[Exploration of the Role of Tumor Suppressor Genes Foxo1 and PTEN in the Tumorigenesis of Mouse Natural Killer-Cell Lymphoma].

Objective: To explore whether tumor suppressor gene Foxo1 and PTEN play a critical role in the tumorigenesis of mouse natural killer-cell lymphoma.

Methods: NKp46-iCre mice were crossed with mice carrying floxed Foxo1 alleles (Foxo1) as well as floxed PTEN alleles (PTEN) to generate mice in which Foxo1 and PTEN in NK cells were knock-out, referred as Foxo1PTEN. The growth and development of the mice and tumor formation were observed.

SET domain containing 1B gene is mutated in primary hepatic neuroendocrine tumors.

Primary hepatic neuroendocrine tumors (PHNETs) are extremely rare NETs originating from the liver. These tumors are associated with heterogeneous prognosis, and few treatment targets for PHNETs have been identified. Because the major genetic alterations in PHNET are still largely unknown, we performed whole-exome sequencing of 22 paired tissues from PHNET patients and identified 22 recurring mutations of somatic genes involved in the following activities: epigenetic modification (BPTF, MECP2 and WDR5), cell cycle (TP53, ATM, MED12, DIDO1 and ATAD5) and neural development (UBR4, MEN1, GLUL and GIGYF2).

Endoscopic ultrasonography-guided poly (lactic acid-co-glycolic acid)-poly (ethylene glycol)-poly (lactic acid-co-glycolic acid) thermogel tunnel creation for natural orifice transluminal endoscopic surgery in porcine model.

Background: Natural orifice transluminal endoscopic surgery (NOTES) is a minimal invasive treatment. However, tissue dissection under endoscopy is still challenging due to the flexibility of endoscopy body and there is still no effective method for establishing a tunnel towards the targeted area. We previously showed that a new kind of thermogel could be submucosallly injected and served as a cushion for endoscopic dissection.

Postoperative adverse events in patients with diabetes undergoing orthopedic and general surgery.

Factors that may result in the occurrence of adverse clinical events in diabetic patients during the postoperative period are not entirely clear. This study evaluated factors that may cause adverse events following elective orthopedic or general surgery.Patients with diabetes who underwent orthopedic or general surgery between January 2010 and October 2015 were retrospectively selected from the General Hospital of People's Liberation Army database.

Pharmacokinetic Properties of Single and Multiple Doses of Ertugliflozin, a Selective Inhibitor of SGLT2, in Healthy Chinese Subjects.

Ertugliflozin, a sodium-glucose cotransporter 2 inhibitor for the treatment of type 2 diabetes mellitus, prevents renal glucose reabsorption resulting in urinary glucose excretion. This open-label, parallel cohort, randomized study conducted in healthy Chinese adults residing in China assessed the pharmacokinetics, tolerability, and safety of 5 mg and 15 mg of ertugliflozin following single (fasted condition) and multiple-dose (fed condition) administration. Sixteen subjects were randomized and completed the study.

Intranasal immunization with recombinant outer membrane protein A induces protective immune response against Stenotrophomonas maltophilia infection.

Stenotrophomonas maltophilia (S. maltophilia), a multi-drug resistant opportunistic pathogen, is associated with nosocomial and community-acquired infections. Preventive and therapeutic strategies for such infections are greatly needed.

Aprepitant for gefitinib-induced refractory pruritus in Chinese malignancy population.

Targeted therapy is an important anti-cancer therapy in non-small cell lung cancer (NSCLC). Pruritus are the common side-effect with gefitinib, an anti-EGFR antibody and tyrosine-kinase inhibitor. We reported case reports to confirm the effects of aprepitant, a neurokinin receptor to management of refractory rash and pruritus in Chinese malignancy population.

Erlotinib versus gemcitabine/cisplatin in Chinese patients with EGFR mutation-positive advanced non-small-cell lung cancer: Crossover extension and post-hoc analysis of the ENSURE study.

Objectives: Sequential combination of epidermal growth factor receptor (EGFR)-tyrosine kinase inhibitors (TKIs) and chemotherapy has shown greater benefits than either treatment alone in non-small-cell lung cancer (NSCLC). In this follow-up of the ENSURE study, we evaluated progression-free survival (PFS) with first-line erlotinib followed by chemotherapy at progression versus the inverse treatment sequence in 175 Chinese patients with EGFR mutation-positive NSCLC.

Materials And Methods: Forty-five of the 175 patients included in the follow-up analysis experienced progressive disease (PD).

LncRNA analysis of lung tissues after hUC-MSCs and FTY720 treatment of lipopolysaccharide-induced acute lung injury in mouse models.

Acute lung injury (ALI), a persistent lung inflammatory response syndrome, may evolve into acute respiratory distress syndrome (ARDS). Characterized by rapid onset, critical features, and a complex etiology, ALI remains a challenging critical respiratory disease. Recently, mesenchymal stem cells (MSCs) have provided a new solution for the treatment of ALI.

Nonreceptor Tyrosine Kinase c-Abl- and Arg-Mediated IRF3 Phosphorylation Regulates Innate Immune Responses by Promoting Type I IFN Production.

The nonreceptor tyrosine kinase c-Abl plays important roles in T cell development and immune responses; however, the mechanism is poorly understood. IFN regulatory factor 3 (IRF3) is a key transcriptional regulator of type I IFN-dependent immune responses against DNA and RNA viruses. The data in this study show that IRF3 is physically associated with c-Abl in vivo and directly binds to c-Abl in vitro.

Risk-Dependent Conditional Survival and Failure Hazard After Radiotherapy for Early-Stage Extranodal Natural Killer/T-Cell Lymphoma.

Importance: Prognosis of early-stage extranodal natural killer/T-cell lymphoma (NKTCL) is usually estimated and stratified at diagnosis, but how the prognosis actually evolves over time for patients who survived after curative treatment is unknown.

Objective: To assess conditional survival and failure hazard over time based on risk categories, previous survival, and treatment.

Design, Setting, And Participants: This retrospective cohort study reviewed the clinical data of 2015 patients with early-stage NKTCL treated with radiotherapy identified from the China Lymphoma Collaborative Group multicenter database between January 1, 2000, and December 31, 2015.

Density of bone metastatic lesions increases after radiotherapy in patients with breast cancer.

The aim of this study was to assess local response to radiotherapy (RT) in a quantitative manner by evaluating the bone density of metastases. Spinal and pelvic bone metastases in 44 patients with breast cancer who were treated between May 2010 and December 2016 were retrospectively assessed. Bone density values of irradiated and unirradiated bone metastases before, 1-3 months after, 4-6 months after, and 7-9 months after RT were compared.

Expert consensus on multidisciplinary therapy of colorectal cancer with lung metastases (2019 edition).

The lungs are the second most common site of metastasis for colorectal cancer (CRC) after the liver. Rectal cancer is associated with a higher incidence of lung metastases compared to colon cancer. In China, the proportion of rectal cancer cases is around 50%, much higher than that in Western countries (nearly 30%).

Use of a three-dimensional printed polylactide-coglycolide/tricalcium phosphate composite scaffold incorporating magnesium powder to enhance bone defect repair in rabbits.

Background: The repair of large bone defects remains challenging for orthopaedic surgeons. Bone grafting remains the method of choice; such grafts fill spaces and enhance bone repair. Therapeutic agents also aid bone healing.

Discovery and evaluation of ZT55, a novel highly-selective tyrosine kinase inhibitor of JAK2 against myeloproliferative neoplasms.

Background: The JAK2-STAT signaling pathway plays a critical role in myeloproliferative neoplasms (MPN). An activating mutation in JAK2 (V617F) is present in ~ 95% of polycythemia vera, essential thrombocythemia, and primary myelofibrosis cases. This study aims to explore the selective JAK2 inhibitor, evaluate the efficacy and possible mechanism of ZT55 on MPN.

Protective and therapeutic application of the depolymerase derived from a novel KN1 genotype of Klebsiella pneumoniae bacteriophage in mice.

Klebsiella pneumoniae is one of the major Gram-negative bacterial pathogens causing hospital-acquired multidrug-resistant infections, and the antimicrobial treatment options are scarce. The lack of available antimicrobials has prompted the development of alternative strategies for the treatment of these infections. In this study, a K.

QingBai decoction regulates intestinal permeability of dextran sulphate sodium-induced colitis through the modulation of notch and NF-κB signalling.

Objective: Chinese Herb QingBai decoction (QBD) has been approved affective in the treatment of IBD patients in clinic. However, the underlying mechanism remains unknown. We aim to investigate the effect of QBD on the mouse model of ulcerative colitis and its possible mechanism.

Switching to anastrozole plus goserelin vs continued tamoxifen for adjuvant therapy of premenopausal early-stage breast cancer: preliminary results from a randomized trial.

Purpose: To assess the efficacy, safety, and quality-of-life impact of switching adjuvant treatment in hormone receptor-positive primary breast cancer patients who are still premenopausal after 2-3 years of tamoxifen therapy to anastrozole plus goserelin as compared with continuing tamoxifen over a total period of 5 years.

Patients And Methods: Hormone receptor-positive, premenopausal, lymph node-positive, or tumor size ≥4 cm breast cancer patients who had received tamoxifen for 2-3 years were randomly assigned to continue tamoxifen treatment (TAM group) or switch to adjuvant anastrozole plus goserelin (ADD group) and continue treatment for another 2-3 years (total treatment duration 5 years). Endpoints evaluated were adverse events (AEs), changes in bone mineral density, quality of life, and disease-free survival-related events.

Identification and validation of alternative splicing isoforms as novel biomarker candidates in hepatocellular carcinoma.

Alternative splicing (AS) is a transcriptional regulation mechanism that participates in multiple aspects of cancer. The present study aimed to identify differential AS events from tumor and non‑tumor samples and investigate the potential of AS as a source of candidate cancer diagnostic biomarkers. Deep RNA sequencing of three paired hepatocellular carcinoma (HCC) tumors and adjacent non‑tumors was applied to identify AS events.

Dual-Modified Novel Biomimetic Nanocarriers Improve Targeting and Therapeutic Efficacy in Glioma.

Glioma is a fatal disease with limited treatment options and very short survival. Although chemotherapy is one of the most important strategies in glioma treatment, it remains extremely clinically challenging largely due to the blood-brain barrier (BBB) and the blood-brain tumor barrier (BBTB). Thus, the development of nanoparticles with both BBB and BBTB penetrability, as well as glioma-targeting feature, is extremely important for the therapy of glioma.

Dual-modified natural high density lipoprotein particles for systemic glioma-targeting drug delivery.

Therapeutic outcome for the treatment of glioma was often limited due to the two barriers involved: the blood-brain barrier (BBB) and blood-brain tumor barrier (BBTB). Therefore, the development of nanocarriers that possess both BBB and BBTB permeability and glioma-targeting ability is of great importance for the chemotherapy of glioma. New frontiers in nanomedicine are advancing the research of new biomaterials.

Crosstalks between mTORC1 and mTORC2 variagate cytokine signaling to control NK maturation and effector function.

The metabolic checkpoint kinase mechanistic/mammalian target of rapamycin (mTOR) regulates natural killer (NK) cell development and function, but the exact underlying mechanisms remain unclear. Here, we show, via conditional deletion of Raptor (mTORC1) or Rictor (mTORC2), that mTORC1 and mTORC2 promote NK cell maturation in a cooperative and non-redundant manner, mainly by controlling the expression of Tbx21 and Eomes. Intriguingly, mTORC1 and mTORC2 regulate cytolytic function in an opposing way, exhibiting promoting and inhibitory effects on the anti-tumor ability and metabolism, respectively.

A Novel Self-Assembled Mitochondria-Targeting Protein Nanoparticle Acting as Theranostic Platform for Cancer.

Self-assembled protein nanoparticles have attracted much attention in biomedicine because of their biocompatibility and biodegradability. Protein nanoparticles have become widely utilized as diagnostic or therapeutic agents for various cancers. However, there are no reports that protein nanoparticles can specifically target mitochondria.