Development of a cell adhesion-based prognostic model for multiple myeloma:Insights into chemotherapy response and potential reversal of adhesion effects

Multiple myeloma(MM)is a hematologic malignancy notorious for its high relapse rate and development of drug resistance,in which cell adhesion-mediated drug resistance plays a critical role.This study integrated four RNA sequencing datasets(CoMMpass,GSE136337,GSE9782,and GSE2658)and focused on analyzing 1706 adhesionrelated genes.Rigorous univariate Cox regression analysis identified 18 key prognosis-related genes,including KIF14,TROAP,FLNA,MSN,LGALS1,PECAM1,and ALCAM,which demonstrated the strongest associations with poor overall survival(OS)in MM patients.To comprehensively evaluate the impact of cell adhesion on MM prognosis,an adhesion-related risk score(ARRS)model was constructed using Lasso Cox regression analysis.The ARRS model emerged as an independent prognostic factor for predicting OS.Furthermore,our findings revealed that a heightened cell adhesion effect correlated with tumor resistance to DNA-damaging drugs,protein kinase inhibitors,and drugs targeting the PI3K/Akt/mTOR signaling pathway.Nevertheless,we identified promising drug candidates,such as tirofiban,pirenzepine,erlotinib,and bosutinib,which exhibit potential in reversing this resistance.In vitro,experiments employing NCIH929,RPMI8226,and AMO1 cell lines confirmed that MM cell lines with high ARRS exhibited poor sensitivity to the aforementioned candidate drugs.By employing siRNA-mediated knockdown of the key ARRS model gene KIF14,we observed suppressed proliferation of NCIH929 cells,along with decreased adhesion to BMSCs and fibronectin.This study presents compelling evidence establishing cell adhesion as a significant prognostic factor in MM.Additionally,potential molecular mechanisms underlying adhesion-related resistance are proposed,along with viable strategies to overcome such resistance.These findings provide a solid scientific foundation for facilitating clinically stratified treatment of MM.

Opportunities and challenges of CD47-targeted therapy in cancer immunotherapy

Cancer immunotherapy has emerged as a promising strategy for the treatment of cancer,with the tumor microenvironment(TME)playing a pivotal role in modulating the immune response.CD47,a cell surface protein,has been identified as a crucial regulator of the TME and a potential therapeutic target for cancer therapy.However,the precise functions and implications of CD47 in the TME during immunotherapy for cancer patients remain incompletely understood.This comprehensive review aims to provide an overview of CD47’s multifaced role in TME regulation and immune evasion,elucidating its impact on various types of immunotherapy outcomes,including checkpoint inhibitors and CAR T-cell therapy.Notably,CD47-targeted therapies offer a promising avenue for improving cancer treatment outcomes,especially when combined with other immunotherapeutic approaches.The review also discusses current and potential CD47-targeted therapies being explored for cancer treatment and delves into the associated challenges and opportunities inherent in targeting CD47.Despite the demonstrated effectiveness of CD47-targeted therapies,there are potential problems,including unintended effects on healthy cells,hematological toxicities,and the development if resistance.Consequently,further research efforts are warranted to fully understand the underlying mechanisms of resistance and to optimize CD47-targeted therapies through innovative combination approaches,ultimately improving cancer treatment outcomes.Overall,this comprehensive review highlights the significance of CD47 as a promising target for cancer immunotherapy and provides valuable insight into the challenges and opportunities in developing effective CD47-targeted therapies for cancer treatment.

Role of savolitinib in advanced gastric adenocarcinoma with meningeal carcinomatosis and cerebellar metastasis:A case report

BACKGROUND Brain metastases(BM)are very rare in gastric adenocarcinoma(GaC),and patients with BMs have a higher mortality rate due to stronger tumor aggressiveness.However,its pathogenesis remains unclear.Genetic testing revealed cellular-mesenchymal epithelial transition factor receptor(MET)amplification.Therefore,treatment with savolitinib,a small molecule inhibitor of c-Met,was selected.CASE SUMMARY A 66-year-old woman was diagnosed with advanced GaC 6 months prior to presentation due to back pain.Cerebellar and meningeal metastases were observed during candonilimab combined with oxaliplatin and capecitabine therapy.The patient experienced frequent generalized seizures and persistent drowsiness in the emergency department.Genetic testing of cerebrospinal fluid and peripheral blood revealed increased MET amplification.After discussing treatment options with the patient,savolitinib tablets were administered.After a month of treatment,the intracranial lesions shrank considerably.CONCLUSION BM is very rare in advanced GaC,especially in meningeal cancer,that is characterized by rapid disease deterioration.There are very few effective treatment options available;however,technological breakthroughs in genomics have provided a basis for personalized treatment.Furthermore,MET amplification may be a key driver of BM in gastric cancer;however,this conclusion requires further investigation.

Associations of serum D-dimer and glycosylated hemoglobin levels with third-trimester fetal growth restriction in gestational diabetes mellitus

BACKGROUND Gestational diabetes mellitus(GDM)is a special type of diabetes that commonly occurs in women during pregnancy and involves impaired glucose tolerance and abnormal glucose metabolism;GDM is diagnosed for the first time during pregnancy and can affect fetal growth and development.AIM To investigate the associations of serum D-dimer(D-D)and glycosylated hemoglobin(HbA1c)levels with third-trimester fetal growth restriction(FGR)in GDM patients.METHODS The clinical data of 164 pregnant women who were diagnosed with GDM and delivered at the Obstetrics and Gynecology Hospital of Fudan University from January 2021 to January 2023 were analyzed retrospectively.Among these women,63 whose fetuses had FGR were included in the FGR group,and 101 women whose fetuses had normal body weights were included in the normal body weight group(normal group).Fasting venous blood samples were collected from the elbow at 28-30 wk gestation and 1-3 d before delivery to measure serum D-D and HbA1c levels for comparative analysis.The diagnostic value of serum D-D and HbA1c levels for FGR was evaluated by receiver operating characteristic analysis,and the influencing factors of third-trimester FGR in GDM patients were analyzed by logistic regression.RESULTS Serum fasting blood glucose,fasting insulin,D-D and HbA1c levels were significantly greater in the FGR group than in the normal group,while the homeostasis model assessment of insulin resistance values were lower(P<0.05).Regarding the diagnosis of FGR based on serum D-D and HbA1c levels,the areas under the curves(AUCs)were 0.826 and 0.848,the cutoff values were 3.04 mg/L and 5.80%,the sensitivities were 81.0%and 79.4%,and the specificities were 88.1%and 87.1%,respectively.The AUC of serum D-D plus HbA1c levels for diagnosing FGR was 0.928,and the sensitivity and specificity were 84.1%and 91.1%,respectively.High D-D and HbA1c levels were risk factors for third-trimester FGR in GDM patients(P<0.05).CONCLUSION D-D and HbA1c levels can indicate the occurrence of FGR in GDM patients in the third trimester of pregnancy to some extent,and their combination can be used as an important index for the early prediction of FGR.

New strategies in the diagnosis and treatment of immune-checkpoint inhibitor-mediated colitis

Immune-checkpoint inhibitor-mediated colitis(IMC)is an increasingly recognized adverse event in cancer immunotherapy,particularly associated with immune checkpoint inhibitors(ICIs)such as anti-cytotoxic T-lymphocyte antigen-4 and anti-programmed cell death protein-1 antibodies.As this revolutionary immunotherapy gains prominence in cancer treatment,understanding,diagnosing,and effectively managing IMC becomes paramount.IMC represents a unique challenge due to its immune-mediated nature and potential for severe complications.However,a precise picture of IMC pathophysiology is currently unavailable.Therefore,we aimed to summarize the existing data while acknowledging the need for further research.This comprehensive review explores the mechanisms underlying ICIs,gastrointestinal adverse effects,and,in particular,IMC’s incidence,prevalence,and features.Our review also emphasizes the importance of recognizing IMC’s distinct clinical and histopathological features to differentiate it from other forms of colitis.Furthermore,this paper highlights the urgentneed for evolving diagnostic methods,therapeutic strategies,and a multidisciplinary approach to effectively manage IMC.

Resilience provides mediating effect of resilience between fear of progression and sleep quality in patients with hematological malignancies

BACKGROUND Hematological tumors are common malignant tumors,with high morbidity and mortality rates.Most patients with hematological malignancies develop sleep disorders that seriously affect their life and health because of acute onset of disease,rapid progression,high recurrence rates,complex treatment methods,and treatment costs.AIM To explore the mediating effect of resilience on fear of disease progression and sleep quality in patients with hematological malignancies.METHODS A cross-sectional analysis of 100 patients with hematological malignancies,treated in the First Affiliated Hospital of Jinzhou Medical University between August 2022 and August 2023,was conducted.Patients were assessed using a general data survey,a simplified scale for the fear of progression(FoP)of disease,a resilience scale,and the Pittsburgh Sleep Quality Index.Statistical analysis was conducted to determine the relationship between various patient characteristics and FoP,resilience,and sleep quality.Spearman’s correlation analysis was used to examine the correlations between mental resilience,FoP,and sleep quality.RESULTS The total FoP score mean value in patients with hematological malignancies was 38.09±5.16;the total resilience score mean value was 40.73±7.04;and the Pittsburgh Sleep Quality Index score mean value was 10.72±1.90.FoP,resilience,and sleep quality of the patients were associated with family per capita monthly income and patient education level(P<0.05).Spearman correlation analysis revealed that FoP was negatively correlated with resilience and sleep quality scores(r=-0.560,-0.537,P<0.01),respectively,and resilience was significantly associated with sleep quality scores(r=0.688,P<0.01).Mediation analysis showed that the mediating effect of resilience between FoP and sleep quality in patients with hematological malignancies was-0.100 and accounted for 50.51%of the total effect.This indicated that FoP directly and indirectly affected sleep quality through the mesomeric effect of resilience.CONCLUSION Resilience is an intermediary variable between FoP and sleep quality in patients with hematological malignancies.Medical staff should evaluate and follow-up FoP and resilience to implement measures to improve sleep quality.

Long noncoding RNAs HAND2-AS1 ultrasound microbubbles suppress hepatocellular carcinoma progression by regulating the miR-873-5p/tissue inhibitor of matrix metalloproteinase-2 axis

BACKGROUND Increasing data indicated that long noncoding RNAs(lncRNAs)were directly or indirectly involved in the occurrence and development of tumors,including hepatocellular carcinoma(HCC).Recent studies had found that the expression of lncRNA HAND2-AS1 was downregulated in HCC tissues,but its role in HCC progression is unclear.Ultrasound targeted microbubble destruction mediated gene transfection is a new method to overexpress genes.AIM To study the role of ultrasound microbubbles(UTMBs)mediated HAND2-AS1 in the progression of HCC,in order to provide a new reference for the treatment of HCC.METHODS In vitro,we transfected HAND2-AS1 siRNA into HepG2 cells by UTMBs,and detected cell proliferation,apoptosis,invasion and epithelial-mesenchymal transition(EMT)by cell counting kit-8 assay,flow cytometry,Transwell invasion assay and Western blotting,respectively.In addition,we transfected miR-837-5p mimic into UTMBs treated cells and observed the changes of cell behavior.Next,the UTMBs treated HepG2 cells were transfected together with miR-837-5p mimic and tissue inhibitor of matrix metalloproteinase-2(TIMP2)overexpression vector,and we detected cell proliferation,apoptosis,invasion and EMT.In vivo,we established a mouse model of subcutaneous transplantation of HepG2 cells and observed the effect of HAND2-AS1 silencing on tumor formation ability.RESULTS We found that UTMBs carrying HAND2-AS1 restricted cell proliferation,invasion,and EMT,encouraged apoptosis,and HAND2-AS1 silencing eliminated the effect of UTMBs.Additionally,miR-873-5p targets the gene HAND2-AS1,which also targets the 3’UTR of TIMP2.And miR-873-5p mimic counteracted the impact of HAND2-AS1.Further,miR-873-5p mimic solely or in combination with pcDNA-TIMP2 had been transformed into HepG2 cells exposed to UTMBs.We discovered that TIMP2 reversed the effect of miR-873-5p mimic caused by the blocked signalling cascade for matrix metalloproteinase(MMP)2/MMP9.In vivo results showed that HAND2-AS1 silencing significantly inhibited tumor formation in mice.CONCLUSION LncRNA HAND2-AS1 promotes TIMP2 expression by targeting miR-873-5p to inhibit HepG2 cell growth and delay HCC progression.

Impact of the economic crisis and drug shortage on Lebanese cancer patients’care

BACKGROUND As a consequence of the economic crisis,the sociopolitical instability and the advent of the coronavirus disease-19 pandemic,nested challenges faced the Lebanese healthcare system.These have resulted in critical shortages of essential resources,including medications vital for oncologic patients.AIM To assess the ramifications of the ongoing economic crisis on oncology patient care focusing on our outpatient oncology department.METHODS A questionnaire was distributed during the month of February 2022 to oncology patients in Hôtel Dieu de France University Hospital in Beirut during their outpatient therapy.The primary objective was to assess the far-reaching impact of the economic crisis on patient care and the resulting psychological implications.RESULTS Among 182 interviewed patients,31.87%experienced treatment interruption mainly due to acute drug shortages.Despite 87.91%of the patients benefiting from third-party coverage,69.60%had to self-pay for their medications leading to 69.78%of patients perceiving that healthcare was more difficult to access after 2020.Psychologically,one-third of the patients exhibited symptoms of anxiety and/or depression,with 7 patients reporting suicidal ideations.Notably,37.93%of patients who interrupted cancer treatment reported a history of comorbidities,and 89.66%who altered their treatment cited financial difficulties.CONCLUSION Lebanese cancer patients face complex challenges spanning economic,healthcare,and psychological realms.Income inequalities exacerbated by the economic crisis hindered healthcare access.

Comparative effectiveness of immunotherapy and chemotherapy in patients with metastatic colorectal cancer stratified by microsatellite instability status

BACKGROUND Immunotherapy have demonstrated promising outcomes in patients with high microsatellite instability(MSI)(MSI-H)metastatic colorectal cancer.However,the comparative effectiveness of Immunotherapy and chemotherapy for patients with low MSI(MSI-L),and microsatellite stable(MSS)metastatic colorectal cancer remains unclear.AIM To investigate immunotherapy vs chemotherapy for treatment of MSI-L/MSS metastatic colorectal cancer,and to evaluate the success of immunotherapy against chemotherapy in managing MSI-H metastatic colorectal cancer during a follow-up of 50 months.METHODS We conducted a retrospective cohort study using the National Cancer Database(NCDB)to evaluate the overall survival(OS)of patients with metastatic colorectal cancer treated with immunotherapy or chemotherapy.The study population was stratified by MSI status(MSI-H,MSI-L,and MSS).Multivariable Cox proportional hazard models were used to assess the association between treatment modality and OS,adjusting for potential confounders.RESULTS A total of 21951 patients with metastatic colorectal cancer were included in the analysis,of which 2358 were MSI-H,and 19593 were MSI-L/MSS.In the MSI-H cohort,immunotherapy treatment(n=142)was associated with a significantly improved median OS compared to chemotherapy(n=860).After adjusting for potential confounders,immunotherapy treatment remained significantly associated with better OS in the MSI-H cohort[adjusted hazard ratio(aHR):0.57,95%confidence interval(95%CI):0.43-0.77,P<0.001].In the MSS cohort,no significant difference in median OS was observed between immunotherapy treatment and chemotherapy(aHR:0.94,95%CI:0.69-1.29,P=0.715).CONCLUSION In this population-based study using the NCDB,immunotherapy treatment was associated with significantly improved OS compared to chemotherapy in patients with MSI-H metastatic colorectal cancer,but not in those with MSI-L/MSS metastatic colorectal cancer.Further studies are warranted to determine the optimal therapeutic approach for patients with MSI-L/MSS metastatic colorectal cancer.

Efficacy and Safety of Iron Isomaltoside Compared with an Oral Iron Supplement in the Management of Patients with Iron Deficiency Anemia

Objective: To evaluate the treatment outcome of iron isomaltoside compared with an oral iron supplement in the management of iron deficiency anemia (IDA). Methods: The study included patients with IDA who visited the Outpatient Clinic of the Department of Hematology, the Affiliated Hospital of Qingdao University from October 2021 to August 2022 and met the inclusion and exclusion criteria. According to the actual application of iron supplementation, the patients were divided into two groups: iron isomaltoside treatment group and oral iron treatment group. Baseline measurements were collected before the start of treatment, and measurements were collected subsequently at intervals of 1 week, 1 month, and 3 months. The hematological parameters analyzed included Hemoglobin (Hb), Mean corpuscular hemoglobin (MCH), Mean Hemoglobin content (MCH), Mean corpuscular Hemoglobin concentration (MCHC), and Platelet (Plt). Safety data and adverse event profiles were recorded. Results: Intra-group comparisons: After 1 month of treatment, the Hb significantly improved (P 0.05). Inter-group comparisons: The biochemical parameters were significantly improved (P 0.05) in the iron isomaltoside group compared with those in the oral iron group after 1 month of iron supplementation in patients with mild and moderate anemia. Adverse reactions were tolerable for the patients in both iron isomaltoside group and oral iron group. Only 1 patient in iron isomaltoside group developed anaphylactic shock during medication and recovered after aggressive rescue. Conclusions: Iron isomaltoside which increases Hb more rapidly compared with the oral iron supplementation has few adverse reactions and good acceptance.

Hematological Malignancies in Sickle Cell Disease Patients: Report of Four Cases in Togo and Literature Review

Background: Hemopathies were rarely observed in major sickle cell disease patients some thirty years ago, probably due to the high mortality rate among the latter as a result of progressive complications. Thanks to advances in the management of sickle cell disease, patients' life expectancy has increased considerably, exposing them more frequently to neoplasia, including hematological malignancies. The increased risk of leukemogenesis is multifactorial and linked to the pathophysiological mechanisms of the clinical manifestations of sickle cell disease. Study Setting: The clinical haematology department of campus teaching hospital and the paediatric onco-haematology unit of Sylvanus Olympio teaching hospital in Lomé were used as study settings. Observations: Four hematologic malignancies were collected in a cohort of 5847 major sickle cell syndromes. The median age of the patients was 31.25 years (extremes: 14 and 58 years) and they were predominantly female (sex ratio M/F = 0.25). Two were on background therapy with hydroxyurea. Among the four patients, there were two cases of acute lymphocytic leukemia, including ALL3 in a 58-year-old SS woman and T-ALL2 in a 12-year-old SC. Then, a case of lymphocytic lymphoma in a 20-year-old SS man was reported and finally a case of chronic myelocytic leukemia in a 33-year-old woman of Sβ+ thalassaemia phenotype. Conclusion: To further report this coexistence, it is therefore essential to systematically consider hematological malignancies during major sickle cell syndromes even if there are similarities in the symptomatology of these two serious pathological situations.

Treatment Efficacy and Safety of Bortezomib Combined with Dexamethasone and Lenalidomide Chemotherapy Regimen for Multiple Myeloma

Objective:To analyze the effect of bortezomib combined with dexamethasone and lenalidomide in the treatment of multiple myeloma.Methods:60 cases of multiple myeloma patients admitted to our hospital from January 2022 to December 2023 were selected randomly,with 30 cases in each group.Bortezomib combined with dexamethasone was administered in the control group,and bortezomib combined with dexamethasone and lenalidomide was given to the observation group,and the treatment effect was analyzed.Results:After treatment,CD^(3+)and CD^(4+)of the observation group were higher than that of the control group,CD^(8+)was lower than that of the control group,and the total treatment efficiency was higher,which was statistically significant(P<0.05),and there was no difference in the total incidence of adverse reactions between the two groups(P>0.05).Conclusion:Bortezomib combined with dexamethasone and lenalidomide is effective in the treatment of multiple myeloma as it regulates the immune function and is safe,thus it can be promoted in clinical practice.

Analysis of the Exploration of Hematology Integration Education Model Guided by“Social Learning Theory”

Diseases of the blood system are highly complicated and involve many aspects.This article aimed to put forward the necessity of integrating quality and professional education,the necessity of learning logic,and the importance of establishing an integrated medical education model when teaching about blood system diseases.According to the requirements of the new medical science,this article puts forward the integration of an“online+offline+clinical”medical education mode based on the social learning theory and a learning evaluation mode based on medical literacy.The fundamental task of cultivating human beings into clinical medical talents with professional ethics,independent learning abilities,interpersonal communication abilities,complex problem-solving abilities,innovative consciousness,and critical thinking was implemented.This article aims to propose an improved construction plan to create a new and improved teaching system in medicine.

Exploration of Curriculum Ideology and Politics Integrating Medical Humanities Cultivation Model to Enhance Medical Core Values

Purpose:To explore the application effect of the cultivation mode of Curriculum Ideology and Political Integration of Medical Humanities to enhance the core values of medicine in the clinical internship stage of medical students.Methods:Students in the clinical internship stage of the First Affiliated Hospital of Baotou Medical College were selected,and a total of 156 students in one random class in each grade were taken as the observation group and received the integration cultivation mode;148 students were taken as the control group and employed the traditional mode.The teaching effect of interns in the two groups was analyzed.Results:The teaching performance of students in both groups after clinical internship teaching was improved compared with that before admission;the teaching performance,teaching effect,teaching evaluation,and teaching satisfaction of the observation group were higher than that of the control group.Conclusion:The integration of the medical humanities training model with curriculum ideology and politics in the clinical internship of medical students is conducive to the improvement of teaching performance,teaching evaluation,teaching satisfaction of teachers and students,and the development and improvement of core values of medical students,which is of good value for teaching application.

2022 Chinese expert consensus and guidelines on clinical management of toxicity in anti-CD19 chimeric antigen receptor T-cell therapy for B-cell non-Hodgkin lymphoma

Adoptive cellular immunotherapy with chimeric antigen receptor(CAR)T cells has emerged as a novel modality for treating relapsed and/or refractory B-cell non-Hodgkin lymphoma(B-NHL).With increasing approval of CAR T-cell products and advances in CAR T cell therapy,CAR T cells are expected to be used in a growing number of cases.However,CAR T-cell-associated toxicities can be severe or even fatal,thus compromising the survival benefit from this therapy.Standardizing and studying the clinical management of these toxicities are imperative.In contrast to other hematological malignancies,such as acute lymphoblastic leukemia and multiple myeloma,anti-CD19 CAR T-cell-associated toxicities in B-NHL have several distinctive features,most notably local cytokine-release syndrome(CRS).However,previously published guidelines have provided few specific recommendations for the grading and management of toxicities associated with CAR T-cell treatment for B-NHL.Consequently,we developed this consensus for the prevention,recognition,and management of these toxicities,on the basis of published literature regarding the management of anti-CD19 CAR T-cell-associated toxicities and the clinical experience of multiple Chinese institutions.This consensus refines a grading system and classification of CRS in B-NHL and corresponding measures for CRS management,and delineates comprehensive principles and exploratory recommendations for managing anti-CD19 CAR T-cell-associated toxicities in addition to CRS.

Preclinical and clinical trials of oncolytic vaccinia virus in cancer immunotherapy:a comprehensive review

Oncolytic virotherapy has emerged as a promising treatment for human cancers owing to an ability to elicit curative effects via systemic administration.Tumor cells often create an unfavorable immunosuppressive microenvironment that degrade viral structures and impede viral replication;however,recent studies have established that viruses altered via genetic modifications can serve as effective oncolytic agents to combat hostile tumor environments.Specifically,oncolytic vaccinia virus(OVV)has gained popularity owing to its safety,potential for systemic delivery,and large gene insertion capacity.This review highlights current research on the use of engineered mutated viruses and gene-armed OVVs to reverse the tumor microenvironment and enhance antitumor activity in vitro and in vivo,and provides an overview of ongoing clinical trials and combination therapies.In addition,we discuss the potential benefits and drawbacks of OVV as a cancer therapy,and explore different perspectives in this field.

Efficacy of concurrent chemoradiotherapy with thalidomide and S-1 for esophageal carcinoma and its influence on serum tumor markers

BACKGROUND Although the current conventional treatment strategies for esophageal carcinoma(EC)have been proven effective,they are often accompanied by serious adverse events.Therefore,it is still necessary to continue to explore new therapeutic strategies for EC to improve the clinical outcome of patients.AIM To elucidate the clinical efficacy of concurrent chemoradiotherapy(CCRT)with thalidomide(THAL)and S-1(tegafur,gimeracil,and oteracil potassium capsules)in the treatment of EC as well as its influence on serum tumor markers(STMs).METHODS First,62 patients with EC treated at the Zibo 148 Hospital between November 2019 and November 2022 were selected and grouped according to the received treatment.Among these,30 patients undergoing CCRT with cis-platinum and 5-fluorouracil were assigned to the control group(Con),and 32 patients receiving CCRT with THAL and S-1 were assigned to the research group(Res).Second,inter-group comparisons were carried out with respect to curative efficacy,incidence of drug toxicities,STMs[carbohydrate antigen 125(CA125)and macrophage inflammatory protein-3α(MIP-3α)],angiogenesis-related indicators[vascular endothelial growth factor(VEGF);VEGF receptor-1(VEGFR-1);basic fibroblast growth factor(bFGF);angiogenin-2(Ang-2)],and quality of life(QoL)[QoL core 30(QLQ-C30)]after one month of treatment.RESULTS The analysis showed no statistical difference in the overall response rate and disease control rate between the two patient cohorts;however,the incidences of grade I–II myelosuppression and gastrointestinal reactions were significantly lower in the Res than in the Con.Besides,the post-treatment CA125,MIP-3α,VEGF,VEGFR-1,bFGF,and Ang-2 Levels in the Res were markedly lower compared with the pre-treatment levels and the corresponding post-treatment levels in the Con.Furthermore,more evident improvements in QLQ-C30 scores from the dimensions of physical,role,emotional,and social functions were determined in the Res.CONCLUSION The above results demonstrate the effectiveness of THAL+S-1 CCRT for EC,which contributes to mild side effects and significant reduction of CA125,MIP-3α,VEGF,VEGFR-1,bFGF,and Ang-2 Levels,thus inhibiting tumors from malignant progression and enhancing patients’QoL.

Immunoregulatory effects of human amniotic mesenchymal stem cells and their exosomes on human peripheral blood mononuclear cells

Background:The immunomodulatory effects of mesenchymal stem cells(MSCs)and their exosomes have been receiving increasing attention.This study investigated the immunoregulatory effects of human amniotic mesenchymal stem cells(hAMSCs)and their exosomes on phytohemagglutinin(PHA)-induced peripheral blood mononuclear cells(PBMCs).Methods:The hAMSCs used in the experiment were identified by light microscopy and flow cytometry,and the differentiation ability of the cells was determined by Oil Red O and Alizarin Red staining.The expressions of transforming growth factor(TGF)-β,indoleamine 2,3-dioxygenase(IDO),cyclooxygenase-2(COX-2),hepatocyte growth factor(HGF),and interleukin(IL)-6 were detected by quantitative real-time polymerase chain reaction and western blotting.PBMCs,hAMSCs,and their exosomes were collected for in vitro group culture.Then the immunoregulatory ability of hAMSCs and their exosomes were analyzed by flow cytometry and Enzymelinked immunosorbent assay.Results:The hAMSCs and exosomes were successfully extracted from the human amniotic membrane.TGF-β,IDO,COX-2,HGF,and IL-6 were significantly expressed in hAMSCs.In vitro co-culture showed that hAMSCs promoted the proliferation of Th2 cells in PHA-induced PBMCs,while hAMSCs and exosomes inhibited the secretion of TNF-αin PHA-induced PBMCs,and promoted the secretion of IL-4 and IL-10,and hAMSCs had more significant effects than exosomes.Conclusions:hAMSCs or exosomes could exert immunoregulatory effects on PHA-induced PBMCs by affecting Th2 cell proliferation and cytokine secretion.

Allogeneic stem cell transplantation in the treatment of acute myeloid leukemia: An overview of obstacles and opportunities

As an important treatment for acute myeloid leukemia, allogeneic hematopoietic stem cell transplantation(allo-HSCT) plays an important role in reducing relapse and improving long-term survival. With rapid advancements in basic research in molecular biology and immunology and with deepening understanding of the biological characteristics of hematopoietic stem cells, allo-HSCT has been widely applied in clinical practice. During allo-HSCT, preconditioning, the donor, and the source of stem cells can be tailored to the patient’s conditions, greatly broadening the indications for HSCT, with clear survival benefits. However, the risks associated with allo-HSCT remain high, i.e. hematopoietic reconstitution failure, delayed immune reconstitution, graft-versus-host disease, and posttransplant relapse, which are bottlenecks for further improvements in allo-HSCT efficacy and have become hot topics in the field of HSCT. Other bottlenecks recognized in the current treatment of individuals diagnosed with acute myeloid leukemia and subjected to allo-HSCT include the selection of the most appropriate conditioning regimen and post-transplantation management. In this paper, we reviewed the progress of relevant research regarding these aspects.

Glucocorticoid-induced thrombotic microangiopathy in paroxysmal nocturnal hemoglobinuria:A case report and review of literature

BACKGROUND Thrombotic microangiopathy(TMA)is a group of disorders that converge on excessive platelet aggregation in the microvasculature,leading to consumptive thrombocytopenia,microangiopathic hemolysis and ischemic end-organ dysfunction.In predisposed patients,TMA can be triggered by many environmental factors.Glucocorticoids(GCs)can compromise the vascular endothelium.However,GC-associated TMA has rarely been reported,which may be due to the lack of awareness of clinicians.Given the high frequency of thrombocytopenia during GC treatment,particular attention should be given to this potentially fatal complication.CASE SUMMARY An elderly Chinese man had a 12-year history of aplastic anemia(AA)and a 3-year history of paroxysmal nocturnal hemoglobinuria(PNH).Three months earlier,methylprednisolone treatment was initiated at 8 mg/d and increased to 20 mg/d to alleviate complement-mediated hemolysis.Following GC treatment,his platelet counts and hemoglobin levels rapidly decreased.After admission to our hospital,the dose of methylprednisolone was increased to 60 mg/d in an attempt to enhance the suppressive effect.However,increasing the GC dose did not alleviate hemolysis,and his cytopenia worsened.Morphological evaluation of the marrow smears revealed increased cellularity with an increased percentage of erythroid progenitors without evident dysplasia.Cluster of differentiation(CD)55 and CD59 expression was significantly decreased on erythrocytes and granulocytes.In the following days,platelet transfusion was required due to severe thrombocytopenia.Observation of platelet transfusion refractoriness indicated that the exacerbated cytopenia may have been caused by the development of TMA due to GC treatment because the transfused platelet concentrates had no defects in glycosylphosphatidylinositol-anchored proteins.We examined blood smears and found a small number of schistocytes,dacryocytes,acanthocytes and target cells.Discontinuation of GC treatment resulted in rapidly increased platelet counts and steady increases in hemoglobin levels.The patient’s platelet counts and hemoglobin levels returned to the levels prior to GC treatment 4 weeks after GC discontinuation.CONCLUSION GCs can drive TMA episodes.When thrombocytopenia occurs during GC treatment,TMA should be considered,and GCs should be discontinued.