[Evaluation of the Short-Term Efficacy and Safety of Orelabrutinib Combined with High-Dose Methotrexate in the First-line Treatment of Elderly Patients with High Risk Primary Central Nervous System Lymphoma].

OBJECTIVE: To explore the short-term efficacy and adverse reactions of orelabrutinib combined with high-dose methotrexate (HD-MTX) in the first-line treatment of elderly high-risk primary central nervous system lymphoma (PCNSL), as well as the survival of patients. METHODS: Twenty-five elderly patients with high-risk primary central nervous system diffuse large B-cell lymphoma admitted to Fujian Provincial Hospital from June 2016 to June 2022 were enrolled in this study, and complete clinical data from all patients were collected retrospectively, and the cut-off for follow-up was December 2022. 15 patients had received temmozolomide combined with HD-MTX regimen for at least four cycles, sequential lenalidomide maintenance therapy, while 10 patients had received orelabrutinib combined with HD-MTX regimen for at least four cycles, sequential orelabrutinib maintenance therapy. The short-term efficacy and adverse reactions of the two groups of patients after treatment were observed. Kaplan-Meier was used to analyze the progression-free survival (PFS) and time to progression (TTP). RESULTS: The objective response rate (ORR) and 2-year median FPS of orelabrutinib combined with HD-MTX regimen group were similar to the temozolomide combined with HD-MTX regimen group (ORR: 100% vs 66.7%; 2-year median PFS: 16 months vs 15 months, P>0.05). The 2-year median TTP of the orelabrutinib+HD-MTX regimen group was better than that of the temozolomide+HD-MTX regimen group (not reached vs 12 months, P<0.05). There were no significant differences in adverse reactions such as gastrointestinal reactions, bone marrow suppression, liver and kidney damage, cardiotoxicity, pneumonia and bleeding between these two groups (P>0.05). CONCLUSION: For elderly patients with high-risk PCNSL, orelabrutinib combined with HD-MTX has reliable short-term efficacy, good safety, and tolerable adverse reactions, which is worthy of clinical promotion.

[Rituximab-Based Regimens for Treatment of Primary Gastric Diffuse Large B-Cell Lymphoma].

OBJECTIVE: To analyze clinical response of the Rituximab-based chemotherapy and prognostic features in patients with primary gastric diffuse large B-cell lymphoma (PGDLBCL). METHODS: From June 2008 to December 2020, the data of 53 PGDLBCL patients were analyzed retrospectively. RESULTS: The median age was 46(25-77) years old in 53 patients including 35 males and 18 females. Stomachache is the most common symptom. The diagnosis were confirmed in 47 patients by endoscopic biopsy and 6 patients by surgery. Twenty-six patients had Ⅰ/Ⅱ1 stage (Lugano staging system) disease and 27 cases had II2/IV stage disease. All patients were treated with chemotherapy, including RCHOP (25/53) and R-DA-EPOCH (28/53). Complete remission rate was 79.2%（42/53）. The 3-year and 5-year overall survival (OS) rates were 77.4% and 69.8%. Univariate analysis showed that lactate dehydrogenase(LDH), Lugano stage and lesion size affected OS. Multivariate Cox regression analysis revealed that IPI score and Lugano stage were independent prognosis risk factors affecting OS. The patients in the R-DA-EPOCH group presented better survival outcomes than those in the RCHOP group with late stage (P5-year OS=0.035). CONCLUSION: Rituximab in combination with chemotherapy is the backbone of therapy for PGDLBCL. IPI score and Lugano stage are independent prognosis risk factors affecting OS of PGDLBCL. R-DA-EPOCH can be superior to R-CHOP as a first-line regimen in PGDLBCL patients with late stage.

circGFRA1 affects the sensitivity of triple-negative breast cancer cells to paclitaxel via the miR-361-5p/TLR4 pathway.

In recent years, the role of circular RNAs (circRNAs) in tumours has attracted widespread attention. Some circRNAs have been reported to play a role in triple-negative breast cancer (TNBC). However, circRNAs have rarely been reported in terms of TNBC resistance. This study aimed to clarify that circGFRA1 affects the sensitivity of TNBC cells to paclitaxel (PTX) by the miR-361-5p/TLR4 pathway. Compared with the non-PTX-resistant TNBC cell line MDA-MB-231, the expression of circGFRA1 in the PTX-resistant TNBC cell line MDA-MB-231.PR was significantly increased. The small hairpin RNA-mediated circGFRA1 knockdown inhibited the resistance of TNBC cells to PTX. RNA pull-down assay and luciferase reporter gene assay confirmed the binding between circGFRA1 and miR-361-5p and between miR-361-5p and TLR4. It has been proven that circGFRA1 knockdown can inhibit the resistance of TNBC cells to PTX by promoting the expression of miR-361-5p, and subsequently reduce the expression of TLR4.

LncRNA KCNQ1OT1 is a key factor in the reversal effect of curcumin on cisplatin resistance in the colorectal cancer cells.

The development of cisplatin resistance is a common cause of cancer recurrence in colorectal cancer (CRC). Though many studies have reported the oncogenic function of long non-coding RNA (LncRNA) KCNQ1OT1 in multiple cancers, few studies explored its role in cisplatin resistance of CRC. Curcumin is a natural phenolic compound extracted from turmeric, which can effectively suppress cisplatin resistance in CRC. This study aims to expound the role of KCNQ1OT1 in cisplatin resistance in CRC cells and whether KCNQ1OT1 participates in the reversal effect of curcumin on cisplatin resistance in CRC. The interplay between KCNQ1OT1 and miR-497 was determined using RNA pull-down assay and dual-luciferase reporter gene assay. The combination of B-cell lymphoma 2 (Bcl-2) and miR-497 was confirmed using dual-luciferase reporter gene assay. Compared with CRC cell line HCT8, the cisplatin-resistant CRC cell line HCT8/DDP exhibited a higher expression level of KCNQ1OT1. Functionally, the silence of KCNQ1OT1 suppressed proliferation and boosted apoptosis in HCT8/DDP cells. Subsequently, we found that KCNQ1OT1 could act as a sponge of miR-497 and remove the suppressive effect of miR-497 on Bcl-2 expression. Curcumin treatment restrained proliferation and facilitated apoptosis in HCT8/DDP cells. While KCNQ1OT1 overexpression removed the effect of curcumin on HCT8/DDP cells via miR-497/ Bcl-2 axis. Finally, the in vivo experiments showed that the inhibitory effect of curcumin on the growth of cisplatin-resistant CRC cells was reserved by the ectopic expression of KCNQ1OT1. In conclusion, KCNQ1OT1 aggravated cisplatin resistance in CRC cells via the miR-497/Bcl-2 axis. Administration of curcumin could effectively downregulate KCNQ1OT1 expression, thus reversing cisplatin resistance in CRC cells.

Chitosan-coated doxorubicin nano-particles drug delivery system inhibits cell growth of liver cancer via p53/PRC1 pathway.

BACKGROUND: Nano-particles have been widely used in target-specific drug delivery system and showed advantages in cancers treatment. This study aims to evaluate the effect of chitosan coated doxorubicin nano-particles drug delivery system in liver cancer. METHODS: The chitosan nano-particles were prepared by using the ionic gelation method. The characterizations of the nano-particles were determined by transmission electron microscopy. The cytotoxicity was detected by MTT assay, and the endocytosis, cell apoptosis and cell cycle were examined by flow cytometry. The protein level was analyzed with western blot. The dual luciferase reporter assay was performed to assess the interaction between p53 and the promoter of PRC1, and chromatin immune-precipitation was used to verify the binding between them. RESULTS: The FA-CS-DOX nano-particles were irregular and spherical particles around 30-40 nm, with uniform size and no adhesion. No significant difference was noted in doxorubicin release rate between CS-DOX and FA-CS-DOX. FA-CS-DOX nano-particles showed stronger cytotoxicity than CS-DOX. FA-CS-DOX nano-particles promoted the apoptosis and arrested cell cycle at G2/M phase, and they up-regulated p53. FA-CS-DOX nano-particles inhibited cell survival through p53/PRC1 pathway. CONCLUSION: Chitosan-coated doxorubicin nano-particles drug delivery system inhibits cell growth of liver cancer by promoting apoptosis and arresting cell cycle at G2/M phase through p53/PRC1 pathway.

[DA-EPOCH Chemotherapy Combined with G-CSF Effectively Mobilizes Autologous PBHSC in NHL Patients].

OBJECTIVE: To study the effect of the DA-EPOCH chemotherapy combined with G-CSF and the CTX therapy with G-CSF on mobilizing and collecting the peripheral blood hematopoietic stem cells and the later hematopoietic recovery. METHODS: Forty patients accepted mobilization and collection of peripheral blood stem cells(PBSC) after treated by CTX+G-CSF and DA-EPOCH+G-CSF therapy respectively, and were treated by auto-transfusion after BEAM pre-regimen. The mobilization efficacy, adverse effects and hematopoietic recovery after autologous transplantation were analyzed retrospectively. RESULTS: During the CTX+G-CSF mobilization, only one patient achieved the white blood cell(WBC) at 0.8×109/L, while the others were with the lowest WBC level above 2.0×109/L. The platelet counts were all normal with the exception of 3 cases at 80×109/L. The median percentage of CD34+ cells in one period of collection was 0.99(0.35-1.30)%. The median MNC was (3.80±2.05)×1010. The cumulative total of mononuclear cell was (5.84±2.48)×108/kg, and the median CD34+ cell count was 3.84(3.91-6.5)×106/kg. During the DA-EPOCH+G-CSF mobilization, the peripheral WBC count of patients were decreased to the lowest level at (0.2-1.4)×109/L. The platelet counts were all above 40×109/L except for 1 case in which the platelet count was reduced to 8×109/L. The median percentage of CD34+ cells in one period of collection was 0.85(0.34-1.2)%. The median MNC was (3.68±1.56)×1010. The cumulative total of mononuclear cells was (6.01±2.26)×108/kg, and the median CD34+ cell count was 4.44(2.7-7.10)×106/kg. There were no statistical differences between the 2 groups in the median percentage of CD34+ cells, the median MNC, the cumulative total of mononuclear cells and the median CD34+ cell counts (P>0.05). The average acquired time for granulocyte engraftment was 10.00(9.00-11.00) days, and for platelet engraftment was 12.50(11.00-17.25) days, with no statistical difference(P>0.05). No death occurred during the process of transplantation. CONCLUSION: DA-EPOCH therapy combined with G-CSF can effectively mobilize the peripheral blood hematopoietic stem cells in NHL patients with higher safety and lower price, and proves to be worth recommending in clinical use.

Laparoscopic surgery assisted by colonoscopy for a submucosal cecal fecalith presenting as acute appendicitis: A case report.

RATIONALE: A cecal submucosal fecalith is extremely rare and is likely to be misdiagnosed as appendicitis with an incarcerated fecalith. PATIENT CONCERNS: This review presents the case of a female patient complaining of recurrent abdominal pain in the right lower quadrant, similar to the clinical symptoms of appendicitis. Physical examination revealed an abdominal tenderness in the right lower quadrant without rebound tenderness or muscular tension. An ultrasound examination found a mass located in the right lower abdomen. Computed tomography showed a high-density shadow in the cecal cavity. DIAGNOSES: A fecalith was detected in the submucosal cecal wall. The postoperative pathologic examination showed that the fecalith was located in the submucosa. INTERVENTIONS: A partial cecal excision was performed under laparoscopic surgery assisted by colonoscopy. OUTCOMES: The patient was discharged 1 week after surgery without postoperative complications. LESSONS: Fecaliths should be considered in the differential diagnosis of submucosal occupying lesions of the cecum.

Pitavastatin suppressed liver cancer cells in vitro and in vivo.

Pitavastatin classically functions as a blood cholesterol-lowering drug. Previously, it was discovered with antiglioma stem cell properties through drug screening. However, whether it can be used for liver cancer cell therapy has never been reported. In this study, the cell viability and colony formation assay were utilized to analyze the cytotoxicity of pitavastatin on liver cancer cells. The cell cycle alteration was checked after pitavastatin treatment. Apoptosis-related protein expression and the effect of caspase inhibitor were also checked. The in vivo inhibitory effect of pitavastatin on the growth of liver tumor was also tested. It was found that pitavastatin inhibited growth and colony formation of liver cancer Huh-7 cells and SMMC7721 cells. It induced arrest of liver cancer cells at the G1 phase. Increased proportion of sub-G1 cells was observed after pitavastatin treatment. Pitavastatin promoted caspase-9 cleavage and caspase-3 cleavage in liver cancer cells. Caspase inhibitor Z-VAD-FMK reversed the cleavage of cytotoxic effect of pitavastatin. Moreover, pitavastatin decreased the tumor growth and improved the survival of tumor-bearing mice. This study suggested the antiliver cancer effect of the old drug pitavastatin. It may be developed as a drug for liver cancer therapy.

[The role of glucagon-like peptide-1 and its receptor in the mechanism of metabolic surgery].

At present, surgery has become one of the treatments for type 2 diabetes, but it is still unclear about the therapeutic mechanism. Many experiments has proved that the anatomical and physiological structure has been altered leading to significant changes related to the secretion of gastrointestinal hormones and neuropeptides. These molecular are related to the metabolism of glucose, functions of islet cells and sensitivity of insulin. Intensive studies of glucagon-like peptide-1 (GLP-1) play an important role in the surgical treatment of diabetes and now it has gained increasing recognition. However, GLP-1 must be combined with GLP-1 receptor (GLP-1R) to execute its function. In this paper we reviewed the role of GLP-1 and its receptor in the mechanism of metabolic surgery.

[Efficacy of remission induction chemotherapy and prognostic analysis in elderly patients with acute myeloid leukemia].

OBJECTIVE: To explore the outcome of remission induction chemotherapy (IC) and prognostic in elderly patients with acute myeloid leukemia (AML). METHODS: The clinical data of 156 AML patients older than 60 years in the Institute of Hematology, Union Hospital of Fujian Medical University from January 2003 to July 2010 were analyzed retrospectively. 104 patients received cytarabine-based regimens, including protocol DA,IA or CAG,while 52 patients received palliative treatment. The median survival time was compared between patients with and without IC. The prognostic factors were evaluated by using univariate and multivariate analyses. RESULTS: 145 (93%) cases were followed-up. The median survival time was 316 days in 96 IC patients, compared with 37 days in 49 PT patients (P < 0.01). Not receiving induction chemotherapy,high-risk karyotype,hyperleukocytosis (> or = 100 x 10(9)/L), Charlson Comorbidity Index (CCI) > or = 2 were adverse prognostic factors of the survival time with univariate analysis, and all were independent poor factors affecting the survival time with multivariate analysis. CONCLUSIONS: IC can improve outcomes in elderly AML patients. The patients with hyperleukocytosis (> or = 100 x 10(9)/L) , high-risk karyotype, CCI > or = 2 and without receiving IC have poorer prognosis.