Efficacy and safety of targeted therapy plus immunotherapy combined with hepatic artery infusion chemotherapy (FOLFOX) for unresectable hepatocarcinoma

BACKGROUND The advent of cutting-edge systemic therapies has driven advances in the treatment of hepatocellular carcinoma(HCC),and therapeutic strategies with multiple modes of delivery have been shown to be more efficacious than mono-therapy.However,the mechanisms underlying this innovative treatment modality have not been elucidated.AIM To evaluate the clinical efficacy of targeted therapy plus immunotherapy combined with hepatic arterial infusion chemotherapy(HAIC)of FOLFOX in patients with unresectable HCC.METHODS We enrolled 53 patients with unresectable HCC who received a combination of targeted therapy,immunotherapy,and HAIC of FOLFOX between December 2020 and June 2021 and assessed the efficacy and safety of the treatment regimen.RESULTS The objective response rate was 60.4%(32/53),complete response was 24.5%(13/53),partial response was 35.9%(19/53),and stable disease was 39.6%(21/53).The median duration of response and median progression-free survival were 9.1 and 13.9 months,respectively.The surgical conversion rate was 34.0%(18/53),and 1-year overall survival was 83.0%without critical complicating diseases or adverse events(AEs).CONCLUSION The regimen of HAIC of FOLFOX,targeted therapy,and immunotherapy was curative for patients with unresectable HCC,with no serious AEs and a high rate of surgical conversion.

Hepatic arterial infusion chemotherapy with anti-angiogenesis agents and immune checkpoint inhibitors for unresectable hepatocellular carcinoma and meta-analysis

BACKGROUND Hepatic arterial infusion chemotherapy(HAIC)has been proven to be an ideal choice for treating unresectable hepatocellular carcinoma(uHCC).HAIC-based treatment showed great potential for treating uHCC.However,large-scale studies on HAIC-based treatments and meta-analyses of first-line treatments for uHCC are lacking.AIM To investigate better first-line treatment options for uHCC and to assess the safety and efficacy of HAIC combined with angiogenesis inhibitors,programmed cell death of protein 1(PD-1)and its ligand(PD-L1)blockers(triple therapy)under real-world conditions.METHODS Several electronic databases were searched to identify eligible randomized controlled trials for this meta-analysis.Study-level pooled analyses of hazard ratios(HRs)and odds ratios(ORs)were performed.This was a retrospective single-center study involving 442 patients with uHCC who received triple therapy or angiogenesis inhibitors plus PD-1/PD-L1 blockades(AIPB)at Sun Yat-sen University Cancer Center from January 2018 to April 2023.Propensity score matching(PSM)was performed to balance the bias between the groups.The Kaplan-Meier method and cox regression were used to analyse the survival data,and the log-rank test was used to compare the suvival time between the groups.RESULTS A total of 13 randomized controlled trials were included.HAIC alone and in combination with sorafenib were found to be effective treatments(P values for ORs:HAIC,0.95;for HRs:HAIC+sorafenib,0.04).After PSM,176 HCC patients were included in the analysis.The triple therapy group(n=88)had a longer median overall survival than the AIPB group(n=88)(31.6 months vs 14.6 months,P<0.001)and a greater incidence of adverse events(94.3%vs 75.4%,P<0.001).CONCLUSION This meta-analysis suggests that HAIC-based treatments are likely to be the best choice for uHCC.Our findings confirm that triple therapy is more effective for uHCC patients than AIPB.

Propofol sedation in routine endoscopy:A case series comparing target controlled infusion vs manually controlled bolus concept

BACKGROUND Many studies have addressed safety and effectiveness of non-anaesthesiologist propofol sedation(NAPS)for gastrointestinal(GI)endoscopy Target controlled infusion(TCI)is claimed to provide an optimal sedation regimen by avoiding under-or oversedation.AIM To assess safety and performance of propofol TCI sedation in comparison with nurse-administered bolus-sedation.METHODS Fouty-five patients undergoing endoscopy under TCI propofol sedation were prospectively included from November 2016 to May 2017 and compared to 87 patients retrospectively included that underwent endoscopy with NAPS.Patients were matched for age and endoscopic procedure.We recorded time of sedation and endoscopy,dosage of medication and adverse events.RESULTS There was a significant reduction in dose per time of propofol administered in the TCI group,compared to the NAPS group(8.2±2.7 mg/min vs 9.3±3.4 mg/min;P=0.046).The time needed to provide adequate sedation levels was slightly but significantly lower in the control group(5.3±2.7 min vs 7.7±3.3 min;P<0.001),nonetheless the total endoscopy time was similar in both groups.No differences between TCI and bolus-sedation was observed for mean total-dosage of propofol rate as well as adverse events.CONCLUSION This study indicates that sedation using TCI for GI endoscopy reduces the dose of propofol necessary per minute of endoscopy.This may translate into less adverse events.However,further and randomized trials need to confirm this trend.

Application of Patient Simulators Combined with Internet plus Scenario Simulation Teaching Models on Intravenous Infusion Nursing Education in China

Objective: To explore the effectiveness of applying patient simulators combined with Internet Plus scenario simulation teaching models on intravenous (IV) infusion nursing education, and to provide scientific evidence for the implementation of advanced teaching models in future nursing education. Methods: Enrolled 60 nurses who took the IV infusion therapy training program in our hospital from January 2022 to December 2023 for research. 30 nurses who were trained in traditional teaching models from January to December 2022 were selected as the control group, and 30 nurses who were trained with simulation-based teaching models with methods including simulated patients, internet, online meetings which can be replayed and scenario simulation, etc. from January to December 2023 were selected as the experimental group. Evaluated the learning outcomes based on the Competency Inventory for Nursing Students (CINS), Problem-Solving Inventory (PSI), comprehensive learning ability, scientific research ability, and proficiency in the theoretical knowledge and practical skills of IV infusion therapy. Nursing quality, the incidence of IV infusion therapy complications and nurse satisfaction with different teaching models were also measured. Results: The scientific research ability, PSI scores, CINS scores, and comprehensive learning ability of the experimental group were better than those of the control group (P 0.05), and their assessment results of practical skills, nursing quality of IV infusion therapy during training, and satisfaction with teaching models were all better than those of the control group with statistical significance (P < 0.05). The incidence of IV infusion therapy complications in the experimental group was lower than that in the control group, indicating statistical significance (P < 0.05). Conclusions: Teaching models based on patient simulators combined with Internet Plus scenario simulation enable nursing students to learn more directly and practice at any time and in any place, and can improve their proficiency in IV infusion theoretical knowledge and skills (e.g. PICC catheterization), core competencies, problem-solving ability, comprehensive learning ability, scientific research ability and the ability to deal with complicated cases. Also, it helps provide high-quality nursing education, improve the nursing quality of IV therapy, reduce the incidence of related complications, and ensure the safety of patients with IV therapy.

Donor-derived CD 19 CAR-T Cells versus Chemotherapy Plus Donor Lymphocyte Infusion for Treatment of Recurrent CD 19-positive B-ALL after Allogeneic Hematopoietic Stem Cell Transplantation

Objective:This study aimed to compare the efficacy of anti-CD19 chimeric antigen receptor T cells(CAR-T cells)versus chemotherapy plus donor lymphocyte infusion(chemo-DLI)for treating relapsed CD 19-positive B-cell acute lymphoblastic leukemia(B-ALL)after allogeneic hematopoietic stem cell transplantation(allo-HSCT).Methods:Clinical data of 43 patients with B-ALL who relapsed after allo-HSCT were retrospectively analyzed.Twenty-two patients were treated with CAR-T cells(CAR-T group),and 21 with chemotherapy plus DLI(chemo-DLI group).The complete remission(CR)and minimal residual disease(MRD)-negative CR rates,leukemia-free survival(LFS)rate,overall survival(OS)rate,and incidence of acute graft-versus-host disease(aGVHD),cytokine release syndrome(CRS)and immune effector cell-associated neurotoxicity syndrome(ICANS)were compared between the two groups.Results:The CR and MRD-negative CR rates in the CAR-T group(77.3%and 61.5%)were significantly higher than those in the chemo-DLI group(38.1%and 23.8%)(P=0.008 and P=0.003).The 1-and 2-year LFS rates in the CAR-T group were superior to those in the chemo-DLI group:54.5%and 50.0%vs.9.5%and 4.8%(P=0.0001 and P=0.00004).The 1-and 2-year OS rates in the CAR-T versus chemo-DLI group were 59.1%and 54.5%vs.19%and 9.5%(P=0.011 and P=0.003).Six patients(28.6%)with grade 2-4 aGVHD were identified in the chemo-DLI group.Two patients(9.1%)in the CAR-T group developed grade 1-2 aGVHD.Nineteen patients(86.4%)developed CRS in the CAR-T group,comprising grade 1-2 CRS in 13 patients(59.1%)and grade 3 CRS in 6 patients(27.3%).Two patients(9.1%)developed grade 1-2 ICANS.Conclusion:Donor-derived anti-CD19 CAR-T-cell therapy may be better,safer,and more effective than chemo-DLI for B-ALL patients who relapse after allo-HSCT.

Efficacy of continuous gastric artery infusion chemotherapy in relieving digestive obstruction in advanced gastric cancer

BACKGROUND Obstruction or fullness after feeding is common in gastric cancer(GC)patients,affecting their nutritional status and quality of life.Patients with digestive obstruction are generally in a more advanced stage.Existing methods,including palliative gastrectomy,gastrojejunostomy,endoluminal stent,jejunal nutrition tube and intravenous chemotherapy,have limitations in treating these symptoms.AIM To analyze the efficacy of continuous gastric artery infusion chemotherapy(cGAIC)in relieving digestive obstruction in patients with advanced GC.METHODS This study was a retrospective study.Twenty-nine patients with digestive obstruction of advanced GC who underwent at least one cycle of treatment were reviewed at The Second Affiliated Hospital of Zhejiang University School of Medicine.The oxaliplatin-based intra-arterial infusion regimen was applied in all patients.Mild systemic chemotherapy was used in combination with local treatment.The clinical response was evaluated by contrast-enhanced computed tomography using Response Evaluation Criteria In Solid Tumors(RECIST)criteria.Digestive tract symptoms and toxic effects were analyzed regularly.A comparison of the Karnofsky Performance Status(KPS)score and Stooler’s Dysphagia Score before and after therapy was made.Univariate survival analysis and multivariate survival analysis were also performed to explore the key factors affecting patient survival.RESULTS All patients finished cGAIC successfully without microcatheter displacement,as confirmed by arteriography.The median follow-up time was 24 mo(95%CI:20.24-27.76 mo).The overall response rate was 89.7%after cGAIC according to the RECIST criteria.The postoperative Stooler’s Dysphagia Score was significantly improved.Twentytwo(75.9%)of the 29 patients experienced relief of digestive obstruction after the first two cycles,and 13(44.8%)initially unresectable patients were then considered radically resectable.The median overall survival time(mOS)was 16 mo(95%CI:9.32-22.68 mo).Patients who received radical surgery had a significantly longer mOS than other patients(P value<0.001).Multivariate Cox regression analysis indicated that radical resection after cGAIC,intravenous chemotherapy after cGAIC,and immunotherapy after cGAIC were independent predictors of mOS.None of the patients stopped treatment because of adverse events.CONCLUSION cGAIC was effective and safe in relieving digestive obstruction in advanced GC,and it could improve surgical conversion possibility and survival time.

Efficacy and safety of propofol target-controlled infusion combined with butorphanol for sedated colonoscopy

BACKGROUND Propofol is a short-acting,rapid-recovering anesthetic widely used in sedated colonoscopy for the early detection,diagnosis and treatment of colon diseases.However,the use of propofol alone may require high doses to achieve the induction of anesthesia in sedated colonoscopy,which has been associated with anesthesia-related adverse events(AEs),including hypoxemia,sinus bradycardia,and hypotension.Therefore,propofol co-administrated with other anesthetics has been proposed to reduce the required dose of propofol,enhance the efficacy,and improve the satisfaction of patients receiving colonoscopy under sedation.AIM To evaluate the efficacy and safety of propofol target-controlled infusion(TCI)in combination with butorphanol for sedation during colonoscopy.METHODS In this controlled clinical trial,a total of 106 patients,who were scheduled for sedated colonoscopy,were prospectively recruited and assigned into three groups to receive different doses of butorphanol before propofol TCI:Low-dose butorphanol group(5μg/kg,group B1),high-dose butorphanol group(10μg/kg,group B2),and control group(normal saline,group C).Anesthesia was achieved by propofol TCI.The primary outcome was the median effective concentration(EC50)of propofol TCI,which was measured using the up-and-down sequential method.The secondary outcomes included AEs in perianesthesia and recovery characteristics.RESULTS The EC50 of propofol for TCI was 3.03μg/mL[95%confidence interval(CI):2.83-3.23μg/mL]in group B2,3.41μg/mL(95%CI:3.20-3.62μg/mL)in group B1,and 4.05μg/mL(95%CI:3.78-4.34μg/mL)in group C.The amount of propofol necessary for anesthesia was 132 mg[interquartile range(IQR),125-144.75 mg]in group B2 and 142 mg(IQR,135-154 mg)in group B1.Furthermore,the awakening concentration was 1.1μg/mL(IQR,0.9-1.2μg/mL)in group B2 and 1.2μg/mL(IQR,1.025-1.5μg/mL)in group B1.Notably,the propofol TCI plus butorphanol groups(groups B1 and B2)had a lower incidence of anesthesia AEs,when compared to group C.Furthermore,no significant differences were observed in the rates of AEs in perianesthesia,including hypoxemia,sinus bradycardia,hypotension,nausea and vomiting,and vertigo,among group C,group B1 and group B2.CONCLUSION The combined use with butorphanol reduces the EC50 of propofol TCI for anesthesia.The decrease in propofol might contribute to the reduced anesthesia-related AEs in patients undergoing sedated colonoscopy.

Double pigtail catheter reduction for seriously displaced intravenous infusion port catheter:A case report

BACKGROUND Implanted intravenous infusion port(TIAP)is mainly used for patients who need central venous infusion and poor peripheral vascular conditions.With the advantages of easy to carry,long maintenance cycle,few complications and excellent quality of life,it has been widely used in the fields of malignant tumor chemotherapy,parenteral nutrition support and repeated blood collection.Implanted intravenous infusion port(IVAP)dislocation can have significant complications if not recognised and reinstated immediately.CASE SUMMARY A 24-year-old man was treated with adjuvant chemotherapy for osteosarcoma.Severe displacement of IVAP catheter was found by chest X-ray examination.The IVAP cannot be used normally.Therefore,we conducted an emergency procedure to reset the catheter through double pigtail catheters,the operation was successful and the infusion port was restored.CONCLUSION When IVAP catheter displacement cannot be reset by conventional techniques,two pigtail catheters can be successfully used instead.

Virtual Reality as an Adjunct to Ketamine Infusion Therapy Increases Patient Satisfaction in the Management of Chronic Pain and Depression: A Retrospective Pilot Study

The management of patients with concomitant chronic pain (CP) and Major Depressive Disorder (MDD) remains challenging for clinicians. Current chronic pharmacologic management is often unsuccessful, or has intolerable side effects to the patients. While not restricted to patients with chronic pain, these patients are often diagnosed with depression, presenting with symptoms such as poor mood, anhedonia, and altered cognitive processes. It is estimated that a substantial proportion of treated patients do not derive a substantive benefit from traditional pharmacological treatments for depression. The present study involved a retrospective review of cases, exploring the patient-reported satisfaction with and tolerability of a novel use of virtual reality (VR), coined KVR, as an adjunct to intravenous ketamine infusion therapies. Specifically, the ketamine-virtual reality protocol was employed as a potential adjunctive intervention for patients suffering from chronic pain and depression. Visual Analog Scores (VAS) associated with pain were significantly lower on the third than on the first assessment day. Montgomery-?sberg Depression Rating Scale (MADRS) scores improved following infusion and across days (i.e., sessions). Lastly, 2/3 of patients preferred the use of VR with their ketamine infusion. The results are considered in terms of implementing prospective studies to examine whether the combination therapies have a synergistic benefit and the nature and magnitude of clinically meaningful treatment effects, if any.

Drop Factor and Infusion Dose Calculation Discrepancies among Nurses in Southern Nigeria: A Cross-Sectional Study

Nurses must deliver infusions as prescribed since too slow or fast a dose could be deleterious to patients. Nurses experience challenges with infusion dose calculations, making them vulnerable to errors. The research team examined drop factor and infusion dose calculation discrepancies among nurses in southern Nigeria. Five university teaching hospitals were involved in this cross-sectional study conducted in 2019. To establish the drop factor of commonly available macro drip sets, the team randomly sourced 25 macro drip sets from the hospitals’ pharmacies. A sample of 291 nurses was selected using a proportionate random sampling technique. The team collected data using the Adult Infusion Dose Calculation Quiz and analyzed it at a 5% significance level. Twenty (80%) of the sampled macro drip sets displayed a drop factor value of 20 drops per milliliter (gtt/ml) on their packaging. When measured experimentally, 25 (100%) of the macro drip sets delivered exactly 20 gtt/ml. Only 36 (12.4%) respondents calculated macro drip infusion doses using the correct drop factor of 20 gtt/ml. Non-attendance of infusion administration training updates significantly increased the risk of error by 38% (p ≤ 0.001). In conclusion, the drop factor of macro drip sets used in southern Nigeria is 20 gtt/ml;nurses were prone to infusing patients at a lower dose than prescribed. Special training in infusion therapy might remedy this concern.

Observation on the Application Effect of Targeted Infusion Safety Nursing in Inpatients with Cancer

Objective:To study the clinical effect of targeted infusion safety nursing during infusion of inpatients with cancer.Methods:From January 1,2020,to January 1,2023,a total of 6,614 infusion patients were treated in The First Affiliated Hospital of Wenzhou Medical University,and 300 inpatients with cancer were selected as the research objects and randomly divided into the observation group and the control group,with 150 patients in each group.The control group received routine infusion nursing,and the observation group received targeted infusion safety nursing.The targeted infusion safety nursing was judged by comparing the nursing quality assessment,incidence of adverse events,patient compliance,and patients’mastery of infusion knowledge between the two groups.clinical effect.Results:After the targeted infusion safety nursing was given to the patients in the observation group,the patients in this group recognized the nursing quality,and the statistical score was higher than that in the control group;the incidence of adverse events in the observation group was lower than that in the control group.The compliance of the observation group was higher than that of the control group.The mastery of health knowledge in the observation group was also higher than that in the control group and the difference was statistically significant(P<0.02).Conclusion:After implementing targeted infusion safety nursing for inpatients with cancer,it can effectively prevent the occurrence of adverse events,improve patient compliance,and increase the mastery of relevant knowledge of patients.

Treating amyotrophic lateral sclerosis with allogeneic Schwann cell-derived exosomal vesicles: a case report

Schwann cells are essential for the maintenance and function of motor neurons,axonal networks,and the neuromuscular junction.In amyotrophic lateral sclerosis,where motor neuron function is progressively lost,Schwann cell function may also be impaired.Recently,important signaling and potential trophic activities of Schwann cell-derived exosomal vesicles have been reported.This case report describes the treatment of a patient with advanced amyotrophic lateral sclerosis using serial intravenous infusions of allogeneic Schwann cell-derived exosomal vesicles,marking,to our knowledge,the first instance of such treatment.An 81-year-old male patient presented with a 1.5-year history of rapidly progressive amyotrophic lateral sclerosis.After initial diagnosis,the patient underwent a combination of generic riluzole,sodium phenylbutyrate for the treatment of amyotrophic lateral sclerosis,and taurursodiol.The patient volunteered to participate in an FDA-approved single-patient expanded access treatment and received weekly intravenous infusions of allogeneic Schwann cell-derived exosomal vesicles to potentially restore impaired Schwann cell and motor neuron function.We confirmed that cultured Schwann cells obtained from the amyotrophic lateral sclerosis patient via sural nerve biopsy appeared impaired(senescent)and that exposure of the patient’s Schwann cells to allogeneic Schwann cell-derived exosomal vesicles,cultured expanded from a cadaver donor improved their growth capacity in vitro.After a period of observation lasting 10 weeks,during which amyotrophic lateral sclerosis Functional Rating Scale-Revised and pulmonary function were regularly monitored,the patient received weekly consecutive infusions of 1.54×1012(×2),and then consecutive infusions of 7.5×1012(×6)allogeneic Schwann cell-derived exosomal vesicles diluted in 40 mL of Dulbecco’s phosphate-buffered saline.None of the infusions were associated with adverse events such as infusion reactions(allergic or otherwise)or changes in vital signs.Clinical lab serum neurofilament and cytokine levels measured prior to each infusion varied somewhat without a clear trend.A more sensitive in-house assay suggested possible inflammasome activation during the disease course.A trend for clinical stabilization was observed during the infusion period.Our study provides a novel approach to address impaired Schwann cells and possibly motor neuron function in patients with amyotrophic lateral sclerosis using allogeneic Schwann cell-derived exosomal vesicles.Initial findings suggest that this approach is safe.

Comparative effectiveness of several adjuvant therapies after hepatectomy for hepatocellular carcinoma patients with microvascular invasion

BACKGROUND For resectable hepatocellular carcinoma(HCC),radical hepatectomy is commonly used as a curative treatment.However,postoperative recurrence significantly diminishes the overall survival(OS)of HCC patients,especially with microva-scular invasion(MVI)as an independent high-risk factor for recurrence.While some studies suggest that postoperative adjuvant therapy may decrease the risk of recurrence following liver resection in HCC patients,the specific role of adju-vant therapies in those with MVI remains unclear.AIM To conduct a network meta-analysis(NMA)to evaluate the efficacy of various adjuvant therapies and determine the optimal adjuvant regimen.METHODS A systematic literature search was conducted on PubMed,EMBASE,and Web of Science until April 6,2023.Studies comparing different adjuvant therapies or comparing adjuvant therapy with hepatectomy alone were included.Hazard ratios(HRs)with 95%confidence intervals were used to combine data on recurrence free survival and OS in both pairwise meta-analyses and NMA.RESULTS Fourteen eligible trials(2268 patients)reporting five different therapies were included.In terms of reducing the risk of recurrence,radiotherapy(RT)[HR=0.34(0.23,0.5);surface under the cumulative ranking curve(SUCRA)=97.7%]was found to be the most effective adjuvant therapy,followed by hepatic artery infusion chemotherapy[HR=0.52(0.35,0.76);SUCRA=65.1%].Regarding OS improvement,RT[HR:0.35(0.2,0.61);SUCRA=93.1%]demonstrated the highest effectiveness,followed by sorafenib[HR=0.48(0.32,0.69);SUCRA=70.9%].INTRODUCTION Hepatocellular carcinoma(HCC)is the sixth most common malignant tumor in the world and ranks third in terms of worldwide malignant tumor mortality rates in 2020[1].Curative treatments for HCC include ablation,radical hepatectomy,and liver transplantation.However,ablation is suitable only for early-stage HCC patients,who represent a small percentage of the overall HCC population.Although liver transplantation serves as the optimal treatment for HCC patients,the scarcity of donor organs restricts the availability of this procedure.Therefore,hepatectomy is the most commonly employed curative treatment for resectable HCC.Unfortunately,the 5-year recurrence rate for patients who undergoing hepatectomy ranges from 50%to 70%[2,3].Recurrence of HCC is associated with several risk factors[4],including single nodule>5 cm,vascular invasion,and multiple nodules.Among these factors,microvascular invasion(MVI)is an independent risk factor for recurrence.MVI is defined as the presence of cancer cells in the lumen of endothelium-lined vessels,typically in the small branches of the portal and hepatic veins of the paracancerous liver tissue,visible only under the microscope[5].Previous studies have shown that among HCC patients who underwent hepatectomy,those with MVI had a higher risk of recurrence and shorter overall survival(OS)than those without MVI[6].Several studies have indicated that adjuvant therapy following curative hepatectomy can prevent recurrence and improve OS in HCC patients with MVI.These postoperative adjuvant therapies include transarterial chemoembolization(TACE)[7],sorafenib[8],hepatic artery infusion chemotherapy(HAIC)[9],and radiotherapy(RT)[10].However,the existing studies mostly compare individual adjuvant therapy with hepatectomy alone.Direct or indirect comparisons between the various adjuvant therapies are lacking.Therefore,we performed the network meta-analysis(NMA)to compare the relative efficacy of each adjuvant therapy to determine the optimal treatment.

Effect of Artemisia annua (Asteraceae) Extracts on Hemolysis in Individuals with G6PD-Deficiency

Individuals with Glucose-6-phosphate dehydrogenase (G6PD) deficiency are susceptible to hemolytic anemia when exposed to pro-oxidant substances. This study investigates the hemolytic impact of Artemisia annua (A. annua) extracts in G6PD-deficient subjects through a mixed experimental approach. In the in vitro phase, red blood cells from G6PD-deficient individuals and rats induced with Dehydroepiandrosterone (DHEA) were exposed to various concentrations of A. annua infusion, with distilled water and physiological saline as positive and negative controls respectively. The in vivo study involved G6PD-deficient Wistar rats divided into three groups receiving A. annua infusion, quinine (positive control), and distilled water (negative control) via gavage. Blood samples were collected for biochemical and hematological analyses. Notably, at a 40% concentration of A. annua infusion, there was a significant increase in the hemolysis rate of G6PD-deficient red blood cells compared to controls (p A. annua exhibited elevated aspartate aminotransferase (129.25 ± 4.55 U/L vs. 80.09 ± 4.03 U/L;p A. annua infusion tested positive for saponins. These findings underscore the risk of hemolysis in G6PD-deficient individuals upon ingesting A. annua.

Advances in Conversion Therapy for Primary Unresectable Hepatocellular Carcinoma

Primary liver cancer is one of the most common malignant tumours in the world, and according to statistics, about half of liver cancers occur in China, which seriously threatens the lives and health of people around the world, especially in China. Hepatocellular carcinoma is the most common type, accounting for about 90 per cent of primary liver cancers. Most patients are asymptomatic in the early stage and fail to pay attention to it. Most of the patients are in the middle or late stage when they are first diagnosed, and only 20% - 30% of them can receive radical hepatectomy. Patients are through the treatment to make the tumour shrinkage and downstaging, to achieve the condition of resectable, that is, the conversion treatment. Conversion therapy has great potential for development and has now become an indispensable treatment for intermediate and advanced hepatocellular carcinoma. However, there are various treatment options for conversion therapy, no uniform guidelines to guide clinical selection, and the overall conversion rate is still low, so it is particularly important to explore appropriate conversion therapy options. This article mainly describes the existing conversion therapies, hoping to provide help and ideas for exploring the best conversion therapies in the future.

THE ANALYTIC RESOLUTIONS AND APPLICATIONS OF THE NON－LINEAR SEEPAGE FLOW EQUATIONS OF COAL INFUSION

hi this paper. the author uses the theory of fluid mechanics. dynamics of fluids in Porous media. gas seepage flow in coal seams and combines the tests in the laboratory with the actual coal infusion to have an investigating and study from the theory to the mechanism of coal infusion to wet coal seams. through the analysis to the process of coal infusion the author builds up the mathematical models and has a detailed discussion to the boundary conditions of coal infusion. Because the equation sets to describe coal infusion are non-linear. we have made a simplification to them to use the dimension analysis theory by leading into the non-dimensions of water pressure of coal infusion, seepage flow rate. increment of coal seam moisture and so on Besides the analytic and approximate solutions have also been discussed. At last. we use the scientific research item of the actual coal infusion to illustrate the effects and importance of the theory to direct actual coal infusion and its designs.

Hepatic artery infusion chemotherapy using mFOLFOX versus transarterial chemoembolization for massive unresectable hepatocellular carcinoma:a prospective non.randomized study

Background: Transarterial chemoembolization(TACE) is recommended as the standard care for unresectable hepatocellular carcinoma(HCC) at Barcelona Clinic Liver Cancer(BCLC) stage A-B. However, the efficacy of TACE on large(> 10 cm) stage A-B HCC is far from satisfactory, and it is proposed that hepatic artery infusion chemotherapy(HAIC)might be a better first-line treatment of this disease. Hence, we compared the safety and efficacy of HAIC with the modified FOLFOX(mFOLFOX) regimen and those ofTACE in patients with massive unresectable HCC.Methods: A prospective, non-randomized, phase II study was conducted on patients with massive unresectable HCC. The protocol involved HAIC with the mFOLFOX regimen(oxaliplatin, 85 mg/m^2 intra-arterial infusion; leucovorin,400 mg/m^2 intra-arterial infusion; and fluorouracil, 400 mg/m2 bolus infusion and 2400 mg/m^2 continuous infusion)every 3 weeks and TACE with 50 mg of epirubicin, 50 mg of lobaplatin, 6 mg of mitomycin, and lipiodol and polyvinyl alcohol particles. The tumor responses, time-to-progression(TTP), and safety were assessed.Results: A total of 79 patients were recruited for this study: 38 in the HAIC group and 41 in the TACE group. The HAIC group exhibited higher partial response and disease control rates than did the TACE group(52.6% vs. 9.8%, P < 0.001;83.8% vs. 52.5%, P = 0.004). The median TTPs for the HAIC and TACE groups were 5.87 and 3.6 months(hazard radio[HR] = 2.35,95% confidence interval [CI] = 1.16-4.76, P = 0.015). More patients in the HAIC group than in the TACE group underwent resection(10 vs. 3,P = 0.033). The proportions of grade 3-4 adverse events(AE) and serious adverse events(SAE) were lower in the HAIC group than in the TACE group(grade 3-4 AEs: 13 vs. 27, P = 0.007;SAEs: 6 vs. 15,p = 0.044). More patients in the TACE group than in the HAIC group had the study treatment terminated early due to intolerable treatment-related adverse events or the withdrawal of consent(10 vs. 2,P = 0.026).Conclusions: HAIC with mFOLFOX yielded significantly better treatment responses and less serious toxicity than did TACE. HAIC might represent a feasible and promising first-line treatment for patients with massive unresectable HCC.

Chemoembolization alone vs combined chemoembolization and hepatic arterial infusion chemotherapy in inoperable hepatocellular carcinoma patients

AIM: To compare the efficacy and safety of chemoem-bolization alone or chemoembolization combined with hepatic arterial infusion chemotherapy(HAIC),including oxaliplatin(OXA),5-fluorouracil(5-FU) and folinic acid(CF),in inoperable hepatocellular carcinoma(HCC) without distant metastasis. METHODS: Eighty-four inoperable HCC patients were enrolled. Thirty-ninepatient sunderwent chemoembolization alone,and the other 45 patients underwent chemoembolization + HAIC(OXA/5-FU/CF) treatment non-randomly. The progression free survival(PFS),objective response rate(ORR),disease control rate(DCR) and adverse reactions were compared between the two groups.RESULTS: A significant difference in the ORR was observed between the chemoembolization alone and chemoembolization + HAIC groups. There was no statistically significant difference in DCR between the two groups. The median PFS(m PFS) showed a significant difference between the two groups. For patients with BCLC stage A/B disease,with or without vessel invasion,the chemoembolization + HAIC group showed better m PFS when compared to chemoembolization alone,but no significant difference was found in patients with BCLC stage C disease. The parameter of pain(grade Ⅲ-Ⅳ) in the chemoembolization + HAIC group was increased statistically. CONCLUSION: Chemoembolization combined with HAIC with OXA/5-FU/CF may be safe and more effective than chemoembolization alone for inoperable HCC patients without distant metastasis.

Autologous mobilized peripheral blood CD34^+ cell infusion in non-viral decompensated liver cirrhosis

AIM: To study the effect of mobilized peripheral blood autologous CD34 positive(CD34+) cell infusion in patients with non-viral decompensated cirrhosis.METHODS: Cirrhotic patients of non-viral etiology were divided into 2 groups based on their willingness to be listed for deceased donor liver transplant(DDLT)(control, n = 23) or to receive autologous CD34+ cell infusion through the hepatic artery(study group, n= 22). Patients in the study group were admitted to hospital and received granulocyte colony stimulating factor injections 520 μg/d for 3 consecutive days to mobilize CD34+ cells from the bone marrow. On day 4,leukapheresis was done and CD34+ cells were isolated using CliniMAC magnetic cell sorter. The isolated CD34+ cells were infused into the hepatic artery under radiological guidance. The patients were discharged within 48 h. The control group received standard of care treatment for liver cirrhosis and were worked up for DDLT as per protocol of the institute. Both groups were followed up every week for 4 wk and then every month for 3 mo.RESULTS: In the control and the study group, the cause of cirrhosis was cryptogenic in 18(78.2%) and16(72.72%) and alcohol related in 5(21.7%) and6(27.27%), respectively. The mean day 3 cell count(cells/μL) was 27.00 ± 20.43 with a viability of 81.84± 11.99%. and purity of 80%-90%. Primary end point analysis revealed that at 4 wk, the mean serum albumin in the study group increased significantly(2.83± 0.36 vs 2.43 ± 0.42, P = 0.001) when compared with controls. This improvement in albumin was,however, not sustained at 3 mo. However, at the end of3 mo there was a statistically significant improvement in serum creatinine in the study group(0.96 ± 0.33 vs 1.42 ± 0.70, P = 0.01) which translated into a significant improvement in the Model for End-Stage Liver Disease score(15.75 ± 5.13 vs 19.94 ± 6.68,P = 0.04). On statistical analysis of secondary end points, the transplant free survival at the end of 1 mo and 3 mo did not show any significant difference(P =0.60) when compared to the control group. There was no improvement in aspartate transaminase, alanine transaminase, and bilirubin at any point in the study population. There was no mortality benefit in the study group. The procedure was safe with no procedural or treatment related complications.CONCLUSION: Autologous CD 34+ cell infusion is safe and effectively improves liver function in the short term and may serve as a bridge to liver transplantation.

Sorafenib combined with embolization plus hepatic arterial infusion chemotherapy for inoperable hepatocellular carcinoma

BACKGROUND There is little evidence of combining sorafenib with hepatic arterial infusion chemotherapy(HAIC)after transarterial chemoembolization(TACE)for intermediate and advanced hepatocellular carcinoma(HCC).It is important to identify that patients with intermediate and advanced HCC are most likely to benefit from this combination therapy.AIM To investigate the safety and clinical outcomes of sorafenib combined with HAIC with folinic acid,5-fluorouracil(5-FU),and oxaliplatin(FOLFOX)after TACE for intermediate and advanced HCC.METHODS This prospective phase II study enrolled patients with intermediate and advanced HCC who underwent treatment with sorafenib combined with TACEHAIC.All patients initially received the standard 400 mg dose of sorafenib twice daily before TACE-HAIC.Participants at our institute with intermediate and advanced HCC underwent routine TACE.Then,the catheter used for embolization was kept in place in the hepatic artery,and oxaliplatin was intraarterially administered for 6 h,followed by 5-FU for 18 h,and folinic acid was intravenously administered for 2 h.The primary endpoints were safety,as evaluated by the Common Terminology and Criteria for Adverse Events version 4.0,and 12-mo progression-free survival(PFS),as analyzed by the Kaplan-Meier method.As secondary endpoints,the objective response rate(ORR)was evaluated by the modified Response Evaluation Criteria for Solid Tumors,and survival time[overall survival(OS)]was analyzed by the Kaplan-Meier method.RESULTS Sixty-six participants at our institute with intermediate and advanced HCC were enrolled in this prospective study(mean age,53.3±11.7 years).Approximately 56.1%of participants had Barcelona Clinic Liver Cancer(BCLC)stage C disease,and 43.9%had BCLC stage B disease.The ORR was 42.4%.The disease control rate was 87.9%.The grade 3-4 toxicities consisted of thrombocytopenia(4.5%),neutropenia(3.0%),and elevated aspartate aminotransferase(12.2%).Hand-foot skin reaction was also observed(40.9%).The median PFS was 13.1 mo(13.5 mo in the BCLC stage B participants and 9.4 mo in the BCLC stage C participants).The 6-mo,12-mo,and 24-mo PFS rates were 75.0%,54.7%,and 30.0%,respectively.The median OS was 21.8 mo.CONCLUSION Sorafenib combined with HAIC(FOLFOX)after TACE may be a feasible treatment choice for intermediate and advanced HCC because this treatment met the prespecified endpoint of a 6-mo PFS rate exceeding 50%and had good patient tolerance.Prospective randomized controlled trials are needed to confirm the effect of this combination therapy.