Comparative Analysis of Hemostatic Efficacy: Local Application of Lancehead Snake Venom Thrombin versus Hemostatic Forceps in Colon Polypectomy.

Background: Colon polypectomy often involves managing bleeding, and the choice of hemostatic methods is critical for patient outcomes. This study addresses the hemostatic effects of lancehead snake venom thrombin compared to hemostatic forceps in the context of colon polypectomy. Objective: To compare and assess the effectiveness and safety of local application of lancehead snake venom thrombin and hemostatic forceps in achieving hemostasis during colon polypectomy. Design: A randomized controlled trial was conducted to investigate and compare the hemostatic outcomes of two different approaches in colon polypectomy. Setting: The study was conducted at the Affiliated Hospital of Hebei University Hospital from January 2022 to June 2022. Participants: A total of 80 patients with colon polyps who met the inclusion criteria were randomly assigned to either the lancehead snake venom thrombin group or the hemostatic forceps group. Interventions: In the hemostatic forceps group, hemostatic forceps were employed to seal the wound post-polyp resection. In the lancehead snake venom thrombin group, aluminium potassium sulfate gel, in conjunction with locally sprayed lancehead snake venom thrombin, was applied to the wound. Primary Outcome Measures: The study assessed (1) intraoperative immediate bleeding and hemostasis; (2) intraoperative hemostasis time; (3) postoperative delayed post-polypectomy bleeding (DPPB); and (4) adverse reactions as primary outcome measures. Results: No significant differences were observed in the incidence rate of intraoperative immediate bleeding and the success rate of intraoperative hemostasis between the two groups. The lancehead snake venom thrombin group exhibited a shorter intraoperative hemostasis time and a lower incidence rate of adverse reactions compared to the hemostatic forceps group. No significant difference was found in the incidence rate of postoperative DPPB between the two groups. Conclusion: Local application of lancehead snake venom thrombin proves to be more effective and safer than hemostatic forceps in promptly managing bleeding during colon polypectomy.

Analysis of Hemostatic Effect and Safety of Local Spray Treatment With Hemocoagulase Bothrops Atrox for Injection After Resection of Colon Polyps.

Context: Postoperative bleeding after resection of colon polyps (CPs) is an extremely common adverse event with endoscopic treatment. Hemocoagulase Bothrops Atrox (HBA) is a newly discovered hemostatic substance that contains thrombin-like and coagulation kinase-like enzymes. However, research is lacking about its use for the treatment of intestinal polyps. Objective: The study intended to examine the hemostatic efficacy and safety of a local spray treatment with HBA, derived from HBA for injection, after CP resection, to provide a new hemostatic method, support HBA's use, and provide evidence for clinical decision making. Design: The research team performed a randomized controlled study. Setting: The study took place at the Affiliated Hospital of Hebei University in Baoding, Hebei, China. Participants: Participants were 200 patients with CP who received treatment at the hospital between December 2020 and December 2022. Intervention: The research team divided participants into two groups with 100 participants each, an intervention group and a control group, using the random number expression method. For hemostasis, the intervention group received a local spray treatment that used HBA for injection, and the control group received metal-clip closure or electrocoagulation. Outcome Measures: The research team measured: (1) the hemostatic efficacy; (2) clinical outcomes-time to hemostasis, hemostasis rate, rebleeding rate, and incidence of late postoperative bleeding; (3) at baseline and at 24h postintervention, the coagulation function-prothrombin time (PT), activated partial thromboplastin time (APTT), thrombin time (TT), and fibrinogen (FIB); (4) at baseline and at 24h postintervention, PLT parameters-platelet count (PLT), procalcitonin (PCT), and mean platelet volume (MPV); (5) economic effects-total number of participants with hemostasis, hospital days, and total hospital costs; and (6) adverse reactions. Results: The total hemostatic efficacy for the intervention group was significantly higher than that of the control group (P = .027), and the time to hemostasis was significantly shorter (P < .001) and the hemostasis rate, rebleeding rate, and incidence of late postoperative bleeding were all significantly lower than those of the control group, at P = .009, P = .009, and P = .048, respectively. In addition, the intervention group's postoperative PT, TT, APTT, FIB, and MPV were all significantly lower than those of the control group (all P < .05), while its PLT and PCT were significantly higher than those of the control group (both P < .05). The intervention group's total number of participants with hemostasis, participants with hemostasis, hospital days, and total cost were significantly lower than those of the control group (all P < .05), while no significant difference existed between the groups in the incidence of adverse effects (P > .05). Conclusions: HBA has an excellent hemostatic effect on intestinal polypectomy, with convenient use and high safety. In the future, popularizing the use of HBA in the treatment of intestinal polypectomy can not only effectively guarantee the postoperative safety of patients but also could reduce their economic burden and improve the quality of clinical medical services.

Clinical Effects of Biling Weitong Granules in Combination with Quadruple Therapy on Refractory Helicobacter pylori Infection.

Objective: The prevalence of antimicrobial resistance in Helicobacter pylori (HP) infection has increased globally. This study aimed to compare the efficacy of Biling Weitong granules (BLWTG) combined with quadruple therapy in patients with refractory HP infection who had previously failed eradication therapy. Methods: This single-center prospective study enrolled patients with two or more consecutive failed HP treatments. A total of 122 patients with previously failed HP treatment from our hospital were recruited as participants and randomly (1:1) allocated to two eradication groups: patients treated with bismuth-containing quadruple therapy (esomeprazole 40 mg, amoxicillin 1.0 g, bismuth potassium citrate 220 mg, and clarithromycin 500 mg, twice daily [EACB group]) for 14 days. And those treated with BLWTG (5 g three times daily) combined with the EACB group for 14 days (BLWTG+EACB group). The therapeutic effects of the two treatment programs were comprehensively evaluated. Results: The study group had a significantly higher improvement rate in symptoms (dull stomach pain, nausea, gastric distension, loss of appetite, and belching) compared to the control group (P < .05). Eight weeks after drug withdrawal, the eradication rates in the control and study groups were 49.18% and 73.77%, respectively. The levels of interleukin-6, C-reactive protein, and tumor necrosis factor-α were significantly lower in both groups after treatment but were significantly lower in the study group than in the control group (P < .05). Conclusions: The combination of BLWTG and standard four-drug therapy had a high eradication rate and low recurrence rate in patients with refractory HP infection. Additionally, this combined therapy could regulate inflammatory reactions and reduce drug-related adverse reactions.

Correlation of Macrophages with Inflammatory Reaction in Ulcerative Colitis and Influence of Curcumin on Macrophage Chemotaxis.

Objective: Our study aimed to elucidate the correlation of macrophage (mø) with the inflammatory reaction in ulcerative colitis (UC) and the influence of curcumin (Cur) on mø chemotaxis in mice with UC. Methods: A total of 49 patients with UC (research group; RG) admitted between June 2020 and October 2021 and 56 healthy individuals (control group; CG) who visited concurrently were selected as the study participants. The peripheral blood mononuclear cells (PBMCs) were analyzed, and M1-type/M2-type mø and inflammatory factors (IFs) interleukin (IL)-1, IL-6, IL-10, tumor necrosis factor alpha (TNF-α) and transforming growth factor beta (TGF-ß) were detected. In addition, 15 BALB/c mice were purchased and divided into the normal group fed normally, the UC model group established with sodium dextran sulfate (DSS) and the Cur group induced by DSS + Cur feeding. Colon tissue mø was collected from mice to measure mø activity via CCK-8 and to quantify levels of IFs and chemokine CCL2 by polymer chain reaction (PCR)c and Western blotting. Results: The RG had a higher percentage of peripheral blood M1-type mø and a lower percentage of M2-type mø and M1/M2 mø ratio than the CG (P < .05). In the RG, IL-1, IL-6 and TNF-α all increased and were inversely correlated with the ratio of M1/M2 mø, while IL-10 and TGF-ß decreased, with a positive connection with the M1/M2 mø ratio. In the UC model mice, mø activity increased, but the apoptosis rate decreased. mø activity was lower in the Cur group than in the model and normal groups; mø apoptosis in the Cur group was higher than in the model group but lower than in the normal group. In addition, proIFs increased and anti-IFs decreased in the model group, and Cur also ameliorated this process. Finally, CCL2 and MCP-1 levels in the model group were also increased, while those in the Cur group were lower compared with the model group. Conclusion: In UC, the M1/M2 mø ratio is severely misadjusted, activation of M1-type mø is enhanced and pro-IFs are released in large quantities. Cur can ameliorate the abnormal activation of mø in mice with UC, inhibit mø chemotaxis and alleviate the inflammatory reaction, which may make it a new option for UC treatment in the future.

NIR phosphorescent cyclometalated platinum (II) complexes with CAIX targeted and nuclear penetration as potent anticancer theragnostic agents.

Although cisplatin drugs have achieved great success in cancer therapy, they also easily cause drug resistance and other side effects. Non-classical platinum (II) complexes with targeted therapy characteristics have become one of the hotspots in the research of new anticancer drugs. In the present work, a series of carbonic anhydrase IX (CAIX)-targeted and inhibited cyclometalated platinum (II) complexes with near-infrared (NIR) phosphorescent emission have been developed, due to the calculation of Molecular docking and the result of CAIX inhibition assay in vitro, all complexes show a high binding affinity and effective inhibition on CAIX in vitro. Moreover, Pt2 shows a significant cellar uptake efficiency, and translocation of red emission in Pt2 from the cytoplasm to nuclear in Hela cell can be recorded by confocal within 24 h, while Pt2 can selectively target and locate in the lysosome of MDA-MB-231 cell, thus resulting in significantly enhanced therapeutic effect on multiple cancer cell lines compared with cisplatin, as well as the killing selectivity towards cancer cell of CAIX-inhibited cyclometalated platinum (II) complex are 6.0-14.6 times higher than that of cisplatin. Hence, our work presents the rational design of Pt (II)-CAIX conjugates as a promising strategy in the application of constructing a new platform for cancer theragnostic agents.

Transcriptional Analysis on Resistant and Susceptible Kiwifruit Genotypes Activating Different Plant-Immunity Processes against Pseudomonas syringae pv. actinidiae.

Pseudomonas syringae pv. actinidiae (Psa), a bacterial pathogen, is a severe threat to kiwifruit production. To elucidate the species-specific interaction between Psa and kiwifruit, transcriptomic-profiles analyses were conducted, under Psa-infected treatment and mock-inoculated control, on shoots of resistant Maohua (MH) and susceptible Hongyang (HY) kiwifruit varieties. The plant hormone-signal transduction and plant-pathogen interaction were significantly enriched in HY compared with MH. However, the starch and sucrose metabolism, antigen processing and presentation, phagosome, and galactose metabolism were significantly enriched in MH compared with HY. Interestingly, the MAP2 in the pathogen/microbe-associated molecular patterns (PAMPs)-triggered immunity (PTI) was significantly up-regulated in MH. The genes RAR1, SUGT1, and HSP90A in the effector-triggered immunity (ETI), and the NPR1 and TGA genes involved in the salicylic acid signaling pathway as regulatory roles of ETI, were significantly up-regulated in HY. Other important genes, such as the CCRs involved in phenylpropanoid biosynthesis, were highly expressed in MH, but some genes in the Ca2+ internal flow or involved in the reactive oxygen metabolism were obviously expressed in HY. These results suggested that the PTI and cell walls involved in defense mechanisms were significant in MH against Psa infection, while the ETI was notable in HY against Psa infection. This study will help to understand kiwifruit bacterial canker disease and provide important theoretical support in kiwifruit breeding.

Codelivery of satraplatin and aminopyrrolic receptor with Pluronic F127-based polyaniline nanoparticles with NIR induced release for combined chemotherapy.

The acquired drug resistance of the platinum-based drug is a main obstacle in cancer therapy. Herein, an aminopyrrolic receptor 1 was synthesized to sensitize satraplatin for overcoming the drug resistance as well as improving tumor targeted ability. Thus, Pluronic F127-based polyaniline nanoparticles were designed to co-deliver satraplatin and aminopyrrolic receptor 1, which could control the drug release with the Near Infrared laser irradiation (808 nm) due to the polyaniline mediated photothermal conversion. Biological evaluation shows prepared nanoparticles (Pt-ARNPs) exhibited more effective cytotoxicity (IC50 = 2.7µM) against the tested cancer cell lines under laser irradiation, compared with free satraplatin or treatment without Near-infrared radiation. Moreover, Pt-ARNPs showed comparable cytotoxicity against A549 and A549/cis cells, implying that the combination of satraplatin and aminopyrrolic receptor 1 with nano carrier might be a promising strategy to reduce platinum resistance and improve therapeutic effect in cancer therapy.

Identification of Six Flavonoids as Novel Cellular Antioxidants and Their Structure-Activity Relationship.

This study is aimed at determining the relationship of flavonoid structures to their chemical and intracellular antioxidant activities. The antioxidant activities of 60 flavonoids were investigated by three different antioxidant assays, including 2,2-diphenyl-1-picrylhydrazyl (DPPH) radical scavenging activity, oxygen radical absorption capacity (ORAC), and cellular antioxidant activity (CAA) assays. The result showed 6 flavonoids as good cellular antioxidants evaluated for the first time. The cellular antioxidant activities of compounds 7-methoxy-quercetin, 3-O-methylquercetin, 8-hydroxy-kaempferol, quercetin-3-O-α-arabinofuranose, kaempferol-7-O-glucopyranoside, and luteolin6-C-glucoside were linked with the upregulation of antioxidant enzyme activities (superoxide dismutase, catalase, and glutathione peroxidase). A structure-activity relationship suggested that 2,3-double bond, 4-keto groups, 3',4'-catechol structure, and 3-hydroxyl in the flavonoid skeleton played important roles in the antioxidant behavior. Furthermore, the cell proliferative assay revealed a low cytotoxicity for 3-O-methylquercetin. The present results provide valuable information for the dietary application of flavonoids with different structures for high antioxidant.

Study of the mechanism of anti-ulcer effects of virgin coconut oil on gastric ulcer-induced rat model.

INTRODUCTION: This study aims to evaluate the gastro-protective effects of virgin coconut oil (VCO) on different ulcer models as compared to the standard drug (omeprazole). MATERIAL AND METHODS: Three groups of rats (6 rats per group for each ulcer model) were pre-treated with distilled water for the negative control group, 30 mg/kg of omeprazole for the positive control group and VCO (2 ml per rat) for the treatment group. Animals were pre-treated for 7 days and ulcers were induced with cold restraint stress, piroxicam, ethanol and pylorus ligation. On day eight, animals were sacrificed and ulcer scores were determined based on macroscopic evaluation. The gastric volume, pH, total acidity and mucus content were measured in the pylorus-ligated model. The levels of antioxidants were determined from the gastric tissue homogenates. RESULTS: Virgin coconut oil significantly (p < 0.001) inhibited the ulceration caused by different inducers. The percentage of inhibition for the VCO-treated group was 78.3%, 84.7%, 72.7% and 73.1%, while for the omeprazole-treated group it was 60.8%, 61.5%, 59% and 53.8% in cold restraint stress, ethanol, piroxicam and pylorus-ligated ulcer models, respectively. Virgin coconut oil significantly (p < 0.001) inhibited gastric juice volume and total acidity for VCO and omeprazole treated groups as compared to the non-treated negative control group. Moreover, VCO and omeprazole caused a significant (p < 0.001) increase of gastric mucus content and pH. Virgin coconut oil also proved to have significantly increased glutathione (GSH) and nitrite levels, whereas the levels of SOD, GP, MDA and CAT were significantly (p < 0.001) reduced by VCO relative to the control group. Virgin coconut oil also significantly (p < 0.001) increased the level of prostaglandin in rat tissue homogenate, similar to the omeprazole treated group. CONCLUSIONS: Virgin coconut oil shows a possible association with antioxidant properties to control the regulation of prostaglandin synthesis and protect against reactive oxygen species damage.

Effect of dehydration techniques on bioactive compounds in hawthorn slices and their correlations with antioxidant properties.

Hawthorn fruits are rich in nutrients and antioxidant compounds. Dehydration is the major processing and preservation method for hawthorn fruits. The rates of moisture loss; polyphenol, flavonoid and triterpenoid acid contents; and antioxidant activities and their relationships were investigated in hawthorn slices that were dried by four dehydration techniques (microwave drying, solar drying, hot air drying and freeze drying) under different operation conditions. The results showed that both the drying method and the processing parameter affected the antioxidants. Microwave drying and hot air drying at high temperatures (≥ 80 °C) resulted in the degradation of the polyphenols, flavonoids and triterpenoid acids in the hawthorn slices. These antioxidant compounds were best preserved by freeze drying and hot air drying at 60 °C. Epicatechin and chlorogenic acid were the major phenolic compounds identified in this research, and these compounds were significantly affected during processing. The antioxidant activities of the hawthorn fruits were significantly related to the total polyphenol, flavonoid and triterpenoid acid contents. Hot air drying at proper temperatures could be suitable for hawthorn slice dehydration processing that conserves the antioxidant properties of the fruit.

Apixaban versus enoxaparin for thromboprophylaxis after hip replacement.

BACKGROUND: There are various regimens for thromboprophylaxis after hip replacement. Low-molecular-weight heparins such as enoxaparin predominantly inhibit factor Xa but also inhibit thrombin to some degree. Orally active, specific factor Xa inhibitors such as apixaban may provide effective thromboprophylaxis with a lower risk of bleeding and improved ease of use. METHODS: In this double-blind, double-dummy study, we randomly assigned 5407 patients undergoing total hip replacement to receive apixaban at a dose of 2.5 mg orally twice daily or enoxaparin at a dose of 40 mg subcutaneously every 24 hours. Apixaban therapy was initiated 12 to 24 hours after closure of the surgical wound; enoxaparin therapy was initiated 12 hours before surgery. Prophylaxis was continued for 35 days after surgery, followed by bilateral venographic studies. The primary efficacy outcome was the composite of asymptomatic or symptomatic deep-vein thrombosis, nonfatal pulmonary embolism, or death from any cause during the treatment period. Patients were followed for an additional 60 days after the last intended dose of study medication. RESULTS: A total of 1949 patients in the apixaban group (72.0%) and 1917 patients in the enoxaparin group (71.0%) could be evaluated for the primary efficacy analysis. The primary efficacy outcome occurred in 27 patients in the apixaban group (1.4%) and in 74 patients in the enoxaparin group (3.9%) (relative risk with apixaban, 0.36; 95% confidence interval [CI], 0.22 to 0.54; P<0.001 for both noninferiority and superiority; absolute risk reduction, 2.5 percentage points; 95% CI, 1.5 to 3.5). The composite outcome of major and clinically relevant nonmajor bleeding occurred in 129 of 2673 patients assigned to apixaban (4.8%) and 134 of 2659 assigned to enoxaparin (5.0%) (absolute difference in risk, -0.2 percentage points; 95% CI, -1.4 to 1.0). CONCLUSIONS: Among patients undergoing hip replacement, thromboprophylaxis with apixaban, as compared with enoxaparin, was associated with lower rates of venous thromboembolism, without increased bleeding. (Funded by Bristol-Myers Squibb and Pfizer; ClinicalTrials.gov number, NCT00423319.).

Apixaban versus enoxaparin for thromboprophylaxis after knee replacement (ADVANCE-2): a randomised double-blind trial.

BACKGROUND: Low-molecular-weight heparins such as enoxaparin are preferred for prevention of venous thromboembolism after major joint replacement. Apixaban, an orally active factor Xa inhibitor, might be as effective, have lower bleeding risk, and be easier to use than is enoxaparin. We assessed efficacy and safety of these drugs after elective total knee replacement. METHODS: In ADVANCE-2, a multicentre, randomised, double-blind phase 3 study, patients undergoing elective unilateral or bilateral total knee replacement were randomly allocated through an interactive central telephone system to receive oral apixaban 2.5 mg twice daily (n=1528) or subcutaneous enoxaparin 40 mg once daily (1529). The randomisation schedule was generated by the Bristol-Myers Squibb randomisation centre and stratified by study site and by unilateral or bilateral surgery with a block size of four. Investigators, patients, statisticians, adjudicators, and steering committee were masked to allocation. Apixaban was started 12-24 h after wound closure and enoxaparin 12 h before surgery; both drugs were continued for 10-14 days, when bilateral ascending venography was scheduled. Primary outcome was the composite of asymptomatic and symptomatic deep vein thrombosis, non-fatal pulmonary embolism, and all-cause death during treatment. The statistical plan required non-inferiority of apixaban before testing for superiority; analysis was by intention to treat for non-inferiority testing. The study is registered at ClinicalTrials.gov, number NCT00452530. FINDINGS: 1973 of 3057 patients allocated to treatment (1528 apixaban, 1529 enoxaparin) were eligible for primary efficacy analysis. The primary outcome was reported in 147 (15%) of 976 apixaban patients and 243 (24%) of 997 enoxaparin patients (relative risk 0.62 [95% CI 0.51-0.74]; p<0.0001; absolute risk reduction 9.3% [5.8-12.7]). Major or clinically relevant non-major bleeding occurred in 53 (4%) of 1501 patients receiving apixaban and 72 (5%) of 1508 treated with enoxaparin (p=0.09). INTERPRETATION: Apixaban 2.5 mg twice daily, starting on the morning after total knee replacement, offers a convenient and more effective orally administered alternative to 40 mg per day enoxaparin, without increased bleeding. FUNDING: Bristol-Myers Squibb; Pfizer.

Apixaban or enoxaparin for thromboprophylaxis after knee replacement.

BACKGROUND: The optimal strategy for thromboprophylaxis after major joint replacement has not been established. Low-molecular-weight heparins such as enoxaparin predominantly target factor Xa but to some extent also inhibit thrombin. Apixaban, a specific factor Xa inhibitor, may provide effective thromboprophylaxis with a low risk of bleeding and improved ease of use. METHODS: In a double-blind, double-dummy study, we randomly assigned patients undergoing total knee replacement to receive 2.5 mg of apixaban orally twice daily or 30 mg of enoxaparin subcutaneously every 12 hours. Both medications were started 12 to 24 hours after surgery and continued for 10 to 14 days. Bilateral venography was then performed. The primary efficacy outcome was a composite of asymptomatic and symptomatic deep-vein thrombosis, nonfatal pulmonary embolism, and death from any cause during treatment. Patients were followed for 60 days after anticoagulation therapy was stopped. RESULTS: A total of 3195 patients underwent randomization, with 1599 assigned to the apixaban group and 1596 to the enoxaparin group; 908 subjects were not eligible for the efficacy analysis. The overall rate of primary events was much lower than anticipated. The rate of the primary efficacy outcome was 9.0% with apixaban as compared with 8.8% with enoxaparin (relative risk, 1.02; 95% confidence interval, 0.78 to 1.32). The composite incidence of major bleeding and clinically relevant nonmajor bleeding was 2.9% with apixaban and 4.3% with enoxaparin (P=0.03). CONCLUSIONS: As compared with enoxaparin for efficacy of thromboprophylaxis after knee replacement, apixaban did not meet the prespecified statistical criteria for noninferiority, but its use was associated with lower rates of clinically relevant bleeding and it had a similar adverse-event profile. (ClinicalTrials.gov number, NCT00371683.)

Selective costimulation modulation using abatacept in patients with active rheumatoid arthritis while receiving etanercept: a randomised clinical trial.

OBJECTIVE: To investigate the efficacy and safety of abatacept in combination with etanercept in patients with active rheumatoid arthritis during a 1-year, randomised, placebo-controlled, double-blind phase, followed by an open-label, long-term extension (LTE). METHODS: Patients continued etanercept (25 mg twice weekly) and were randomised to receive abatacept 2 mg/kg (n = 85) or placebo (n = 36). As the effective dose of abatacept was established as 10 mg/kg in a separate trial, all patients received abatacept 10 mg/kg and etanercept during the LTE. RESULTS: A total of 121 patients were randomised; 80 completed double-blind treatment and entered the LTE. During double-blind treatment, the difference in the percentage of patients achieving the primary end point (modified American College of Rheumatology (ACR) 20 response at 6 months) was not significant between groups (48.2% v 30.6%; p = 0.072). At 1 year, no notable changes in modified ACR responses were observed. Subsequent to the dosing change, similar modified ACR responses were seen during the LTE. Significant improvements in quality of life were observed with abatacept and etanercept versus placebo and etanercept in five of the eight short-form 36 subscales at 1 year. More abatacept and etanercept-treated patients experienced serious adverse events (SAEs) at 1 year than patients receiving placebo and etanercept (16.5% v 2.8%), with 3.5% v 0% experiencing serious infections. CONCLUSION: The combination of abatacept (at a dose of 2 mg/kg during the double-blind phase and 10 mg/kg during the LTE) and etanercept was associated with an increase in SAEs, including serious infections, with limited clinical effect. On the basis of the limited efficacy findings and safety concerns, abatacept in combination with etanercept should not be used for rheumatoid arthritis treatment.