Changes in the gut microbiota and derived fecal metabolites may play a role in tacrolimus-induced diabetes in mice.

Aims: A notable scarcity of research has focused on examining alterations in gut microbiota and its metabolites within tacrolimus (TAC)-induced diabetes models.

Methods: Tacrolimus-induced changes in glucose and lipid metabolism indices were analyzed through different routes of administration. The potential role of gut microbiota and its metabolites in TAC-induced diabetes was investigated using 16S rRNA sequencing and non-targeted metabolomics.

Gut microbiota and metabolomic profile changes play critical roles in tacrolimus-induced diabetes in rats.

Aims: Hyperglycemia is one of the adverse effects of tacrolimus (TAC), but the underlying mechanism is not fully identified. We used multi-omics analysis to evaluate the changes in the gut microbiota and metabolic profile of rats with TAC-induced diabetes.

Methods: To establish a diabetic animal model, Sprague Dawley rats were divided randomly into two groups.

Endoscopic ultrasound-guided biliary drainage percutaneous transhepatic bile duct drainage in the management of malignant obstructive jaundice.

Background: Malignant obstructive jaundice (MOJ) is a condition characterized by varying degrees of bile duct stenosis and obstruction, accompanied by the progressive development of malignant tumors, leading to high morbidity and mortality rates. Currently, the two most commonly employed methods for its management are percutaneous transhepatic bile duct drainage (PTBD) and endoscopic ultrasound-guided biliary drainage (EUS-BD). While both methods have demonstrated favorable outcomes, additional research needs to be performed to determine their relative efficacy.

[Research progress of diagnostic and therapeutic value of carbon dioxide-derived indicators in patients with sepsis].

Effectively assessing oxygen delivery and demand is one of the key targets for fluid resuscitation in sepsis. Clinical signs and symptoms, blood lactic acid levels, and mixed venous oxygen saturation (SvO) or central venous oxygen saturation (ScvO) all have their limitations. In recent years, these limitations have been overcome through the use of derived indicators from carbon dioxide (CO) such as mixed veno-arterial carbon dioxide partial pressure difference (Pv-aCO, PCO gap, or ΔPCO), the ratio of mixed veno-arterial carbon dioxide partial pressure difference to arterial-mixed venous oxygen content difference (Pv-aCO/Ca-vO).

The novel TERF2::PDGFRB fusion gene enhances tumorigenesis via PDGFRB/STAT5 signalling pathways and sensitivity to TKI in ph-like ALL.

Patients with Philadelphia chromosome-like acute lymphoblastic leukaemia (Ph-like ALL) often face a grim prognosis, with PDGFRB gene fusions being commonly detected in this subgroup. Our study has unveiled a newfound fusion gene, TERF2::PDGFRB, and we have found that patients carrying this fusion gene exhibit sensitivity to dasatinib. Ba/F3 cells harbouring the TERF2::PDGFRB fusion display IL-3-independent cell proliferation through activation of the p-PDGFRB and p-STAT5 signalling pathways.

Deer antlers: the fastest growing tissue with least cancer occurrence.

Deer antlers are a bony organ solely able to acquired distinct unique attributes during evolution and all these attributes are against thus far known natural rules. One of them is as the fastest animal growing tissue (2 cm/day), they are remarkably cancer-free, despite high cell division rate. Although tumor-like nodules on the long-lived castrate antlers in some deer species do occur, but they are truly benign in nature.

Prognostication refinement in NPM1-mutated acute myeloid leukemia stratified by FLT3-ITD status with different induction doses of cytarabine.

Objective: We aimed to retrospectively discern the heterogeneity of outcomes from clinicopathological characteristics and next-generation sequencing (NGS) data in adult patients with NPM1-mutated (NPM1 ) acute myeloid leukemia (AML) induced with standard-dose (SD, 100-200 mg/m ) and intermediate-dose (ID, 1000-2000 mg/m ) cytarabine arabinose (Ara-C).

Methods: In the entire cohort and FLT3-ITD subgroups, multivariate Logistic and Cox regression analyses were used to analyze the comprehensive complete remission (cCR) rate after one or two induction cycles, event-free survival (EFS), and overall survival (OS).

Results: Among a total of 203 NPM1 patients evaluable for clinical outcome, 144 (70.

Immune response in COVID-19: what is next?

The coronavirus disease 2019 (COVID-19) has been a global pandemic for more than 2 years and it still impacts our daily lifestyle and quality in unprecedented ways. A better understanding of immunity and its regulation in response to SARS-CoV-2 infection is urgently needed. Based on the current literature, we review here the various virus mutations and the evolving disease manifestations along with the alterations of immune responses with specific focuses on the innate immune response, neutrophil extracellular traps, humoral immunity, and cellular immunity.

[Association of Next Generation Sequencing Based Genotypic Profiling with MICM Characteristics in NPM1 Mutated Acute Myeloid Leukemia].

Objective: To explain the clinicobiological heterogeneity of NPM1 mutated (NPM1) acute myeloid leukemia (AML) by analyzing the association between next-generation sequencing (NGS) profiles and MICM characteristics in patients with this AML subtype.

Methods: Data of 238 NPM1 patients with available NGS information on 112 genes related to blood disease was collected, and χ test and nonparametric test were used to analyze the distribution association between NGS-detecting mutations and conventional MICM parameters.

Results: In entire NPM1 cohort, totaling 240 NPM1 mutation events were identified, of whom 10 (10/240, 4.

Comparative Evaluation of the Effect of Metformin and Insulin on Gut Microbiota and Metabolome Profiles of Type 2 Diabetic Rats Induced by the Combination of Streptozotocin and High-Fat Diet.

Lately, an increasing number of studies have investigated the relationship between metformin and gut microbiota, suggesting that metformin exerts part of its hypoglycemic effect through the microbes. However, its underlying mechanism remains largely undetermined. In the present study, we investigated the effects of metformin on gut microbiota and metabolome profiles in serum and compared it with insulin treatment in rats with type 2 diabetes mellitus (T2DM).

Effects of type 2 diabetes and metformin on salivary microbiota in patients with chronic periodontitis.

Diabetes is closely associated with periodontitis, however, the effects of type 2 diabetes and metformin treatment on the salivary microbiota in chronic periodontitis patients are still insufficiently studied. Saliva was collected from ten patients with moderate to severe chronic periodontitis (CP group) and 20 patients with type 2 diabetes mellitus (T2DM) and moderate to severe chronic periodontitis (ten patients were newly diagnosed with diabetes without drug treatment (DM group), and ten patients were treated with metformin (CP-DM-MET group)). Total DNA was extracted.

Lung mesenchymal stromal cells influenced by Th2 cytokines mobilize neutrophils and facilitate metastasis by producing complement C3.

Pre-metastatic niche formation is critical for the colonization of disseminated cancer cells in distant organs. Here we find that lung mesenchymal stromal cells (LMSCs) at pre-metastatic stage possess potent metastasis-promoting activity. RNA-seq reveals an upregulation of complement 3 (C3) in those LMSCs.

Methylprednisolone Induces Neuro-Protective Effects via the Inhibition of A1 Astrocyte Activation in Traumatic Spinal Cord Injury Mouse Models.

Traumatic spinal cord injury (TSCI) leads to pathological changes such as inflammation, edema, and neuronal apoptosis. Methylprednisolone (MP) is a glucocorticoid that has a variety of beneficial effects, including decreasing inflammation and ischemic reaction, as well as inhibiting lipid peroxidation. However, the efficacy and mechanism of MP in TSCI therapy is yet to be deciphered.

Metabolic Changes Precede Radiation-Induced Cardiac Remodeling in Beagles: Using Noninvasive F-FDG (F-Fludeoxyglucose) and N-Ammonia Positron Emission Tomography/Computed Tomography Scans.

Background This study was performed to characterize the metabolic, functional, and structural cardiac changes in a canine model of radiation-induced heart disease by serial in vivo imaging and ex vivo analyses. Methods and Results Thirty-six dogs were randomly assigned to control or irradiated groups at 3 time points (months 3, 6, and 12 after radiation; each group comprised 6 dogs). The left anterior myocardium of dogs in irradiated groups was irradiated locally with a single dose of 20-Gy X-ray.

MicroRNA-1271-5p inhibits the tumorigenesis of ovarian cancer through targeting E2F5 and negatively regulates the mTOR signaling pathway.

Background: MicroRNA-1271-5p (miR-1271-5p) has been reported to participate in the progression of many human cancers. However, the role of miR-1271-5p still remains unclear in ovarian cancer (OC). Therefore, we explored the effect of miR-1271-5p on the development of OC in present study.

[Expression and Prognostic Value of MiR-155 in Patients with Chronic Lymphocytic Leukemia].

Objective: To explore the expression of miR-155 in patients with chronic lymphocytic leukemia (CLL) and its correlation with the clinical and biological features in CLL.

Methods: The expression of miR-155 was detected by quantitative real time polymerase chain reaction (qRT-PCR) in the peripheral mononuclear cells collected from 73 CLL patients and CD19 positive B cells collected from 60 healthy controls, respectively. The expression of miR-155 in CLL patients was compared with the healthy controls, and the correlation of miR-155 expression with the clinical characteristics of CLL patients such as age, sex, Binet stage, cytogenetic and molecular genetic, as well as the relationship of miR-155 expression level with time to treatment (TTT) and overall survival (OS) was further analysed.

Comparison of the 8th union for international cancer control lymph node staging system for gastric cancer with two other lymph node staging systems.

The log odds of positive lymph nodes (LODDS) and the metastatic lymph node ratio (MLR) staging systems have previously been demonstrated to exhibit advantages compared with the tumor-node-metastasis (TNM) staging system in predicting the prognosis of gastric cancer. The current study compared the prognostic significance of the newest Union for International Cancer Control Node classification with the LODDS and MLR staging systems. From September 2010 to December 2012, all medical records for patients with gastric cancer at the Third Affiliated Hospital of Soochow University were retrospectively analyzed and the clinicopathologic characteristics were reviewed.

Progress in diagnosis and surgical treatment of perihilar cholangiocarcinoma.

Cholangiocarcinomas are heterogeneous biliary tract tumors that cause devastating disease. Perihilar cholangiocarcinoma (PHC) is the most common type of biliary tract cancer and are associated with a high mortality. Diagnoses of PHC depend on the results of its clinical presentation, serum biomarkers and imaging techniques.

[Effect of Additional Chromosomal Abnormalities on the Outcome of CML-CP Patients Receiving TKI Therapy].

Objectives: To explore the effect of additional chromosomal abnormalities on the prognosis and outcome of CML-CP patients receiving imatinib therapy.

Methods: The clinical and genetic data of 589 CML-CP patients receiving imatinib treatment between May 2009 and October 2014 in the 1st Affiliated Hospital of Soochow University were analyzed, the 589 patients were divided into 5 groups according to the karyotypes at the initial diagnosis. The OS(overall survival), PFS (progression-free survival), EFS (event-free survival), Cumulative MMR (major molecular remission) and Cumulative CCyR (complete cytogenetic remission) were calculated by using the Kaplan-Meier method and compared by using the log-rank text by Graphpad 6.

A novel molecular mechanism of microRNA-21 inducing pulmonary fibrosis and human pulmonary fibroblast extracellular matrix through transforming growth factor β1-mediated SMADs activation.

Pulmonary fibrosis (PF), characterized by the destruction of lung tissue architecture and the abnormal deposition of extracellular matrix (ECM) proteins, currently has no satisfactory treatment. The role of microRNA (miR)-21 in PF has been reported; the current study attempted to investigate a novel molecular mechanism by which miR-21 exerted its function. Consistent with previous studies, miR-21 inhibition reduced ECM protein levels in bleomycin (BLM)-induced mouse model of PF.

Distinctive profiles of tumor-infiltrating immune cells and association with intensity of infiltration in colorectal cancer.

Tumor-infiltrating immune cells are heterogeneous and consist of characteristic compartments, including T helper (Th)1 and regulatory T (Treg) cells that exhibit distinctive biological functions. The present study investigated the profile of infiltrating immune cells from surgically removed tumor tissues from patients with colorectal cancer. The characteristic transcription factors of Th1 and Th2 cells, Treg cells, Th17 cells and T follicular helper (Tfh) cells were analyzed.

A causal relationship between the neurotherapeutic effects of miR182/7a and decreased expression of PRDM5.

Background: Spinal cord injury (SCI) is terrible damage resulting in the deficiencies and necrosis of neurology and causes infinite inconvenience to sufferers. The therapy of SCI still meets a larger number of problems. Therefore, the underlying mechanism and novel therapy of acute SCI (ASCI) are urgent to explore.

Combretastatin A4 phosphate treatment induces vasculogenic mimicry formation of W256 breast carcinoma tumor in vitro and in vivo.

The purpose of this study was to investigate the effect of combretastatin A4 phosphate (CA4P) on vasculogenic mimicry (VM) channel formation in vitro and in vivo after a single-dose treatment and the underlying mechanism involved in supporting VM. In vitro model of three-dimensional cultures was used to test the effect of CA4P on the tube formation of Walker 256 cells. Western blot analysis was conducted to assess the expression of hypoxia-inducible factor (HIF)-1α and VM-associated markers.

PD806: a novel oral vascular disrupting agent shows antitumor and antivascular effects in vitro and in vivo.

The aim of this study was to investigate the antitumor and antivascular effects of PD806, a new oral prodrug of AVE8063 in vitro and in vivo. The cytotoxicity of PD806 was determined against H22, Walker 256, A549, MCF-7, and BEL-7402 cells using MTT assays. Plasma pharmacokinetic analysis of AVE8063 generated in rats after a single oral administration of PD806 was carried out using the high-performance liquid chromatography method.