Chronic pain, as a stress state, is one of the critical factors for determining depression, and their coexistence tends to further aggravate the severity of both disorders. Unfortunately, their association remains unclear, which creates a bottleneck problem for managing chronic pain-induced depression. In recent years, studies have found considerable overlaps between pain- and depression-induced neuroplasticity changes and neurobiological mechanism changes. Such overlaps are vital to facilitating the occurrence and development of chronic pain and chronic pain-induced depression. In this review, we summarized the role of neuroplasticity in the occurrence and development of the two disorders in question and explored individualized application strategies of analgesic drugs and antidepressants that have different pharmacological effects in the treatment of chronic pain-induced depression. Therefore, this review may provide new insights into the understanding of association between chronic pain and depression.

Background:Epilepsy is a chronic brain disease that is caused by various factors and characterized by recurrent, episodic and temporary central nervous system dysfunction which results due to excessive discharge of brain neurons. In the past decades, despite the continuous development of antiepileptic drugs, there are still many patients with epilepsy progressing to drug-resistant epilepsy. Currently, surgical treatment is one of important way to cure drug-resistant epilepsy.Methods:Data were collected from Web of Science, Medline, Pubmed, through searching of these keywords: “surgery” and “drug-resistant epilepsy”.Results:An increasing number of studies have shown that surgery plays an important role in the treatment of drug-resistant epilepsy. Moreover, the comprehensive treatment mainly based on surgery can achieve the remission and even cure of drug-resistant epilepsy.Conclusion:In this review, we discuss the pathogenesis of drug-resistant epilepsy and the comprehensive treatment mainly based on surgery; this review may provide a reference for the clinical treatment of drug-resistant epilepsy.

The tumor cells have some metabolic characteristics of the original tissues, and the metabolism of the tumor cells is closely related to autophagy. However, the mechanism of autophagy and metabolism in chemotherapeutic drug resistance is still poorly understood. In this study, we investigated the role and mechanism of autophagy and glucose metabolism in chemotherapeutic drug resistance by using cholangiocarcinoma QBC939 cells with primary cisplatin resistance and hepatocellular carcinoma HepG2 cells. We found that QBC939 cells with cisplatin resistance had a higher capacity for glucose uptake, consumption, and lactic acid generation, and higher activity of the pentose phosphate pathway compared with HepG2 cells, and the activity of PPP was further increased after cisplatin treatment in QBC939 cells. It is suggested that there are some differences in the metabolism of glucose in hepatocellular carcinoma and cholangiocarcinoma cells, and the activation of PPP pathway may be related to the drug resistance. Through the detection of autophagy substrates p62 and LC3, found that QBC939 cells have a higher flow of autophagy, autophagy inhibitor chloroquine can significantly increase the sensitivity of cisplatin in cholangiocarcinoma cells compared with hepatocellular carcinoma HepG2 cells. The mechanism may be related to the inhibition of QBC939 cells with higher activity of the PPP, the key enzyme G6PDH, which reduces the antioxidant capacity of cells and increases intracellular ROS, especially mitochondrial ROS. Therefore, we hypothesized that autophagy and the oxidative stress resistance mediated by glucose metabolism may be one of the causes of cisplatin resistance in cholangiocarcinoma cells. It is suggested that according to the metabolism characteristics of tumor cells, inhibition of autophagy lysosome pathway with chloroquine may be a new route for therapeutic agents against cholangiocarcinoma.

Pyroptosis, which is a mode of programmed cell death, has proven effective for cancer therapy. However, efficient pyroptosis inducers for tumor treatment are limited. This study proposes biodegradable K 3 ZrF 7 :Yb/Er upconversion nanoparticles (ZrNPs) as pyroptosis inducers for cancer immunotherapy. ZrNPs, which are similar to ion reservoirs, can be dissolved inside cancer cells and release high amounts of K + and [ZrF 7 ] 3− ions, resulting a surge in intracellular osmolarity and homeostasis imbalance. This further induces an increase in reactive oxygen species (ROS), caspase-1 protein activation, gasdermin D (GSDMD) cleavage, and interleukin-1β (IL-1β) maturity, and results in cytolysis. In vivo tests confirm that ZrNPs-induced pyroptosis exhibits superior antitumor immunity activity confirmed by enhanced dendritic cells (DCs) maturity and frequency of effector-memory T cells, as well as observably inhibiting tumor growth and pulmonary metastasis. This work is believed to extend the biomedical applications of upconversion nanomaterials and deepen the understanding of intrinsic immunomodulatory activity of nanomaterials.

Primary liver cancer is a common kind of digestive cancers with high malignancy, causing 745,500 deaths each year. Hepatocellular carcinoma is the major pathological type of primary liver cancer. Traditional treatment methods for patients with hepatocellular carcinoma have shown poor efficacy in killing residual cancer cells for a long time. In recent years, tumor immunotherapy has emerged as a promising method owing to its safety and efficacy with respect to delaying the progression of advanced tumors and protecting postoperative patients against tumor relapse and metastasis. Immune tolerance and suppression in tumor microenvironments are the theoretical basis of immunotherapy. Adoptive cell therapy functions by stimulating and cultivating autologous lymphocytes ex vivo and then reinfusing them into the patient to kill cancer cells. Cancer vaccination is performed using antigenic substances to activate tumor-specific immune responses. Immune checkpoint inhibitors can reactivate tumor-specific T cells and develop an antitumor effect by suppressing checkpoint-mediated signaling. Oncolytic viruses may selectively replicate in tumor cells and cause lysis without harming normal tissues. Here, we briefly introduce the mechanism of immunosuppression in hepatocellular carcinoma and summarize the rationale of the four major immunotherapeutic approaches with their current advances.