Heterogeneity in peripheral blood immune lymphocyte subsets predicts the response of immunotherapy or chemoradiotherapy in advanced lung cancer: an analysis across different pathological types, treatment modalities and age.

Background: The shaping of the tumor immune microenvironment does not only rely on tumor-infiltrating lymphocytes but on the recruitment of lymphocytes in peripheral blood. Monitoring peripheral blood lymphocyte subsets level (PBLSL) can predict treatment response and prognosis with immune checkpoint inhibitors. This study investigated the heterogeneity of PBLSL in response to chemoradiotherapy (CRT) or combined with immunotherapy (CRIT) in advanced lung cancer patients. Methods: 77 patients with advanced lung cancer receiving CRT or CRIT were divided into treatment-responsive and non-responsive groups based on efficacy. The study analyzed short-term efficacy and progression-free survival (PFS) according to baseline PBLSL and explored the impact under different stratifications, including treatment modality, pathology type, and age. Results: In all patients, higher levels of B cells, higher CD4+/CD8+ T cell ratios, and lower CD8+ T cell levels were associated with better short-term outcomes (P = 0.0035, P = 0.044, P = 0.022). Subgroup analysis revealed that in the CRT group, higher B cell levels correlated with improved efficacy (P = 0.011) and superior PFS (P = 0.048, HR = 0.3886, 95% CI = 0.1696 to 0.8902). In the CRIT group, higher CD4+ T cell levels, lower CD8+ T cell levels, and higher CD4+/CD8+ T cell ratios were linked to better efficacy (P = 0.038, P = 0.047, P = 0.017). For adenocarcinoma patients, higher CD4+/CD8+ T cell ratios and lower CD8+ T cell levels predicted better efficacy (P = 0.0155, P = 0.0119). B cell levels were significant in squamous cell carcinoma (P = 0.0291), while no PBLSL was predictive for small cell lung cancer. Among patients under 65, higher B cell levels were linked to improved efficacy and prolonged PFS (P = 0.0036, P = 0.0332, HR = 0.4111, 95% CI = 0.1973 to 0.8563). For patients over 65, differences in CD4+ T cell levels and CD4+/CD8+ T cell ratios were significant (P = 0.0433, P = 0.0338). Conclusion: PBLSL predicted efficacy and prognosis in various patient stratifications, suggesting PBLSL is a reliable predictor for CRT and CRIT in advanced lung cancer. Detecting different cellular subpopulations helps identify patients with significant treatment responses across different stratifications.

Real-time monitoring of small extracellular vesicles (sEVs) by in vivo flow cytometry.

Extracellular vesicles (EVs) are vesicular structures comprised of a bilayer lipid membrane, released by living cells. There is a growing body of evidence for their functionality, indicating that small EVs (sEVs) can mediate specific forms of intercellular communication. The future applications of sEVs hold great promise, not only as diagnostic markers but also as therapeutic agents. However, the greatest difficulty in the clinical translation of sEVs is that they are currently poorly understood, especially concerning their in vivo behaviour. In this study, we provide a novel method for monitoring sEVs in blood circulation based on in vivo flow cytometry (IVFC). We have demonstrated that the height of the IVFC signal baseline is proportional to the concentration of sEVs. Moreover, we have found out that the peaks in the IVFC signal are generated by the aggregation or cellular uptake of sEVs. In vivo monitoring of sEVs clearance from the blood indicates that PEGylated sEVs have a longer residence time and exhibit less aggregation in circulation compared to non-PEGylated sEVs. These studies reveal that IVFC enables real-time in vivo monitoring of circulating sEVs, which can provide valuable insights into the pharmacokinetics and cellular targeting capabilities of sEVs.

Comprehensive validation of a compact laser speckle contrast imaging system for vascular function assessment: from the laboratory to the clinic.

Proper organ functioning relies on adequate blood circulation; thus, monitoring blood flow is crucial for early disease diagnosis. Laser speckle contrast imaging (LSCI) is a noninvasive technique that is widely used for measuring superficial blood flow. In this study, we developed a portable LSCI system using an 805-nm near-infrared laser and a monochrome CMOS camera with a 10 × macro zoom lens. The system achieved a high-resolution imaging (1280 × 1024 pixels) with a working distance of 10 to 35 cm. The relative flow velocities were visualized via a spatial speckle contrast analysis algorithm with a 5 × 5 sliding window. In vitro experiments demonstrated the system's ability to image flow velocities in a fluid model, and a linear relationship was observed between the actual flow rate and the relative flow rate obtained by the system. The correlation coefficient (R2) exceeded 0.83 for volumetric flow rates of 0 to 0.2 ml/min when channel widths were greater than 1.2 mm, and R2 > 0.94 was obtained for channel widths exceeding 1.6 mm. Comparisons with laser Doppler flowmetry (LDF) revealed a strong positive correlation between the LSCI and LDF results. In vivo experiments captured postocclusive reactive hyperemic responses in rat hind limbs and human palms and feet. The main research contribution is the development of this compact and portable LSCI device, as well as the validation of its reliability and convenience in various scenarios and environments. Future applications of this technology include evaluating blood flow changes during skin injuries, such as abrasions, burns, and diabetic foot ulcers, to aid medical institutions in treatment optimization and to reduce treatment duration.

Exploring the multifaceted role of ginkgolides and bilobalide from Ginkgo biloba in mitigating metabolic disorders.

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.

The Effect of Organic Vegetable Mixed Juice on Blood Circulation and Intestine Flora: Randomized, Double-Blinded, Placebo-Controlled Clinical Trial.

Epidemiological evidence suggests that fruit and vegetable intake significantly positively affects cardiovascular health. Since vegetable juice is more accessible than raw vegetables, it attracts attention as a health functional food for circulatory diseases. Therefore, this study measured blood lipids, antioxidants, blood circulation indicators, and changes in the microbiome to confirm the effect of organic vegetable mixed juice (OVJ) on improving blood circulation. This 4-week, randomized, double-blinded, placebo-controlled study involved adult men and women with borderline total cholesterol (TC) and low-density lipoprotein (LDL) levels. As a result, blood lipid profile indicators, such as TC, triglycerides, LDL cholesterol, and apolipoprotein B, decreased (p < 0.05) in the OVJ group compared with those in the placebo group. Additionally, the antioxidant biomarker superoxide dismutase increased (p < 0.05). In contrast, systolic and diastolic blood viscosities, as blood circulation-related biomarkers, decreased (p < 0.05) in the OVJ group compared with those in the placebo group. After the intervention, a fecal microbiome analysis confirmed differences due to changes in the intestinal microbiome composition between the OVJ and placebo groups. In conclusion, our research results confirmed that consuming OVJ improves blood circulation by affecting the blood lipid profile, antioxidant enzymes, and microbiome changes.

Characterization of oral biomarkers during early healing at augmented dental implant sites.

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.

Comparative effectiveness and safety of four traditional Chinese medicine injections with invigorating blood circulation, equivalent effect of anticoagulation or antiplatelet in acute myocardial infarction: a Bayesian network meta-analysis.

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.

[Blood flow restriction training (BFRT) in patients before and after total knee arthroplasty]. / "Blood-flow-restriction"-Training (BFRT) bei Patienten vor und nach Knieendoprothetik.

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.

Extracorporeal membrane oxygenation states basilar artery thrombectomy and left posterior cerebral artery stent thrombectomy: A case report.

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.

Lessons for Cardiovascular Clinical Investigators: The Tumultuous 2,500-Year Journey of Physicians Who Ignited Our Fire.

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.

Assessment of Uterine Blood Flow in Mild Primary Dysmenorrhea.

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.

Quantifying Diaphragm Blood Flow With Contrast-Enhanced Ultrasound in Humans.

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.

Quantitative analysis of similarity between cerebral arterial blood volume and intracranial pressure pulse waveforms during intracranial pressure plateau waves.

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.

Attenuated polyethylene glycol immunogenicity and overcoming accelerated blood clearance of a fully PEGylated dendrimer.

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.

[Clinical experience of Tianxiong Granules in treatment of hypertension based on treatment principle of supressing Yang and promoting blood circulation].

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.

Advances in Composite Biofilm Biomimetic Nanodrug Delivery Systems for Cancer Treatment.

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.

Evaluation of the blood flow in reconstructed gastric tube and its relation to anastomosis leakage.

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.

Detoxification and Activating Blood Circulation Decoction Promotes Reendothelialization of Damaged Blood Vessels via VEGF Signaling Pathway Activation by miRNA-126.

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.

Endothelial Cell Flow-Mediated Quiescence Is Temporally Regulated and Utilizes the Cell Cycle Inhibitor p27.

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.