Lysosome-Targeting Bacterial Outer Membrane Vesicles for Tumor Specific Degradation of PD-L1.

Increased expression of immune check point genes, such as PD-L1, is one of the main reasons for immunosuppression, especially for colon cancer. Development of novel therapeutic strategies is of great importance to improve the prognosis. In this study, outer membrane vesicles (OMV) derived from Gram-negative bacteria are engineered to immune checkpoint blockade nanosystem for efficient elicitation of anti-tumor immunity.

Discovery of a potent Gilteritinib-based FLT3-PROTAC degrader for the treatment of Acute myeloid leukemia.

Fms-like tyrosine receptor kinase 3 (FLT3) proteolysis targeting chimeras (PROTACs) emerge as a promising approach to overcome the limitations of FLT3 inhibitors, while the development of orally bioavailable FLT3-PROTACs faces great challenges. Here, we report the rational design and evaluation of a series of Gilteritinib-based FLT3-PROTACs. Among them, B3-2 exhibited the strongest antiproliferative activity against FLT3-ITD mutant AML cells, and significantly induced FLT3-ITD protein degradation.

Clinical value of circulating tumour cells in evaluating the efficacy of continuous hepatic arterial infusion among colorectal cancer patients.

Few studies have been conducted to evaluate the efficacy of HAIC using circulating tumour cells (CTCs). In this study, a total of 100 patients who received HAIC treatment and CTC detection were selected. The results showed that after HAIC treatment, the levels of CTC, carbohydrate antigen 19-9 (CA19-9) and carcinoembryonic antigen (CEA) decreased.

Recent advances in IgG4-related autoimmune pancreatitis.

The incidence of IgG4-related autoimmune pancreatitis (IgG4-AIP) is high in Asia and other countries, and unnecessary treatment is often undertaken due to both missed diagnosis and misdiagnosis in clinical practice. Although IgG4-AIP has attracted increasing attention, the details of IgG4-AIP pathogenesis and systemic immune response, including its relationship to tumor pathogenesis, are still unclear. In recent years, research on serum immunological detection, pathological features, clinical manifestations, diagnosis and treatment measures for IgG4-AIP has gradually increased.

Discovery of a Novel Orally Bioavailable FLT3-PROTAC Degrader for Efficient Treatment of Acute Myeloid Leukemia and Overcoming Resistance of FLT3 Inhibitors.

Fms-like tyrosine receptor kinase 3 (FLT3) proteolysis-targeting chimeras (PROTACs) represent a promising approach to eliminate the resistance of FLT3 inhibitors. However, due to the poor druggability of PROTACs, the development of orally bioavailable FLT3-PROTACs faces great challenges. Herein, a novel orally bioavailable FLT3-ITD degrader with excellent pharmacokinetic properties was discovered through reasonable design.

Insights into the biosynthesis of palladium nanoparticles for oxygen reduction reaction by genetically engineered bacteria of Shewanella oneidensis MR-1.

Owing to the increasing need for green synthesis and environmental protection, the utilization of biological organism-derived carbons as supports for noble-metal electrocatalysts has garnered public interest. Nevertheless, the mechanism by which microorganisms generate nanometals has not been fully understood yet. In the present study, we used genetically engineered bacteria of Shewanella oneidensis MR-1 (∆SO4317, ∆SO4320, ∆SO0618 and ∆SO3745) to explore the effect of surface substances including biofilm-associated protein (bpfA), protein secreted by type I secretion systems (TISS) and type II secretion systems (T2SS), and lipopolysaccharide in microbial synthesis of metal nanoparticles.

Discovery of a Novel CSF-1R Inhibitor with Highly Improved Pharmacokinetic Profiles and Superior Efficacy in Colorectal Cancer Immunotherapy.

Blocking CSF-1/CSF-1R pathway has emerged as a promising strategy to remodel tumor immune microenvironment (TME) by reprogramming tumor-associated macrophages (TAMs). In this work, a novel CSF-1R inhibitor with a highly improved pharmacokinetic profile and in vivo anticolorectal cancer (CRC) efficiency was successfully discovered. could effectively reprogram M2-like TAMs to M1 phenotype and reshape the TME by inducing the recruitment of CD8 T cells into tumors and reducing the infiltration of immunosuppressive Tregs/MDSCs.

YTHDC1 promotes the malignant progression of gastric cancer by promoting ROD1 translocation to the nucleus.

RNA-binding proteins (RBPs) make vital impacts on tumor progression and are important potential targets for tumor treatment. Previous studies have shown that RBP regulator of differentiation 1 (ROD1), enriched in the nucleus, is abnormally expressed and functions as a splicing factor in tumors; however, the mechanism underlying its involvement in gastric cancer (GC) is unknown. In this study, ROD1 is found to stimulate GC cell proliferation and metastasis and is related to poor patient prognosis.

Multidrug-resistant Klebsiella Pneumoniae Infection Led to Resection of the Graft in a Small Bowel Transplant Recipient: A Case Report and Review of the Literature.

Background: Infection due to multidrug-resistant Klebsiella pneumoniae is a common cause of graft resection after small bowel transplantation. We report a failed case in which the intestinal graft was resected 18 days after the operation due to postoperative infection with multidrug-resistant K pneumoniae and a literature review of other common causes of small bowel transplantation failure have been reported.

Methods: A female, 29 years of age, underwent partial living small bowel transplantation for short bowel syndrome.

Comparison of thoracoabdominal versus abdominal-transhiatal surgical approaches in Siewert type II adenocarcinoma at the esophagogastric junction: Protocol for a prospective multicenter randomized controlled trial.

Background: Siewert type II adenocarcinoma of the esophagogastric junction (Siewert II AEG) can be resected by the right thoracoabdominal surgical approach (RTA) or abdominal-transhiatal surgical approach (TH) under minimally invasive conditions. Although both surgical methods achieve complete tumor resection, there is a debate as to whether the former method is superior to or at least noninferior to the latter in terms of surgical safety. Currently, a small number of retrospective studies have compared the two surgical approaches, with inconclusive results.

Prognostic model based on m6A-associated lncRNAs in esophageal cancer.

Background: This research aimed to build an m6A-associated lncRNA prognostic model of esophageal cancer that can be used to predict outcome in esophageal cancer patients.

Methods: RNA sequencing transcriptome data and clinical information about patients with esophageal cancer were obtained according to TCGA. Twenty-four m6A-associated genes were selected based on previous studies.

Study protocol for feasibility and safety of adopting early oral feeding in post total laparoscopic total gastrectomy (overlap esophagojejunostomy): A multicentre randomized controlled trial.

Background: Total laparoscopic total gastrectomy (TLTG) for gastric cancer, especially with overlap esophagojejunostomy, has been verified that it has advantages of minimally invasion, less intraoperative bleeding, and faster recovery. Meanwhile, early oral feeding (EOF) after the operation has been demonstrated to significantly promote early rehabilitation in patients, particularly with distal gastrectomy. However, due to the limited application of TLTG, there is few related research proving whether it is credible or safe to adopt EOF after TLTG (overlap esophagojejunostomy).

Influence of Comprehensive Nursing Intervention Combined with WeChat Platform Propaganda and Education of ERAS Concept on Postoperative Functional Recovery of Patients with Gallbladder Polyps.

To analyze the effect of comprehensive nursing intervention based on ERAS's concept in laparoscopic gallbladder polyp (GP) surgery on patients' postoperative quality of life and nursing job satisfaction. Ninety patients with polyps were included in this article until October 2021. In this format, the 45 cases are divided into governing bodies and committees according to their processing time.

Work Efficiency and Economic Efficiency of Actual Driving Test of Proton Exchange Membrane Fuel Cell Forklift.

A 3.5 tonne forklift containing proton exchange membrane fuel cells (PEMFCs) and lithium-ion batteries was manufactured and tested in a real factory. The work efficiency and economic applicability of the PEMFC forklift were compared with that of a lithium-ion battery-powered forklift.

Clinical study on flipped classroom and mind map in newly recruited nurses' pre-job training.

Background: Traditional pre-job training mainly provides theoretical lectures and operational skill training for new nurses. However, it has a single teaching method, lacks in comprehensiveness and flexibility, and has unsatisfactory teaching effects. The purpose of this article is to evaluate the influence of the flipped classroom and mind map in the pre-job training of newly recruited nurses.

Microbial synthesis of efficient palladium electrocatalyst with high loadings for oxygen reduction reaction in acidic medium.

Whereas limited amount of precious metal adsorbed by bacteria conflicting the needs of high loadings for better catalytic performances, cell disruption technology was adopted to smash Shewanella cells in this work, releasing abundant oxygen functional groups inside the cells for better adsorption of palladium ion. Then palladium catalysts were synthesized in two ways: 1) Pd catalyst supported on carbonized-broken-bacterial (Pd/FHNC) was obtained after direct carbonization and reduction; 2) Electrospinning technology was used to spin the broken Shewanella into fibers, and Pd nanoparticles supported on nitrogen-doped carbon nanofiber (Pd/NCNF) was prepared following carbonization and hydrogen reduction. The as-prepared catalysts exhibit excellent oxygen reduction reaction (ORR) electrocatalytic performance in the acid medium.

Surgical treatment for cryptoglandular and Crohn's perianal fistulas: Protocol of an umbrella review.

Introduction: A high prevalence of cryptoglandular and Crohn's perianal fistulas has been reported worldwide, and several surgical options are available for the management of anal fistula, with varying clinical efficacy. However, currently, the available evidence for the effectiveness of these surgical approaches are lacking and of concern in terms of the credibility and strength. The purpose of this study is to evaluate the credibility of the published systematic reviews and meta-analyses that assess the efficacy and safety of the surgical options for cryptoglandular and Crohn's perianal fistulas through an umbrella review.

MiR-4729 regulates TIE1 mRNA m6A modification and angiogenesis in hemorrhoids by targeting METTL14.

Background: Hemorrhoids are a frequently-occurring disease of the anorectal system that is often accompanied by vascular hyperplasia and edema. A METTL14-mediated RNA N-6 methyladenosine (m6A) modification can improve mRNA stability and increase its transcriptional and translational activities, closely related to the occurrence of many diseases.

Methods: Western blot, qPCR, and immunofluorescence staining were used to detect the levels of gene and protein expression.

Transcriptome Based System Biology Exploration Reveals Homogeneous Tumorigenicity of Alimentary Tract Malignancy.

Malignancies of alimentary tract include esophageal carcinoma (ESCA), stomach adenocarcinoma (STAD), colon adenocarcinoma (COAD), and rectum adenocarcinoma (READ). Despite of their similarities in cancer development and progression, there are numerous researches concentrating on single tumor but relatively little on their common mechanisms. Our study explored the transcriptomic data of digestive tract cancers from The Cancer Genome Atlas database, yielding their common differentially expressed genes including 1,700 mRNAs, 29 miRNAs, and 362 long non-coding RNAs (lncRNAs).

Construction and Characterization of KRAS Immune Lipid Magnetic Balls for Colorectal Cancer Circulating Tumor Cells.

Objective: The purpose of this study was to prepare and characterize a lipid magnetic ball modified with KRAS antibodies on the surface and to isolate circulating tumor cells of colorectal cancer with mutations.

Methods: The microemulsion method was used to form lipid bilayers to encapsulate Fe3O4 nanoparticles with superparamagnetism to form lipid magnetic balls, and antibodies were formed on the surface to form immune lipid magnetic balls.

Results: Compared with traditional EpCAM antibody-modified lipid magnetic balls, it can effectively improve the capture ability of colorectal cancer circulating tumor cells with mutation, the capture rate reaches 92.

Aberrant expression for microRNA is potential crucial factors of haemorrhoid.

Background: Haemorrhoids occur commonly and frequently in the human digestive system. There are diverse causes of haemorrhoids and their in-depth pathogenesis is still currently unclear.

Methods: In this study, we explored haemorrhoids from an epigenetics perspective by employing RNA-Seq for comprehensive and in-depth analysis of the differences in microRNA (miRNA) transcripts between haemorrhoidal tissue and normal tissue in 48 patients with Grade II and above haemorrhoids.

Area-specific economic status should be regarded as a vital factor affecting the occurrence, development and outcome of cervical cancer.

For patients with cervical cancer, despite the incidence and mortality rates have been declining in recent years, due to its huge population base, cervical cancer has always been a serious public health problem. Our research placed emphasis on the indices greatly associated with overall area-specific social economic status, making up for the defects of traditional research which only pay attention to the situation of some specific disease or patients' individual social status. A total of 39160 women identified cervical cancer were concluded in our study from the Surveillance, Epidemiology, and End Results (SEER) 18 Program data between 1980 and 2014.

Development of screening tools to predict the risk of recurrence and related complications following anal fistula surgery: protocol for a prospective cohort study.

Introduction: Postoperative recurrence and related complications are common and related to poor outcomes in patients with anal fistula (AF). Due to being associated with short-term and long-term cure rates, perioperative complications have received widespread attention following AF surgery. This study aims to identify a set of predictive factors to develop risk prediction models for recurrence and related complications following AF surgery.