ObjectiveChinese patent medicines for cardiovascular and cerebrovascular diseases are diverse and complex in their efficacy. The traditional classification method based on efficacy categories has certain limitations and cannot meet the clinical needs for individualized drug selection and variety comparison. This article， based on the formulation compatibility analysis technology of "Tangye Jingfa Tu"， clarifies the composition and efficacy characteristics of common Chinese patent medicines used for cardiovascular and cerebrovascular diseases， providing support for the precise selection of these medicines. MethodsFifty-six representative Chinese patent medicines， covering all the efficacy subcategories of "stasis-resolving agents" in the National Basic Medical Insurance， Work Injury Insurance， and Maternity Insurance Drug Catalogue （2023） （more than 50% of the total）， were selected for the study. Within the knowledge system of "Tangye Jingfa Tu"， the compatibility structure of herbal flavors and the proportion structure of herbal quantities for each Chinese patent medicine were determined. The correlation between these structures and the efficacy categories was analyzed to identify the similarities and differences among the selected Chinese patent medicines. Additionally， the efficacy was reclassified and compared according to the theoretical framework of tonifying and purging methods of five Zang organs in the "Tangye Jingfa Tu". ResultsThe representative Chinese patent medicines included in the analysis were Shexiang Baoxin pills， Danshen tablets， Qili Qiangxin capsules， Breviscapine tablets， etc.， covering all the efficacy subcategories of "stasis-resolving agents". Among the 56 representative Chinese patent medicines， salty flavor was the most common （48）， followed by pungent （33）， and sweet （26）. According to the dominant herbal flavor， salty flavor was the most common （37）， followed by pungent （9）， and sour （5）. According to the dominant herbal quantity， salty flavor was the most common （27）， followed by sour （7）， and pungent （5）. Furthermore， Chinese patent medicines with different efficacy subtypes showed different flavor characteristics. For example， most Qi-invigorating and blood-activating agents contained sweet drugs for tonifying the spleen （9/10）， most Qi-moving and blood-activating agents contained pungent drugs for tonifying the liver （7/8）， and all kidney-invigorating and blood-activating agents contained bitter drugs for tonifying the kidneys （6/6）. However， the efficacy classification of individual medicines did not always align with the compatibility characteristics of their formulas， as seen with Dengyin Naotong capsules. ConclusionThe formulations of Chinese patent medicines for cardiovascular and cerebrovascular diseases predominantly feature salty， sour， and pungent flavors， which largely conform to the therapeutic principles of "nourishing the heart with salt and soothing the heart with sour" and the liver-heart， heart-spleen mother-child treatment relationship shown in the "Tangye Jingfa Tu". Using the "Tangye Jingfa Tu" framework to conduct research on the structure and efficacy characteristics of Chinese patent medicines is objective and effective.

ObjectiveChinese patent medicines for cardiovascular and cerebrovascular diseases are diverse and complex in their efficacy. The traditional classification method based on efficacy categories has certain limitations and cannot meet the clinical needs for individualized drug selection and variety comparison. This article， based on the formulation compatibility analysis technology of "Tangye Jingfa Tu"， clarifies the composition and efficacy characteristics of common Chinese patent medicines used for cardiovascular and cerebrovascular diseases， providing support for the precise selection of these medicines. MethodsFifty-six representative Chinese patent medicines， covering all the efficacy subcategories of "stasis-resolving agents" in the National Basic Medical Insurance， Work Injury Insurance， and Maternity Insurance Drug Catalogue （2023） （more than 50% of the total）， were selected for the study. Within the knowledge system of "Tangye Jingfa Tu"， the compatibility structure of herbal flavors and the proportion structure of herbal quantities for each Chinese patent medicine were determined. The correlation between these structures and the efficacy categories was analyzed to identify the similarities and differences among the selected Chinese patent medicines. Additionally， the efficacy was reclassified and compared according to the theoretical framework of tonifying and purging methods of five Zang organs in the "Tangye Jingfa Tu". ResultsThe representative Chinese patent medicines included in the analysis were Shexiang Baoxin pills， Danshen tablets， Qili Qiangxin capsules， Breviscapine tablets， etc.， covering all the efficacy subcategories of "stasis-resolving agents". Among the 56 representative Chinese patent medicines， salty flavor was the most common （48）， followed by pungent （33）， and sweet （26）. According to the dominant herbal flavor， salty flavor was the most common （37）， followed by pungent （9）， and sour （5）. According to the dominant herbal quantity， salty flavor was the most common （27）， followed by sour （7）， and pungent （5）. Furthermore， Chinese patent medicines with different efficacy subtypes showed different flavor characteristics. For example， most Qi-invigorating and blood-activating agents contained sweet drugs for tonifying the spleen （9/10）， most Qi-moving and blood-activating agents contained pungent drugs for tonifying the liver （7/8）， and all kidney-invigorating and blood-activating agents contained bitter drugs for tonifying the kidneys （6/6）. However， the efficacy classification of individual medicines did not always align with the compatibility characteristics of their formulas， as seen with Dengyin Naotong capsules. ConclusionThe formulations of Chinese patent medicines for cardiovascular and cerebrovascular diseases predominantly feature salty， sour， and pungent flavors， which largely conform to the therapeutic principles of "nourishing the heart with salt and soothing the heart with sour" and the liver-heart， heart-spleen mother-child treatment relationship shown in the "Tangye Jingfa Tu". Using the "Tangye Jingfa Tu" framework to conduct research on the structure and efficacy characteristics of Chinese patent medicines is objective and effective.

The renin-angiotensin-aldosterone system (RAAS) is crucial for regulating blood pressure and maintaining fluid balance, while clock genes are essential for sustaining biological rhythms and regulating metabolism. There exists a complex interplay between RAAS and clock genes that may significantly contribute to the development of various cardiovascular and metabolic diseases. Although current literature has identified correlations between these two systems, the specific mechanisms of their interaction remain unclear. Moreover, the interaction patterns under different physiological and pathological conditions need further investigation. This review summarizes the synergistic roles of the RAAS and clock genes in cardiovascular diseases, explores their molecular mechanisms and pathophysiological connections, discusses the application of chronotherapy, and highlights potential future research directions, aiming to provide novel insights for the prevention and treatment of related diseases.
Humans ; Renin-Angiotensin System/genetics* ; Cardiovascular Diseases/genetics* ; CLOCK Proteins/physiology* ; Animals

This study aimed to explore the therapeutic mechanisms of Colquhounia Root Tablets(CRT) in treating diabetic kidney disease(DKD) by integrating biomolecular network mining with animal model verification. By analyzing clinical transcriptomics data, an interaction network was constructed between candidate targets of CRT and DKD-related genes. Based on the topological eigenvalues of network nodes, 101 core network targets of CRT against DKD were identified. These targets were found to be closely related to multiple pathways associated with type 2 diabetes, immune response, and metabolic reprogramming. Given that immune-inflammatory imbalance driven by metabolic reprogramming is one of the key pathogenic mechanisms of DKD, and that many core network targets of CRT are involved in this pathological process, receptor for advanced glycation end products(RAGE)-reactive oxygen species(ROS)-phosphatidylinositol 3-kinase(PI3K)-protein kinase B(AKT)-nuclear factor-κB(NF-κB)-NOD-like receptor family pyrin domain containing 3(NLRP3) signaling axis was selected as a candidate target for in-depth research. Further, a rat model of DKD induced by a high-sugar, high-fat diet and streptozotocin was established to evaluate the pharmacological effects of CRT and verify the expression of related targets. The experimental results showed that CRT could effectively correct metabolic disturbances in DKD, restore immune-inflammatory balance, and improve renal function and its pathological changes by inhibiting the activation of the RAGE-ROS-PI3K-AKT-NF-κB-NLRP3 signaling axis. In conclusion, this study reveals that CRT alleviates the progression of DKD through dual regulation of metabolic reprogramming and immune-inflammatory responses, providing strong experimental evidence for its clinical application in DKD.
Animals ; Diabetic Nephropathies/metabolism* ; Receptor for Advanced Glycation End Products/genetics* ; NF-kappa B/genetics* ; Signal Transduction/drug effects* ; Rats ; NLR Family, Pyrin Domain-Containing 3 Protein/genetics* ; Proto-Oncogene Proteins c-akt/genetics* ; Drugs, Chinese Herbal/administration & dosage* ; Male ; Phosphatidylinositol 3-Kinases/genetics* ; Reactive Oxygen Species/metabolism* ; Humans ; Plant Roots/chemistry* ; Rats, Sprague-Dawley ; Tablets/administration & dosage*

Peptide-based radiopharmaceuticals targeting integrin α5β1 show promise for precise tumor diagnosis and treatment. However, current peptide-based radioligands that target α5β1 demonstrate inadequate in vivo performance owing to limited tumor retention. The use of PEGylation to enhance the tumor retention of radiopharmaceuticals by prolonging blood circulation time poses a risk of increased blood toxicity. Therefore, a PEGylation strategy that boosts tumor retention while minimizing blood circulation time is urgently needed. Here, we developed a PEGylation-enabled peptide multidisplay platform (PEGibody) for PR_b, an α5β1 targeting peptide. PEGibody generation involved PEGylation and self-assembly. [⁶⁴Cu]QM-2303 PEGibodies displayed spherical nanoparticles ranging from 100 to 200 nm in diameter. Compared with non-PEGylated radioligands, [⁶⁴Cu]QM-2303 demonstrated enhanced tumor retention time due to increased binding affinity and stability. Importantly, the biodistribution analysis confirmed rapid clearance of [⁶⁴Cu]QM-2303 from the bloodstream. Administration of a single dose of [¹⁷⁷Lu]QM-2303 led to robust antitumor efficacy. Furthermore, [⁶⁴Cu]/[¹⁷⁷Lu]QM-2303 exhibited low hematological and organ toxicity in both healthy and tumor-bearing mice. Therefore, this study presents a PEGibody-based radiotheranostic approach that enhances tumor retention time and provides long-lasting antitumor effects without prolonging blood circulation lifetime. The PEGibody-based radiopharmaceutical [⁶⁴Cu]/[¹⁷⁷Lu]QM-2303 shows great potential for positron emission tomography imaging-guided targeted radionuclide therapy for α5β1-overexpressing tumors.

Objective To explore the relationship between triglyceride-glucose index(TyG)and acute ischemic stroke with large vessel occlusion(AIS-LVO)of anterior circulation.Methods A retrospective study was conducted on patients with anterior circulation AIS-LVO who underwent emergency endovascular thrombectomy at Neurovascular Center of The First Affiliated Hospital of Naval Medical University from Jan.2018 to Dec.2019.According to modified Rankin scale(mRS)score 90 d after operation,the patients were assigned to favorable outcome group(mRS score 0-2)or unfavorable outcome group(mRS score 3-6),and the TyG was compared.According to the median of TyG,the patients were assigned to low-TyG group(TyG＜8.57)or high-TyG group(TyG ≥8.57),and the clinical data,laboratory indexes,and imaging characteristics were compared.Receiver operating characteristic curve was used to evaluate the predictive value of TyG for poor prognosis.Results A total of 135 patients were enrolled,with 72 in the favorable outcome group and 63 in the unfavorable outcome group.The TyG of the unfavorable outcome group was significantly higher than that of the favorable outcome group(8.82+0.63 vs 8.43+0.60,P＜0.001).There were 67 patients in the low-TyG group and 68 in the high-TyG group.Compared with the low-TyG group,the proportion of patients with hyperlipidemia history(P=0.003),systolic blood pressure at admission(P=0.018),fasting blood glucose level(P＜0.001),and triglyceride level(P＜0.001)were significantly higher in the high-TyG group,the infarct core volume was significantly larger(P=0.025),the high density lipoprotein-cholesterol level was significantly lower(P=0.013),and the mRS score 90 d after operation was significantly higher(3[1,5]vs 1[0,5],P=0.049).The TyG had certain predictive value for poor prognosis in anterior circulation AIS-LVO patients(area under curve value=0.662,95％confidence interval 0.571-0.753).Conclusion TyG is elevated in anterior circulation AIS-LVO patients with poor prognosis,and may be a potential prognostic indicator for anterior circulation AIS-LVO patients.

Endo-beta-N-acetylglucosaminidase (ENGase) is widely distributed in various organisms. The first reported ENGase activity was detected in Diplococcus pneumoniae in 1971. The protein (Endo D) was purified and its peptide sequence was determined in 1974. Three ENGases (Endo F1-F3) were discovered in Flavobacterium meningosepticum from 1982 to 1993. After that, the activity was detected from different species of bacteria, yeast, fungal, plant, mice, human, etc. Multiple ENGases were detected in some species, such as Arabidopsis thaliana and Trichoderma atroviride. The first preliminary crystallographic analysis of ENGase was conducted in 1994. But to date, only a few ENGases structures have been obtained, and the structure of human ENGase is still missing. The currently identified ENGases were distributed in the GH18 or GH85 families in Carbohydrate-Active enZyme (CAZy) database. GH18 ENGase only has hydrolytic activity, but GH85 ENGase has both hydrolytic and transglycosylation activity. Although ENGases of the two families have similar (β/α)8-TIM barrel structures, the active sites are slightly different. ENGase is an effective tool for glycan detection andglycan editing. Biochemically, ENGase can specifically hydrolyze β‑1,4 glycosidic bond between the twoN-acetylglucosamines (GlcNAc) on core pentasaccharide presented on glycopeptides and/or glycoproteins. Different ENGases may have different substrate specificity. The hydrolysis products are oligosaccharide chains and a GlcNAc or glycopeptides or glycoproteins with a GlcNAc. Conditionally, it can use the two products to produce a new glycopeptides or glycoprotein. Although ENGase is a common presentation in cell, its biological function remains unclear. Accumulated evidences demonstrated that ENGase is a none essential gene for living and a key regulator for differentiation. No ENGase gene was detected in the genomes of Saccharomyces cerevisiae and three other yeast species. Its expression was extremely low in lung. As glycoproteins are not produced by prokaryotic cells, a role for nutrition and/or microbial-host interaction was predicted for bacterium produced enzymes. In the embryonic lethality phenotype of the Ngly1-deficient mice can be partially rescued by Engase knockout, suggesting down regulation of Engase might be a solution for stress induced adaptation. Potential impacts of ENGase regulation on health and disease were presented. Rabeprazole, a drug used for stomach pain as a proton inhibitor, was identified as an inhibitor for ENGase. ENGases have been applied in vitro to produce antibodies with a designated glycan. The two step reactions were achieved by a pair of ENGase dominated for hydrolysis of substrate glycoprotein and synthesis of new glycoprotein with a free glycan of designed structure, respectively. In addition, ENGase was also been used in cell surface glycan editing. New application scenarios and new detection methods for glycobiological engineering are quickly opened up by the two functions of ENGase, especially in antibody remodeling and antibody drug conjugates. The discovery, distribution, structure property, enzymatic characteristics and recent researches in topical model organisms of ENGase were reviewed in this paper. Possible biological functions and mechanisms of ENGase, including differentiation, digestion of glycoproteins for nutrition and stress responding were hypothesised. In addition, the role of ENGase in glycan editing and synthetic biology was discussed. We hope this paper may provide insights for ENGase research and lay a solid foundation for applied and translational glycomics.

In this study, the effective substance group and molecular mechanism of Rhei Radix et Rhizoma-Persicae Semen combination (RRR-PS) in activating blood circulation and dispelling blood stasis were investigated by integrating efficacy experiments, network pharmacology and HPLC. The rat model of blood stasis syndrome was established, and the blood rheology index and coagulation four comprehensive evaluation were carried out. The results showed that compared with the model group, the whole blood viscosity, erythrocyte sedimentation rate and erythrocyte aggregation index of the rats in the RRR-PS group were significantly callback (P < 0.01). Network pharmacology found that RRR-PS combination exerted the effect of activating blood circulation and dispelling blood stasis by acting on calmodulin-1 (CALM1), nitric oxide synthase-2 (NOS2), glucocorticoid receptor (NR3C1) and other targets, regulating platelet activation, peroxisome proliferator-activated receptor (PPAR), vascular endothelial growth factor A (VEGF) and other signaling pathways, and found key components: sennoside B, (+)-catechin, emodin, physcion, rhein, aloe-emodin, chrysophanol, gallic acid. HPLC was used to explore the dissolution rate of key components. The results showed that the contents of catechin, emodin, chrysophanol and physcion were significantly increased after RRR-PS combination (P < 0.01). In summary, RRR-PS has a significant effect on promoting blood circulation and removing blood stasis, and its mechanism of action is related to promoting angiogenesis, anti-coagulation, anti-thrombosis and anti-inflammation. The efficacy is related to the change of solvent system and the large dissolution of catechin, emodin, chrysophanol and physcion after the RRR-PS combination. The results of the study can further provide a reference for the follow-up study on the active substances and mechanism of the RRR-PS combination. Animal experiments have been approved by the Experimental Animal Committee of Shaanxi University of Traditional Chinese Medicine (No. SUCMDL20210309002).

Objective:To summarize the characteristics of color doppler flow imaging (CDFI) of ocular toxocariasis (OT) in children.Methods:A retrospective clinical study. From July 2014 to June 2020, 61 OT patients with 61 eyes diagnosed through clinical and laboratory testing in the Department of Ophthalmology of Beijing Tongren Hospital of Capital Medical University were included in the study. There were 45 males with 45 eyes and 16 females with 16 eye (male: female=2.81:1). Age were (6.93±2.50) years. The right eye and left eye were 29 and 32 eyes, respectively. Both eyes of the patient underwent two-dimensional ultrasound and CDFI examination. Two dimensional ultrasound was used to estimate the axial length (AL) of the affected eyes and healthy eyes on the opposite side. Among them, 52 cases were measured for AL using optical biometry and/or A-mode ultrasound. Vitreoretinal surgery was performed within one week after ultrasound examination. Two-dimensional ultrasound was used to observe the morphology of vitreous opacity, its connection to the eyeball wall, and whether posterior vitreous detachment and retinal detachment have occurred. CDFI examination was used to observe the presence of blood flow signals on the pathological membrane. The detection rates of different forms of vitreous opacity and traction retinal detachment were calculated. The location of proliferative lesions in the eye was analyzed. Paired t-test was performed to compare the AL of the affected eye and the healthy eye on the opposite side. Perform Kappa consistency test on the location of proliferative lesions was used during CDFI examination and vitreoretinal surgery. Results:All affected eyes have varying degrees of vitreous opacity. Among them, 23 eyes (37.7%, 23/61) showed typical "Christmas tree" like turbidity; 27 eyes (44.3%, 27/61) had clustered and striped echoes; 9 eyes (14.8%, 9/61) had weak punctate and strip echoes. Two eyes (3.3%, 2/61) showed a large amount of dense punctate and strip-shaped echoes. There were 50 eyes (82.0%, 50/61) with traction retinal detachment, of which 46 eyes (92.0%, 46/50) had visible blood flow signals on the detached retina, and the remaining 4 eyes (8.0%, 4/50) had no blood flow signals. During CDFI and surgery, there were 5 (8.2%, 5/61) and 4 (6.6%, 4/61) eyes with visible proliferative lesions in the periphery, respectively; 18 (29.5%, 18/61) and 14 (23.0%, 14/61) eyes were distributed in the posterior pole, respectively; there were 38 (62.3%, 38/61) and 43 (70.5%, 43/61) eyes with both peripheral and posterior polar regions, respectively. The consistency between CDFI and surgery in detecting the location of proliferative lesions was good ( κ=0.832, 95% confidence interval 0.691-0.973, P<0.001). The two-dimensional ultrasound measurement results showed that the AL of the affected eye was shorter than that of the contralateral healthy eye in 46 cases (75.4%, 46/61). Among the 52 patients who underwent AL biometry, the AL of the affected eye was shorter than that of the contralateral healthy eye by (0.63±0.68) mm, and the difference was statistically significant ( t=-6.738, P<0.05). Conclusions:CDFI can clearly display various intraocular lesions (vitreous opacity and traction retinal detachment) and eyeball sizes in children with OT. Vitreous opacity is often manifested as "Christmas tree" like, clustered, strip-shaped.