Sangjuyin， as a pungent and cooling agent with precise therapeutic effect， is a classic pungent formula for cooling relief of the epidermis， which is highly respected by medical practitioners. This formula is from the Wenbing Tiaobian written by WU Jutong in the Qing dynasty， on the basis of which subsequent medical practitioners have made additions and subtractions to apply it. The authors used the bibliometric method to systematically organize the medical books from the Qing dynasty and the Republic of China and modern literature to analyze the composition， concoction， decoction， efficacy， and previous and modern application of Sangjuyin. After examination， the drug base of this formula is basically clear. Armeniacae Semen Amarum is the dried mature seeds of Armeniaca vulgaris， family Rosaceae. Forsythiae Fructus is the dried fruit of Forsythia suspensa， family Mulleinaceae. Menthae Haplocalycis Herba is the dried above-ground part of Mentha haplocalyx， family Labiatae. Mori Folium is the dried leaves of Morus alba， family Moraceae. Chrysanthemi Flos is the dried head of Chrysanthemum morifolium， family Asteraceae. Platycodonis Radix is the dried root of Eryngium grandiflorum， family Eryngium. Glycyrrhizae Radix et Rhizoma is the dried root and rhizome of Glycyrrhiza uralensis of the Leguminosae family， and Phragmitis Rhizoma is the fresh or dried rhizome of Phragmites communis of the Gramineae family. It is recommended that the eight drugs be used in raw form as medicine. The dosage and method of decoction were converted into a modern single dosage of 7.46 g Armeniacae Semen Amarum， 5.60 g Forsythiae Fructus， 2.98 g Menthae Haplocalycis Herba， 9.33 g Mori Folium， 3.73 g Chrysanthemi Flos， 7.46 g Platycodonis Radix， 2.98 g Glycyrrhizae Radix et Rhizoma， and 11.19 g Phragmitis Rhizoma， with 400 mL water added， and the solution was boiled to obtain 200 mL， taken twice a day. Sangjuyin has the efficacy of dispersing wind and clearing heat， promoting lung and relieving cough， and it is used for treating the initial onset of wind-warmth and the evidence of evil spirits in the lungs and collaterals. Modern research has shown that Sangjuyin is often used in the treatment of cough， pneumonia， rhinitis， and other respiratory diseases， and the results of this study provide a reference for the later development of Sangjuyin.

OBJECTIVE To study the ameliorative effect and mechanism of Forsythia suspensa-Lonicera japonica herb pair on acute lung injury （ALI） based on serum exosomal microRNA （miRNA）. METHODS The rats were randomly divided into a blank group （normal saline）， model group （nomal saline）， and F. suspensa-L. japonica herb pair group （2.55 g/kg）， with 10 rats in each group. Except for the blank group， the other groups were used to establish an ALI model by intratracheal dripping of 5 mg/ mL lipopolysaccharides. After modeling， each group was given relevant medicine/normal saline intragastrically， once a day， for 3 consecutive days. After the last medication， the pathological status of lung tissue was observed； lung wet-to-dry weight ratio and leukocyte counts in bronchoalveolar lavage fluid （BALF） were determined. The levels of inflammatory factors [tumor necrosis factor-α（TNF-α）， interleukin-1β （IL-1β）， IL-10] in BALF were determined. Exosomes were isolated from rat serum， and high- throughput sequencing technology was employed to screen differentially expressed miRNA within the exosomes， followed by Kyoto Encyclopedia of Genes and Genomes （KEGG） enrichment analysis. Based on the screened differentially expressed miRNA and the enriched KEGG pathways， in vitro cellular experiments were conducted for validation. RESULTS The animal experimental results demonstrated that after intervention with the F. suspensa-L. japonica herb pair， the wet-to-dry weight ratio， the number of leukocytes in BALF， as well as the levels of TNF-α and IL-1β in BALF of ALI rats were all significantly reduced （P＜0.01）， while the level of IL-10 was significantly increased （P＜0.01）. The results of high-throughput sequencing experiments revealed that the F. suspensa-L. japonica herb pair could significantly up-regulate the expressions of miR-345-3p， miR-194-5p， miR-653-5p， and others in exosomes. Among them， the KEGG pathways involved in the target genes of differentially expressed miRNA included the hypoxia-inducible factor-1（HIF-1） signaling pathway， among others. The results of cellular E-mail：huang.haiying@126.com validation experiments showed that overexpressed miR-345-3p could significantly elevate the level of IL-10 in the cell supernatant （P＜0.01）， while significantly reducing the levels of TNF-α and IL-1β in the cell supernatant， as well as the mRNA and protein expression levels of protein kinase B1， phosphatidylinositol 3- kinase， and HIF-1α （P＜0.01）. CONCLUSIONS F. suspensa-L. japonica herb pair can alleviate inflammatory responses and thereby exert a therapeutic effect in improving ALI by up-regulating the expression of miR-345-3p in serum exosomes and inhibiting the activity of the HIF-1 signaling pathway.

Coronary heart disease is a cardiovascular disease that affects coronary arteries. It presents high incidence and high mortality worldwide, bringing a serious threat to human health and quality of life. Salviae Miltiorrhizae Radix et Rhizoma derived from Salvia miltiorrhiza is widely used in the treatment of cardiovascular diseases, such as coronary heart disease. Salvianolic acid B is an active component in Salviae Miltiorrhizae Radix et Rhizoma extracts, and studies have shown that it has anti-inflammatory, antioxidant, apoptosis-and autophagy-regulating, anti-fibrosis, and metabolism-modulating effects. This article reviews the research progress regarding the therapeutic effect of salvianolic acid B on coronary heart disease in the recent decade. It elaborates on the role and mechanism of salvianolic acid B in treating coronary heart disease from multiple perspectives, such as the inhibition of thrombosis, improvement of blood circulation, reduction of myocardial cell injury, and inhibition of cardiac remodeling. This article provides a theoretical basis for the application of Chinese medicinal materials and TCM prescriptions containing salvianolic acid B in the treatment of coronary heart disease.
Humans ; Benzofurans/administration & dosage* ; Coronary Disease/genetics* ; Drugs, Chinese Herbal/administration & dosage* ; Salvia miltiorrhiza/chemistry* ; Animals ; Depsides

Forsythia suspensa is a traditional Chinese medicine and a commonly used landscaping plant. Its dried fruit is used in medicine for its functions of clearing heat, removing toxins, reducing swelling, dissipating masses, and dispersing wind and heat. It possesses extremely high medicinal and economic value. However, the genetic differentiation and diversity of its wild populations remain unclear. In this study, chloroplast genome sequences were obtained from 15 wild individuals of F. suspensa using high-throughput sequencing technology. The sequence characteristics and intraspecific variations were analyzed. The results were as follows:(1) The full length of the F. suspensa chloroplast genome ranged from 156 184 to 156 479 bp, comprising a large single-copy region, a small single-copy region, and two inverted repeat regions. The chloroplast genome encoded a total of 132 genes, including 87 protein-coding genes, 37 tRNA genes, and 8 rRNA genes.(2) A total of 166-174 SSR loci, 792 SNV loci, and 63 InDel loci were identified in the F. suspensa chloroplast genome, indicating considerable genetic variation among individuals.(3) Population structure analysis revealed that F. suspensa could be divided into five or six groups. Both the population structure analysis and phylogenetic reconstruction results indicated significant genetic variation within the wild populations of F. suspensa, with no obvious correlation between intraspecific genetic differentiation and geographical distribution. This study provides new insights into the genetic diversity and differentiation within F. suspensa species and offers additional references for the conservation of species diversity and the utilization of germplasm resources in wild F. suspensa.
Genome, Chloroplast ; Forsythia/classification* ; Phylogeny ; Genetic Variation ; Chloroplasts/genetics* ; Microsatellite Repeats

To explore the common irritant components in different base sources of Polygonati Rhizoma(PR). A rabbit eye irritation experiment was conducted to compare the irritant effects of raw products of Polygonatum kingianum, P. officinale, and P. multiflorum. The irritant effects of different solvent extraction parts and needle crystals of PR were compared, and the irritant components were screened. The morphology and structure of the purified needle crystal of PR were observed by microscope and scanning electron microscope and characterized by X-ray diffraction. Rabbit eye irritation and mouse abdominal inflammation model were used to evaluate rabbit eye irritation scores, inflammatory mediators, inflammatory factors levels in the peritoneal exudate of mice, with the peritoneal pathological section used as indicators. The inflammatory effect of needle crystals of PR was studied, and the content of calcium oxalate in three kinds of PR was determined by HPLC. The common protein in three kinds of PR was screened and compared by double enzymatic hydrolysis in solution combined with mass spectrometry. The results showed that three kinds of PR raw products had certain irritant effects on rabbit eyes, among which P. kingianum had the strongest irritant effect. There were no obvious irritant effects in the different solvent extraction parts of P. kingianum. Compared with the blank group, the needle crystal of PR had a significant irritant effect on rabbit eyes, and the inflammatory mediators and inflammatory factors in the peritoneal exudate were significantly increased(P<0.05) in a dose-dependent manner. Meanwhile, the peritoneal tissue of mice was damaged with significant inflammatory cell infiltration after intraperitoneal injection of needle crystal, indicating that needle crystal had an inflammatory effect. Microscope and scanning electron microscope observations showed that the needle crystals of PR were slender, with a length of about 100-200 μm and sharp ends. X-ray diffraction analysis showed that the needle crystals of PR were calcium oxalate monohydrate crystals. The results of HPLC showed that the content of calcium oxalate in P. kingianum was the highest among the three kinds of PR. It was speculated that the content of needle crystal in P. kingianum was higher than that in P. officinale and P. multiflorum, which was consistent with the results of the rabbit eye irritation experiment. The results of mass spectrometry showed that ribosome inactivating protein and mannose/sialic acid binding lectin were related to inflammation and cell metabolism in all three kinds of PR. There was no obvious irritant effect in different solvent extracts of PR. The calcium oxalate needle crystal contained was the main irritant component of PR, and three kinds of PR contained common ribosome inactivating protein and mannose/sialic acid binding lectin, which may be related to the inflammatory irritant effect of PR.
Animals ; Rabbits ; Mice ; Polygonatum/chemistry* ; Drugs, Chinese Herbal/toxicity* ; Rhizome/chemistry* ; Male ; Eye/drug effects* ; Female ; Humans

OBJECTIVE: To explore the current research status and hotspots in the field of biomechanics of diabetic foot by bibliometric analysis methods. METHODS: Literatures related to biomechanics of diabetic foot published in the Web of Scienc Core Collection (WoSCC) from 1981 to 2024 were searched. CiteSpace software and R language bibliometrics plugin were used to conduct a visual analysis of annual publication volume of the literature, including publication volume of each country and region, the publication situation of authors and institutions, the citation situation of individual literature, and the co-occurrence network of keywords. RESULTS: Totally 996 literatures were included, and the number of published papers increased steadily. The United States (261 papers) and China (89 papers) were the top two countries in terms of the number of published papers. The mediating centrality of the United States was 0.94, and that of China was 0.01. Scholars such as Cavanagh and institutions like the Cleveland Clinic were at the core of research in this field. High-frequency keywords include plantar pressure (plantar pressure), diabetic foot (diabetic foot), ulceration (ulcer), etc. The research focuses on plantar pressure, ulcer formation and prevention, etc. CONCLUSION Biomechanical research on diabetic foot mainly focuses on the pressure distribution on the sole of the foot, callus formation, mechanical analysis of soft tissues on the sole of the foot, and the study of plantar decompression caused by Achilles tendon elongation. The research trend has gradually shifted from focusing on joint range of motion to gait and the design of braces and assistive devices, and has begun to pay attention to muscle strength, gait imbalance and proprioception abnormalities.
Humans ; Diabetic Foot/physiopathology* ; Biomechanical Phenomena ; Bibliometrics

Ischemic stroke (IS) is a globally life-threatening disease. Presently, few therapeutic medicines are available for treating IS, and rt-PA is the only drug approved by the US Food and Drug Administration (FDA) in the US. In fact, many agents showing excellent neuroprotection but no blood flow-improving activity in animals have not achieved ideal clinical efficacy, while thrombolytic drugs only improving blood flow without neuroprotection have limited their wider application. To address these challenges and meet the huge unmet clinical need, we have designed and identified a novel compound AAPB with dual effects of neuroprotection and cerebral blood flow improvement. AAPB significantly reduced cerebral infarction and neural function deficit in tMCAO rats, pMCAO rats, and IS rhesus monkeys, as well as displayed exceptional safety profiles and excellent pharmacokinetic properties in rats and dogs. AAPB has now entered phase I of clinical trials fighting IS in China.

Disrupted bone morphogenetic protein type 2 receptor (BMPR2) signaling in endothelial cells drives pulmonary arterial hypertension (PAH). However, targeted recovery of this signaling pathway by lipid nanoparticles (LNPs) has not been explored as a therapy. Here, we employed Design of Experiments to optimize the delivery efficiency of LNPs targeting pulmonary endothelial cells developed by our laboratory, resulting in a remarkable 35-fold increase in a simplified three-component formulation without helper lipids. Administration of BMPR2 mRNA LNPs effectively reversed established PAH in two experimental rat models (monocrotaline or SU5416-hypoxia) by reversing pulmonary vascular remodeling. Specifically, BMPR2 mRNA LNPs replenished the expression of BMPR2 protein and subsequently activated downstream pathways, as confirmed by elevated levels of p-SMAD1/5/9 and ID1 proteins. The relief of pulmonary arterial occlusion was demonstrated by thinned pulmonary arterial media and decreased proportion of full muscularized vessels. Alleviation of right ventricular hypertrophy was indicated by declined Fulton index, the cross-sectional area of right ventricular cardiomyocytes as well as collagen deposition. Effective recovery of right ventricular function was evidenced by increased pulmonary artery flow acceleration time/pulmonary artery flow ejection time ratio. These findings underscore the potential of restoring BMPR2 signaling through pulmonary endothelial cell-specific LNPs for treating PAH.

OBJECTIVES: To investigate the structural changes of rat thoracic aorta and changes in expression levels of Bmal1 and cyclins in thoracic aorta endothelial cells following heat stress. METHODS: Twenty male SD rats were randomized equally into control group and heat stress group. After exposure to 32 ℃ for 2 weeks in the latter group, the rats were examined for histopathological changes and Bmal1 expression in the thoracic aorta using HE staining and immunohistochemistry. In the cell experiments, cultured rat thoracic aortic endothelial cells (RTAECs) were incubated at 40 ℃ for 12 h with or without prior transfection with a Bmal1-specific small interfering RNA (si-Bmal1) or a negative sequence. In both rat thoracic aorta and RTAECs, the expressions of Bmal1, the cell cycle proteins CDK1, CDK4, CDK6, and cyclin B1, and apoptosis-related proteins Bax and Bcl-2 were detected using Western blotting. TUNEL staining was used to detect cell apoptosis in rat thoracic aorta, and the changes in cell cycle distribution and apoptosis in RTAECs were analyzed with flow cytometry. RESULTS: Compared with the control rats, the rats exposed to heat stress showed significantly increased blood pressures and lowered heart rate with elastic fiber disruption and increased expressions of Bmal1, cyclin B1 and CDK1 in the thoracic aorta (P<0.05). In cultured RTAECs, heat stress caused significant increase of Bmal1, cyclin B1 and CDK1 protein expression levels, which were obviously lowered in cells with prior si-Bmal1 transfection. Bmal1 knockdown also inhibited heat stress-induced increase of apoptosis in RTAECs as evidenced by decreased expression of Bax and increased expression of Bcl-2. CONCLUSIONS Heat stress upregulates Bmal1 expression and causes alterations in expressions of cyclins to trigger apoptosis of rat thoracic aorta endothelial cells, which can be partly alleviated by suppressing Bmal1 expression.
Animals ; ARNTL Transcription Factors/genetics* ; Male ; Aorta, Thoracic/metabolism* ; Rats ; Rats, Sprague-Dawley ; Endothelial Cells/metabolism* ; Apoptosis ; Cells, Cultured ; Heat-Shock Response ; Cyclin B1/metabolism* ; CDC2 Protein Kinase/metabolism* ; Cyclins/metabolism* ; RNA, Small Interfering ; bcl-2-Associated X Protein/metabolism*

During the hyperacute phase of intracerebral hemorrhage (ICH), the mass effect and blood components mechanically lead to brain damage and neurotoxicity. Our findings revealed that the mass effect and transferrin precipitate neuronal oxidative stress and iron uptake, culminating in ferroptosis in neurons. M6A (N6-methyladenosine) modification, the most prevalent mRNA modification, plays a critical role in various cell death pathways. The Fto (fat mass and obesity-associated protein) demethylase has been implicated in numerous signaling pathways of neurological diseases by modulating m6A mRNA levels. Regulation of Fto protein levels in neurons effectively mitigated mass effect-induced neuronal ferroptosis. Applying nanopore direct RNA sequencing, we identified voltage-dependent anion channel 3 (Vdac3) as a potential target associated with ferroptosis. Fto influenced neuronal ferroptosis by regulating the m6A methylation of Vdac3 mRNA. These findings elucidate the intricate interplay between Fto, Vdac3, m6A methylation, and ferroptosis in neurons during the hyperacute phase post-ICH and suggest novel therapeutic strategies for ICH.
Ferroptosis/physiology* ; Alpha-Ketoglutarate-Dependent Dioxygenase FTO/genetics* ; Animals ; Neurons/metabolism* ; Transferrin/pharmacology* ; Mice ; Methylation ; Mice, Inbred C57BL ; Adenosine/metabolism* ; RNA, Messenger/metabolism* ; Male ; Oxidative Stress/physiology*