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1.
J Tradit Chin Med ; 44(3): 537-544, 2024 Jun.
Article En | MEDLINE | ID: mdl-38767638

OBJECTIVE: To explore the early hemostatic mechanism of Jianpi Yiqi Shexue decoction (, JYSD) in treating immune thrombocytopathy (ITP), based on the functional homeostasis of brain-intestine axis and blood neurotransmitter METHODS: Non-drug treatment cases: Healthy volunteers were selected as normal control group and compared with patients with dysfunctional uterine bleeding, gastrointestinal tumors with bleeding and ITP, to detect the changes of blood 5-hydroxytryptamine (5-HT), ß-endorphin (ß-EP), vasoactive intestinal peptide (VIP) and compare the changes of blood neuro-transmitters in patients with different disease symptoms. Drug treatment cases: According to the randomized controlled multicenter clinical trial, 272 ITP patients were randomly divided into three groups: treatment group (JYSD) combined group (JYSD + Prednisone) control group (Prednisone). The changes of blood neuro-transmitter (5-HT, ß-EP, VIP) before and after treatment were detected on the basis of peripheral blood platelet (PLT) and grade score. RESULTS: Non-drug treatment cases: compared with the normal control group, the 5-HT level was higher, and the VIP and ß-EP levels were both lower in the ITP group (P < 0.001), and the 5-HT, VIP and ß-EP levels in the Gastrointestinal tumors with bleeding group were also lower compared with the normal control group (P < 0.05, 0.001). Drug treatment cases: The PLT grading scores of the combination group and the control group after treatment were lower than that before treatment (P < 0.05, 0.001). The PLT grading score of the 3 groups were compared in pairs after treatment: the combination group was the lowest among the 3 groups, which was better than the treatment group, but no better than the control group (vs the treatment group, P = 0.005, vs the control group, P = 0.709). The statistical results of full analysis set (FAS) and per protocol set (PPS) were consistent. The bleeding symptom scores of the treatment and combination groups began to drop 7 d after treatment, and kept dropping 14 d after treatment until the end of the study (P < 0.05). On the other hand, the control group started to show favorable results 14 d after treatment (P < 0.05). The FAS and PPS analysis results were consistent. In the control group, the 5-HT level was higher and VIP level was lower after treatment, compared with those before treatment (P < 0.05, 0.001). The ß-EP levels were both increased in the treatment and combination group after treatment, compared with those before treatment (P < 0.05). After treatment, the ß-EP levels in the treatment and control groups were significantly lower compared with the combination groups (P < 0.05). After treatment, compared with the control group, the VIP levels in the treatment and combination groups were up-regulated, and the differences were statistically significant by rank sum test (P < 0.01), and by t-test (P = 0.0002, 0.0001). CONCLUSIONS: The prednisone tablet is better than the JYSD in increasing the level of PLT, while prednisone tablet combined with JYSD has more advantages in improving patients' peripheral blood PLT levels. However, in improving the bleeding time of ITP patients, the combination of the two drugs was significantly delayed compared with the single usage, showing the characteristics and advantages of traditional Chinese medicine. JYSD can regulate the neurotransmitter level of ITP patients through the function of the brain-gut axis, mobilize 5-HT in the blood of ITP patients to promote the contraction of blood vessels and smooth muscles, and activate the coagulation mechanism are the early hemostatic mechanisms of JYSD. Up-regulate the levels of ß-EP and balancing VIP levels may be an important part of the immune mechanism of JYSD for regulating ITP patients.


Drugs, Chinese Herbal , Serotonin , Humans , Drugs, Chinese Herbal/administration & dosage , Female , Middle Aged , Adult , Male , Serotonin/blood , Aged , Young Adult , Vasoactive Intestinal Peptide/blood , Purpura, Thrombocytopenic, Idiopathic/drug therapy , Purpura, Thrombocytopenic, Idiopathic/blood , beta-Endorphin/blood , Adolescent , Hemostatics/administration & dosage , Hemostasis/drug effects
2.
Carbohydr Polym ; 338: 122148, 2024 Aug 15.
Article En | MEDLINE | ID: mdl-38763731

Alginate-based materials present promising potential for emergency hemostasis due to their excellent properties, such as procoagulant capability, biocompatibility, low immunogenicity, and cost-effectiveness. However, the inherent deficiencies in water solubility and mechanical strength pose a threat to hemostatic efficiency. Here, we innovatively developed a macromolecular cross-linked alginate aerogel based on norbornene- and thiol-functionalized alginates through a combined thiol-ene cross-linking/freeze-drying process. The resulting aerogel features an interconnected macroporous structure with remarkable water-uptake capacity (approximately 9000 % in weight ratio), contributing to efficient blood absorption, while the enhanced mechanical strength of the aerogel ensures stability and durability during the hemostatic process. Comprehensive hemostasis-relevant assays demonstrated that the aerogel possessed outstanding coagulation capability, which is attributed to the synergistic impacts on concentrating effect, platelet enrichment, and intrinsic coagulation pathway. Upon application to in vivo uncontrolled hemorrhage models of tail amputation and hepatic injury, the aerogel demonstrated significantly superior performance compared to commercial alginate hemostatic agent, yielding reductions in clotting time and blood loss of up to 80 % and 85 %, respectively. Collectively, our work illustrated that the alginate porous aerogel overcomes the deficiencies of alginate materials while exhibiting exceptional performance in hemorrhage, rendering it an appealing candidate for rapid hemostasis.


Alginates , Gels , Hemostasis , Hemostatics , Alginates/chemistry , Animals , Hemostatics/chemistry , Hemostatics/pharmacology , Hemostasis/drug effects , Gels/chemistry , Porosity , Hemorrhage/drug therapy , Blood Coagulation/drug effects , Mice , Male , Cross-Linking Reagents/chemistry , Biocompatible Materials/chemistry , Biocompatible Materials/pharmacology
3.
Molecules ; 29(9)2024 Apr 23.
Article En | MEDLINE | ID: mdl-38731410

Cirsium japonicum Fisch. ex DC. (CF) and Cirsium setosum (Willd.) MB (CS) are commonly used clinically to stop bleeding and eliminate carbuncles. Still, CF is mainly used for treating inflammation, while CS favors hemostasis. Therefore, the present study used UHPLC-MS to analyze the main chemical constituents in CF-CS extract. We optimized the extraction process using single-factor experiments and response surface methodology. Afterward, the hemostatic and anti-inflammatory effects of CF-CS extract were investigated by determining the clotting time in vitro, the bleeding time of rabbit trauma, and the induction of rabbit inflammation using xylene and lipopolysaccharide. The study of hemostatic and anti-inflammatory effects showed that the CF-CS, CF, and CS extract groups could significantly shorten the coagulation time and bleeding time of rabbits compared with the blank group (p < 0.01); compared with the model group, it could dramatically inhibit xylene-induced ear swelling in rabbits and the content of TNF-α, IL-6, and IL-1ß in the serum of rabbits (p < 0.01). The results showed that combined CF and CS synergistically increased efficacy. CF-CS solved the problem of the single hemostatic and anti-inflammatory efficacy of a single drug, which provided a new idea for the research and development of natural hemostatic and anti-inflammatory medicines.


Anti-Inflammatory Agents , Cirsium , Hemostatics , Plant Extracts , Animals , Rabbits , Anti-Inflammatory Agents/pharmacology , Anti-Inflammatory Agents/chemistry , Anti-Inflammatory Agents/isolation & purification , Cirsium/chemistry , Hemostatics/pharmacology , Hemostatics/chemistry , Hemostatics/isolation & purification , Plant Extracts/pharmacology , Plant Extracts/chemistry , Chromatography, High Pressure Liquid , Inflammation/drug therapy , Inflammation/pathology , Male
4.
Carbohydr Polym ; 337: 122135, 2024 Aug 01.
Article En | MEDLINE | ID: mdl-38710549

The biggest obstacle to treating wound healing continues to be the production of simple, inexpensive wound dressings that satisfy the demands associated with full process of repair at the same time. Herein, a series of injectable composite hydrogels were successfully prepared by a one-pot method by utilizing the Schiff base reaction as well as hydrogen bonding forces between hydroxypropyl chitosan (HCS), ε-poly-l-lysine (EPL), and 2,3,4-trihydroxybenzaldehyde (TBA), and multiple cross-links formed by the reversible coordination between iron (III) and pyrogallol moieties. Notably, hydrogel exhibits excellent physicochemical properties, including injectability, self-healing, water retention, and adhesion, which enable to fill irregular wounds for a long period, providing a suitable moist environment for wound healing. Interestingly, the excellent hemostatic properties of the hydrogel can quickly stop bleeding and avoid the serious sequelae of massive blood loss in acute trauma. Moreover, the powerful antimicrobial and antioxidant properties also protect against bacterial infections and reduce inflammation at the wound site, thus promoting healing at all stages of the wound. The study of biohydrogel with multifunctional integration of wound treatment and smart medical treatment is clarified by this line of research.


Chitosan , Hemostatics , Hydrogels , Polylysine , Wound Healing , Wound Healing/drug effects , Hydrogels/chemistry , Hydrogels/pharmacology , Chitosan/chemistry , Chitosan/pharmacology , Chitosan/analogs & derivatives , Polylysine/chemistry , Polylysine/pharmacology , Animals , Hemostatics/chemistry , Hemostatics/pharmacology , Anti-Bacterial Agents/pharmacology , Anti-Bacterial Agents/chemistry , Mice , Staphylococcus aureus/drug effects , Escherichia coli/drug effects , Humans , Anti-Infective Agents/pharmacology , Anti-Infective Agents/chemistry , Schiff Bases/chemistry , Schiff Bases/pharmacology , Rats
5.
Cochrane Database Syst Rev ; 5: CD013421, 2024 May 02.
Article En | MEDLINE | ID: mdl-38695613

BACKGROUND: During vascular interventions, connections that link arteries, veins, or synthetic grafts, which are known as an 'anastomosis', may be necessary. Vascular anastomoses can bleed from the needle holes that result from the creation of the anastomoses. Various surgical options are available for achieving hemostasis, or the stopping of bleeding, including the application of sealants directly onto the bleeding vessels or tissues. Sealants are designed for use in vascular surgery as adjuncts when conventional interventions are ineffective and are applied directly by the surgeon to seal bleeding anastomoses. Despite the availability of several different types of sealants, the evidence for the clinical efficacy of these hemostatic adjuncts has not been definitively established in vascular surgery patients. OBJECTIVES: To evaluate the benefits and harms of sealants as adjuncts for achieving anastomotic site hemostasis in patients undergoing vascular surgery. SEARCH METHODS: The Cochrane Vascular Information Specialist conducted systematic searches of the following databases: the Cochrane Vascular Specialised Register via the Cochrane Register of Studies; the Cochrane Central Register of Controlled Trials (CENTRAL); MEDLINE via Ovid; Embase via Ovid ; and CINAHL via EBSCO. We also searched ClinicalTrials.gov and the WHO International Clinical Trials Registry Platform for clinical trials. Reference lists of included trials and relevant reviews were also searched. The latest search date was 6 March 2023. SELECTION CRITERIA: We included randomized controlled trials that compared fibrin or synthetic sealant use with alternative interventions (e.g. manual compression, reversal of anticoagulation) for achieving anastomotic-site hemostasis in vascular surgery procedures. We included participants who underwent the creation of an anastomosis during vascular surgery. We excluded non-vascular surgery patients. DATA COLLECTION AND ANALYSIS: We have used standard Cochrane methods. Our primary outcomes were time to hemostasis, failure of hemostatic intervention, and intraoperative blood loss. Our secondary outcomes were operating time, death from bleeding complications up to 30 days, postoperative bleeding up to 30 days, unplanned return to the operating room for bleeding complications management up to 30 days, quality of life, and adverse events. We used GRADE to assess the certainty of evidence for each outcome. MAIN RESULTS: We found 24 randomized controlled trials that included a total of 2376 participants who met the inclusion criteria. All trials compared sealant use with standard care controls, including oxidized cellulose, gelatin sponge, and manual compression. All trials were at high risk of performance bias, detection bias, and other sources of bias. We downgraded the certainty of evidence for risk of bias concerns, inconsistency, imprecision and possible publication bias. Combining data on time to hemostasis showed that sealant use may reduce the mean time to hemostasis compared to control (mean difference (MD) -230.09 seconds, 95% confidence interval (CI) -329.24 to -130.94; P < 0.00001; 7 studies, 498 participants; low-certainty evidence). Combining data on failure of hemostatic intervention showed that sealant use may reduce the rate of failure compared to control, but the evidence is very uncertain (risk ratio (RR) 0.46, 95% CI 0.35 to 0.61; P < 0.00001; 17 studies, 2120 participants; very low-certainty evidence). We did not detect any clear differences between the sealant and control groups for intraoperative blood loss (MD -32.69 mL, 95% CI -96.21 to 30.83; P = 0.31; 3 studies, 266 participants; low-certainty evidence); operating time (MD -18.72 minutes, 95% CI -40.18 to 2.73; P = 0.09; 4 studies, 436 participants; low-certainty evidence); postoperative bleeding (RR 0.78, 95% CI 0.59 to 1.04; P = 0.09; 9 studies, 1216 participants; low-certainty evidence), or unplanned return to the operating room (RR 0.27, 95% CI 0.04 to 1.69; P = 0.16; 8 studies, 721 participants; low-certainty evidence). No studies reported death from bleeding or quality of life outcomes. AUTHORS' CONCLUSIONS: Based on meta-analysis of 24 trials with 2376 participants, our review demonstrated that sealant use for achieving anastomotic hemostasis in vascular surgery patients may result in reduced time to hemostasis, and may reduce rates of hemostatic intervention failure, although the evidence is very uncertain, when compared to standard controls. Our analysis showed there may be no differences in intraoperative blood loss, operating time, postoperative bleeding up to 30 days, and unplanned return to the operating room for bleeding complications up to 30 days. Deaths and quality of life could not be analyzed. Limitations include the risk of bias in all studies. Our review has demonstrated that using sealants may reduce the time required to achieve hemostasis and the rate of hemostatic failure. However, a significant risk of bias was identified in the included studies, and future trials are needed to provide unbiased data and address other considerations such as cost-effectiveness and adverse events with sealant use.


Anastomosis, Surgical , Hemostasis, Surgical , Randomized Controlled Trials as Topic , Vascular Surgical Procedures , Humans , Hemostasis, Surgical/methods , Hemostatics/therapeutic use , Fibrin Tissue Adhesive/therapeutic use , Blood Loss, Surgical/prevention & control , Tissue Adhesives/therapeutic use
8.
Best Pract Res Clin Gastroenterol ; 69: 101912, 2024 Mar.
Article En | MEDLINE | ID: mdl-38749579

Endoscopic resection techniques have evolved over time, allowing effective and safe resection of the majority of pre-malignant and early cancerous lesions in the gastrointestinal tract. Bleeding is one of the most commonly encountered complications during endoscopic resection, which can interfere with the procedure and result in serious adverse events. Intraprocedural bleeding is relatively common during endoscopic resection and, in most cases, is a mild and self-limiting event. However, it can interfere with the completion of the resection and may result in negative patient-related outcomes in severe cases, including the need for hospitalization and blood transfusion as well as the requirement for radiological or surgical interventions. Appropriate management of intraprocedural bleeding can improve the safety and efficacy of endoscopic resection, and it can be readily achieved with the use of several endoscopic hemostatic tools. In this review, we discuss the recent advances in the approach to intraprocedural bleeding complicating endoscopic resection, with a focus on the various endoscopic hemostatic tools available to manage such events safely and effectively.


Gastrointestinal Hemorrhage , Hemostasis, Endoscopic , Humans , Hemostasis, Endoscopic/methods , Hemostasis, Endoscopic/adverse effects , Hemostasis, Endoscopic/instrumentation , Gastrointestinal Hemorrhage/surgery , Gastrointestinal Hemorrhage/etiology , Treatment Outcome , Endoscopy, Gastrointestinal/adverse effects , Endoscopy, Gastrointestinal/methods , Blood Loss, Surgical/prevention & control , Hemostatics/administration & dosage , Hemostatics/therapeutic use
9.
Best Pract Res Clin Gastroenterol ; 69: 101907, 2024 Mar.
Article En | MEDLINE | ID: mdl-38749583

A significant problem encountered in the resection of large, complex colonic polyps is delayed bleeding. This can occur up to two weeks after the procedure and is a significant source of comorbidity. Untreated it can prove life threatening. It is therefore a priority of modern endoscopy to develop and employ techniques to minimaize this. In this article we will review and discuss the evidence base and controversies in this field, with cold EMR technique, Post-EMR clip closure, and topical haemostatic agents.


Colonic Polyps , Colonoscopy , Postoperative Hemorrhage , Humans , Colonic Polyps/surgery , Postoperative Hemorrhage/prevention & control , Postoperative Hemorrhage/etiology , Colonoscopy/adverse effects , Endoscopic Mucosal Resection/adverse effects , Time Factors , Hemostatics/therapeutic use , Hemostatics/administration & dosage , Treatment Outcome , Gastrointestinal Hemorrhage/prevention & control , Gastrointestinal Hemorrhage/etiology
10.
Eur J Anaesthesiol ; 41(5): 327-350, 2024 May 01.
Article En | MEDLINE | ID: mdl-38567679

BACKGROUND: Anticoagulation is essential for the treatment and prevention of thromboembolic events. Current guidelines recommend direct oral anticoagulants (DOACs) over vitamin K antagonists in DOAC-eligible patients. The major complication of anticoagulation is serious or life-threatening haemorrhage, which may necessitate prompt haemostatic intervention. Reversal of DOACs may also be required for patients in need of urgent invasive procedures. This guideline from the European Society of Anaesthesiology and Intensive Care (ESAIC) aims to provide evidence-based recommendations and suggestions on how to manage patients on DOACs undergoing urgent or emergency procedures including the treatment of DOAC-induced bleeding. DESIGN: A systematic literature search was performed, examining four drug comparators (dabigatran, rivaroxaban, apixaban, edoxaban) and clinical scenarios ranging from planned to emergency surgery with the outcomes of mortality, haematoma growth and thromboembolic complications. The GRADE (Grading of Recommendations, Assessment, Development and Evaluation) methodology was used to assess the methodological quality of the included studies. Consensus on the wording of the recommendations was achieved by a Delphi process. RESULTS: So far, no results from prospective randomised trials comparing two active comparators (e.g. a direct reversal agent and an unspecific haemostatic agent such as prothrombin complex concentrate: PCC) have been published yet and the majority of publications were uncontrolled and observational studies. Thus, the certainty of evidence was assessed to be either low or very low (GRADE C). Thirty-five recommendations and clinical practice statements were developed. During the Delphi process, strong consensus (>90% agreement) was achieved in 97.1% of recommendations and consensus (75 to 90% agreement) in 2.9%. DISCUSSION: DOAC-specific coagulation monitoring may help in patients at risk for elevated DOAC levels, whereas global coagulation tests are not recommended to exclude clinically relevant DOAC levels. In urgent clinical situations, haemostatic treatment using either the direct reversal or nonspecific haemostatic agents should be started without waiting for DOAC level monitoring. DOAC levels above 50 ng ml-1 may be considered clinically relevant necessitating haemostatic treatment before urgent or emergency procedures. Before cardiac surgery under activated factor Xa (FXa) inhibitors, the use of andexanet alfa is not recommended because of inhibition of unfractionated heparin, which is needed for extracorporeal circulation. In the situation of DOAC overdose without bleeding, no haemostatic intervention is suggested, instead measures to eliminate the DOACs should be taken. Due to the lack of published results from comparative prospective, randomised studies, the superiority of reversal treatment strategy vs. a nonspecific haemostatic treatment is unclear for most urgent and emergency procedures and bleeding. Due to the paucity of clinical data, no recommendations for the use of recombinant activated factor VII as a nonspecific haemostatic agent can be given. CONCLUSION: In the clinical scenarios of DOAC intake before urgent procedures and DOAC-induced bleeding, practitioners should evaluate the risk of bleeding of the procedure and the severity of the DOAC-induced bleeding before initiating treatment. Optimal reversal strategy remains to be determined in future trials for most clinical settings.


Hemostatics , Heparin , Humans , Heparin/therapeutic use , Prospective Studies , Hemorrhage/prevention & control , Anticoagulants , Hemostatics/therapeutic use , Administration, Oral
13.
Platelets ; 35(1): 2337907, 2024 Dec.
Article En | MEDLINE | ID: mdl-38602463

Protein S (PS) is a vital endogenous anticoagulant. It plays a crucial role in regulating coagulation by acting as a cofactor for the activated protein C (APC) and tissue factor pathway inhibitor (TFPI) pathways. Additionally, it possesses direct anticoagulant properties by impeding the intrinsic tenase and prothrombinase complexes. Protein S oversees the coagulation process in both the initiation and propagation stages through these roles. The significance of protein S in regulating blood clotting can be inferred from the significant correlation between deficits in protein S and an elevated susceptibility to venous thrombosis. This is likely because activated protein C and tissue factor pathway inhibitor exhibit low efficacy as anticoagulants when no cofactors exist. The precise biochemical mechanisms underlying the roles of protein S cofactors have yet to be fully elucidated. Nevertheless, recent scientific breakthroughs have significantly enhanced comprehension findings for these functions. The diagnosis of protein S deficiency, both from a technical and genetic standpoint, is still a subject of debate due to the complex structural characteristics of the condition. This paper will provide an in-depth review of the molecular structure of protein S and its hemostatic effects. Furthermore, we shall address the insufficiency of protein S and its methods of diagnosis and treatment.


What is the purpose of this summary? To provide an in-depth review of the molecular structure of protein S and its hemostatic effects.To address the deficiency of protein S and its methods of diagnosis and treatment.What is known? Protein S operates as an anticoagulant through its roles as a cofactor for APC, TFPI, and an inhibitor of FIXa.Protein S deficiency can be either inherited or acquired.What is new? Plasma protein S and platelet-derived protein S contribute to regulating coagulation and maintaining hemostasis. Protein S can be used as a potential promising treatment target for persons diagnosed with hemophilia.


Anticoagulants , Hemostatics , Humans , Anticoagulants/pharmacology , Anticoagulants/therapeutic use , Protein C , Blood Coagulation
14.
Clin Appl Thromb Hemost ; 30: 10760296241246002, 2024.
Article En | MEDLINE | ID: mdl-38591954

Background: Although hepatocellular carcinoma (HCC) is frequently associated with thrombosis, it is also associated with liver cirrhosis (LC) which causes hemostatic abnormalities. Therefore, hemostatic abnormalities in patients with HCC were examined using a clot waveform analysis (CWA). Methods: Hemostatic abnormalities in 88 samples from HCC patients, 48 samples from LC patients and 153 samples from patients with chronic liver diseases (CH) were examined using a CWA-activated partial thromboplastin time (APTT) and small amount of tissue factor induced FIX activation (sTF/FIXa) assay. Results: There were no significant differences in the peak time on CWA-APTT among HCC, LC, and CH, and the peak heights of CWA-APTT were significantly higher in HCC and CH than in HVs and LC. The peak heights of the CWA-sTF/FIXa were significantly higher in HCC than in LC. The peak times of the CWA-APTT were significantly longer in stages B, C, and D than in stage A or cases of response. In the receiver operating characteristic (ROC) curve, the fibrin formation height (FFH) of the CWA-APTT and CWA-sTF/FIXa showed the highest diagnostic ability for HCC and LC, respectively. Thrombosis was observed in 13 HCC patients, and arterial thrombosis and portal vein thrombosis were frequently associated with HCC without LC and HCC with LC, respectively. In ROC, the peak time×peak height of the first derivative on the CWA-sTF/FIXa showed the highest diagnostic ability for thrombosis. Conclusion: The CWA-APTT and CWA-sTF/FIXa can increase the evaluability of HCC including the association with LC and thrombotic complications.


Carcinoma, Hepatocellular , Hemostatics , Liver Neoplasms , Thrombosis , Humans , Carcinoma, Hepatocellular/complications , Liver Neoplasms/complications , Thrombosis/etiology , Thromboplastin , Liver Cirrhosis/complications
15.
Int J Mol Sci ; 25(7)2024 Mar 24.
Article En | MEDLINE | ID: mdl-38612447

Hemophilia A (HA) is a common X-linked recessive hereditary bleeding disorder. Coagulation factor VIII (FVIII) is insufficient in patients with HA due to the mutations in the F8 gene. The restoration of plasma levels of FVIII via both recombinant B-domain-deleted FVIII (BDD-FVIII) and B-domain-deleted F8 (BDDF8) transgenes was proven to be helpful. FVIII-Padua is a 23.4 kb tandem repeat mutation in the F8 associated with a high F8 gene expression and thrombogenesis. Here we screened a core enhancer element in FVIII-Padua for improving the F8 expression. In detail, we identified a 400 bp efficient enhancer element, C400, in FVIII-Padua for the first time. The core enhancer C400 extensively improved the transcription of BDDF8 driven by human elongation factor-1 alpha in HepG2, HeLa, HEK-293T and induced pluripotent stem cells (iPSCs) with different genetic backgrounds, as well as iPSCs-derived endothelial progenitor cells (iEPCs) and iPSCs-derived mesenchymal stem cells (iMSCs). The expression of FVIII protein was increased by C400, especially in iEPCs. Our research provides a novel molecular target to enhance expression of FVIII protein, which has scientific value and application prospects in both viral and nonviral HA gene therapy strategies.


Hemophilia A , Hemostatics , Humans , Factor VIII/genetics , Hemophilia A/genetics , Hemophilia A/therapy , Genetic Therapy , Enhancer Elements, Genetic
16.
Int J Mol Sci ; 25(7)2024 Mar 28.
Article En | MEDLINE | ID: mdl-38612610

This prospective study aimed to assess the feasibility of chitosan biomaterial and subcutaneous gel implantation in an ovine model, with implications for women with genital prolapse. Twenty-four ewes were divided into four groups (n = 6 per group): chitosan type B, chitosan type C, chitosan unmodified injections, and polypropylene mesh. Ovine models were chosen due to their morphological resemblance to human reproductive organs. Animals were sacrificed after 90 days for macroscopic, pathomorphological, and immunohistochemical analysis. In the chitosan type B group, IL-6 and IL-10 levels decreased after 28 days, while chitosan type C and injection groups exhibited higher IL-6 than IL-10 levels. The polypropylene group displayed the highest IL-6 and lowest IL-10 levels. Histological examination of the polypropylene group revealed no degenerative changes or inflammation, whereas chitosan injection induced local inflammation. Other groups exhibited no degenerative changes. Ewes implanted with chitosan displayed reduced inflammation compared to polypropylene-implanted ewes. Chitosan implantation facilitated vaginal tissue healing, in contrast to polypropylene mesh, which led to extrusion. While chitosan holds promise as an alternative to polypropylene mesh, further research is imperative for comprehensive evaluation. This study suggests the potential of a chitosan biomaterial in pelvic organ prolapse treatment, warranting additional investigation.


Chitosan , Hemostatics , Pelvic Organ Prolapse , Sheep , Animals , Female , Humans , Interleukin-10 , Interleukin-6 , Polypropylenes , Prospective Studies , Pelvic Organ Prolapse/surgery , Biocompatible Materials/pharmacology , Inflammation , Vagina
17.
Haemophilia ; 30 Suppl 3: 29-38, 2024 Apr.
Article Af | MEDLINE | ID: mdl-38562115

Acquired bleeding disorders can develop in previously healthy people irrespective of age or gender but are particularly common in patients with certain underlying conditions. Here, we review recent advances in the management of acquired haemophilia A (AHA), acquired von Willebrand syndrome (AVWS), and patients with hemostatic abnormalities due to chronic liver disease (CLD). Patients with AHA can now benefit from prophylaxis with emicizumab, a therapeutic antibody that mimics the function of activated coagulation factor VIII. The treatment of AVWS remains challenging in many situations and requires careful consideration of the underlying condition. Haemostatic abnormalities in CLD are often compensated by proportional reduction in pro and anti-haemostatic factors resulting in sustained or even increased thrombin generation. Consequently, bleeding in CLD is rarely caused by haemostatic failure and infusion of plasma or coagulation factor concentrates may not be effective.


Hemophilia A , Hemostatics , von Willebrand Diseases , Humans , von Willebrand Diseases/complications , von Willebrand Diseases/drug therapy , Hemorrhage/etiology , Hemophilia A/complications , Hemophilia A/drug therapy , Blood Coagulation Factors , von Willebrand Factor/therapeutic use
18.
Haemophilia ; 30 Suppl 3: 128-134, 2024 Apr.
Article En | MEDLINE | ID: mdl-38571337

Advances in haematological therapies for people with complex or rare inherited bleeding disorders (IBD) have resulted in them living longer, retaining their natural teeth with greater expectations of function and aesthetics. Dental management strategies need to evolve to meet these challenges. Utilising low level laser diode therapy to reduce pre-operative inflammation to reduce the intraoperative and postoperative burden on haemostasis is described in a case series of 12 patients. For these individuals who previously required further medical management to support haemostasis or experienced such prolonged haemorrhage sufficient to warrant hospital admission, haemostasis was achieved in the dental surgery such that they were able to return home with no further medical intervention or overnight stays. Global inequities in accessing novel treatments for complex or rare IBD necessitates a comprehensive understanding of the local haemostatic agents available to dentists and the most commonly used agents and techniques are described including the use of single tooth anaesthesia (STA). STA is a computerised delivery mechanism that allows routine dental procedures that would previously have required block injections needing factor replacement therapy to be undertaken safely and effectively with no additional haemostatic intervention. The challenges of inhibitors in oral surgery are explained and discussed although more research and evidence is required to establish new treatment protocols. The importance of establishing good dental health in the quality of life of people with complex or rare IBD is highlighted with respect to the dental specific impact that more novel therapies may have on people with IBD.


Blood Coagulation Disorders, Inherited , Hemostatics , Humans , Quality of Life , Tooth Extraction , Dental Care
19.
Clin Oral Investig ; 28(5): 244, 2024 Apr 07.
Article En | MEDLINE | ID: mdl-38583113

OBJECTIVES: To compare oral adhesive bandages with the classic compression method and evaluate the clinical efficacy of this wound dressing material in improving postoperative comfort, wound healing, and hemostasis in tooth extraction. MATERIALS AND METHODS: The study was designed as a randomized controlled clinical trial. A total of 120 patients were recruited and randomly assigned to the study group and the control group. In the study group, oral adhesive bandages were used as wound dressing. In the control group, patients bit on cotton balls and gauze, as usual. Hemorrhage, comfort, and healing levels were evaluated at postoperative 1 h, 24 h, and 7 days. The adhesion time of the oral adhesive bandages was also recorded. RESULTS: The average adhesion time of the oral adhesive bandages was 26.6 h. At postoperative 1 and 24 h, the hemostatic levels of the oral adhesive bandage group were significantly higher than those of the control group. The oral adhesive bandage group also reported significantly higher comfort scores than the control group. Both groups had similar healing levels and side effects. But the mean score for wound healing was slightly higher in the oral adhesive bandage group. CONCLUSIONS: Oral adhesive bandages were more effective than cotton balls and gauze in providing hemostatic and comfort effects on extraction wounds. CLINICAL RELEVANCE: Oral adhesive bandages possess clinical value in the management of extraction wounds.


Hemostatics , Humans , Hemostatics/therapeutic use , Bandages , Tooth Extraction , Dental Care , Hemostasis
20.
World J Gastroenterol ; 30(15): 2087-2090, 2024 Apr 21.
Article En | MEDLINE | ID: mdl-38681987

Upper gastrointestinal (GI) hemorrhage presents a substantial clinical challenge. Initial management typically involves resuscitation and endoscopy within 24 h, although the benefit of very early endoscopy (< 12 h) for high-risk patients is debated. Treatment goals include stopping acute bleeding, preventing rebleeding, and using a multimodal approach encompassing endoscopic, pharmacological, angiographic, and surgical methods. Pharmacological agents such as vasopressin, prostaglandins, and proton pump inhibitors are effective, but the increase in antithrombotic use has increased GI bleeding morbidity. Endoscopic hemostasis, particularly for nonvariceal bleeding, employs techniques such as electrocoagulation and heater probes, with concerns over tissue injury from monopolar electrocoagulation. Novel methods such as Hemospray and Endoclot show promise in creating mechanical tamponades but have limitations. Currently, the first-line therapy includes thermal probes and hemoclips, with over-the-scope clips emerging for larger ulcer bleeding. The gold probe, combining bipolar electrocoagulation and injection, offers targeted coagulation but has faced device-related issues. Future advancements involve combining techniques and improving endoscopic imaging, with studies exploring combined approaches showing promise. Ongoing research is crucial for developing standardized and effective hemorrhage management strategies.


Gastrointestinal Hemorrhage , Hemostasis, Endoscopic , Humans , Gastrointestinal Hemorrhage/therapy , Gastrointestinal Hemorrhage/diagnosis , Gastrointestinal Hemorrhage/etiology , Hemostasis, Endoscopic/methods , Hemostasis, Endoscopic/instrumentation , Hemostatics/therapeutic use , Electrocoagulation/methods , Treatment Outcome , Endoscopy, Gastrointestinal/methods
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