Identification of prognostic biomarkers for cholangiocarcinoma by combined analysis of molecular characteristics of clinical MVI subtypes and molecular subtypes.

Cholangiocarcinoma (CCA) is widely noted for its high degree of malignancy, rapid progression, and limited therapeutic options. This study was carried out on transcriptome data of 417 CCA samples from different anatomical locations. The effects of lipid metabolism related genes and immune related genes as CCA classifiers were compared. Key genes were derived from MVI subtypes and better molecular subtypes. Pathways such as epithelial mesenchymal transition (EMT) and cell cycle were significantly activated in MVI-positive group. CCA patients were classified into three (four) subtypes based on lipid metabolism (immune) related genes, with better prognosis observed in lipid metabolism-C1, immune-C2, and immune-C4. IPTW analysis found that the prognosis of lipid metabolism-C1 was significantly better than that of lipid metabolism-C2 + C3 before and after correction. KRT16 was finally selected as the key gene. And knockdown of KRT16 inhibited proliferation, migration and invasion of CCA cells.

[Efficacy and safety of rituximab in children and adolescents with mature B-cell non-Hodgkin's lymphoma: a Meta analysis]. / 利妥昔单抗治疗儿童及青少年成熟Bç»†èƒžéžéœå¥‡é‡‘æ·‹å·´ç˜¤ç–—æ•ˆåŠå®‰å ¨æ€§çš„Meta分析.

OBJECTIVES: To study the efficacy and safety of rituximab combined with chemotherapy in the treatment of children and adolescents with mature B-cell non-Hodgkin's lymphoma (B-NHL) through a Meta analysis. METHODS: The databases including PubMed, Embase, the Cochrane Library, ClinicalTrials.gov, Web of Science, China National Knowledge Infrastructure, Wanfang Data, and Weipu were searched to obtain 10 articles on rituximab in the treatment of mature B-NHL in children and adolescents published up to June 2022, with 886 children in total. With 3-year event-free survival (EFS) rate, 3-year overall survival (OS) rate, complete remission rate, mortality rate, and incidence rate of adverse reactions as outcome measures, RevMan 5.4 software was used for Meta analysis, subgroup analysis, sensitivity analysis, and publication bias analysis. RESULTS: The rituximab+chemotherapy group showed significant increases in the 3-year EFS rate (HR=0.38, 95%CI: 0.25-0.59, P<0.001), 3-year OS rate (HR=0.29, 95%CI: 0.14-0.61, P=0.001), and complete remission rate (OR=3.72, 95%CI: 1.89-7.33, P<0.001) as well as a significant reduction in the mortality rate (OR=0.31, 95%CI: 0.17-0.57, P<0.001), as compared with the chemotherapy group without rituximab. There was no significant difference in the incidence rate of adverse reactions between the two groups (OR=1.28, 95%CI: 0.85-1.92, P=0.24). CONCLUSIONS: The addition of rituximab to the treatment regimen for children and adolescents with mature B-cell non-Hodgkin's lymphoma can bring significant survival benefits without increasing the incidence of adverse reactions.

[Clinical features and prognosis of children with Burkitt's lymphoma: an analysis of 62 cases]. / 儿童伯基特淋巴瘤62例临床特征及预后分析.

OBJECTIVES: To study the clinical features and chemotherapy response of Burkitt's lymphoma (BL) in children and the influence of rituximab on the prognosis of children with BL. METHODS: A retrospective analysis was performed for the medical data of 62 children with BL, including clinical features, therapeutic efficacy, and prognostic factors. The Cox regression model was used to identify the factors associated with poor prognosis in children with BL. According to whether rituximab was used, the children with advanced (stage III/IV) BL were divided into two groups: chemotherapy plus rituximab and chemotherapy alone. The prognosis was compared between the two groups. RESULTS: For these 62 children, the median age of onset was 5 years (range 1-14 years), and there were 58 boys (94%) and 4 girls (6%). The primary site was abdominal cavity in 41 children (66%), and head and neck in 16 children (26%). There were 1 child with stage I BL (2%), 8 with stage II BL (13%), 33 with stage III BL (53%), and 20 with stage IV BL (32%). The median follow-up time was 29 months, with progression/recurrence observed in 15 children (24%), and the 3-year overall survival (OS) rate and event-free survival (EFS) rate were 82.8%±5.2% and 77.3%±5.8%, respectively. For the children with stage III/IV BL, there was a significant difference in the 3-year the OS rate between the chemotherapy plus rituximab group (16 children) and the chemotherapy alone group (30 children) (93.3%±6.4% vs 65.6%±9.9%, P=0.042), while there was no significant difference in the 3-year EFS rate between the two groups (86.2%±9.1% vs 61.8%±10.1%, P>0.05). The Cox regression analysis showed that central nervous system involvement, lactate dehydrogenase >1 000 U/L, and early incomplete remission were the factors associated with poor prognosis (P<0.05). CONCLUSIONS: Chemotherapy combined with rituximab can improve the prognosis of children with stage III/IV BL. Central nervous system involvement, elevated lactate dehydrogenase level, and early incomplete remission may indicate a poor prognosis in children with BL.

[Risk factors for acute kidney injury after hematopoietic stem cell transplantation in children: a retrospective study]. / å„¿ç«¥é€ è¡€å¹²ç»†èƒžç§»æ¤åŽæ€¥æ€§è‚¾æŸä¼¤ç›¸å ³å±é™©å› ç´ çš„å›žé¡¾æ€§ç ”ç©¶.

OBJECTIVES: To investigate the risk factors for acute kidney injury (AKI) after hematopoietic stem cell transplantation (HSCT) in children. METHODS: A retrospective analysis was performed on the medical data of 111 children who underwent HSCT from January 2018 to January 2020. A multivariate logistic regression analysis was used to identify the risk factors for AKI. The Kaplan-Meier survival analysis was used to compare the prognosis in children with different grades of AKI. RESULTS: Graft-versus-host disease (grade Ⅱ-Ⅳ) (OR=4.406, 95%CI: 1.501-12.933, P=0.007), hepatic veno-occlusive disease (OR=4.190, 95%CI: 1.191-14.740, P=0.026), and thrombotic microangiopathy (OR=10.441, 95%CI: 1.148-94.995, P=0.037) were closely associated with the development of AKI after HSCT. The children with stage Ⅲ AKI had a lower 1-year survival rate than those without AKI or with stage Ⅰ AKI or stage Ⅱ AKI (28.6%±12.1% vs 82.8%±5.2%/81.7%±7.4%/68.8%±11.6%; P<0.05). CONCLUSIONS: Children with stage Ⅲ AKI after HSCT have a higher mortality rate. Graft-versus-host disease, hepatic veno-occlusive disease, and thrombotic microangiopathy are closely associated with the development of AKI after HSCT.

[Langerhans cell histiocytosis involving the oral and maxillofacial region: an analysis of 12 cases].

OBJECTIVE: To study the clinical features of Langerhans cell histiocytosis (LCH) involving the oral and maxillofacial region in children. METHODS: A retrospective analysis was performed for the clinical data of 12 children with LCH involving the oral and maxillofacial region who were hospitalized and treated from September 2012 to September 2017, including clinical manifestations, pathological features, treatment and prognosis. RESULTS: Of the 12 children, 8 (67%) had multiple system involvement and 7 (58%) had the involvement of organs at risk. Bone was the most common affected site (11 children, 92%), among whom 7 children had the involvement of the mandible. Oral soft tissue involvement manifested as gingival ulcer or hyperplasia in 4 children, loose teeth in 5 children, oral mucosal lesions in 2 children, and nodular lesions in 1 child. Pathological examination showed positive CDla in 11 children and positive CD207, CD68, S-100, and LCA in 12 children. Surgery combined with chemotherapy was the major treatment method, and surgical resection alone was performed for focal lesions. After treatment, 11 children were cured or improved and 1 gave up treatment and was lost to follow-up. No recurrence was observed. CONCLUSIONS: LCH children with oral and maxillofacial involvement often have the involvement of multiple systems and organs at risk, with the mandible as the most common affected site. These children may also have the involvement of gingiva, oral mucosa and teeth. Surgery combined with chemotherapy is the major treatment method, and the patients generally have a good prognosis without recurrence.

[Vasodilation effect and mechanism of extraction of Tongmai Yangxin Pills (TMYX) on isolated rat mesenteric artery].

The aim of the present study is to evaluate the vasodilation effects of Tongmai Yangxin Pills (TMYX) on rat mesenteric artery as well as its mechanism of action. The relaxation effects of TMYX extracts with different concentrations were determined on isolated rat mesenteric artery in normal condition as well as pretreating by phenylephrine and KCl. Vascular relaxation effects of TMTX were also determined in mesenteric artery preincubated with L-ANME and indomethacin or in endothelium denuded mesenteric artery. Moreover, effects of TMYX by 50 mg·L⁻¹ on NO secretion and the phosphorylation of eNOS in a cellular model of human umbilical vein endothelial cell (HUVEC) pretreated with or without L-NAME were also observed. The experimental results showed that TMYX has no obvious effect on vasodilation of arteries in normal or KCl pretreated condition, while it can dose-dependently relax the rat mesenteric artery with intact endothelium stimulated with phenylephrine at a maximal diastolic rate of (64.71±10.03)%. After preincubating with L-NAME for 15 min or removal of mesenteric artery endothelium, the maximal diastolic rate was decreased to (35.77±8.93)% and (25.85±10.84)% respectively. However, preincubating with indomethacin had no inhibitory effect on TMYX induced vascular relaxation. Meanwhile, TMYX at 50 mg·L⁻¹ could increase the expression of P-eNOS and the secretion of NO in HUVEC. L-NAME significantly inhibited NO release and phosphorylation of eNOS induced by TMYX. The results suggested TMYX exerted endothelium-dependent relaxation effects against PE-induced contractions of isolated rat mesenteric artery through NO-cGMP signaling pathway.

[Clinical features and prognosis of malignancy-associated hemophagocytic lymphohistiocytosis in children: a clinical analysis of 24 cases].

OBJECTIVE: To investigate the clinical features and prognosis of malignancy-associated hemophagocytic lymphohistiocytosis (MAHS) in children. METHODS: A retrospective analysis was performed for the primary diseases, clinical features, and prognosis of 24 children with MAHS. RESULTS: Among the 24 children, 11 (46%) had MAHS induced by tumor and 13 (54%) had chemotherapy-associated MAHS. As for primary diseases, 17 children had acute leukemia, 6 had lymphoma, and 1 had neuroblastoma. The most common clinical manifestations were pyrexia, respiratory symptoms, and hepatosplenomegaly. The most common laboratory abnormalities were hemocytopenia, elevated serum ferritin, and elevated lactate dehydrogenase. Of the 24 children, 22 were treated according to the HLH-2004 protocol and 2 gave up treatment; 18 children died, 1 was lost to follow-up, and 5 survived. The survival time ranged from 3 days to 2 years and 4 months (median 28 days). CONCLUSIONS: Children with MAHS have various clinical features and extremely poor treatment outcomes.

[Significance of Th17/Treg imbalance in children with primary immune thrombocytopenia].

OBJECTIVE: To investigate the significance of Th17/Treg imbalance in the development and treatment of primary immune thrombocytopenia (ITP) in children. METHODS: Thirty-two children diagnosed with ITP between May and August, 2015 and 22 healthy children were enrolled. Flow cytometry was used to determine the Th17/Treg ratio in peripheral blood of healthy children and children with ITP before and after treatment with immunoglobulin. RESULTS: Compared with the patients with ITP before treatment, the healthy children and the patients treated with immunoglobulin had a significantly lower percentage of Th17 cells in CD4+ T cells, a significantly lower Th17/Treg ratio, and a significantly higher percentage of Treg cells in CD4+ T cells in peripheral blood (P<0.05). In the 32 ITP children treated with immunoglobulin, 20 had complete response, 4 had response, and 8 had no response. The patients with complete response had a significantly lower percentage of Th17 cells in CD4+ T cells and a significantly lower Th17/Treg ratio in peripheral blood than the patients without response (P<0.05). CONCLUSIONS: The Th17/Treg imbalance can be found in children with ITP. Immunoglobulin can improve the cellular immune function by regulation of the Th17/Treg ratio. The Th17/Treg ratio may serve as an indicator for assessing the therapeutic effects of ITP.

[Roles of follicular helper T cells and follicular regulatory T cells in pathogenesis of Henoch-Schönlein purpura in children].

OBJECTIVE: To study the roles of follicular helper T (Tfh) cells and follicular regulatory T (Tfr) cells in the pathogenesis of Henoch-Schönlein purpura (HSP) in children. METHODS: Peripheral blood samples were collected from 40 HSP children and 25 healthy controls. The percentages of Tfh and Tfr cells were measured by flow cytometry; the mRNA expression levels of Bcl-6, c-MAF, Blimp-1, and PD-1 in peripheral blood were measured by real-time polymerase chain reaction. RESULTS: Compared with the controls, the children with HSP had significantly increased percentage of Tfh cells and Tfh/Tfr ratio but a significantly reduced percentage of Tfr cells in the peripheral blood (P<0.05). Compared with the controls, the children with HSP had significantly increased mRNA expression of Bcl-6 and c-MAF but significantly reduced mRNA expression of Blimp-1 in CD4+ T cells (P<0.05), and had significantly increased mRNA expression of PD-1 but significantly reduced mRNA expression of Blimp-1 in CD4+CD25+ regulatory T cells (P<0.05). CONCLUSIONS: Abnormal percentages of Tfh and Tfr cells may be involved in the pathogenesis of HSP in children, and over-expression of Bcl-6, c-MAF, and PD-1 mRNA and inhibited expression of Blimp-1 mRNA may be considered as important reasons for abnormal percentages of Tfh and Tfr cells.

[Clinical features of childhood hemophagocytic syndrome and its association with human parvovirus B19 infection].

OBJECTIVE: To investigate the association of childhood hemophagocytic syndrome (HPS) with human parvovirus B19 (HPVB19) infection, and to analyze the clinical features of this disease. METHODS: ELISA and quantitative real-time PCR were used to detect HPVB19-IgM, HPVB19-IgG and HPVB19-DNA in 65 children with HPS (HPS group) and 65 healthy children (control group). The HPS group was divided into HPVB19-infected (n=14) and non-infected (n=51) groups according to the detection results of HPVB19-DNA. The clinical data of two groups were compared. RESULTS: The positive rate of HPVB19-IgM in the HPS group (26%, 17/65) was significantly higher than that in the control group (9%, 6/65) (P=0.011), and there was no significant difference in the positive rate of HPVB19-IgG between the HPS (38%, 25/65) and control groups (29%, 19/65) (P=0.266). The infection rate of HPVB19 in the HPS group (22%, 14/65) was significantly higher than that in the control group (3%, 2/65) (P=0.001). Compared with the non-infected group, the HPVB19-infected group had significantly lower platelet count and hemoglobin level on admission, significantly more severe liver function damage, a significantly earlier onset time, and a significantly longer course of disease (P<0.05). CONCLUSIONS: The pathogenesis of HPS may be associated with HPVBl9 infection. HPVBl9-infected children with HPS have more acute onset, more severe clinical manifestations, and a longer disease duration.

CD24 mediates gastric carcinogenesis and promotes gastric cancer progression via STAT3 activation.

The development of gastric cancer (GC) is a complex multistep process, including numerous genetic and epigenetic changes. CD24 is associated with enhanced invasiveness of GC and a poor prognosis. However, the mechanism by which CD24 induces GC progression remains poorly characterized. Here, we found that the expression of CD24 gradually increased in samples of normal gastric mucosa, non-atrophic chronic gastritis, chronic atrophic gastritis (CAG), CAG with intestinal metaplasia, dysplasia and GC. Moreover, the knockdown of CD24 induced significant levels of apoptosis in GC cells via the mitochondrial apoptotic pathway. CD24 may also promote cellular invasion and regulate the expression of E-cadherin, fibronectin and vitamin D receptor in GC cells. The activation of signal transducer and activator of transcription 3 (STAT3) may mediate CD24-induced GC survival and invasion in vitro. Furthermore, CD24-induced GC progression and STAT3 activation could also be detected in vivo and in clinical GC tissues samples. Taken together, our results indicate that CD24 mediates gastric carcinogenesis and may promote GC progression by suppressing apoptosis and promoting invasion, with the activation of STAT3 playing a critical role.

The role of ERK2 in colorectal carcinogenesis is partly regulated by TRAPPC4.

The extracellular signal-regulated kinase (ERK), mitogen-activated protein kinase (MAPK) pathway is an important cell proliferation pathway. We previously reported that the transport protein particle complex 4 (TRAPPC4), ERK2 interaction may activate ERK1/2, modulate pERK2 nuclear localization and regulate proliferation and apoptosis in colorectal cancer (CRC) cells. The present study further investigated the function of the TRAPPC4-ERK2 interaction in CRC in vitro and in vivo. Silencing of TRAPPC4 induced G0/G1 phase cell cycle arrest, upregulated p21 and downregulated cyclin B1 in CRC cells. Overexpression of TRAPPC4 after ERK2 silencing decreased the percentage of G0/G1 phase cells, increased the percentage of G2/M and S phase cells, downregulated p21, upregulated cyclin B1, and enhanced CRC cell viability. Immunohistochemical staining revealed that knockdown of TRAPPC4 downregulated pERK2, whereas overexpression of TRAPPC4 upregulated pERK2. Epidermal growth factor (EGF) stimulated upregulation of TRAPPC4 and pERK2 in SW1116 cells; EGF stimulation or overexpression of TRAPPC4 induced pERK2 nuclear translocation. Silencing of TRAPPC4 reduced SW1116 xenograft tumor growth in vivo, whereas overexpression of TRAPPC4 increased tumor growth, compared to control tumors. Moreover, modulation of TRAPPC4 expression in vivo affected the levels of pERK2 in the cytoplasm and nucleus and expression of p21. These results conclusively demonstrate that TRAPPC4 regulates ERK2 activation and also affects the distribution of activated pERK2 in CRC cells. The ability of ERK2 to play a role in colorectal carcinogenesis depends, at least in part, on TRAPPC4.

Role of STAT3 and vitamin D receptor in EZH2-mediated invasion of human colorectal cancer.

The polycomb group protein enhancer of zeste homologue 2 (EZH2), which has histone methyltransferase (HMT) activity, is overexpressed in malignant tumours. However, the role of EZH2 in colorectal cancer (CRC) invasion is little known. Here we investigated the clinical significance, biological effects, and mechanisms of EZH2 signalling. Knockdown of EZH2 significantly reduced cell invasion and secretion of matrix metalloproteinases 2/9 (MMP2/9) in in vitro studies. Knockdown of EZH2 dramatically increased overall survival and decreased metastasis of lung in in vivo studies. Conversely, overexpression of EZH2 significantly increased lung metastasis and shortened overall survival when compared with control tumours. EZH2-induced CRC cell invasion may depend on down-regulation of vitamin D receptor (VDR), which is considered to be a marker of CRC invasion. EZH2 regulates the histone trimethylation of lysine 27 (H3K27me3) in the VDR promoter. Moreover, we found that STAT3 directly binds to the EZH2 promoter and regulates VDR down-regulation in CRC cells. Significant inverse correlations were observed between the expression of EZH2 and pSTAT3 and that of VDR in CRC tissues compared with normal tissue in patients. We show the role of EZH2 in CRC metastasis and identify VDR as a target gene of EZH2. EZH2 expression may be directly regulated by STAT3, and STAT3 may play an important role in EZH2-mediated VDR down-regulation in CRC. This pathway may provide potential targets in aggressive CRC.

Early detection and prognosis evaluation for hepatocellular carcinoma by circulating tumour DNA methylation: A multicentre cohort study.

BACKGROUND: Early diagnosis of hepatocellular carcinoma (HCC) can significantly improve patient survival. We aimed to develop a blood-based assay to aid in the diagnosis, detection and prognostic evaluation of HCC. METHODS: A three-phase multicentre study was conducted to screen, optimise and validate HCC-specific differentially methylated regions (DMRs) using next-generation sequencing and quantitative methylation-specific PCR (qMSP). RESULTS: Genome-wide methylation profiling was conducted to identify DMRs distinguishing HCC tumours from peritumoural tissues and healthy plasmas. The twenty most effective DMRs were verified and incorporated into a multilocus qMSP assay (HepaAiQ). The HepaAiQ model was trained to separate 293 HCC patients (Barcelona Clinic Liver Cancer (BCLC) stage 0/A, 224) from 266 controls including chronic hepatitis B (CHB) or liver cirrhosis (LC) (CHB/LC, 96), benign hepatic lesions (BHL, 23), and healthy controls (HC, 147). The model achieved an area under the curve (AUC) of 0.944 with a sensitivity of 86.0% in HCC and a specificity of 92.1% in controls. Blind validation of the HepaAiQ model in a cohort of 523 participants resulted in an AUC of 0.940 with a sensitivity of 84.4% in 205 HCC cases (BCLC stage 0/A, 167) and a specificity of 90.3% in 318 controls (CHB/LC, 100; BHL, 102; HC, 116). When evaluated in an independent test set, the HepaAiQ model exhibited a sensitivity of 70.8% in 65 HCC patients at BCLC stage 0/A and a specificity of 89.5% in 124 patients with CHB/LC. Moreover, HepaAiQ model was assessed in paired pre- and postoperative plasma samples from 103 HCC patients and correlated with 2-year patient outcomes. Patients with high postoperative HepaAiQ score showed a higher recurrence risk (Hazard ratio, 3.33, p < .001). CONCLUSIONS: HepaAiQ, a noninvasive qMSP assay, was developed to accurately measure HCC-specific DMRs and shows great potential for the diagnosis, detection and prognosis of HCC, benefiting at-risk populations.

Cell-free DNA testing for early hepatocellular carcinoma surveillance.

BACKGROUND: Liver cirrhosis (LC) is the highest risk factor for hepatocellular carcinoma (HCC) development worldwide. The efficacy of the guideline-recommended surveillance methods for patients with LC remains unpromising. METHODS: A total of 4367 LCs not previously known to have HCC and 510 HCCs from 16 hospitals across 11 provinces of China were recruited in this multi-center, large-scale, cross-sectional study. Participants were divided into Stage Ⅰ cohort (510 HCCs and 2074 LCs) and Stage Ⅱ cohort (2293 LCs) according to their enrollment time and underwent Tri-phasic CT/enhanced MRI, US, AFP, and cell-free DNA (cfDNA). A screening model called PreCar Score was established based on five features of cfDNA using Stage Ⅰ cohort. Surveillance performance of PreCar Score alone or in combination with US/AFP was evaluated in Stage Ⅱ cohort. FINDINGS: PreCar Score showed a significantly higher sensitivity for the detection of early/very early HCC (Barcelona stage A/0) in contrast to US (sensitivity of 51.32% [95% CI: 39.66%-62.84%] at 95.53% [95% CI: 94.62%-96.38%] specificity for PreCar Score; sensitivity of 23.68% [95% CI: 14.99%-35.07%] at 99.37% [95% CI: 98.91%-99.64%] specificity for US) (P < 0.01, Fisher's exact test). PreCar Score plus US further achieved a higher sensitivity of 60.53% at 95.08% specificity for early/very early HCC screening. INTERPRETATION: Our study developed and validated a cfDNA-based screening tool (PreCar Score) for HCC in cohorts at high risk. The combination of PreCar Score and US can serve as a promising and practical strategy for routine HCC care. FUNDING: A full list of funding bodies that contributed to this study can be found in Acknowledgments section.

Roles of STAT3 and ZEB1 proteins in E-cadherin down-regulation and human colorectal cancer epithelial-mesenchymal transition.

The progression of colorectal carcinoma (CRC) to invasive and metastatic disease may involve localized occurrences of epithelial-mesenchymal transition (EMT). However, mechanisms of the EMT process in CRC progression are not fully understood. We previously showed that knockdown of signal transducer and activator of transcription 3 (STAT3) up-regulated E-cadherin (a key component in EMT progression) in CRC. In this study, we examined the roles of STAT3 in CRC EMT and ZEB1, an EMT inducer, in STAT3-induced down-regulation of E-cadherin. Knockdown of STAT3 significantly increased E-cadherin and decreased N-cadherin and vimentin expressions in highly invasive LoVo CRC cells. Meanwhile, overexpression of STAT3 significantly reduced E-cadherin and enhanced N-cadherin and vimentin expressions in weakly invasive SW1116 CRC cells. Activation of STAT3 significantly increased CRC cell invasiveness and resistance to apoptosis. Knockdown of STAT3 dramatically enhanced chemosensitivity of CRC cells to fluorouracil. STAT3 regulated ZEB1 expression in CRC cells, and the STAT3-induced decrease in E-cadherin and cell invasion depended on activation of ZEB1 in CRC cells. Additionally, pSTAT3(Tyr-705) and ZEB1 expressions were significantly correlated with TNM (tumor, lymph node, and metastasis stages) (p < 0.01). In conclusion, STAT3 may directly mediate EMT progression and regulate ZEB1 expression in CRC. ZEB1 may participate in STAT3-induced cell invasion and E-cadherin down-regulation in CRC cells. The expressions of pSTAT3(Tyr-705) and ZEB1 may be positively associated with CRC metastasis. Our data may provide potential targets to prevent and/or treat CRC invasion and metastasis.

An integrated analysis of the association between Ts gene polymorphisms and clinical outcome in gastric and colorectal cancer patients treated with 5-FU-based regimens.

Thymidylate synthetase is the major target of 5-fluorouracil (5-FU), which is widely used for the treatment of gastric cancer (GC) and colorectal cancer (CRC). This meta-analysis aimed to elucidate the effect of Ts polymorphisms on the efficacy of 5-FU-based chemotherapy in GC and CRC patients. Individual data were analyzed from 10 studies of 1102 GC and CRC patients treated with 5-FU-based regimens. The primary outcomes of interest were overall survival (OS) and progression-free survival (PFS). Data were pooled using the program STATA version 10.0 (Stata Corporation, College Station, TX). The relationship between the Ts polymorphism and survival following 5FU-based treatment of GC and CRC patients was systematically summarized. Compared with the C allele, the G allele was associated with shorter PFS but with similar OS in Caucasian CRC patients. Compared with the 3R/3R genotype, the 2R/3R or 2R/2R genotype was associated with the same PFS, but with a shorter OS, particularly in Caucasian CRC patients. These results show a correlation between survival following 5-FU-based therapy and tumor genotype in Caucasian CRC patients. Larger studies and further clinical trials are required to confirm this observation.

Laparoscopic spleen-preserving distal pancreatectomy with or without splenic vessel conservation: a retrospective study of 20 cases.

BACKGROUND/AIMS: To compare the outcomes and potential morbidities of laparoscopic spleen-preserving distal pancreatectomy with or without splenic vessel preservation in patients with benign or low-grade malignant pancreatic lesions. METHODOLOGY: Twenty patients who underwent spleen-preserving distal pancreatectomy were retrospectively analyzed. All the patients had benign or low-grade malignant pancreatic lesions that had not invaded the spleen. Twelve patients underwent Kimura's procedure and eight patients underwent Warshaw's. Perioperative data, and procedure-specific complications were compared between the two groups. RESULTS: Age, gender, and body mass index were comparable between the two groups. Operative time and intraoperative blood loss were significantly lower for patients who underwent Warshaw's procedure than for those who received Kimura's (p <0.05 for both). There were no significant differences between the two groups with regard to perioperative blood transfusions, length of postoperative hospital stays, or complication rates. Splenic infarction and gastric varices developed only in patients who underwent Warshaw's procedure (one case each). CONCLUSIONS: Our results suggest that the Kimura technique should be the first choice for patients with benign or low-grade malignant pancreatic lesions. Warshaw's technique was associated with a higher incidence of several complications. However, Warshaw's can increase the success rate of splenic preservation in some cases.

[Effectiveness of anti-CD47 antibody and Ara-C combination targeting therapy NOD/SCID mouse of myeloid leukemia].

OBJECTIVE: To study the prognostic significance of CD47 in a NOD/SCID mouse model of acute myeloid leukemia (AML) and the best strategy for targeted therapy for this disease. METHODS: CD34(+)CD38(-) leukemia stem cells (LSCs) were separated and transplanted into NOD/SCID mice to establish a mouse model of acute monocytic leukemia (AMoL). Anti-human CD47 antibody, alone or combined with cytosine arabinoside (Ara-C), was used to treat the mice with AMoL for 7-14 days, and therapeutic efficacy was assessed. LSCs were cultured together with mouse macrophages in culture medium containing anti-CD47 or anti-CD45 monoclonal antibody for 2 hours, to observe the phagocytic ability of macrophages to LSCs. RESULTS: CD34(+)CD38(-) LSCs existed among THP-1 cells, with a content of about (0.12 ± 0.06)%, and a mouse model of AML was successfully established after the purified CD34(+)CD38(-) LSCs (97.0% ± 1.7%) were transplanted into NOD/SCID mice. The in vivo experiment showed that mice with AMoL had the most significant decrease in CD33(+)CD45(+) leukemia cells in peripheral blood and bone marrow and survived the longest after being treated with Ara-C (7 days) plus anti-CD47 monoclonal antibody (14 days) (P < 0.01). After 2 hours of in vitro culture, the phagocytic index in the culture medium containing anti-CD47 monoclonal antibody was significantly higher than in the culture medium containing anti-CD45 monoclonal antibody (76.9% ± 12.2% vs 7.60% ± 2.4%; P < 0.05). CONCLUSIONS: High expression of CD47 is an adverse prognostic factor in AML. Combination therapy with anti-CD47 monoclonal antibody and Ara-C can effectively eliminate leukemia cells and LSCs, demonstrating great clinical significance in curing AML.

The development of a cSMART-based integrated model for hepatocellular carcinoma diagnosis.

BACKGROUND: Hepatocellular carcinoma (HCC) generally arises from a background of liver cirrhosis (LC). Patients with cirrhosis and suspected HCC are recommended to undergo serum biomarker tests and imaging diagnostic evaluation. However, the performance of routine diagnostic methods in detecting early HCC remains unpromising. METHODS: Here, we conducted a large-scale, multicenter study of 1675 participants including 490 healthy controls, 577 LC patients, and 608 HCC patients from nine clinical centers across nine provinces of China, profiled gene mutation signatures of cell-free DNA (cfDNA) using Circulating Single-Molecule Amplification and Resequencing Technology (cSMART) through detecting 931 mutation sites across 21 genes. RESULTS: An integrated diagnostic model called "Combined method" was developed by combining three mutation sites and three serum biomarkers. Combined method outperformed AFP in the diagnosis of HCC, especially early HCC, with sensitivities of 81.25% for all stages and 66.67% for early HCC, respectively. Importantly, the integrated model exhibited high accuracy in differentiating AFP-negative, AFP-L3-negative, and PIVKA-II-negative HCCs from LCs.