BACKGROUND Nonalcoholic fatty liver disease(NAFLD)is the most common cause of chronic liver disease worldwide.Studies have shown a strong association between nonalcoholic steatohepatitis(NASH)cirrhosis and portal vein...BACKGROUND Nonalcoholic fatty liver disease(NAFLD)is the most common cause of chronic liver disease worldwide.Studies have shown a strong association between nonalcoholic steatohepatitis(NASH)cirrhosis and portal vein thrombosis.Specifically,there is paucity of data on the association of NASH and venous thromboembolism(VTE),with one such study predicting a 2.5-fold increased risk for VTE compared to other liver diseases in hospitalized patients.The mechanism is believed to be a hepatocellular injury,which causes a chronic inflammatory state leading to the unregulated activation of procoagulant factors.There has been no prior analysis of the degree of steatosis and fibrosis(measured using transient elastography,commonly known as FibroScan)in NASH and its association with VTE.AIM To examine the association between the degree of hepatic steatosis and fibrosis,quantified by transient elastography,and the incidence of VTE in patients with NASH.METHODS In our case-control study,we included patients with a documented diagnosis of NASH.We excluded patients with inherited thrombophilia,hemoglobinopathy,malignancy,alcohol use disorder,autoimmune hepatitis,and primary biliary cirrhosis.The collected data included age,demographics,tobacco use,recreational drug use,medical history,and vibration controlled transient elastography scores.VTE-specific data included the location,type of anticoagulant,need for hospital stay,and history of VTE recurrence.Steatosis was categorized as S0-S1(mild)and S2-S3(moderate to severe)based on the controlled attenuation parameter score.Fibrosis was classified based on the kilopascal score and graded as F0-F1(Metavir stage),F2,F3,and F4(cirrhosis).χ^(2) and Mann-Whitney U tests were used for the qualitative and quantitative variable analyses,respectively.Furthermore,we performed a logistic regression using VTE as the dependent variable.RESULTS A total of 415 patients were analyzed,and 386 met the inclusion criteria.51 and 335 patients were included in the VTE and non-VTE groups,respectively.Patients with VTE had a mean age of 60.63 years compared to 55.22 years in the non-VTE group(P<0.014).Patients with VTE had a higher body mass index(31.14 kg/m²vs 29.30 kg/m²)and a higher prevalence of diabetes mellitus(29.4%vs 13.1%).The history of NASH was significantly higher in the VTE group(45.1%vs 30.4%,P<0.037).Furthermore,moderate-to-severe steatosis was significantly higher in the VTE group(66.7%vs 47.2%,P<0.009).Similarly,the F2-F4 fibrosis grade had a prevalence of 58.8%in the VTE group compared to 38.5%in the non-VTE group(P<0.006).On logistic regression,using VTE as a dependent variable,diabetes mellitus had an odds ratio(OR)=1.702(P<0.015),and F2-F4 fibrosis grade had an OR=1.5(P<0.033).CONCLUSION Our analysis shows that NASH is an independent risk factor for VTE,especially deep vein thrombosis.There was a statistically significant association between the incidence of VTE,moderate-to-severe steatosis,and fibrosis.All hospitalized patients should be considered for medical thromboprophylaxis,particularly those with NASH.展开更多
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 ste...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.展开更多
Objectives: To explore the relationship between thrombin-antithrombin complex (TAT), plasmin—α plasmin inhibitor complex (PIC), thrombomodulin (TM), tissue plasminogen activator/plasminogen activator inhibitor-1 com...Objectives: To explore the relationship between thrombin-antithrombin complex (TAT), plasmin—α plasmin inhibitor complex (PIC), thrombomodulin (TM), tissue plasminogen activator/plasminogen activator inhibitor-1 complex (t-PAIC) and Gastric cancer. Methods: The plasma levels of TAT, TM, t-PAIC and PIC in patients with gastric cancer (40 in the initial diagnosis group and 35 in the post-treatment group) and 40 healthy controls were measured by chemiluminescent enzyme immunoassay. Then analyze the differences between these indicators in different stages of gastric cancer patients and healthy controls. Results: 1) The plasma levels of TAT, TM, t-PAIC and PIC in the newly diagnosed gastric cancer group were higher than those in the control group and the post-treatment group (P 0.05). 2) The plasma levels of TAT, TM, t-PAIC and PIC were not significantly different among the effective treatment group, the ineffective treatment group and the healthy control group. Conclusion: The changes of TAT, TM, t-PAIC and PIC levels are closely related to the development of patients with gastric cancer, and their increase may indicate that patients have a high risk of thrombosis.展开更多
BACKGROUND Anemia in infants and young children can have long-term effects on cognitive and physical development.In Ma'anshan City,China,there has been growing concern about the prevalence of anemia among children...BACKGROUND Anemia in infants and young children can have long-term effects on cognitive and physical development.In Ma'anshan City,China,there has been growing concern about the prevalence of anemia among children aged 6 to 36 mo.Understanding the factors influencing this condition is crucial for targeted interventions and improving overall child health in the region.AIM To analyze the anemia status and influencing factors of infants and young children aged 6 to 36 mo in Ma'anshan City,China.Providing scientific evidence for reducing the incidence of anemia and improving the health level of children in this age group.METHODS The study encompassed 37698 infants and young children,aged from 6 to 36 mo,who underwent health examinations at the Ma'anshan Maternal and Child Health Hospital from January 2018 to October 2022 were included in the study.Basic information,physical examination,and hemoglobin detection data were collected.Descriptive analysis was used to analyze the prevalence of anemia in children in the region,and univariate analysis was used to analyze the influencing factors of anemia.RESULTS The mean hemoglobin level of infants and young children aged 9 to 36 mo increased with age,and the anemia detection rate decreased with age.The anemia detection rate in rural infants aged 6,9,and 12 mo was higher than that in urban infants.Although the anemia detection rate was higher in 6-mo-old boys than girls,it was higher in 24-mo-old girls than boys.There were statistically significant differences in the anemia detection rates among 9-mo-old and 12-mo-old infants with different nutritional statuses(emaciation,overweight,obese,and normal).Moreover,there were no statistically significant differences in anemia detection rates among infants and young children with different nutritional statuses at other ages.Besides,the anemia detection rates in obese infants aged 9 and 12 mo were higher than those in normal and overweight infants,with statistically significant differences.Finally,there were no statistically significant differences in the anemia detection rates between emaciation infants and those with other nutritional statuses.CONCLUSION The anemia situation among infants and young children aged 6 to 36 mo in Ma'anshan City,China,is relatively prominent and influenced by various factors.Our result shown that attention should be paid to the anemic infant and young child population,with strengthened education and targeted prevention and dietary guidance to help them establish good living habits,improve nutritional status,and reduce the occurrence of anemia to improve children's health levels.展开更多
Invasive fungal infections are a major challenging problem in the management of febrile neutropenia (FN) in patients with hematologic malignancies. Liposomal amphotericin B (L-AmB) or micafungin (MCFG) has been widely...Invasive fungal infections are a major challenging problem in the management of febrile neutropenia (FN) in patients with hematologic malignancies. Liposomal amphotericin B (L-AmB) or micafungin (MCFG) has been widely used as a first-line empirical antifungal therapy for suspected fungal infection in such patients. However, there are several issues in patients receiving these agents: drug related toxicities for L-AmB and breakthrough fungal infections for MCFG. In order to make the best use of these 2 agents, we conducted a prospective study of sequential therapy from MCFG to L-AmB, and evaluated the efficacy and safety of this strategy in FN patients with hematologic malignancies. A total of 18 patients were enrolled, and 11 patients who fulfilled the protocol defined criteria were evaluated. Underlying diseases consisted of acute leukemia (n = 9), non-Hodgkin lymphoma (n = 1), and myelodysplastic syndrome (n = 1). Treatment success was achieved in 8 patients (72.7%). Drug-related adverse events occurred in 8 patients (72.7%). All of those adverse events except one case were below grade 2. Three patients required discontinuation of L-AmB. Although our empirical antifungal sequential therapy seems to be encouraging for antibiotics-refractory FN in patients with hematologic malignancies, further investigation in large-scale studies is warranted.展开更多
BACKGROUND The May-Hegglin anomaly is among a group of genetic disorders known as MYH9-related disease.Patients with inherited platelet disorders such as May-Hegglin anomaly are at a variably increased risk for bleedi...BACKGROUND The May-Hegglin anomaly is among a group of genetic disorders known as MYH9-related disease.Patients with inherited platelet disorders such as May-Hegglin anomaly are at a variably increased risk for bleeding due to a combination of platelet dysfunction and thrombocytopenia.Patients admitted to the hospital with coronavirus disease 2019(COVID-19)infection are at an increased risk for a venous thromboembolism event(VTE).The National Institutes of Health COVID-19 treatment guidelines recommend using a prophylactic dose of heparin as VTE prophylaxis for adults who are receiving high-flow oxygen.We describe a patient admitted for COVID-19 infection with pneumonia and a history of May-Hegglin anomaly.The patient presented a challenge to determine prophylactic anticoagulation as there are no clear guidelines for this patient population.CASE SUMMARY Herein,we describe the case of a 39-year-old woman admitted with acute hypoxic respiratory failure secondary to COVID-19 pneumonia.She had a history of May-Hegglin anomaly and demonstrated risk for bleeding since childhood,including a life-threatening bleeding event at the age of 9 years requiring blood and platelet transfusions.Her baseline platelet count was 40-50×109/L throughout her adult life.Her family history was also notable for May-Hegglin disorder in her mother,maternal uncle,maternal grandfather and her son.Computed tomography/pulmonary angiography revealed bilateral consolidative opacities consistent with multifocal pneumonia.Complete blood count was notable for platelet count of 54×109/L.She was admitted for inpatient respiratory support with high-flow oxygen per nasal cannula and was managed with guideline-directed therapy for COVID-19,including baricitinib and dexamethasone.The Hematology/Oncology consultation team was requested to assist with management of VTE prophylaxis in the setting of active COVID-19 infection and an inherited bleeding disorder.After review of the literature and careful consideration of risks and benefits,it was decided to treat the patient with prophylactic enoxaparin.She was closely monitored in the hospital for bleeding and worsening thrombocytopenia.She had no bleeding or signs of VTE.Her respiratory status improved,and she was discharged home after 5 d of hospitalization with supplemental oxygen by nasal cannula and dexamethasone.At the 6-month follow-up,the patient successfully discontinued her home oxygen use after only a few weeks following discharge.CONCLUSION The patient presented a challenge to determine prophylactic anticoagulation as anticoagulation guidelines exist for patients with COVID-19,but there are no clear guidelines for management of patients with COVID-19 and inherited bleeding disorders,particularly those with MYH9-related disease.She was discharged after recovery from the COVID-19 infection without bleeding or thrombosis.As there are no published guidelines for this situation,we present a pragmatic,informed approach to a patient with MYH9-related disease who had an indication for anticoagulation.展开更多
BACKGROUND Limited knowledge exists regarding the casual associations linking blood metabolites and the risk of developing colorectal cancer.AIM To investigate causal associations between blood metabolites and colon c...BACKGROUND Limited knowledge exists regarding the casual associations linking blood metabolites and the risk of developing colorectal cancer.AIM To investigate causal associations between blood metabolites and colon cancer.METHODS The study utilized a two-sample Mendelian randomization(MR)analysis to investigate the causal impact of 486 blood metabolites on colorectal cancer.The primary method of analysis used was the inverse variance weighted model.To further validate the results several sensitivity analyses were performed,including Cochran's Q test,MR-Egger intercept test,and MR robust adjusted profile score.These additional analyses were conducted to ensure the reliability and robustness of the findings.RESULTS After rigorous selection for genetic variation,486 blood metabolites were included in the MR analysis.We found Mannose[odds ratio(OR)=2.09(1.10-3.97),P=0.024],N-acetylglycine[OR=3.14(1.78-5.53),P=7.54×10^(-8)],X-11593-O-methylascorbate[OR=1.68(1.04-2.72),P=0.034],1-arachidonoylglycerophosphocholine[OR=4.23(2.51-7.12),P=6.35×10^(-8)]and 1-arachidonoylglycerophosphoethanolamine 4[OR=3.99(1.17-13.54),P=0.027]were positively causally associated with colorectal cancer,and we also found a negative causal relationship between Tyrosine[OR=0.08(0.01-0.63),P=0.014],Urate[OR=0.25(0.10-0.62),P=0.003],N-acetylglycine[0.73(0.54-0.98),P=0.033],X-12092[OR=0.89(0.81-0.99),P=0.028],Succinylcarnitine[OR=0.48(0.27-0.84),P=0.09]with colorectal cancer.A series of sensitivity analyses were performed to confirm the rigidity of the results.CONCLUSION This study showed a causal relationship between 10 blood metabolites and colorectal cancer,of which 5 blood metabolites were found to be causal for the development of colorectal cancer and were confirmed as risk factors.The other five blood metabolites are protective factors.展开更多
AIM: To report the long-term outcome of patients after complete ablation of non-neoplastic Barrett's esophagus (BE) with respect to BE relapse and development of intraepithelial neoplasia or esophageal adenocarcin...AIM: To report the long-term outcome of patients after complete ablation of non-neoplastic Barrett's esophagus (BE) with respect to BE relapse and development of intraepithelial neoplasia or esophageal adenocarcinoma.METHODS: In 70 patients with histologically proven nonneoplastic BE, complete BE ablation was achieved by argon plasma coagulation (APC) and high-dose proton pump inhibitor therapy (120 mg omeprazole daily). Sixty-six patients (94.4%) underwent further surveillance endoscopy. At each surveillance endoscopy four-quadrant biopsies were taken from the neo-squamous epithelium at 2 cm intervals depending on the pre-treatment length of BE mucosa beginning at the neo-Z-line, and from any endoscopically suspicious lesion.RESULTS: The median follow-up of 66 patients was 51 mo (range 9-85 mo) giving a total of 280.5 patient years.A mean of 6 biopsies were taken during surveillance endoscopies. In 13 patients (19.7%) tongues or islands suspicious for BE were found during endoscopy. In 8 of these patients (12.1%) non-neoplastic BE relapse was confirmed histologically giving a histological relapse rate of 3% per year. In none of the patients, intraepithelial neoplasia nor an esophageal adenocarcinoma was detected.Logistic regression analysis identified endoscopic detection of islands or tongues as the only positive predictor of BE relapse (P = 0.0004).CONCLUSION: The long-term relapse rate of nonneoplastic BE following complete ablation with high-power APC is low (3% per year).展开更多
Venous thromboembolism event(VTE) is a common and morbid complication in cancer patients. Patients with gastrointestinal cancers often suffer from symptomatic or incidental splanchnic vein thrombosis, impaired liver f...Venous thromboembolism event(VTE) is a common and morbid complication in cancer patients. Patients with gastrointestinal cancers often suffer from symptomatic or incidental splanchnic vein thrombosis, impaired liver function and/or thrombocytopenia. These characteristics require a thorough risk/benefit evaluation for individual patients. Considering the risk factors for the development of VTE and bleeding events in addition to recent study results may be helpful for correct initiation of primary pharmacological prevention and treatment of cancer-associated thrombosis(CAT), preferably with low molecular weight heparins(LMWH). Whereas thromboprophylaxis is most often recommended in hospitalized surgical and non-surgical patients with malignancy, there is less agreement as to its duration. With regard to ambulatory cancer patients, the lack of robust data results in low grade recommendations against routine use of anticoagulant drugs. Anticoagulation with LMWH for the first months is the evidence-based treatment for acute CAT, but duration of secondary prevention and the drug of choice are unclear. Based on published guidelines and literature, this review will focus on prevention and treatment strategies of VTE in patients with gastrointestinal cancers.展开更多
Objective To measure the quantities and apoptosis-related protein levels of B lymphocyte in the patients with immunorelated pancytopenia(IRP)and explore the action of B lymphocyte in the pathogenic mechanism of IRP. M...Objective To measure the quantities and apoptosis-related protein levels of B lymphocyte in the patients with immunorelated pancytopenia(IRP)and explore the action of B lymphocyte in the pathogenic mechanism of IRP. Methods Quantities of whole B lymphocytes and CD5+ B lymphocytes as well as the expressions of Fas and Bcl-2 in B lymphocytes in 35 patients with untreated IRP, 15 IRP patients in complete remission (CR), and 10 normal controls were assayed by flow cytometry. Results The percentages of B lymphocyte and CD5+ B lymphocyte were significantly higher in untreated IRP patients than in CR IRP patients and normal controls (P<0.05), and there was no significant difference between the latter two groups (P>0.05). There was no significant difference of Fas expression in B lymphocyte among three groups (P>0.05). The expression of Bcl-2 in B lymphocyte was significantly higher in untreated patients than in CR patients or normal controls (P<0.01), and significantly higher in CR patients than in normal controls (P<0.01). The apoptosis-related index was significantly lower in untreated patients than in CR patients or normal controls (P<0.05), and significantly lower in CR patients than in normal controls (P<0.05). The percentage of B lymphocyte was positively correlated with post-treated response time(r=0.53, P<0.01). Conclusion The production of auto-antibodies in IRP patients probably has some relationship with the abnormal quantities of B lymphocyte and its subpopulations as well as with the inhibition of B lymphocyte apoptosis.展开更多
Utilization of mesenchymal stromal cells(MSCs) for the treatment of Crohn's disease and ulcerative colitis is of translational interest.Safety of MSC therapy has been well demonstrated in early phase clinical tria...Utilization of mesenchymal stromal cells(MSCs) for the treatment of Crohn's disease and ulcerative colitis is of translational interest.Safety of MSC therapy has been well demonstrated in early phase clinical trials but efficacy in randomized clinical trials needs to be demonstrated.Understanding MSC mechanisms of action to reduce gut injury and inflammation is necessary to improve current ongoing and future clinical trials.However, two major hurdles impede the direct translation of data derived from animal experiments to the clinical situation:(1) limitations of the currently available animal models of colitis that reflect human inflammatory bowel diseases(IBD).The etiology and progression of human IBD are multifactorial and hence a challenge to mimic in animal models; and(2) Species specific differences in the functionality of MSCs derived from mice versus humans.MSCs derived from mice and humans are not identical in their mechanisms of action in suppressing inflammation.Thus, preclinical animal studies with murine derived MSCs cannot be considered as an exact replica of human MSC based clinical trials.In the present review, we discuss the therapeutic properties of MSCs in preclinical and clinical studies of IBD.We also discuss the challenges and approaches of using appropriate animal models of colitis, not only to study putative MSC therapeutic efficacy and their mechanisms of action, but also the suitability of translating findings derived from such studies to the clinic.展开更多
AIM: To investigate the differentiation status and key factors to facilitate hepatic differentiation of human bone-marrow-derived mesenchymal stem cells (MSCs). METHODS: Human MSCs derived from bone marrow were induce...AIM: To investigate the differentiation status and key factors to facilitate hepatic differentiation of human bone-marrow-derived mesenchymal stem cells (MSCs). METHODS: Human MSCs derived from bone marrow were induced into hepatocyte-like cells following a previously published protocol. The differentiation status of the hepatocyte-like cells was compared with various human hepatoma cell lines. Overexpression of hepatocyte nuclear factor (HNF)-4α was mediated by adenovirus infection of these hepatocyte-like cells. The expression of interesting genes was then examined by either re-verse transcription-polymerase chain reaction (RT-PCR) or real-time RT-PCR methods. RESULTS: Our results demonstrated that the differentiation status of hepatocyte-like cells induced from human MSCs was relatively similar to poorly differentiated human hepatoma cell lines. Interestingly, the HNF-4 isoform in induced MSCs and poorly differentiated human hepatoma cell lines was identified as HNF4γ instead of HNF-4α. Overexpression of HNF-4α in induced MSCs significantly enhanced the expression level of hepatic-specific genes, liver-enriched transcription factors, and cytochrome P450 (P450) genes. CONCLUSION: Overexpression of HNF-4α improves the hepatic differentiation of human MSCs from bone marrow and is a simple way of providing better cell sources for clinical applications.展开更多
Background: The programmed cell death-1(PD-1)/programmed cell death-ligand 1(PD-L1) pathway inhibits the activation of T cells and plays a crucial role in the negative regulation of cellular and humoral immune respons...Background: The programmed cell death-1(PD-1)/programmed cell death-ligand 1(PD-L1) pathway inhibits the activation of T cells and plays a crucial role in the negative regulation of cellular and humoral immune responses.Diffuse large B-cell lymphoma(DLBCL) is the most common lymphoid malignancy in adults. In the present study, we aimed to detect the expression of PD-L1 in DLBCL and to analyze its relationship with prognosis.Methods: We reviewed medical records of 204 newly diagnosed DLBCL patients in Sun Yat-sen University Cancer Center between October 2005 and August 2012. The expression of PD-L1 in tumor tissues from these 204 patients was detected using immunohistochemical(IHC) assay. The expression of anaplastic lymphoma kinase(ALK), CD5,CD30, and C-Myc in tumor specimens from 109 patients was detected using IHC, and Epstein-Barr virus(EBV)-encoded RNAs(EBERs) were detected using fluorescence in situ hybridization. The Spearman method was used for correlation analysis. The Kaplan-Meier method with log-rank test was used for univariate analysis. Cox proportional hazards model was used for multivariate analysis.Results: Of the 204 patients, 100(49.0%) were PD-L1-positive in tumor cells and 44(21.6%) were PD-L1-positive in tumor microenvironment. PD-L1 expression in tumor cells and tumor microenvironment were more common in the non-germinal center B-cell-like(GCB) subtype than in the GCB subtype(P = 0.02 and P= 0.04). Patients with PD-L1 expression in tumor microenvironment were more likely to be resistant to first-line chemotherapy when compared with the patients without PD-L1 expression in tumor microenvironment(P = 0.03). PD-L1 expression in tumor microenvironment was negatively correlated with C-Myc expression(r =-0.20, P = 0.04). No correlations were detected between PD-L1 expression and the expression of ALK, CD5, and CD30 as well as EBERs. The 5-year overall survival(OS)rates were 50.0% and 67.3% in patients with and without PD-L1 expression in tumor cells(P = 0.02). PD-L1 expression in tumor cells was an independent risk predictor for OS(P < 0.01).Conclusions: PD-L1 expression is more common in the non-GCB subtype than in the GCB subtype. PD-L1 expression in tumor microenvironment has a negative correlation with C-Myc. PD-L1 positivity predicts short survival in DLBCL patients. For patients with PD-L1 expression, more strategy such as anti-PD-L1 antibody treatment should be recommended.展开更多
AIM: To evaluate the endoscopic manifestations and prognoses of gastrointestinal (GI) mantle cell lymphoma (MCL). METHODS: A database search at the Department of Pathology of Okayama University Graduate School of Medi...AIM: To evaluate the endoscopic manifestations and prognoses of gastrointestinal (GI) mantle cell lymphoma (MCL). METHODS: A database search at the Department of Pathology of Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences revealed 57 MCL patients with GI involvement. Clinical records were available for 35 of the 57 patients from 21 institutions, and those 35 patients were enrolled in this study. We summarized the gross types of endoscopic features, event-free survival (EFS), and overall survival (OS) of those patients.RESULTS: Of the 35 patients, GI involvement in the esophagus, stomach, and duodenum was found in 2 (5.7%), 26 (74.3%), and 12 (34.3%) patients, respectively. Twenty-one of the 35 patients underwent colonoscopy; among them, GI involvement in the ileum, cecum, colon, and rectum was found in 10 (47.6%), 3 (14.3%), 12 (57.1%), and 10 (47.6%), respectively. Various lesions, such as superficial, protruded, fold thickening, or ulcerative, were found in the stomach, whereas multiple lymphomatous polyposis (MLP) was dominant from the duodenum to the rectum. Twelve patients were treated with a hyper-CVAD/MA regimen, and they had better OS (3-year rate, 88.3% vs 46.4%, P < 0.01) and better EFS (3-year rate, 66.7% vs 33.8%, P < 0.05) than the remaining 23 patients who were not treated with this regimen. CONCLUSION: MLP was a representative form of intestinal involvement, whereas a variety of lesions were found in the stomach. The hyper-CVAD/MA regimen may improve survival in these patients.展开更多
Colorectal cancer is the second most common cause of cancer-related death in many industrialized countries and is characterized by a heterogenic pool of cells with distinct differentiation patterns. Recently, the conc...Colorectal cancer is the second most common cause of cancer-related death in many industrialized countries and is characterized by a heterogenic pool of cells with distinct differentiation patterns. Recently, the concept that cancer might arise from a rare population of cells with stem cell-like properties has received support with regard to several solid tumors, including colorectal cancer. According to the cancer stem cell hypothesis, cancer can be considered a disease in which mutations either convert normal stem cells into aberrant counterparts or cause a more differentiated cell to revert toward a stem cell-like behaviour; either way these cells are thought to be responsible for tumor generation and propagation. The statement that only a subset of cells drives tumor formation has major implications for the development of new targeted therapeutic strategies aimed at eradicating the tumor stem cell population. This review will focus on the biology of normal and malignant colonic stem cells, which might contribute to our understanding of the mechanisms responsible for tumor development and resistance to therapy.展开更多
Despite numerous advances in treatment options,advanced gastric cancer(AGC)remains a major public health issue and the leading cause of cancer-related deaths.Cisplatin is one of the most effective broadspectrum antica...Despite numerous advances in treatment options,advanced gastric cancer(AGC)remains a major public health issue and the leading cause of cancer-related deaths.Cisplatin is one of the most effective broadspectrum anticancer drugs for AGC and a doublet combination regimen of either cisplatin-based or 5-fluorouracil(5FU)-based chemotherapy is generally used for treatment of patients with AGC.However,there is still no consensus on the best regimen for treating AGC.Recently,various new chemotherapeutic agents,including oral 5FU,taxanes,and irinotecan,have been identified as improving the outcomes for AGC when used as a single agent or in combination with nonplatinum chemotherapy.Nonetheless,it is still unclear whether non-platinum-based chemotherapy is a viable treatment option for patients with AGC.Accordingly,this review focuses on the efficacy and tolerability of non-platinum-based chemotherapy for patients with AGC.展开更多
Hepatocellular carcinoma(HCC) is one of the most common malignancies leading to high mortality rates in the general population; in cirrhotic patients, it is the primary cause of death. The diagnosis is usually delayed...Hepatocellular carcinoma(HCC) is one of the most common malignancies leading to high mortality rates in the general population; in cirrhotic patients, it is the primary cause of death. The diagnosis is usually delayed in spite of at-risk population screening recommendations, i.e., patients infected with hepatitis B or C virus. Hepatocarcinogenesis hinges on a great number of genetic and molecular abnormalities that lead to tumor angiogenesis and foster their dissemination potential. The diagnosis is mainly based on imaging studies such as computed tomography and magnetic resonance, in which lesions present a characteristic classical pattern of early arterial enhancement followed by contrast medium "washout" in late venous phase. On occasion, when imaging studies are not conclusive, biopsy of the lesion must be performed to establish the diagnosis. The Barcelona Clinic Liver Cancer staging method is the most frequently used worldwide and recommended by the international guidelines of HCC management. Currently available treatments include tumor resection, liver transplant, sorafenib and locoregional therapies(alcoholization, radiofrequency ablation, chemoembolization). The prognosis of hepatocarcinoma is determined according to the lesion's stage and in cirrhotic patients, on residual liver function. Curative treatments, such as liver transplant, are sought in patients diagnosed in early stages; patients in more advanced stages, were not greatly benefitted by chemotherapy in terms of survival until the advent of target molecules such as sorafenib.展开更多
Mammalian target of rapamycin (mTOR) is aberrantly activated in many cancer types, and two rapamycin derivatives are currently approved by the Food and Drug Administration (FDA) of the United States for treating renal...Mammalian target of rapamycin (mTOR) is aberrantly activated in many cancer types, and two rapamycin derivatives are currently approved by the Food and Drug Administration (FDA) of the United States for treating renal cell carcinoma. Mechanistically, mTOR is hyperactivated in human cancers either due to the genetic activation of its upstream activating signaling pathways or the genetic inactivation of its negative regulators. The tumor suppressor liver kinase B1 (LKB1), also known as serine/threonine kinase 11 (STK11), is involved in cell polarity, cell detachment and adhesion, tumor metastasis, and energetic stress response. A key role of LKB1 is to negatively regulate the activity of mTOR complex 1 (mTORC1). This review summarizes the molecular basis of this negative interaction and recent research progress in this area.展开更多
Krüppel-like factors (KLFs) are evolutionarily conserved zinc finger-containing transcription factors with diverseregulatory functions in cell growth, proliferation, differentiation, and embryogenesis. KLF4 and K...Krüppel-like factors (KLFs) are evolutionarily conserved zinc finger-containing transcription factors with diverseregulatory functions in cell growth, proliferation, differentiation, and embryogenesis. KLF4 and KLF5 are two closelyrelated members of the KLF family that have a similar tissue distribution in embryos and adults. However, the two KLFsoften exhibit opposite effects on regulation of gene transcription, despite binding to similar, if not identical, cis-actingDNA sequences. In addition, KLF4 and 5 exert contrasting effects on cell proliferation in many instances; while KLF4is an inhibitor of cell growth, KLF5 stimulates proliferation. Here we review the biological properties and biochemicalmechanisms of action of the two KLFs in the context of growth regulation.展开更多
基金This protocol was developed,reviewed,and sanctioned by the joint institutional review board at MetroWest Medical Center under Approval No.2020-035.
文摘BACKGROUND Nonalcoholic fatty liver disease(NAFLD)is the most common cause of chronic liver disease worldwide.Studies have shown a strong association between nonalcoholic steatohepatitis(NASH)cirrhosis and portal vein thrombosis.Specifically,there is paucity of data on the association of NASH and venous thromboembolism(VTE),with one such study predicting a 2.5-fold increased risk for VTE compared to other liver diseases in hospitalized patients.The mechanism is believed to be a hepatocellular injury,which causes a chronic inflammatory state leading to the unregulated activation of procoagulant factors.There has been no prior analysis of the degree of steatosis and fibrosis(measured using transient elastography,commonly known as FibroScan)in NASH and its association with VTE.AIM To examine the association between the degree of hepatic steatosis and fibrosis,quantified by transient elastography,and the incidence of VTE in patients with NASH.METHODS In our case-control study,we included patients with a documented diagnosis of NASH.We excluded patients with inherited thrombophilia,hemoglobinopathy,malignancy,alcohol use disorder,autoimmune hepatitis,and primary biliary cirrhosis.The collected data included age,demographics,tobacco use,recreational drug use,medical history,and vibration controlled transient elastography scores.VTE-specific data included the location,type of anticoagulant,need for hospital stay,and history of VTE recurrence.Steatosis was categorized as S0-S1(mild)and S2-S3(moderate to severe)based on the controlled attenuation parameter score.Fibrosis was classified based on the kilopascal score and graded as F0-F1(Metavir stage),F2,F3,and F4(cirrhosis).χ^(2) and Mann-Whitney U tests were used for the qualitative and quantitative variable analyses,respectively.Furthermore,we performed a logistic regression using VTE as the dependent variable.RESULTS A total of 415 patients were analyzed,and 386 met the inclusion criteria.51 and 335 patients were included in the VTE and non-VTE groups,respectively.Patients with VTE had a mean age of 60.63 years compared to 55.22 years in the non-VTE group(P<0.014).Patients with VTE had a higher body mass index(31.14 kg/m²vs 29.30 kg/m²)and a higher prevalence of diabetes mellitus(29.4%vs 13.1%).The history of NASH was significantly higher in the VTE group(45.1%vs 30.4%,P<0.037).Furthermore,moderate-to-severe steatosis was significantly higher in the VTE group(66.7%vs 47.2%,P<0.009).Similarly,the F2-F4 fibrosis grade had a prevalence of 58.8%in the VTE group compared to 38.5%in the non-VTE group(P<0.006).On logistic regression,using VTE as a dependent variable,diabetes mellitus had an odds ratio(OR)=1.702(P<0.015),and F2-F4 fibrosis grade had an OR=1.5(P<0.033).CONCLUSION Our analysis shows that NASH is an independent risk factor for VTE,especially deep vein thrombosis.There was a statistically significant association between the incidence of VTE,moderate-to-severe steatosis,and fibrosis.All hospitalized patients should be considered for medical thromboprophylaxis,particularly those with NASH.
基金Research Program of Health Committee of Hunan Province(202106010870)to Xin Tian.
文摘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.
文摘Objectives: To explore the relationship between thrombin-antithrombin complex (TAT), plasmin—α plasmin inhibitor complex (PIC), thrombomodulin (TM), tissue plasminogen activator/plasminogen activator inhibitor-1 complex (t-PAIC) and Gastric cancer. Methods: The plasma levels of TAT, TM, t-PAIC and PIC in patients with gastric cancer (40 in the initial diagnosis group and 35 in the post-treatment group) and 40 healthy controls were measured by chemiluminescent enzyme immunoassay. Then analyze the differences between these indicators in different stages of gastric cancer patients and healthy controls. Results: 1) The plasma levels of TAT, TM, t-PAIC and PIC in the newly diagnosed gastric cancer group were higher than those in the control group and the post-treatment group (P 0.05). 2) The plasma levels of TAT, TM, t-PAIC and PIC were not significantly different among the effective treatment group, the ineffective treatment group and the healthy control group. Conclusion: The changes of TAT, TM, t-PAIC and PIC levels are closely related to the development of patients with gastric cancer, and their increase may indicate that patients have a high risk of thrombosis.
文摘BACKGROUND Anemia in infants and young children can have long-term effects on cognitive and physical development.In Ma'anshan City,China,there has been growing concern about the prevalence of anemia among children aged 6 to 36 mo.Understanding the factors influencing this condition is crucial for targeted interventions and improving overall child health in the region.AIM To analyze the anemia status and influencing factors of infants and young children aged 6 to 36 mo in Ma'anshan City,China.Providing scientific evidence for reducing the incidence of anemia and improving the health level of children in this age group.METHODS The study encompassed 37698 infants and young children,aged from 6 to 36 mo,who underwent health examinations at the Ma'anshan Maternal and Child Health Hospital from January 2018 to October 2022 were included in the study.Basic information,physical examination,and hemoglobin detection data were collected.Descriptive analysis was used to analyze the prevalence of anemia in children in the region,and univariate analysis was used to analyze the influencing factors of anemia.RESULTS The mean hemoglobin level of infants and young children aged 9 to 36 mo increased with age,and the anemia detection rate decreased with age.The anemia detection rate in rural infants aged 6,9,and 12 mo was higher than that in urban infants.Although the anemia detection rate was higher in 6-mo-old boys than girls,it was higher in 24-mo-old girls than boys.There were statistically significant differences in the anemia detection rates among 9-mo-old and 12-mo-old infants with different nutritional statuses(emaciation,overweight,obese,and normal).Moreover,there were no statistically significant differences in anemia detection rates among infants and young children with different nutritional statuses at other ages.Besides,the anemia detection rates in obese infants aged 9 and 12 mo were higher than those in normal and overweight infants,with statistically significant differences.Finally,there were no statistically significant differences in the anemia detection rates between emaciation infants and those with other nutritional statuses.CONCLUSION The anemia situation among infants and young children aged 6 to 36 mo in Ma'anshan City,China,is relatively prominent and influenced by various factors.Our result shown that attention should be paid to the anemic infant and young child population,with strengthened education and targeted prevention and dietary guidance to help them establish good living habits,improve nutritional status,and reduce the occurrence of anemia to improve children's health levels.
文摘Invasive fungal infections are a major challenging problem in the management of febrile neutropenia (FN) in patients with hematologic malignancies. Liposomal amphotericin B (L-AmB) or micafungin (MCFG) has been widely used as a first-line empirical antifungal therapy for suspected fungal infection in such patients. However, there are several issues in patients receiving these agents: drug related toxicities for L-AmB and breakthrough fungal infections for MCFG. In order to make the best use of these 2 agents, we conducted a prospective study of sequential therapy from MCFG to L-AmB, and evaluated the efficacy and safety of this strategy in FN patients with hematologic malignancies. A total of 18 patients were enrolled, and 11 patients who fulfilled the protocol defined criteria were evaluated. Underlying diseases consisted of acute leukemia (n = 9), non-Hodgkin lymphoma (n = 1), and myelodysplastic syndrome (n = 1). Treatment success was achieved in 8 patients (72.7%). Drug-related adverse events occurred in 8 patients (72.7%). All of those adverse events except one case were below grade 2. Three patients required discontinuation of L-AmB. Although our empirical antifungal sequential therapy seems to be encouraging for antibiotics-refractory FN in patients with hematologic malignancies, further investigation in large-scale studies is warranted.
文摘BACKGROUND The May-Hegglin anomaly is among a group of genetic disorders known as MYH9-related disease.Patients with inherited platelet disorders such as May-Hegglin anomaly are at a variably increased risk for bleeding due to a combination of platelet dysfunction and thrombocytopenia.Patients admitted to the hospital with coronavirus disease 2019(COVID-19)infection are at an increased risk for a venous thromboembolism event(VTE).The National Institutes of Health COVID-19 treatment guidelines recommend using a prophylactic dose of heparin as VTE prophylaxis for adults who are receiving high-flow oxygen.We describe a patient admitted for COVID-19 infection with pneumonia and a history of May-Hegglin anomaly.The patient presented a challenge to determine prophylactic anticoagulation as there are no clear guidelines for this patient population.CASE SUMMARY Herein,we describe the case of a 39-year-old woman admitted with acute hypoxic respiratory failure secondary to COVID-19 pneumonia.She had a history of May-Hegglin anomaly and demonstrated risk for bleeding since childhood,including a life-threatening bleeding event at the age of 9 years requiring blood and platelet transfusions.Her baseline platelet count was 40-50×109/L throughout her adult life.Her family history was also notable for May-Hegglin disorder in her mother,maternal uncle,maternal grandfather and her son.Computed tomography/pulmonary angiography revealed bilateral consolidative opacities consistent with multifocal pneumonia.Complete blood count was notable for platelet count of 54×109/L.She was admitted for inpatient respiratory support with high-flow oxygen per nasal cannula and was managed with guideline-directed therapy for COVID-19,including baricitinib and dexamethasone.The Hematology/Oncology consultation team was requested to assist with management of VTE prophylaxis in the setting of active COVID-19 infection and an inherited bleeding disorder.After review of the literature and careful consideration of risks and benefits,it was decided to treat the patient with prophylactic enoxaparin.She was closely monitored in the hospital for bleeding and worsening thrombocytopenia.She had no bleeding or signs of VTE.Her respiratory status improved,and she was discharged home after 5 d of hospitalization with supplemental oxygen by nasal cannula and dexamethasone.At the 6-month follow-up,the patient successfully discontinued her home oxygen use after only a few weeks following discharge.CONCLUSION The patient presented a challenge to determine prophylactic anticoagulation as anticoagulation guidelines exist for patients with COVID-19,but there are no clear guidelines for management of patients with COVID-19 and inherited bleeding disorders,particularly those with MYH9-related disease.She was discharged after recovery from the COVID-19 infection without bleeding or thrombosis.As there are no published guidelines for this situation,we present a pragmatic,informed approach to a patient with MYH9-related disease who had an indication for anticoagulation.
基金Supported by the General Project of Medical and Health Technology Plan of Zhejiang Province,No.2020KY845.
文摘BACKGROUND Limited knowledge exists regarding the casual associations linking blood metabolites and the risk of developing colorectal cancer.AIM To investigate causal associations between blood metabolites and colon cancer.METHODS The study utilized a two-sample Mendelian randomization(MR)analysis to investigate the causal impact of 486 blood metabolites on colorectal cancer.The primary method of analysis used was the inverse variance weighted model.To further validate the results several sensitivity analyses were performed,including Cochran's Q test,MR-Egger intercept test,and MR robust adjusted profile score.These additional analyses were conducted to ensure the reliability and robustness of the findings.RESULTS After rigorous selection for genetic variation,486 blood metabolites were included in the MR analysis.We found Mannose[odds ratio(OR)=2.09(1.10-3.97),P=0.024],N-acetylglycine[OR=3.14(1.78-5.53),P=7.54×10^(-8)],X-11593-O-methylascorbate[OR=1.68(1.04-2.72),P=0.034],1-arachidonoylglycerophosphocholine[OR=4.23(2.51-7.12),P=6.35×10^(-8)]and 1-arachidonoylglycerophosphoethanolamine 4[OR=3.99(1.17-13.54),P=0.027]were positively causally associated with colorectal cancer,and we also found a negative causal relationship between Tyrosine[OR=0.08(0.01-0.63),P=0.014],Urate[OR=0.25(0.10-0.62),P=0.003],N-acetylglycine[0.73(0.54-0.98),P=0.033],X-12092[OR=0.89(0.81-0.99),P=0.028],Succinylcarnitine[OR=0.48(0.27-0.84),P=0.09]with colorectal cancer.A series of sensitivity analyses were performed to confirm the rigidity of the results.CONCLUSION This study showed a causal relationship between 10 blood metabolites and colorectal cancer,of which 5 blood metabolites were found to be causal for the development of colorectal cancer and were confirmed as risk factors.The other five blood metabolites are protective factors.
文摘AIM: To report the long-term outcome of patients after complete ablation of non-neoplastic Barrett's esophagus (BE) with respect to BE relapse and development of intraepithelial neoplasia or esophageal adenocarcinoma.METHODS: In 70 patients with histologically proven nonneoplastic BE, complete BE ablation was achieved by argon plasma coagulation (APC) and high-dose proton pump inhibitor therapy (120 mg omeprazole daily). Sixty-six patients (94.4%) underwent further surveillance endoscopy. At each surveillance endoscopy four-quadrant biopsies were taken from the neo-squamous epithelium at 2 cm intervals depending on the pre-treatment length of BE mucosa beginning at the neo-Z-line, and from any endoscopically suspicious lesion.RESULTS: The median follow-up of 66 patients was 51 mo (range 9-85 mo) giving a total of 280.5 patient years.A mean of 6 biopsies were taken during surveillance endoscopies. In 13 patients (19.7%) tongues or islands suspicious for BE were found during endoscopy. In 8 of these patients (12.1%) non-neoplastic BE relapse was confirmed histologically giving a histological relapse rate of 3% per year. In none of the patients, intraepithelial neoplasia nor an esophageal adenocarcinoma was detected.Logistic regression analysis identified endoscopic detection of islands or tongues as the only positive predictor of BE relapse (P = 0.0004).CONCLUSION: The long-term relapse rate of nonneoplastic BE following complete ablation with high-power APC is low (3% per year).
文摘Venous thromboembolism event(VTE) is a common and morbid complication in cancer patients. Patients with gastrointestinal cancers often suffer from symptomatic or incidental splanchnic vein thrombosis, impaired liver function and/or thrombocytopenia. These characteristics require a thorough risk/benefit evaluation for individual patients. Considering the risk factors for the development of VTE and bleeding events in addition to recent study results may be helpful for correct initiation of primary pharmacological prevention and treatment of cancer-associated thrombosis(CAT), preferably with low molecular weight heparins(LMWH). Whereas thromboprophylaxis is most often recommended in hospitalized surgical and non-surgical patients with malignancy, there is less agreement as to its duration. With regard to ambulatory cancer patients, the lack of robust data results in low grade recommendations against routine use of anticoagulant drugs. Anticoagulation with LMWH for the first months is the evidence-based treatment for acute CAT, but duration of secondary prevention and the drug of choice are unclear. Based on published guidelines and literature, this review will focus on prevention and treatment strategies of VTE in patients with gastrointestinal cancers.
文摘Objective To measure the quantities and apoptosis-related protein levels of B lymphocyte in the patients with immunorelated pancytopenia(IRP)and explore the action of B lymphocyte in the pathogenic mechanism of IRP. Methods Quantities of whole B lymphocytes and CD5+ B lymphocytes as well as the expressions of Fas and Bcl-2 in B lymphocytes in 35 patients with untreated IRP, 15 IRP patients in complete remission (CR), and 10 normal controls were assayed by flow cytometry. Results The percentages of B lymphocyte and CD5+ B lymphocyte were significantly higher in untreated IRP patients than in CR IRP patients and normal controls (P<0.05), and there was no significant difference between the latter two groups (P>0.05). There was no significant difference of Fas expression in B lymphocyte among three groups (P>0.05). The expression of Bcl-2 in B lymphocyte was significantly higher in untreated patients than in CR patients or normal controls (P<0.01), and significantly higher in CR patients than in normal controls (P<0.01). The apoptosis-related index was significantly lower in untreated patients than in CR patients or normal controls (P<0.05), and significantly lower in CR patients than in normal controls (P<0.05). The percentage of B lymphocyte was positively correlated with post-treated response time(r=0.53, P<0.01). Conclusion The production of auto-antibodies in IRP patients probably has some relationship with the abnormal quantities of B lymphocyte and its subpopulations as well as with the inhibition of B lymphocyte apoptosis.
文摘Utilization of mesenchymal stromal cells(MSCs) for the treatment of Crohn's disease and ulcerative colitis is of translational interest.Safety of MSC therapy has been well demonstrated in early phase clinical trials but efficacy in randomized clinical trials needs to be demonstrated.Understanding MSC mechanisms of action to reduce gut injury and inflammation is necessary to improve current ongoing and future clinical trials.However, two major hurdles impede the direct translation of data derived from animal experiments to the clinical situation:(1) limitations of the currently available animal models of colitis that reflect human inflammatory bowel diseases(IBD).The etiology and progression of human IBD are multifactorial and hence a challenge to mimic in animal models; and(2) Species specific differences in the functionality of MSCs derived from mice versus humans.MSCs derived from mice and humans are not identical in their mechanisms of action in suppressing inflammation.Thus, preclinical animal studies with murine derived MSCs cannot be considered as an exact replica of human MSC based clinical trials.In the present review, we discuss the therapeutic properties of MSCs in preclinical and clinical studies of IBD.We also discuss the challenges and approaches of using appropriate animal models of colitis, not only to study putative MSC therapeutic efficacy and their mechanisms of action, but also the suitability of translating findings derived from such studies to the clinic.
基金Supported by Grant MG-098-PP-08 from the National Health Research Institutes, Taiwan
文摘AIM: To investigate the differentiation status and key factors to facilitate hepatic differentiation of human bone-marrow-derived mesenchymal stem cells (MSCs). METHODS: Human MSCs derived from bone marrow were induced into hepatocyte-like cells following a previously published protocol. The differentiation status of the hepatocyte-like cells was compared with various human hepatoma cell lines. Overexpression of hepatocyte nuclear factor (HNF)-4α was mediated by adenovirus infection of these hepatocyte-like cells. The expression of interesting genes was then examined by either re-verse transcription-polymerase chain reaction (RT-PCR) or real-time RT-PCR methods. RESULTS: Our results demonstrated that the differentiation status of hepatocyte-like cells induced from human MSCs was relatively similar to poorly differentiated human hepatoma cell lines. Interestingly, the HNF-4 isoform in induced MSCs and poorly differentiated human hepatoma cell lines was identified as HNF4γ instead of HNF-4α. Overexpression of HNF-4α in induced MSCs significantly enhanced the expression level of hepatic-specific genes, liver-enriched transcription factors, and cytochrome P450 (P450) genes. CONCLUSION: Overexpression of HNF-4α improves the hepatic differentiation of human MSCs from bone marrow and is a simple way of providing better cell sources for clinical applications.
基金supported by National Natural Science Foundation of China(Nos.81672686,81372883,and 81001052)Natural Science Foundation of Guangdong Province,China(No.2015A030313020)+2 种基金Science and Technology Planning Project of Guangdong Province,China(No.2011B031800222)Young Talents Key Project of Sun Yat-sen University(No.2015ykzd13)the Sister Institution Network Fund of MD Anderson Cancer Center
文摘Background: The programmed cell death-1(PD-1)/programmed cell death-ligand 1(PD-L1) pathway inhibits the activation of T cells and plays a crucial role in the negative regulation of cellular and humoral immune responses.Diffuse large B-cell lymphoma(DLBCL) is the most common lymphoid malignancy in adults. In the present study, we aimed to detect the expression of PD-L1 in DLBCL and to analyze its relationship with prognosis.Methods: We reviewed medical records of 204 newly diagnosed DLBCL patients in Sun Yat-sen University Cancer Center between October 2005 and August 2012. The expression of PD-L1 in tumor tissues from these 204 patients was detected using immunohistochemical(IHC) assay. The expression of anaplastic lymphoma kinase(ALK), CD5,CD30, and C-Myc in tumor specimens from 109 patients was detected using IHC, and Epstein-Barr virus(EBV)-encoded RNAs(EBERs) were detected using fluorescence in situ hybridization. The Spearman method was used for correlation analysis. The Kaplan-Meier method with log-rank test was used for univariate analysis. Cox proportional hazards model was used for multivariate analysis.Results: Of the 204 patients, 100(49.0%) were PD-L1-positive in tumor cells and 44(21.6%) were PD-L1-positive in tumor microenvironment. PD-L1 expression in tumor cells and tumor microenvironment were more common in the non-germinal center B-cell-like(GCB) subtype than in the GCB subtype(P = 0.02 and P= 0.04). Patients with PD-L1 expression in tumor microenvironment were more likely to be resistant to first-line chemotherapy when compared with the patients without PD-L1 expression in tumor microenvironment(P = 0.03). PD-L1 expression in tumor microenvironment was negatively correlated with C-Myc expression(r =-0.20, P = 0.04). No correlations were detected between PD-L1 expression and the expression of ALK, CD5, and CD30 as well as EBERs. The 5-year overall survival(OS)rates were 50.0% and 67.3% in patients with and without PD-L1 expression in tumor cells(P = 0.02). PD-L1 expression in tumor cells was an independent risk predictor for OS(P < 0.01).Conclusions: PD-L1 expression is more common in the non-GCB subtype than in the GCB subtype. PD-L1 expression in tumor microenvironment has a negative correlation with C-Myc. PD-L1 positivity predicts short survival in DLBCL patients. For patients with PD-L1 expression, more strategy such as anti-PD-L1 antibody treatment should be recommended.
文摘AIM: To evaluate the endoscopic manifestations and prognoses of gastrointestinal (GI) mantle cell lymphoma (MCL). METHODS: A database search at the Department of Pathology of Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences revealed 57 MCL patients with GI involvement. Clinical records were available for 35 of the 57 patients from 21 institutions, and those 35 patients were enrolled in this study. We summarized the gross types of endoscopic features, event-free survival (EFS), and overall survival (OS) of those patients.RESULTS: Of the 35 patients, GI involvement in the esophagus, stomach, and duodenum was found in 2 (5.7%), 26 (74.3%), and 12 (34.3%) patients, respectively. Twenty-one of the 35 patients underwent colonoscopy; among them, GI involvement in the ileum, cecum, colon, and rectum was found in 10 (47.6%), 3 (14.3%), 12 (57.1%), and 10 (47.6%), respectively. Various lesions, such as superficial, protruded, fold thickening, or ulcerative, were found in the stomach, whereas multiple lymphomatous polyposis (MLP) was dominant from the duodenum to the rectum. Twelve patients were treated with a hyper-CVAD/MA regimen, and they had better OS (3-year rate, 88.3% vs 46.4%, P < 0.01) and better EFS (3-year rate, 66.7% vs 33.8%, P < 0.05) than the remaining 23 patients who were not treated with this regimen. CONCLUSION: MLP was a representative form of intestinal involvement, whereas a variety of lesions were found in the stomach. The hyper-CVAD/MA regimen may improve survival in these patients.
基金Supported by Italian Association for Cancer Research
文摘Colorectal cancer is the second most common cause of cancer-related death in many industrialized countries and is characterized by a heterogenic pool of cells with distinct differentiation patterns. Recently, the concept that cancer might arise from a rare population of cells with stem cell-like properties has received support with regard to several solid tumors, including colorectal cancer. According to the cancer stem cell hypothesis, cancer can be considered a disease in which mutations either convert normal stem cells into aberrant counterparts or cause a more differentiated cell to revert toward a stem cell-like behaviour; either way these cells are thought to be responsible for tumor generation and propagation. The statement that only a subset of cells drives tumor formation has major implications for the development of new targeted therapeutic strategies aimed at eradicating the tumor stem cell population. This review will focus on the biology of normal and malignant colonic stem cells, which might contribute to our understanding of the mechanisms responsible for tumor development and resistance to therapy.
基金Supported by Kyungpook National University Research Fund,2012
文摘Despite numerous advances in treatment options,advanced gastric cancer(AGC)remains a major public health issue and the leading cause of cancer-related deaths.Cisplatin is one of the most effective broadspectrum anticancer drugs for AGC and a doublet combination regimen of either cisplatin-based or 5-fluorouracil(5FU)-based chemotherapy is generally used for treatment of patients with AGC.However,there is still no consensus on the best regimen for treating AGC.Recently,various new chemotherapeutic agents,including oral 5FU,taxanes,and irinotecan,have been identified as improving the outcomes for AGC when used as a single agent or in combination with nonplatinum chemotherapy.Nonetheless,it is still unclear whether non-platinum-based chemotherapy is a viable treatment option for patients with AGC.Accordingly,this review focuses on the efficacy and tolerability of non-platinum-based chemotherapy for patients with AGC.
文摘Hepatocellular carcinoma(HCC) is one of the most common malignancies leading to high mortality rates in the general population; in cirrhotic patients, it is the primary cause of death. The diagnosis is usually delayed in spite of at-risk population screening recommendations, i.e., patients infected with hepatitis B or C virus. Hepatocarcinogenesis hinges on a great number of genetic and molecular abnormalities that lead to tumor angiogenesis and foster their dissemination potential. The diagnosis is mainly based on imaging studies such as computed tomography and magnetic resonance, in which lesions present a characteristic classical pattern of early arterial enhancement followed by contrast medium "washout" in late venous phase. On occasion, when imaging studies are not conclusive, biopsy of the lesion must be performed to establish the diagnosis. The Barcelona Clinic Liver Cancer staging method is the most frequently used worldwide and recommended by the international guidelines of HCC management. Currently available treatments include tumor resection, liver transplant, sorafenib and locoregional therapies(alcoholization, radiofrequency ablation, chemoembolization). The prognosis of hepatocarcinoma is determined according to the lesion's stage and in cirrhotic patients, on residual liver function. Curative treatments, such as liver transplant, are sought in patients diagnosed in early stages; patients in more advanced stages, were not greatly benefitted by chemotherapy in terms of survival until the advent of target molecules such as sorafenib.
基金supported by NIH Grant R01-CA140571 (to W.Z.)P01-CA116676 (to W.Z. and P.V.). W.Z. is an Anise McDaniel BrockScholar, Georgia Cancer Coalition Scholar, and American Cancer Research Scholar
文摘Mammalian target of rapamycin (mTOR) is aberrantly activated in many cancer types, and two rapamycin derivatives are currently approved by the Food and Drug Administration (FDA) of the United States for treating renal cell carcinoma. Mechanistically, mTOR is hyperactivated in human cancers either due to the genetic activation of its upstream activating signaling pathways or the genetic inactivation of its negative regulators. The tumor suppressor liver kinase B1 (LKB1), also known as serine/threonine kinase 11 (STK11), is involved in cell polarity, cell detachment and adhesion, tumor metastasis, and energetic stress response. A key role of LKB1 is to negatively regulate the activity of mTOR complex 1 (mTORC1). This review summarizes the molecular basis of this negative interaction and recent research progress in this area.
基金This work was in part supported by grants from the National Institutes of Health(DK52230,DK64399 and CA84197).
文摘Krüppel-like factors (KLFs) are evolutionarily conserved zinc finger-containing transcription factors with diverseregulatory functions in cell growth, proliferation, differentiation, and embryogenesis. KLF4 and KLF5 are two closelyrelated members of the KLF family that have a similar tissue distribution in embryos and adults. However, the two KLFsoften exhibit opposite effects on regulation of gene transcription, despite binding to similar, if not identical, cis-actingDNA sequences. In addition, KLF4 and 5 exert contrasting effects on cell proliferation in many instances; while KLF4is an inhibitor of cell growth, KLF5 stimulates proliferation. Here we review the biological properties and biochemicalmechanisms of action of the two KLFs in the context of growth regulation.
