Humans ; Lymphoma ; diagnosis ; therapy ; Molecular Targeted Therapy

With computer and manual search of literatures on the comparison of concurrent with sequential adjuvant radio-chemotherapy after mastectomy for breast cancer, 4 eligible randomized controlled trials were found; the RevMan 5.0 software was used for Meta-analysis. The results showed that concurrent radio-chemotherapy reduced local recurrence more prominently than sequential radio-chemotherapy in patients with positive axillary lymph nodes( P = 0. 003 ). However, differences in 5-year overall survival,5-year disease-free survival and metastasis-free survival between two groups were not significant (P =0. 670,P =0. 200, P =0. 350).

Objective To evaluate the influence of preconditioning with and anti-myosinmonoclonal antibody (mAb2G4)-nuclear factor-kappa B decoy oligodeoxynucleotide (ODN)-lipofectamine (lip) on hypoxia-reoxygenation (H/R) injury in H9c2 cardiomyocytes.Methods H9c2 cardiomyocytes were seeded in 6-well plate at the density of 1×105/ml (2 ml/well),and were divided into 3 groups (n=9 each) using a random number table:control group (group C),H/R group and mAb2G4-ODN-lip group (group MOL).The cells underwent 2 h of hypoxia in an air-tight bag,followed by 1 h reoxygenation.In MOL group,the cells were treated with mAb2G4-ODN-lip (2 μg ODN) for 4 h and then cultured in the common culture medium for 8 h before hypoxia.At the end of reoxygenation,proliferation of cells was measured using MTT assay,and the cells and supernatant of the culture medium were collected to determine the activity of lactate dehydrogenas (LDH),content of malondialdehyde (MDA),concentrations of tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6) (by ELISA).The rate of proliferation inhibition was calculated.Results Compared with group C,the rate of proliferation inhibition,LDH activity,MDA content,and concentrations of TNF-α and IL-6 were significantly increased in the other two groups.Compared with group H/R,the rate of proliferation inhibition,LDH activity,MDA content,and concentrations of TNF-α and IL-6 were significantly decreased in MOL group.Conclusion mAb2G4-ODN-lip can mitigate H/R injury in H9c2 cardiomyocytes.

Objective To evaluate the effect of oxycodone preconditioning on liver injury induced by intestinal ischemia-reperfusion (I/R) in rats and the role of different opioid receptors.Methods Fiftyfour adult male Sprague-Dawley rats, weighing 200-300 g, were randomly divided into 9 groups (n =6 each) using a random number table: sham operation group (group S), group I/R, oxycodone preconditioning group (group OP) , μ receptor antagonist CTOP group (group CTOP) , δ receptor antagonist naltrindole group (group NTD), κ receptor antagonist nor-binaltorphimne group (group BNI), CTOP + oxycodo ne preconditioning group (group CTOP+OP) , naltrindole + oxycodone preconditioning group (group NTD+ OP) , and nor-binaltorphimne + oxycodone preconditioning group (BNI+OP).The model of intestinal I/R was established by occlusion of the superior mesenteric artery for 45 min followed by 2 h reperfusion in anesthetized rats.The superior mesenteric artery was only exposed, but not occluded in group S.In OP,COTP+OP, NTD+OP and BNI+OP groups, oxycodone 0.5 mg/kg was injected intravenously at 10 min prior to ischemia.COTP 1 mg/kg and naltrindole 5 mg/kg were injected intravenously at 20 min prior to ischemia in COTP+OP and NTD+OP groups, respectively.Nor-binaltorphimne 5 mg/kg was injected intravenously at 25 min prior to ischemia in group BNI+OP.In CTOP and NTD groups, the corresponding doses of CTOP and naltrindole were injected intravenously at 10 min prior to ischemia.In group BNI, the corresponding dose of nor-binaltorphimne was injected intravenously at 15 min prior to ischemia.The rats were sacrificed at 2 h of reperfusion, and left hepatic lobes were removed for microscopic examination and for detection of apoptosis in liver cells (using TUNEL).The apoptosis index (AI) was calculated.Results Compared with group S, the AI was significantly increased in the other groups (P＜0.05).Compared with group I/R, the AI was significantly decreased (P＜0.05) , and the pathological changes of livers were reduced in OP, COTP+OP, NTD+OP and BNI+OP groups, and no significant change was found in AI and pathological changes of livers in CTOP, NTD and BNI groups (P＞0.05).Compared with group OP, the AI was significantly increased (P＜0.05), and the pathological changes of livers were aggravated in COTP+ OP, NTD+OP and BNI+OP groups.There was no significant difference in AI and pathological changes of livers among groups COTP+OP, NTD+OP and BNI+OP (P＞0.05).Conclusion Oxycodone preconditioning can mitigate liver injury induced by intestinal I/R in rats, and μ, δ and κ receptors mediate the role with comparable effects.

Th22,a new subset of helper T cells,which is char-acterized by the secretion of interleukin-22(IL-22),could infil-trate to the epidermis in individuals with inflammatory skin disor-ders.This article introduces the action of Th22 and IL-22 in in-flammatory skin diseases,including psoriasis,atopic dermatitis, systemic lupus erythematosus,systemic sclerosis,aiming at re-vealing the role of Th22 and IL-22 in these diseases,which would not only provide some novel targets of drugs for inflamma-tory skin diseases,but also promote the researches on the pre-vention and treatment of these diseases.

BACKGROUND AND OBJECTIVESkeletal metastase is one of the most common complications related to advanced cancer. The aim of this study is to analyze the effectiveness and safety of radiotherapy plus intravenous bisphosphonates versus radiotherapy alone for treating bone metastasis.

METHODSWe searched the Cochrane Library, PubMed, EMBASE, CBM, CNKI and VIP, as well as the reference lists of reports and reviews. The quality of included trials was evaluated by the Cochrane Handbook. Data were extracted and evaluated by two reviewers independently. The Cochrane Collaboration's Rev-Man 5.0 was used for data analysis.

RESULTSTwenty-two trials involving 1 585 patients were included. Compared with radiotherapy alone, radiotherapy plus intravenous bisphosphonates was more effective in total effective rate of pain relive (RR = 1.21, 95% CI: 1.13-1.30, P < 0.001), average abated time (WMD = 16.00, 95% CI: 10.12-21.88, P < 0.001), and quality of life (RR = 1.25, 95% CI: 1.08-1.45, P = 0.003, with significant differences. Side effects have no significant differences between the two groups except fever (RR = 5.61, 95% CI: 3.11-10.13, P < 0.001).

CONCLUSIONCurrent evidence supports more effective of radiotherapy plus intravenous bisphosphonates for bone metastases. The combine treatment is safe and effective.

Bone Neoplasms ; psychology ; secondary ; therapy ; Combined Modality Therapy ; Diphosphonates ; therapeutic use ; Humans ; Quality of Life

OBJECTIVETo investigate promoter methylation status of LITAF gene in B-cell lymphoma and to explore transcription regulation of 5-Aza-2'-deoxycytidine (5-Aza-CdR) on LITAF gene.

METHODSOne hundred and five paraffin specimens including 54 cases of diffuse large B cell lymphoma (DLBCL), 15 small lymphocytic lymphoma (SLL), 8 mucosa-associated lymphoid tissue lymphoma (MALT) and 6 follicular lymphoma (FL) were included. Five reactive lymphoid hyperplasia samples were collected as control. Methylation status of CpG island in LITAF gene in the specimens and in Raji, Pfeiffer and Daudi cell lines were detected by methylation-specific PCR (MSP). LITAF expression in Raji, Pfeiffer and Daudi cell lines with or without 5-Aza-CdR treatment was detected by Western blot and immunohistochemistry. The inhibitory ratio in the three cell lines was measured by MTT assay.

RESULTSThe frequency of LITAF gene methylation in B-cell lymphoma was 89.5% (94/105) . Among them, 3.8% (4/105) showed complete hypermethylation. In control group, however, there was no methylation in CpG island of LITAF gene promoter. The expression of LITAF was recovered or increased along with the cell growth inhibition when the cells exposed to demethylating reagent.

CONCLUSIONSLITAF gene silencing with aberrant CpG methylation is probably one of the critical events to the oncogenesis of B-cell lymphoma, which may have important implications as a candidate marker for diagnosis and target gene therapy.

Adult ; Azacitidine ; analogs & derivatives ; metabolism ; Cell Line, Tumor ; CpG Islands ; DNA Methylation ; Gene Silencing ; Humans ; Lymphoma, B-Cell ; genetics ; metabolism ; Lymphoma, B-Cell, Marginal Zone ; genetics ; Lymphoma, Large B-Cell, Diffuse ; genetics ; Nuclear Proteins ; genetics ; metabolism ; Polymerase Chain Reaction ; Promoter Regions, Genetic ; Transcription Factors ; genetics ; metabolism

Objective:To explore the efficacy of subcutaneous injection of granulocyte-macrophage colony-stimulating factor (GM-CSF) in preventing invasive fungal disease (IFD) in patients with multiple myeloma (MM).Methods:The clinical data of 222 patients who were admitted to the Second Hospital of Harbin Medical University from January 2015 to June 2021 were retrospectively analyzed. The patients was given GM-CSF (3-5 μg·kg -1·d -1, GM-CSF group) or granulocyte colony-stimulating factor (G-CSF, 2-5 μg·kg -1·d -1, G-CSF group) when neutrophils (ANC) ≤1.5×10 9/L after induction chemotherapy. Patients were discontinued when white blood cell count (WBC) ≥10.0×10 9/L. The incidence of IFD (including confirmed, clinical and proposed diagnosis) and breakthrough invasive fungal infections was compared between the two groups. Results:The incidence of IFD was 8.1% (18/222) in all patients. The incidence of IFD was 3.5% (3/85) and 10.9% (15/137) in the GM-CSF and G-CSF groups, respectively, and the difference between the two groups was statistically significant ( χ2 = 3.88, P = 0.049). In 9 patients of GM-CSF group receiving fungal infection prophylaxis and in 15 patients of G-CSF group receiving fungal infection prophylaxis, the incidence of breakthrough invasive fungal infections was 0 and 7 cases, respectively, and the difference between the two groups was statistically significant ( P = 0.022). Conclusions:GM-CSF application in MM patients can reduce the incidence of IFD and breakthrough invasive fungal infections.

Immune checkpoint inhibitors (ICIs) are widely used in clinic, and the incidence of rare adverse events are increasing. The aim of this paper is to better define the rare adverse effect of diabetes mellitus associated with ICIs. We report 2 cases of diabetes mellitus associated with ICIs. Literature review was conducted and we discussed the clinical presentation, potential mechanisms and suggestions for optimal management. Two patients were both elderly women, case 1 had increased blood glucose after 7 months of using Durvalumab, and cases 2 had diabetic ketoacidosis after 6 weeks of using Pembrolizumab. Both patients were administered exogenous insulin to control blood glucose. Case 1 has been treated with Durvalumab until now and case 2 discontinued using of Pembrolizumab. HLA genotypes and other factors may explain the risk factors of diabetes associated with ICIs in some individuals. Diabetes mellitus associated with ICIs is an uncommon but potentially life-threatening endocrine system adverse event, which requires doctors to be vigilant. The patients who use ICIs need to monitor blood glucose. If they have hyperglycemia, endocrinologists should be asked to assist in diagnosis and treatment.
.
Aged ; Blood Glucose ; Diabetes Mellitus/drug therapy* ; Female ; Humans ; Immune Checkpoint Inhibitors/adverse effects* ; Lung Neoplasms/drug therapy*

Modulating Tankyrases (TNKS), interactions with USP25 to promote TNKS degradation, rather than inhibiting their enzymatic activities, is emerging as an alternative/specific approach to inhibit the Wnt/β-catenin pathway. Here, we identified UAT-B, a novel neoantimycin analog isolated from Streptomyces conglobatus, as a small-molecule inhibitor of TNKS-USP25 protein-protein interaction (PPI) to overcome multi-drug resistance in colorectal cancer (CRC). The disruption of TNKS-USP25 complex formation by UAT-B led to a significant decrease in TNKS levels, triggering cell apoptosis through modulation of the Wnt/β-catenin pathway. Importantly, UAT-B successfully inhibited the CRC cells growth that harbored high TNKS levels, as demonstrated in various in vitro and in vivo studies utilizing cell line-based and patient-derived xenografts, as well as APC^min/+ spontaneous CRC models. Collectively, these findings suggest that targeting the TNKS-USP25 PPI using a small-molecule inhibitor represents a compelling therapeutic strategy for CRC treatment, and UAT-B emerges as a promising candidate for further preclinical and clinical investigations.