A novel methylation-detection panel for HPV associated high-grade squamous intraepithelial lesion and cervical cancer screening.

Cervical cancer (CC) was considered to be the most common gynaecological cancer, with an estimated 342,000 deaths worldwide each year, as the majority of patients were diagnosed at an advanced stage of the disease. The purpose of this study was to evaluate the predictive value of multi-locus methylation assay for the early detection of CC. The cervical exfoliated cell samples from 492 HPV-positive females with cervical lesions were collected and subjected to methylation detection of gene FAM19A4, EPB41L3 and PAX1 after bisulfite conversion.

Safety and Clinical Response to Combined Immunotherapy with Autologous iNKT Cells and PD-1CD8 T Cells in Patients Failing First-line Chemotherapy in Stage IV Pancreatic Cancer.

Purpose: A phase I clinical trial was conducted to assess the safety and feasibility of invariant natural killer T (iNKT) cells combined with PD-1CD8 T cells in patients with advanced pancreatic cancer and failing the first-line chemotherapy.

Patients And Methods: Fifteen eligible patients were enrolled, of whom 9 received at least three cycles of treatment each. In total, 59 courses were administered.

Improving the expansion of human tumor-reactive CD8 + T cells by targeting toll-like receptors.

Toll-like receptors (TLRs) are important pattern recognition receptor(s) known to mediate the sensing of invading pathogens and subsequent immune responses. In this study, we investigate whether TLRs could be explored for the preparation of human CD8 T cell products used in adoptive cell therapy (ACT). Following characterization of TLRs expression on human CD8 T cells, we screened TLR-specific agonists for their ability to act in concert with anti-CD3 to stimulate the proliferation of these cells and corroborated the observed co-stimulatory effect by transcriptional profiling analyses.

Feasibility of iNKT cell and PD-1+CD8+ T cell-based immunotherapy in patients with lung adenocarcinoma: Preliminary results of a phase I/II clinical trial.

We performed a single-arm exploratory clinical trial that is ongoing and registered at ClinicalTrials.gov (NCT03093688). Patients were infused with autologous iNKT cells, PD-1 + CD8+ T cells, and dendritic cells every 3-5 weeks, which was considered 1 cycle.

Prevalence of pediatric Kashin-Beck disease in Tibet.

Introduction: To estimate the prevalence of Kashin-Beck disease (KBD) among children in 2017 in Changdu of Tibet.

Methods: We adopted a four-step recruitment to include children aged 7-12 years from seven identified historically endemic counties in Changdu. Posterior-anterior radiographs of right hand and wrist were taken and were graded at four sites (metaphysis, epiphysis, and bony end of phalanges and metacarpal and carpal bones).

Correlation Between Early Plasma Interleukin 37 Responses With Low Inflammatory Cytokine Levels and Benign Clinical Outcomes in Severe Acute Respiratory Syndrome Coronavirus 2 Infection.

Background: The immune protective mechanisms during severe acute respiratory syndrome coronavirus (SARS-CoV-2) infection remain to be deciphered for the development of an effective intervention approach.

Methods: We examined early responses of interleukin 37 (IL-37), a powerful anti-inflammatory cytokine, in 254 SARS-CoV-2-infected patients before any clinical intervention and determined its correlation with clinical prognosis.

Results: Our results demonstrated that SARS-CoV-2 infection causes elevation of plasma IL-37.

An open-label, randomized trial of the combination of IFN-κ plus TFF2 with standard care in the treatment of patients with moderate COVID-19.

Background: Epidemic outbreaks caused by SARS-CoV-2 are worsening around the world, and there are no target drugs to treat COVID-19. IFN-κ inhibits the replication of SARS-CoV-2; and TFF2 is a small secreted polypeptide that promotes the repair of mucosal injury and reduces the inflammatory responses. We used the synergistic effect of both proteins to treat COVID-19.

Negative regulation between the expression levels of receptor for hyaluronic acid-mediated motility and hyaluronan leads to cell migration in pancreatic cancer.

Receptor for hyaluronic acid (HA)-mediated motility (RHAMM) expression is upregulated in pancreatic ductal adenocarcinoma (PDAC). In the present study, small interfering RNA knockdown was used to investigate the regulatory mechanism and function of RHAMM in PDAC cells. Reverse transcription-quantitative PCR was used to measure the mRNA expression levels of RHAMM, hyaluronan synthases (HAS1, HAS2 and HAS3) and hyaluronidases (HYAL1, HYAL2 and HYAL3) in eight PDAC cell lines.

A clinical pilot study on the safety and efficacy of aerosol inhalation treatment of IFN-κ plus TFF2 in patients with moderate COVID-19.

Background: The outbreak of a new coronavirus (SARS-CoV-2) poses a great challenge to global public health. New and effective intervention strategies are urgently needed to combat the disease.

Methods: We conducted an open-label, non-randomized, clinical trial involving moderate COVID-19 patients according to study protocol.

Pure nongestational uterine choriocarcinoma in postmenopausal women: a case report with literature review.

Nongestational choriocarcinoma is rare, especially in postmenopausal women. It may be derived from the transformation of germ cells or dedifferentiation of other tumor tissue cells. It is usually found in the ovaries but rarely in the uterus.

Enhanced Opsonization-Independent Phagocytosis and High Response Ability to Opsonized Antigen-Antibody Complexes: A New Role of Kupffer Cells in the Accelerated Blood Clearance Phenomenon upon Repeated Injection of PEGylated Emulsions.

The accelerated blood clearance (ABC) phenomenon is an immune response against the first injection of PEGylated colloidal drug delivery systems (CDDSs), which causes the accelerated clearance of the second dose. The enhanced complement-mediated phagocytic activity of Kupffer cells is responsible for accelerated second-dose clearance. Nevertheless, few studies have focused on the role of Kupffer cells in the induction phase of the ABC phenomenon.

Neutrophil-mediated delivery of pixantrone-loaded liposomes decorated with poly(sialic acid)-octadecylamine conjugate for lung cancer treatment.

Poly(sialic acid) (PSA) is a natural hydrophilic biodegradable and non-immunogenic biopolymer, receptors for its monomer are expressed on peripheral blood neutrophils (PBNs), which plays important roles in the progression and invasion of tumors. A poly(sialic acid)-octadecylamine conjugate (PSA-ODA) was synthesized and then anchor it on the surface of liposomal pixantrone (Pix-PSL), to achieve an improved anticancer effect. The liposomes were prepared using a remote loading method via a pH gradient, and then assessed for particle size, zeta potential encapsulation efficiency, in vitro release, and in vitro cytotoxicity.

4-Methylumbelliferone inhibits enhanced hyaluronan synthesis and cell migration in pancreatic cancer cells in response to tumor-stromal interactions.

Hyaluronic acid (HA) in tumor stroma promotes tumor invasion and progression. 4-Methylumbelliferone (4-MU) is a potent HA synthesis inhibitor. In the present study, the effects of 4-MU on enhanced HA synthesis and cell migration in pancreatic ductal adenocarcinoma (PDAC) cells, in response to co-culture with stromal fibroblasts, was investigated.

KIAA1199/CEMIP/HYBID overexpression predicts poor prognosis in pancreatic ductal adenocarcinoma.

Background: KIAA1199 (also known as CEMIP or HYBID), a newly identified protein involved in hyaluronan degradation, has been suggested to play a critical role in cancer progression. The aim of this study was to investigate the expression and functional significance of KIAA1199 in pancreatic ductal adenocarcinoma (PDAC).

Methods: Using quantitative real-time RT-PCR, we analyzed KIAA1199 mRNA expression in 6 PDAC cell lines and frozen tissues from 14 patients with PDAC.

Increased Expression of HYAL1 in Pancreatic Ductal Adenocarcinoma.

Objectives: Increased production and processing (degradation) of hyaluronan (HA) is critical for cancer invasion and metastasis. Although HA is known to be overexpressed in pancreatic ductal adenocarcinoma (PDAC), little is known about the expression and biological significance of HA-degrading enzymes, hyaluronidases (HYALs), in PDAC.

Methods: Expression of HYALs mRNA was examined in PDAC cells by quantitative real-time RT-PCR.

The 12-3-12 cationic gemini surfactant as a novel gastrointestinal bioadhesive material for improving the oral bioavailability of coenzyme Q10 naked nanocrystals.

To improve the oral bioavailability of nanocrystalline drug preparations, the cationic 12-3-12 quaternary ammonium surfactant gemini was introduced into nanocrystals as a novel gastrointestinal bioadhesive material. Coenzyme Q10 (CoQ10), a typical Biopharmaceutics Classification System (BCS) class II drug, was used as a model drug. The 12-3-12 gemini surfactant was added to the preparation at a low concentration and imbued the particles with abundant positive charges.

Targeting hyaluronan for the treatment of pancreatic ductal adenocarcinoma.

Progression of cancer is often associated with interactions between cancer cells and extracellular matrix (ECM) surrounding them. Increasing evidence has suggested that accumulation of hyaluronan (HA), a major component of ECM, provides a favorable microenvironment for cancer progression. Pancreatic ductal adenocarcinoma (PDAC) is characterized typically by a dense desmoplastic stroma with a large amount of HA, making this molecule as an attractive target for therapy.

Hyaluronan stimulates pancreatic cancer cell motility.

Hyaluronan (HA) accumulates in pancreatic ductal adenocarcinoma (PDAC), but functional significance of HA in the aggressive phenotype remains unknown. We used different models to investigate the effect of HA on PDAC cell motility by wound healing and transwell migration assay. Changes in cell motility were examined in 8 PDAC cell lines in response to inhibition of HA production by treatment with 4-methylumbelliferone (4-MU) and to promotion by treatment with 12-O-tetradecanoyl-phorbol-13-acetate (TPA) or by co-culture with tumor-derived stromal fibroblasts.

A novel epigenetic mechanism regulating hyaluronan production in pancreatic cancer cells.

Pancreatic ductal adenocarcinoma (PDAC) is characterized by an abundant stroma enriched with hyaluronan (HA), a major component of extracellular matrix known to play a critical role in tumor progression. The mechanisms that regulate HA synthesis in PDAC are poorly understood. To investigate whether DNA methylation and HA production from PDAC cells are associated, we studied the effect of 5-aza-2'-deoxycitidine (5-aza-dC), an inhibitor of DNA methylation, or DNA methyltransferase 1 (DNMT1) knockdown by small interfering RNA, on the HA production from PDAC cells.

Receptor for Hyaluronic Acid-Mediated Motility is Associated with Poor Survival in Pancreatic Ductal Adenocarcinoma.

Receptor for hyaluronic acid (HA)-mediated motility (RHAMM) is a nonintegral cell surface receptor involved in the aggressive phenotype in a wide spectrum of human malignancies, but the significance of RHAMM in pancreatic ductal adenocarcinoma (PDAC) remains unknown. In this study, we investigated the expression of RHAMM and its clinical relevance in PDAC. RHAMM mRNA expression was examined in 8 PDAC cell lines and in primary pancreatic cancer and adjacent non-tumor tissues from 14 patients using real-time RT-PCR.

Accelerated blood clearance phenomenon upon cross-administration of PEGylated nanocarriers in beagle dogs.

The cross-administration of nanocarriers modified by poly(ethylene glycol) (PEG), named PEGylated nanocarriers, a type of combination therapy, is becoming an increasingly important method of long-term drug delivery, to decrease side effects, avoid multidrug resistance, and increase therapeutic efficacy. However, repeated injections of PEGylated nanocarriers induces the accelerated blood clearance (ABC) phenomenon, prevents long circulation, and can cause adverse effects owing to alterations in the biodistribution of the drug. Although the nature of the ABC phenomenon that is induced by repeated injections of PEGylated nanocarriers has already been studied in detail, there are few reports on the immune response elicited by the cross-administration of PEGylated nanocarriers.

Tolerance-like innate immunity and spleen injury: a novel discovery via the weekly administrations and consecutive injections of PEGylated emulsions.

There has been an increasing interest in the study of the innate immune system in recent years. However, few studies have focused on whether innate immunity can acquire tolerance. Therefore, in this study, we investigated tolerance in the innate immune system via the consecutive weekly and daily injections of emulsions modified with polyethylene glycol (PEG), referred to as PEGylated emulsions (PE).

Self-assembled micelles of novel amphiphilic copolymer cholesterol-coupled F68 containing cabazitaxel as a drug delivery system.

Despite being one of the most promising amphiphilic block copolymers, use of Pluronic F68 in drug delivery is limited due to its high critical micelle concentration (CMC). In this study, we developed a novel F68 derivative, cholesterol-coupled F68 (F68-CHMC). This new derivative has a CMC of 10 μg/mL, which is 400-fold lower than that of F68.