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The ancient Ginkgo biloba tree grows across various regions, with distinctive leaves emitting a unique fragrance. Its extract contains flavonoids, organic acids, and terpenoids. Ginkgolide and bilobalide, which are G. biloba leaf extracts, offer diverse pharmaceutical benefits, including antioxidant, anti-inflammatory, and neuroprotective properties. The antioxidant and anti-inflammatory properties of these compounds are crucial for mitigating neurodegeneration, particularly in diseases such as Alzheimer's disease. Additionally, their effectiveness in countering oxidative stress and inflammation highlights their potential to prevent cardiovascular ailments. This study also suggests that these compounds have a promising impact on lipid metabolism, suggesting their significance in addressing obesity-related metabolic disorders. In conclusion, ginkgolides and bilobalide exhibit promising effects in sustaining the integrity of the nervous and endocrine systems, along with the modulation of lipid metabolism. The diverse health benefits suggest that these compounds could serve as promising therapeutic interventions for various conditions, including neurological, cardiovascular, and metabolic diseases.

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BACKGROUND: In healthy individuals, blood flow restriction training (BFRT) has shown positive effects on muscle mass, strength, fatigue resistance, as well as tendon and bone metabolism. BFRT reduces blood flow in the extremities using inflatable cuffs, creating local muscular hypoxia, which produces an anabolic metabolic environment. This promotes significant muscular and cardiovascular adaptations even at low mechanical training loads. KNEE ENDOPROSTHESES: BFRT also shows promising initial results in pre- and postoperative applications for knee endoprostheses (KTEP). Both preoperative and postoperative BFRT can improve muscle strength and joint function, accelerate recovery, and alleviate pain. Although the method is generally safe, potential risks such as discomfort and rare side effects must be considered. Clear application protocols are still lacking, necessitating further research and individualized programs to achieve optimal training effects. BFRT thus offers an innovative way to effectively rehabilitate patients despite their low load tolerance.

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AIM: The aim of this study is to assess early wound healing expression of local angiogenic biomarkers following connective tissue graft (CTG) at dental implant sites. METHODS: Twenty-eight subjects with single dental implants exhibiting a soft tissue dehiscence were included and randomly treated with CTG, either with coronally advanced flap (CAF) or with tunnel technique (TUN). Peri-implant crevicular fluid (PICF) was collected at the midfacial and midlingual aspect of the implant sites at baseline and at 3, 7, 14, 30, and 90 days after the surgical intervention. The expression of angiogenin (ANG), fibroblast growth factor-2 (FGF-2), platelet-derived growth factor (PDGF), tissue inhibitor of metalloproteinases-2 (TIMP-2), and vascular endothelial growth factor (VEGF) was investigated over a period of 3 months. Patient-reported outcomes, clinical measurements, and ultrasonography scans at multiple time points were also evaluated. RESULTS: The longitudinal regression revealed a significant difference in the expression of VEGF and TIMP-2 between CAF- and TUN-treated sites over 3 months (p = .033 and p = .004, respectively), whereas no significant differences were observed for ANG, FGF-2 and PDGF between the two groups. At 7 days, a direct correlation was observed between ANG levels and ultrasonographic color velocity in the CAF group (p < .001) and between ANG levels and ultrasonographic color power in the TUN group (p = .028). VEGF levels and ultrasonographic mean perfused area of the CTG were significantly correlated at the 7-day time point (p < .001 for both CAF and TUN). The expression of VEGF at 7 days was directly associated with mucosal thickness gain at 1 year (p < .001 for both groups). Early TIMP-2 expression showed an inverse correlation with time to recovery (p = .002). TIMP-2 levels at 3 months exhibited inverse correlations with mean dehiscence coverage (p = .004) and the rate of complete dehiscence coverage (p = .012). CONCLUSION: PICF biomarkers can be used to monitor early wound healing events following soft tissue grafting at implant sites. VEGF and TIMP-2 showed correlations with the 1-year clinical and volumetric outcomes, as well as with post-operative patient-reported outcomes and Doppler Ultrasonographic tissue perfusion-related parameters.

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Background: Traditional Chinese medicine injections with invigorating blood circulation (TCMI-IBCs), which have been used as antithrombosis therapies, are widely employed by Chinese clinicians as adjuvant therapy for acute myocardial infarction (AMI). Objective: A Bayesian network meta-analysis was conducted to contrast the effectiveness and safety of four TCMI-IBCs in AMI. Methods: Eight Databases were thoroughly searched before 31 December 2023, for randomized controlled trials (RCTs) focusing on the application of TCMI-IBCs combined with conventional treatments (CT) to treat AMI. All-cause mortality (ACM) was the major endpoint. Secondary outcomes included bleeding events, malignant arrhythmia (MA), recurrent myocardial infarction (RMI), left ventricular ejection fraction (LVEF), and adverse events. Stata17.0 and GeMTC software were employed for Bayesian network meta-analysis. Results: A total of 73 eligible RCTs involving 7,504 patients were enrolled. Puerarin injection (PI), Danhong injection (DI), sodium Tanshinone IIA Sulfonate injection (STSI), and Danshen Chuanxiongqin injection (DCI) combined with CT can significantly reduce the occurrence of ACM and improve LVEF in AMI (P < 0.05), while without significant impact on bleeding events or MA (P > 0.05). STSI + CT would be the optimal treatment strategy in lowering RMI and ACM. DI + CT was the most likely to be the optimal strategy in reducing MA occurrence and improving LVEF. CT was likely the most effective strategy in reducing bleeding events. However, DI + CT exhibited the least favorable safety. Conclusion: TCMI-IBCs + CT had potential benefits in the treatment of AMI. STSI + CT showed the most favorable performance in treating AMI, followed by DI combined with CT. Systematic Review Registration: https://www.crd.york.ac.uk/PROSPERO/display_record.php?RecordID=384067, identifier CRD42022384067.

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BACKGROUND: Extracorporeal membrane oxygenation (ECMO) is a new type of extracorporeal respiratory and circulatory assistance device. It can drain venous blood out of the body and inject it into veins or arteries after being oxygenated by an oxygenator (membrane lung) to replace lung and heart functions in a short time. ECMO can provide tissue blood perfusion and gas exchange almost equivalent to cardiac output and extend the effective treatment time window for patients with acute circulatory failure to restore cardiopulmonary function. CASE SUMMARY: We report a case of an 81-year-old woman who underwent whole cerebral angiography, basilar artery thrombectomy and stent thrombectomy in the posterior artery of the left brain after implantation of ECMO. The patient was admitted to the hospital due to myocardial infarction. Considering that the cause of the patient's disturbance of consciousness was unknown and cerebrovascular accident could not be ruled out after the implantation of ECMO, the department of Radioactive Intervention performed cerebral angiography. And the result of the angiography indicated vascular occlusion. After the basilar artery thrombectomy and stent thrombectomy in the posterior artery of the left brain, the patency of the occlusive vessel was achieved. CONCLUSION: Although the patient eventually died of circulatory failure, the result of this case verifies the feasibility of cerebral angiography and thrombectomy in patients with implanted ECMO in the intubated state.

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Whereas medical practice stems from Hippocrates, cardiovascular science originates with Aristotle. The Hippocratic philosophy was championed by Galen (129-216 CE), whose advocacy of a tripartite soul found favor in the early Christian Church. In contrast, Aristotle's works were banned as heresy by ecclesiastical authority, only to survive and prosper in the Islamic Golden Age (775-1258 CE). Galen theorized that the circulation consisted of separate venous and arterial systems. Blood was produced in the liver and traveled centrifugally through veins. When arriving in the right ventricle, venous blood passed through tiny pores in the ventricular septum into the left ventricle, where it became aerated by air passing from the lungs through the pulmonary veins to the left side of the heart. Following arrival at distal sites, arterial blood disappeared, being consumed by the tissues, requiring that the liver needed to continually synthesize new blood. The heart was viewed as a sucking organ, and the peripheral pulse was deemed to result from changes in arterial tone, rather than cardiac systole. Galen's framework remained undisputed and dominated medical thought for 1,300 years, but the reintroduction of Aristotelian principles from the Islamic world into Europe (through the efforts of the Toledo School of Translators) were nurtured by the academic freedom and iconoclastic environment uniquely cultivated at the University of Padua, made possible by Venetian rebellion against papal authority. At Padua, the work of Andreas Vesalius, Realdo Colombo, Hieronymus Fabricius ab Acquapendente, and William Harvey (1543-1628) methodically destroyed Galen's model, leading to the modern concept of a closed-ended circulation. Yet, due to political forces, Harvey was ridiculed, as was James Lind, who performed the first prospective controlled trial, involving citrus fruits for scurvy (1747); it took nearly 50 years for his work to be accepted. Even the work of William Withering (1785), the father of cardiovascular pharmacology, was tarnished by professional jealously and the marketing campaign of a pharmaceutical company. Today's cardiovascular investigators should understand that major advances are routinely derided by the medical establishment for political or personal reasons; and it may take decades or centuries for important work to be accepted.

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Purpose: We aimed to assess uterine and arcuate artery Doppler indices in patients with mild primary dysmenorrhea. Patients and Methods: A total of 55 patients were included, consisting of women without dysmenorrhea (n=26, group A) and women with mild primary dysmenorrhea (n=29, group B). Doppler measurements of the uterine and arcuate arteries were performed in both groups on the 1st-2nd days and 21st-24th days (midluteal phase) of the menstrual cycle using transvaginal ultrasound and compared between the groups. The severity of dysmenorrhea was assessed using visual analog scale scores. Results: Doppler measurements of the uterine and arcuate arteries performed on the 1st-2nd days of the menstrual cycle and the midluteal phase were similar between the groups (p>0.05). There was a significant decrease in the intragroup measurements of uterine and arcuate arteries performed on the first day of menstruation and the luteal phase in both groups (p<0.01). Conclusion: Doppler findings of the uterine and arcuate arteries did not differ between patients with and without mild primary dysmenorrhea. The etiology of primary dysmenorrhea mainly involves ischemia and vasoconstriction, but mild primary dysmenorrhea appears to be associated with a different etiology other than decreased tissue perfusion.

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BACKGROUND: Despite the known interplay between blood flow and function, to our knowledge, there is currently no minimally invasive method to monitor diaphragm hemodynamics. We used contrast-enhanced ultrasound to quantify relative diaphragm blood flow (Q˙DIA) in humans and assessed the technique's efficacy and reliability during graded inspiratory pressure threshold loading. We hypothesized that: (1) Q˙DIA would linearly increase with pressure generation, and (2) that there would be good test-retest reliability and interanalyzer reproducibility. RESEARCH QUESTION: Can we validate what is, to our knowledge, the first minimally invasive method to measure relative diaphragm blood flow in humans? STUDY DESIGN AND METHODS: Quantitative contrast-enhanced ultrasound of the costal diaphragm was performed in healthy participants (10 male participants, 6 female participants; mean age 28 ± 5 years; BMI 22.8 ± 2.0 kg/m) during unloaded breathing and three stages of loaded breathing on two separate days. Gastric and esophageal balloon catheters measured transdiaphragmatic pressure. Ultrasonography was performed during a constant-rate IV infusion of lipid-stabilized microbubbles following each stage. Ultrasound images were acquired after a destruction-replenishment sequence and diaphragm specific time-intensity data were used to determine Q˙DIA by two individuals. RESULTS: Transdiaphragmatic pressure for unloaded and each loading stage were 15.2 ± 0.8, 26.1 ± 0.8, 34.6 ± 0.8, and 40.0 ± 0.8 percentage of the maximum, respectively. Q˙DIA increased with each stage of loading (3.1 ± 3.1, 6.9 ± 3.6, 11.0 ± 4.9, and 13.5 ± 5.4 acoustic units/s; P < .0001). The linear relationship between diaphragmatic flow and pressure was reproducible from day to day. Q˙DIA had good to excellent test-retest reliability (0.86 [0.77, 0.92]; P < .0001) and excellent interanalyzer reproducibility (0.93 [0.90, 0.95]; P < .0001) with minimal bias. INTERPRETATION: Relative Q˙DIA measurements had valid physiological underpinnings, were reliable day-to-day, and were reproducible analyzer-to-analyzer. This study indicated that contrast-enhanced ultrasound is a viable, minimally invasive method for assessing costal Q˙DIA in humans and may provide a tool to monitor diaphragm hemodynamics in clinical settings.

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OBJECTIVES: Anastomotic leakage in esophageal cancer surgery may be reduced by evaluating the blood flow to the reconstructed organ, but quantitative evaluation of arterial and venous blood flow is difficult. This study aimed to quantitatively assess blood flow using a new technique, as well as determine the relationship between the blood flow in the gastric tube and anastomotic leakage using near-infrared spectroscopy. METHODS: This single-center, observational study included 50 patients aged 51-82 years who underwent radical esophagectomy with gastric tube reconstruction for esophageal cancer between June 2022 and January 2023. Regional tissue oxygen saturation was measured at the antrum (point X), the anastomotic point (point Z), and the midpoint between points X and Z (point Y) before and after gastric tube formation. These three points of oxygen saturation were investigated in relation to anastomotic leakage. RESULTS: When comparing the presence of leakage to its absence, regional tissue oxygen saturation at points X and Z after gastric tube formation was significantly lower (X: p = 0.03, Z: p = 0.02), with the decreasing rate significantly higher at point Z (p = 0.01). There was no significant difference in the decreasing rate of regional tissue oxygen saturation between points X and Y (X: p = 0.052, Y: p = 0.83). CONCLUSION: Regional tissue oxygen saturation levels may be useful for measuring blood flow and could be a predictor of anastomotic leakage.

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Introduction: Both intracranial pressure (ICP) and cerebral arterial blood volume (CaBV) have a pulsatile character related to the cardiac cycle. The evolution of the shape of ICP pulses under increasing ICP or decreasing intracranial compliance is well documented. Nevertheless, the exact origin of the alterations in the ICP morphology remains unclear. Research question: Does ICP pulse waveform become similar to non-invasively estimated CaBV pulse during ICP plateau waves. Material and methods: A total of 15 plateau waves recorded in 15 traumatic brain injured patients were analyzed. CaBV pulse waveforms were calculated using global cerebral blood flow model from transcranial Doppler cerebral blood flow velocity (CBFV) signals. The difference index (DI) was used to quantify the similarity between ICP and CaBV waveforms. DI was calculated as the sum of absolute sample-by-sample differences between ICP and CaBV waveforms, representing the area between the pulses. Results: ICP increased (19.4 mm Hg [Q1-Q3: 18.2-23.4 mm Hg] vs. 42.7 mm Hg [Q1-Q3: 36.5-45.1 mm Hg], p < 0.001) while CBFV decreased (44.2 cm/s [Q1-Q3: 34.8-69.5 cm/s] vs. 32.9 cm/s [Q1-Q3: 24.7-68.2 cm/s], p = 0.002) during plateau waves. DI was smaller during the plateau waves (20.4 [Q1-Q3: 15.74-23.0]) compared to the baselines (26.3 [Q1-Q3: 24.2-34.7], p < 0.001). Discussion and conclusion: The area between corresponding ICP and CaBV pulse waveforms decreased during the plateau waves which suggests they became similar in shape. CaBV may play a significant role in determining the shape of ICP pulses during the plateau waves and might be a driving force in formulating ICP elevation.

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Single biofilm biomimetic nanodrug delivery systems based on single cell membranes, such as erythrocytes and cancer cells, have immune evasion ability, good biocompatibility, prolonged blood circulation, and high tumor targeting. Because of the different characteristics and functions of each single cell membrane, more researchers are using various hybrid cell membranes according to their specific needs. This review focuses on several different types of biomimetic nanodrug-delivery systems based on composite biofilms and looks forward to the challenges and possible development directions of biomimetic nanodrug-delivery systems based on composite biofilms to provide reference and ideas for future research.

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Hypertension is the most common chronic disease in clinics and has become the most common risk factor for cardiovascular diseases. Because of its high incidence rate, disability rate, and mortality, it has attracted worldwide attention. Despite continuous progress in modern medicine in the treatment of hypertension with new antihypertensive drugs such as Zilebesiran, a nucleic acid drug that acts on microRNA, direct renin inhibitors, and renal sympathetic blockade, the control rate is still not ideal. How to effectively prevent and control hypertension has become one of the urgent clinical challenges to be solved. Traditional Chinese medicine(TCM) has a long record of treating hypertension and has accumulated rich experience, including theoretical understanding, effective single medicine, compound medicine, traditional Chinese patent medicines, and classic famous prescriptions. In TCM, hypertension belongs to the categories of diseases such as dizziness and headache. Previous literature and clinical studies have found that hypertension has key pathogenesis such as fire syndrome, fluid syndrome, deficiency syndrome, and blood stasis syndrome. Among them, the hyperactivity of liver Yang is closely related to blood pressure fluctuations, blood pressure variability, inflammation, and sympathetic activity stimulation. Internal obstruction by blood stasis is closely related to the damage of target organs such as the heart, brain, and kidneys in hypertension. Therefore, the two key pathogenesis of liver yang hyperactivity and internal obstruction by blood stasis run through the entire process of hypertension. Previous studies have found that the effective empirical formula Tianxiong Granules, based on the principles of suppressing Yang and promoting blood circulation, originated from the classic formula Xiongqiong Tianma Pills in Yu Yao Yuan Fang. It is composed of Gastrodiae Rhizoma, Chuanxiong Rhizoma, Puerariae Lobatae Radix, Achyranthis Bidentatae Radix, and Cyathulae Radix and has significant therapeutic effects in the treatment of hypertension. The clinical indications include headache, dizziness, bloating, strong neck, and weak waist and legs. At the same time, it may be accompanied by poor speech, thirst, normal or loose stools, soreness in the waist and legs, lower limb pain, muscle and pulse spasm, menstrual and abdominal pain, dark red tongue, strong pulse strings, or straight and long pulse strings that pass through the mouth of an inch. In the combination rule, it can be used according to the different pathogenesis stages of hypertension patients. In the fire syndrome stage, it is often combined with Tianma Gouteng Decoction and Chaihu Jia Longgu Muli Decoction. In the fluid syndrome stage, it is often combined with Banxia Baizhu Tianma Decoction. In the deficiency syndrome stage, it is often combined with Liuwei Dihuang Pills and Shenqi Pills. In terms of dosage, it is important to focus on the main symptoms and adjust the dosage of key drugs based on blood pressure values. Some drugs can be used in sufficient quantities. By analyzing the compatibility of Tianxiong Granules, clinical application indications, combined formula experience, and dosage application experience, we provide effective treatment methods and more options for TCM to treat hypertension with Yang hyperactivity and blood stasis syndrome.

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Polyethylene glycol (PEG) is a popular biocompatible polymer and PEGylated nanoparticles passively accumulate in tumor tissues because of their enhanced permeability and retention effects. Recently, the anti-PEG immunity of PEGylated nanoparticles has become an issue that needs to be solved for their clinical applications. Dendrimers are highly branched and well-defined polymers with many terminal groups, which act as potent drug carriers. In this study, we examined the pharmacokinetics, biodistribution, anti-PEG immunity, and tumor accumulation of a fully PEGylated polyamidoamine (PAMAM) dendrimer after the first and second injections and compared them to those of a PEGylated liposome with the same lipid component as Doxil®. The PEGylated dendrimer showed greater blood circulation than that of the PEGylated liposome after the first and second injections in rats. In mice injected with the PEGylated dendrimer, much less anti-PEG immunoglobulin M (IgM) was generated than that in mice injected with the PEGylated liposome. The PEGylated dendrimer accumulated in the tumor after both the first and second injections. Our results indicated that the PEGylated dendrimer with a small size and high PEG density showed attenuated anti-PEG immunity and overcame the accelerated blood clearance phenomenon, which is useful for drug delivery systems for cancer treatment.

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The occurrence of in-stent restenosis (ISR) poses a significant challenge for percutaneous coronary intervention (PCI). Thus, the promotion of vascular reendothelialization is essential to inhibit endothelial proliferation. In this study, we clarified the mechanism by which Detoxification and Activating Blood Circulation Decoction (DABCD) promotes vascular reendothelialization to avoid ISR by miRNA-126-mediated modulation of the vascular endothelial growth factor (VEGF) signaling pathway. A rat model of post-PCI restenosis was established by balloon injury. The injured aortic segment was collected 14 and 28 d after model establishment. Our findings indicate that on the 14th and 28th days following balloon injury, DABCD reduced intimal hyperplasia and inflammation and promoted vascular reendothelialization. Additionally, DABCD markedly increased nitric oxide (NO) expression and significantly decreased ET-1 production in rat serum. DABCD also increased the mRNA level of endothelial nitric oxide synthase (eNOS) and the protein expression of VEGF, p-Akt, and p-extracellular signal-regulated kinase (ERK)1/2 in vascular tissue. Unexpectedly, the expression of miR-126a-5p mRNA was significantly lower in the aortic tissue of balloon-injured rats than in the aortic tissue of control rats, and higher miR-126a-5p levels were observed in the DABCD groups. The results of this study indicated that the vascular reendothelialization effect of DABCD on arterial intimal injury is associated with the inhibition of neointimal formation and the enhancement of vascular endothelial activity. More specifically, the effects of DABCD were mediated, at least in part, through miR-126-mediated VEGF signaling pathway activation.

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Hormonal changes during the menopause transition may lead to vasomotor symptoms, including hot flashes (HFs) and neuropsychiatric symptoms such as anxiety and irritability. We hypothesized that the effects of cassis polyphenol (CaP) to improve microcirculation and vasorelaxation may alleviate menopausal symptoms. We performed a randomized, double-blind, parallel-group, placebo-controlled trial involving 59 healthy women (mean [standard deviation] age, 51.3 [4.3] years; body mass index, 20.8 [2.6] kg/m2). Participants experiencing subjective menopausal symptoms consumed CaP tablets (400 mg/d, CaP group) or placebo tablets (placebo group) for 4 weeks. Participants were evaluated using questionnaires at baseline, during the 4-week intervention period, and during a 2-week postinterventional observation period. The primary objective was to evaluate the effects of supplementation with CaP on HFs in healthy Japanese women with menopausal symptoms. Additional assessments included the modified Kupperman menopausal index, World Health Organization-5 Well-Being Index, World Health Organization quality-of-life 26-item index, State-Trait Anxiety Inventory (anxiety and trait components), and Oguri-Shirakawa-Azumi sleep inventory (middle-aged and elderly versions). During the 4-week intervention period, no significant between-group differences were detected in the HF frequency, HF score, sweating frequency, menopausal symptoms, quality of life, anxiety, or sleep. During the 2-week postintervention observational period, the HF score and sweating frequency were significantly decreased in the CaP group compared with the placebo group. These findings suggest that twice daily intake of CaP for 4 weeks does not alleviate menopause symptoms, but the improvement observed in the CaP intake group during the postintervention period warrants confirmation through further large-scale studies.

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BACKGROUND: Endothelial cells regulate their cell cycle as blood vessels remodel and transition to quiescence downstream of blood flow-induced mechanotransduction. Laminar blood flow leads to quiescence, but how flow-mediated quiescence is established and maintained is poorly understood. METHODS: Primary human endothelial cells were exposed to laminar flow regimens and gene expression manipulations, and quiescence depth was analyzed via time-to-cell cycle reentry after flow cessation. Mouse and zebrafish endothelial expression patterns were examined via scRNA-seq (single-cell RNA sequencing) analysis, and mutant or morphant fish lacking p27 were analyzed for endothelial cell cycle regulation and in vivo cellular behaviors. RESULTS: Arterial flow-exposed endothelial cells had a distinct transcriptome, and they first entered a deep quiescence, then transitioned to shallow quiescence under homeostatic maintenance conditions. In contrast, venous flow-exposed endothelial cells entered deep quiescence early that did not change with homeostasis. The cell cycle inhibitor p27 (CDKN1B) was required to establish endothelial flow-mediated quiescence, and expression levels positively correlated with quiescence depth. p27 loss in vivo led to endothelial cell cycle upregulation and ectopic sprouting, consistent with loss of quiescence. HES1 and ID3, transcriptional repressors of p27 upregulated by arterial flow, were required for quiescence depth changes and the reduced p27 levels associated with shallow quiescence. CONCLUSIONS: Endothelial cell flow-mediated quiescence has unique properties and temporal regulation of quiescence depth that depends on the flow stimulus. These findings are consistent with a model whereby flow-mediated endothelial cell quiescence depth is temporally regulated downstream of p27 transcriptional regulation by HES1 and ID3. The findings are important in understanding endothelial cell quiescence misregulation that leads to vascular dysfunction and disease.

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Siphons are devices that transport liquids uphill between two containers. It has been proposed that a siphon principle operates in closed circulatory systems, as best exemplified by the circulation of blood in mammals. This principle is supposed to ensure that no additional work is necessary to pump blood above the level of the heart, and that there is no gravitational static pressure gradient in the column of blood. The first statement is correct, while we demonstrate that, ignoring hydraulic resistance to blood flow, the static pressure gradient is equal to the hydrostatic gradient in a siphon model of blood circulation, although the details of the proof do not depend on the geometry of the circulatory system and the proof can be trivially extended to other models such as a vascular waterfall. This implies that the controversy over the siphon principle has no implications for the description of blood circulation, and that mechanisms such as the "baffle," which some authors have appealed to in order to obtain the expected gradient, are not necessary. In our discussion, we also discuss empirical data that appear to provide additional verification of our results, as well as several everyday occurrences that provide additional support.

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XRD diffraction and IR absorption were investigated for raw loess powder and heat-treated loess powder. Raw loess retains its useful minerals, but loses their beneficial properties when calcined at 850 °C and 1050 °C. To utilize the useful minerals, loess balls were made using a low-temperature wet-drying method. The radiant energy and transmittance were measured for the loess balls. Far-infrared ray (FIR) emitted from loess bio-balls is selectively absorbed as higher vibrational energy by water molecules. FIR can raise the body's core temperature, thereby improving blood flow through the body's thermoregulatory mechanism. In an exploratory study with 40 participants, when the set temperature of the loess ball mat was increased from 25 °C to 50 °C, blood flow increased by 39.01%, from 37.48 mL/min to 52.11 mL/min, in the left middle finger; in addition, it increased by 39.62%, from 37.15 mL/min to 51.87 mL/min, in the right middle finger. The FIR emitted from loess balls can be widely applied, in various forms, to diseases related to blood flow, such as cold hands and feet, diabetic foot, muscle pain, and menstrual pain.

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Hedgehog (Hh) signaling is crucial in cardiovascular development and maintenance. However, the biological role of Patched1 (Ptch1), an inhibitory receptor of the Hh signaling pathway, remains elusive. In this study, a Ptch1 ortholog was characterized in Nile tilapia (Oreochromis niloticus), and its function was investigated through CRISPR/Cas9 gene knockout. When one-cell embryos were injected with CRISPR/Cas9 targeting ptch1, the mutation efficiency exceeded 70%. During 0-3 days post fertilization (dpf), no significant differences were observed between the ptch1 mutant group and the control group; at 4 dpf (0 day after hatching), about 10% of the larvae showed an angiogenesis defect and absence of blood flow; from 5 dpf, most larvae exhibited an elongated heart, large pericardial cavity, and blood leakage and coagulation, ultimately dying during the 6-8 dpf period due to the lack of blood circulation. Consistently, multiple differentially expressed genes related to angiogenesis, blood coagulation, and heart development were enriched in the ptch1 mutants. Furthermore, Smoothened (Smo) antagonist (cyclopamine) treatment of the ptch1 mutants greatly rescued the cardiovascular disorders. Collectively, our study suggests that Ptch1 is required for cardiovascular development and vascular integrity via Smo signaling, and excessive Hh signaling is detrimental to cardiovascular development.

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