Postoperative pain-related outcomes and perioperative pain management in China: a population-based study.

Background: Postoperative pain poses a significant challenge to the healthcare system and patient satisfaction and is associated with chronic pain and long-term narcotic use. However, systemic assessment of the quality of postoperative pain management in China remains unavailable. Methods: In this cross-sectional study, we analyzed data collected from a nationwide registry, China Acute Postoperative Pain Study (CAPOPS), between September 2019 and August 2021. Patients aged 18 years or above were required to complete a self-reported pain outcome questionnaire on the first postoperative day (POD1). Perioperative pain management and pain-related outcomes, including the severity of pain, adverse events caused by pain or pain management, and perception of care and satisfaction with pain management were analyzed. Findings: A total of 26,193 adult patients were enrolled. There were 48.7% of patients who had moderate-to-severe pain on the first day after surgery, and pain severity was associated with poor recovery and patient satisfaction. The systemic opioid use was 68% on the first day after surgery, and 89% of them were used with intravenous patient-controlled analgesia, while the rate of postoperative nerve blocks was low. Interpretation: Currently, almost half of patients still suffer from moderate-to-severe pain after surgery in China. The relatively high rate of systemic opioid use and low rate of nerve blocks used after surgery suggests that more effort is needed to improve the management of acute postoperative pain in China. Funding: National Key Research and Development Program of China (No. 2018YFC2001905).

Kirsten Rat Sarcoma Viral Oncogene Homologue (KRAS) Mutations in the Occurrence and Treatment of Pancreatic Cancer.

Pancreatic cancer is a highly malignant tumor with a 5-year survival rate of less than 6%, and incidence increasing year by year globally. Pancreatic cancer has a poor prognosis and a high recurrence rate, almost the same as the death rate. However, the available effective prevention and treatment measures for pancreatic cancer are still limited. The genome variation is one of the main reasons for the development of pancreatic cancer. In recent years, with the development of gene sequencing technology, in-depth research on pancreatic cancer gene mutation presents that a growing number of genetic mutations are confirmed to be in a close relationship with invasion and metastasis of pancreatic cancer. Among them, KRAS mutation is a special one. Therefore, it is particularly important to understand the mechanism of the KRAS mutation in the occurrence and development of pancreatic cancer, and to explore the method of its transformation into clinical tumor molecular targeted treatment sites, to further improve the therapeutic effect on pancreatic cancer. Therefore, to better design chemical drugs, this review based on the biological functions of KRAS, summarized the types of KRAS mutations and their relationship with pancreatic cancer and included the downstream signaling pathway Raf-MEK-ERK, PI3K-AKT, RalGDS-Ral of KRAS and the current medicinal treatment methods for KRAS mutations. Moreover, drug screening and clinical treatment for KRAS mutated cell and animal models of pancreatic cancer are also reviewed along with the prospect of targeted medicinal chemistry therapy for precision treatment of pancreatic cancer in the future.

PTK2 promotes cancer stem cell traits in hepatocellular carcinoma by activating Wnt/ß-catenin signaling.

Emerging evidence indicates that cancer stem cells (CSCs) are involved in tumorigenesis, tumor recurrence, and therapeutic resistance in hepatocellular carcinoma (HCC). However, the mechanisms underlying HCC CSC regulation remain largely unknown. Here we report our analysis of 97 paraffin-embedded HCC tumor specimens. We found that protein tyrosine kinase 2 (PTK2) expression correlated with liver CSC marker expression, overall survival, and recurrence-free survival in HCC patients. Our results further showed that PTK2 activated Wnt/ß-catenin signaling by promoting nuclear accumulation of ß-catenin in HCC cells. In this manner, PTK2 activates CSC traits and drives tumorigenicity in HCC cells, leading to HCC recurrence and sorafenib resistance. Moreover, PTK2 expression was negatively correlated with its level of promoter methylation. PTK2 apparently acts as an oncogene by increasing CSC traits and tumorigenicity in HCC. The present data suggest that PTK2 may be a novel prognostic biomarker for HCC recurrence, and a therapeutic target for HCC treatment.

Osseointegration of layer-by-layer polyelectrolyte multilayers loaded with IGF1 and coated on titanium implant under osteoporotic condition.

PURPOSE: Titanium implant is a widely used method for dental prosthesis restoration. Nevertheless, in patients with systemic diseases, including osteoporosis, diabetes, and cancer, the success rate of the implant is greatly reduced. This study investigates a new implant material loaded with insulin-like growth factor 1 (IGF1), which could potentially improve the implant success rate, accelerate the occurrence of osseointegration, and provide a new strategy for implant treatment in osteoporotic patients. MATERIALS AND METHODS: Biofunctionalized polyelectrolyte multilayers (PEMs) with polyethylenimine as the excitation layer and gelatin/chitosan loaded with IGF1 were prepared on the surface of titanium implant by layer-by-layer self-assembly technique. The physical and chemical properties of the biofunctionalized PEMs, the biological characteristics of bone marrow mesenchymal stem cells (BMMSCs), and bone implant contact correlation test indexes were detected and analyzed in vitro and in vivo using osteoporosis rat model. RESULTS: PEMs coatings loaded with IGF1 (TNS-PEM-IGF1-100) implant promoted the early stage of BMMSCs adhesion. Under the action of body fluids, the active coating showed sustained release of growth factors, which in turn promoted the proliferation and differentiation of BMMSCs and the extracellular matrix. At 8 weeks from implant surgery, the new bone around the implants was examined using micro-CT and acid fuchsin/methylene blue staining. The new bone formation increased with time in each group, while the TNS-PEM-IGF1-100 group showed the highest thickness and continuity. CONCLUSION: TNS-PEM-IGF1-100 new implants can promote osseointegration in osteoporotic conditions both in vivo and in vitro and provide a new strategy for implant repair in osteoporotic patients.