focus is on dispelling wind and stopping cough， supplemented by tonification. During the remission phase， tonifying deficiency and supporting the upright qi is emphasized， with coordinated regulation of the lungs， spleen and kidneys alongside clearing residual pathogens， so that the pathogenic are eliminated and the body restored， leading to natural resolution of cough and reversal of adverse qi flow.

ObjectiveTo investigate the mechanism of Baihuan Xiaoyao Decoction （Xiaoyaosan added with Lilii Bulbus and Albiziae Cortex） in alleviating depression-like behaviors of juvenile rats by regulating the polarization of microglia. MethodSixty juvenile SD rats were randomized into normal control， model， fluoxetine， and low-， medium-， and high-dose （5.36， 10.71， 21.42 g·kg^-1， respectively） Baihuan Xiaoyao decoction groups. The rat model of juvenile depression was established by chronic unpredictable mild stress （CUMS）. The sucrose preference test （SPT） was carried out to examine the sucrose preference of rats. Forced swimming test （FST） was carried out to measure the immobility time of rats. The open field test （OFT） was conducted to measure the total distance， the central distance， the number of horizontal crossings， and the frequency of rearing. Morris water maze （MWM） was used to measure the escape latency and the number of crossing the platform. The immunofluorescence assay was employed to detect the expression of inducible nitric oxide synthase （iNOS， the polarization marker of M1 microglia） and CD206 （the polarization marker of M2 microglia）. Real-time polymerase chain reaction was employed to determine the mRNA levels of iNOS， CD206， pro-inflammatory cytokines ［tumor necrosis factor （TNF）-α， interleukin （IL）-1β， and IL-6］ and anti-inflammatory cytokines （IL-4 and IL-10） in the hippocampus. Western blotting was employed to determine the protein levels of iNOS and CD206 in the hippocampus. The levels of IL-4 and IL-6 in the hippocampus were detected by enzyme-linked immunosorbent assay. ResultCompared with the normal control group， the model rats showed a reduction in sucrose preference （P<0.05）， an increase in immobility time （P<0.05）， decreased motor and exploratory behaviors （P<0.05）， and weakened learning and spatial memory （P<0.05）. In addition， the model rats showed up-regulated mRNA and protein levels of iNOS and mRNA levels of IL-1β， IL-6， and TNF-α （P<0.05）. Compared with the model group， Baihuan Xiaoyao decoction increased the sucrose preference value （P<0.05）， shortened the immobility time （P<0.01）， increased the motor and exploratory behaviors （P<0.05）， and improved the learning and spatial memory （P<0.01）. Furthermore， the decoction down-regulated the positive expression and protein level of iNOS， lowered the levels of TNF-α， IL-1β， and IL-6 （P<0.01）， promoted the positive expression of CD206， and elevated the levels of IL-4 and IL-10 （P<0.01） in the hippocampus of the high dose group. Moreover， the high-dose Baihuan Xiaoyao decoction group had higher sucrose preference value （P<0.01）， shorter immobility time （P<0.01）， longer central distance （P<0.01）， stronger learning and spatial memory （P<0.01）， higher positive expression and protein level of iNOS （P<0.01）， lower levels of TNF-α， IL-1β， and IL-6 （P<0.05， P<0.01）， lower positive expression and mRNA level of iNOS （P<0.05）， and higher levels of IL-4 and IL-10 （P<0.05， P<0.01） than the fluoxetine group. ConclusionBaihuan Xiaoyao decoction can improve the depression-like behavior of juvenile rats by inhibiting the M1 polarization and promoting the M2 polarization of microglia in the hippocampus.