Phenotypic Profiling of Tigecycline-resistant Klebsiella pneumoniae Strains Induced In vitro.

Tigecycline is one of the last-resort treatment options for infections caused by carbapenem-resistant Klebsiella pneumoniae (KP). Unfortunately, tigecycline resistance is increasingly reported and causes an unprecedented public health crisis worldwide. Although studies on tigecycline resistance are expanding, the underlying mechanisms are not fully understood.

PD-L1 antibody conjugated dihydrotanshinone I-loaded polymeric nanoparticle for targeted cancer immunotherapy combining PD-L1 blockade with immunogenic cell death.

Purpose: Combination immune checkpoint inhibitors (ICI) with chemotherapeutic agents has proven to be highly promising in cancer therapy. However, low response rate, immune-related adverse events, and lack of effectively targeted co-delivery strategy are still major hurdles to overcome for this combination therapeutic regimen. Herein, programmed death-L1 (PD-L1) antibody modified and dihydrotanshinone I (DHT) loaded nanoparticle was prepared for tumor targeting drug delivery, thus achieving immune checkpoint blockade (ICB) and immunogenic cell death (ICD) synergistic anti-tumor effects.

Survival Benefit of Lenvatinib Plus PD-1 Inhibitor with or Without HAIC in Advanced Hepatocellular Carcinoma Beyond Oligometastasis: a Multicenter Cohort Study.

Purpose: The outcome between Lenvatinib plus programmed cell death protein-1 (PD-1) inhibitor and Lenvatinib in HCC beyond oligometastasis was unclear. In this multicenter, we compared the prognosis of Lenvatinib plus PD-1 inhibitor with Lenvatinib in HCC beyond oligometastasis.

Patients And Methods: A total of 296 patients from six institutions were included.

A self-reported symptom-based decision-making model helps to rule out outpatient cases at low risk for CRC before colonoscopy.

Objectives: Effective exclusion of low-risk symptomatic outpatient cases for colorectal cancer (CRC) remains diagnostic challenges. We aimed to develop a self-reported symptom-based decision-making model for application in outpatient scenarios.

Methods: In total, 8233 symptomatic cases at risk for CRC, as judged by outpatient physicians, were involved in this study at seven medical centers.

KKL-35 inhibits growth of Staphylococcus aureus by systematically changing bacterial phenotypes.

KKL-35 is a new oxadiazole compound with potent broad-spectrum antibacterial activity against a number of gram-positive and gram-negative bacteria. However, its influences on bacterial growth are unclear. This study is to investigate phenotypic changes of Staphylococcus aureus (SA) caused by KKL-35 and evaluate antibacterial activity of combinations of KKL-35 with 7 class of antibiotics available in medical facilities.

[Prognosis and risk factors for mortality in cirrhotic patients with probable spontaneous bacterial peritonitis].

Objective: To investigate the survival outcomes and risk factors for mortality in cirrhotic patients with probable spontaneous bacterial peritonitis (SBP).

Methods: We retrospectively analyzed the clinical data of 323 cirrhotic patients with ascites admitted from June 2021 to May 2022, including 115 patients with SBP [ascites polymorphonuclear leucocyte (PMN) count ≥250/mm], 52 patients with bacterascites (PMN count < 250/mm with positive microbiological finding in ascites), 67 patients with probable SBP (PMN count < 250/mm with negative microbiological finding in ascites but clinical symptoms of SBP) and 89 patients without infection (PMN count < 250/mm with negative microbiological finding without clinical symptoms of SBP). The clinical characteristics, laboratory data and 90-day mortality of the patients were compared among the 4 groups.

Clinical significance of serum lactate and lactate dehydrogenase levels for disease severity and clinical outcomes in patients with colorectal cancer admitted to the intensive care unit.

Objective: Serum lactate (LA) and lactate dehydrogenase (LDH) levels have a major impact on the clinical treatment of malignant tumors and critically ill patients. Nevertheless, the assessment of disease severity in oncology patients admitted to the intensive care unit (ICU) remains incomplete when considering the serum LA and LDH levels. This study aimed to investigate the significance of serum LDH and LA levels in assessing disease severity and predicting clinical outcomes in patients with colorectal cancer (CRC) admitted to the ICU.

A novel imaging index for predicting adverse progression in acute-on-chronic liver failure related to hepatitis B virus: the low erector spine index.

Background: It is widely known that muscle mass influences the outcomes of many chronic diseases. Erector spine mass is a convenient parameter obtained from routine abdominal computed tomography (CT). The clinical application value of erector spine mass, and whether erector spine mass could predict the outcome of disease has not been studied.

Genetic alterations and molecular mechanisms underlying hereditary intrahepatic cholestasis.

Hereditary cholestatic liver disease caused by a class of autosomal gene mutations results in jaundice, which involves the abnormality of the synthesis, secretion, and other disorders of bile acids metabolism. Due to the existence of a variety of gene mutations, the clinical manifestations of children are also diverse. There is no unified standard for diagnosis and single detection method, which seriously hinders the development of clinical treatment.

Differential Diagnosis of Benign and Malignant Breast Papillary Neoplasms on MRI With Non-mass Enhancement.

Rationale And Objectives: To explore the differential diagnosis of benign and malignant papillary neoplasms on MRI with non-mass enhancement.

Materials And Methods: A total of 48 patients with surgically confirmed papillary neoplasms showing non-mass enhancement were included. Clinical findings, mammography and MRI features were retrospectively analyzed, and lesions were described according to the breast imaging report and data system (BI-RADS).

Treatment of neurofibromatosis type II with anlotinib: a case report and literature review.

Patients with neurofibromatosis type II (NF2) usually require surgical treatment, but the probability of tumor recurrence remains high after surgical resection. Moreover, because most of NF2 lesions involve the facial nerve, the risk of facial nerve injury during the surgery is high. Stereotactic radiotherapy can be used to treat some cases of NF2.

Anlotinib reduces the suppressive capacity of monocytic myeloid-derived suppressor cells and potentiates the immune microenvironment normalization window in a mouse lung cancer model.

By exploring the effects of an antiangiogenic small molecule drug named anlotinib on the levels of myeloid-derived suppressor cells (MDSCs) in a mouse xenograft model of lung cancer, the role of anti-angiogenesis in remodeling the immune microenvironment was discussed. In addition, the impact of anlotinib on the normalization of the immune microenvironment and time window was examined, providing a theoretical basis for the optimization of clinical strategies applying anlotinib combined with PD-1 inhibitors. On the basis of the LLC mouse xenograft model, MDSCs and MDSCs + immune microenvironment were examined in tissues, respectively, according to different samples.

Engineered anti-PDL1 with IFNα targets both immunoinhibitory and activating signals in the liver to break HBV immune tolerance.

Objective: The purpose of this study is to develop an anti-PDL1-based interferon (IFN) fusion protein to overcome the chronic hepatitis B virus (HBV)-induced immune tolerance, and combine this immunotherapy with a HBV vaccine to achieve the functional cure of chronic hepatitis B (CHB) infection.

Design: We designed an anti-PDL1-IFNα heterodimeric fusion protein, in which one arm was derived from anti-PDL1 antibody and the other arm was IFNα, to allow targeted delivery of IFNα into the liver by anti-PDL1 antibody. The effect of the anti-PDL1-IFNα heterodimer on overcoming hepatitis B surface antigen (HBsAg) vaccine resistance was evaluated in chronic HBV carrier mice.

Neutrophil-mediated delivery of the combination of colistin and azithromycin for the treatment of bacterial infection.

Novel treatment strategies are in urgent need to deal with the rapid development of antibiotic-resistant superbugs. Combination therapies and targeted drug delivery have been exploited to promote treatment efficacies. In this study, we loaded neutrophils with azithromycin and colistin to combine the advantages of antibiotic combinations, targeted delivery, and immunomodulatory effect of azithromycin to treat infections caused by Gram-negative pathogens.

Period-Dependent Survival Benefit of Percutaneous Microwave Ablation for Hepatocellular Carcinoma: A 12-Year Real-World, Multicentric Experience.

Introduction: Although microwave ablation (MWA) is a promising technique for hepatocellular carcinoma (HCC) treatment, its 10-year efficacy is unknown.

Objective: The objective of the study was to assess whether the advances in MWA for HCC translated into a real-world survival benefit.

Methods: This retrospective study included 2,354 patients with Barcelona Clinic Liver Cancer (BCLC) stage 0 to B from 5 hospitals, with at least 2 years of follow-up for all the patients.

A Machine Learning Model Based on Health Records for Predicting Recurrence After Microwave Ablation of Hepatocellular Carcinoma.

Background And Aim: Early recurrence (ER) presents a challenge for the survival prognosis of patients with hepatocellular carcinoma (HCC). The aim of this study was to investigate machine learning (ML) models using clinical data for predicting ER after microwave ablation (MWA).

Methods: Between August 2005 and December 2019, 1574 patients with early-stage HCC underwent MWA at four hospitals were reviewed.

The advanced development of molecular targeted therapy for hepatocellular carcinoma.

Hepatocellular carcinoma (HCC), one of the most common malignant tumors in China, severely threatens the life and health of patients. In recent years, precision medicine, clinical diagnoses, treatments, and innovative research have led to important breakthroughs in HCC care. The discovery of new biomarkers and the promotion of liquid biopsy technologies have greatly facilitated the early diagnosis and treatment of HCC.

MBD3 promotes hepatocellular carcinoma progression and metastasis through negative regulation of tumour suppressor TFPI2.

Background: The mechanism of recurrence and metastasis of hepatocellular carcinoma (HCC) is complex and challenging. Methyl-CpG binding domain protein 3 (MBD3) is a key epigenetic regulator involved in the progression and metastasis of several cancers, but its role in HCC remains unknown.

Methods: MBD3 expression in HCC was detected by immunohistochemistry and its association with clinicopathological features and patient's survival was analysed.

First-line PD-1/PD-L1 inhibitors plus chemotherapy versus bevacizumab plus chemotherapy for advanced non-squamous non-small cell lung cancer: A Bayesian network meta-analysis of randomized controlled trials.

Chemotherapy in combination with immune checkpoint inhibitor (ICI) or bevacizumab has demonstrated a superior effect for non-squamous non-small cell lung cancer (NS-NSCLC). There are still few randomized controlled trials (RCTs) investigating the differences between ICI plus chemotherapy (ICI-chemotherapy) and bevacizumab plus chemotherapy (Bev-chemotherapy) in first-line treatment of NS-NSCLC. We identified RCTs in databases and conference abstracts presented at international conferences by Sep 1, 2021.

Case Report: Benefits of a NSCLC Patient With EGFR A289G/F287_G288insHA cis Mutations From Immunotherapy in Combination With Antiangiogenesis and Chemotherapy and Sequential Treatment of EGFR-TKI.

We presented a 67-year-old nonsmoking female lung adenocarcinoma patient with novel epidermal growth factor receptor (EGFR) A289G/F287_G288insHA cis mutations who responded positively to sintilimab combined with regorafenib and albumin paclitaxel, and sequential treatment of icotinib. Gene mutations in patients were detected by next-generation sequencing (NGS) technology, and changes in gene mutations before and after treatments were observed by ctDNA monitoring. We observed the efficacy of the patient through chest computed tomography (CT) imaging and carcinoembryonic antigen (CEA) level and found that the patient benefited from immunotherapy in combination with antiangiogenesis and chemotherapy for more than 1 year, CEA levels initially fell sharply and then rebounded during the treatment period.

Potential effect of epigenetic drugs in the treatment of multiple-site extramedullary plasmacytoma involving the respiratory system: a case report and review of the literature.

We report the case of a 23-year-old man with a medical history of idiopathic thrombocytopenic purpura (ITP) and newly diagnosed with the Epstein-Barr virus (EBV)-positive multiple-site extramedullary plasmacytoma (EMP), which involves the respiratory system. The patient was referred to our hospital because of progressive nasal congestion and nasal mass. Nasopharyngoscopy and bronchoscopy were performed.