Identification of Key Genes and Pathways in Oxaliplatin-Induced Neuropathic Pain Through Bioinformatic Analysis.

Background: The mechanism of Chemotherapy-induced neuropathic pain (NP) remains obscure. This study was aimed to uncover the key genes as well as protein networks that contribute to Oxaliplatin-induced NP. Material/Methods: Oxaliplatin frequently results in a type of Chemotherapy-induced NP that is marked by heightened sensitivity to mechanical and cold stimuli, which can lead to intolerance and discontinuation of medication. We investigated whether these different etiologies lead to similar pathological outcomes by targeting shared genetic targets or signaling pathways. Gene expression data were obtained from the Gene Expression Comprehensive Database (GEO) for GSE38038 (representing differential expression in the spinal nerve ligation model rats) and GSE126773 (representing differential expression among the Oxaliplatin-induced NP model rats). Differential gene expression analysis was performed using GEO2R. Results: Protein-protein interaction (PPI) analysis identified 260 co-differentially expressed genes (co-DEGs). Subsequently, Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis revealed three shared pathways involved in both models: Kaposi sarcoma-associated herpesvirus (KSHV) infection, Epstein-Barr virus (EBV) infection, and AGE-RAGE signaling pathway in diabetic complications. Further bioinformatics analysis highlighted eight significantly up-regulated genes in the NP group: Mapk14, Icam1, Cd44, IL6, Cxcr4, Stat1, Casp3 and Fgf2. Our results suggest that immune dysfunction, inflammation-related factors or regulating inflammation factors may also be related to Oxaliplatin-induced NP. Additionally, we analyzed a dataset (GSE145222) involving chronic compression of DRGs (CCD) and control groups. CCD model is a classic model for studying NP. We assessed these hub genes' expression levels. In contrast with the control groups, the hub genes were up-regulated in CCD groups, the difference was statistically significant, except Stat1. Conclusion: Our research significantly contributes to elucidating the mechanisms underlying the occurrence as well as the progression of Oxaliplatin-induced NP. We have identified crucial genes and signaling pathways associated with this condition.

Predicting Response to Radiotherapy in Breast Cancer-Induced Bone Pain: Relationship Between Pain and Serum Cytokine Expression Levels After Radiotherapy.

Introduction: Breast cancer is the second leading cause of cancer-associated death in women. Herein, we explored the associations of cytokines, pain, and bone metastasis between patients before and after radiotherapy in breast cancer with bone metastasis. The pain caused by metastasis was effectively relieved by external radiation therapy. However, the underlying mechanisms remain unknown. Methods and Results: In this case-controlled study, we enrolled healthy individuals (n = 10) and bone metastatic cancer patients (n = 30). Peripheral venous blood samples were collected from healthy controls, and one week before and after radiotherapy, the peripheral venous blood and clinical characteristics of cancer patients were collected. We analyzed the blood cytokine profile, quality of life (QOL), and pain score of patients pre- and post-radiotherapy to explore the possible causes of pain relief. Both the pain score and QOL significantly improved after radiotherapy. The serum cytokine profiles of patients were significantly different before radiotherapy than after. Meanwhile, only three cytokines differed between post-radiotherapy and healthy controls. We believe radiotherapy stimulated local immune storms in bone tissue and promoted significant changes in cytokines pre- and post-radiotherapy. Therefore, the bone microenvironment of early breast cancer patients with bone metastasis pain can be restored after radiotherapy. Restoring a healthy bone environment can not only relieve the pain but also improve the patient's QOL. Conclusion: Tumor cells can effectively activate immune cells in the bone microenvironment through direct interaction, releasing many factors and promoting bone metastasis. Early local radiotherapy of bone metastases can restore the microenvironment and improve the QOL and prognosis of patients, thereby comprehending a novel target for prevention, treatment, and therapy of bone metastases.

Study on the Correlation between Pain and Cytokine Expression in the Peripheral Blood of Patients with Bone Metastasis of Malignant Cancer Treated Using External Radiation Therapy.

The incidence of cancer is increasing worldwide on a yearly basis, with the number of patients with bone metastases also increasing annually. Events associated with bone metastases can seriously affect patient quality of life, through pain, hypercalcemia, bone marrow regeneration disorders, and spinal cord compression. In this nonrandomized controlled clinical trial study, we focused on the relationship between bone metastasis, pain, and cytokines before and after radiotherapy. We hypothesized that radiotherapy alters the cytokine profile of the local bone environment. Combined with the analgesic effects of radiotherapy, certain cytokines may be very sensitive to radiation. External radiation therapy is commonly used to treat cancer patients with bone metastases and can effectively relieve metastasis-related pain, although its underlying mechanisms have not been fully elucidated. For this case-control study, we recruited 30 cancer patients with bone metastasis and 30 healthy individuals. Peripheral venous blood from healthy individuals was collected. The clinical characteristics and peripheral venous blood were collected from patients one week before and one week after radiotherapy. The preradiotherapy and postradiotherapy pain scores, quality of life (QOL), and blood cytokine profiles of the patients to that of the controls were collected to identify pain-related cytokines. Finally, the pain score and the quality of life score improved significantly after radiotherapy. Moreover, the preradiotherapy and postradiotherapy blood cytokine profiles of the patients showed significant differences, indicating that the analgesic effect of radiotherapy against bone metastases is mediated via altered cytokine production. Furthermore, some cytokines were more sensitive to radiotherapy. The levels of MIP-1δ, MCP-2, TIMP-1, RANTES, IGFBP3, and TNF-α showed significant differences in the pairwise comparative analysis and may therefore mediate pain associated with bone metastasis.

Infections Caused by Carbapenemase-Producing Klebsiella pneumoniae: Microbiological Characteristics and Risk Factors.

The spread of carbapenemase-producing Klebsiella pneumoniae (CPKP) worldwide is a serious problem. This retrospective, matched case-control, parallel study in a tertiary teaching hospital analyzed the microbiological and clinical characteristics of CPKP infection, focusing on the risk factors for carbapenem resistance and patient mortality. The hospital department with the highest incidence of CPKP infections was the intensive care unit. All CPKP strains examined were positive for blakpc-2, and 84.8% of CPKP were ST11. Hypervirulent phenotype was identified in 22.7% of the patients with CPKP, with these strains displaying a high incidence of positivity for entB, ybtS, and iutA. Multivariate conditional logistic regression analysis demonstrated that Pitt bacteremia score >4, prior stomach tube, continuous renal replacement therapy (CRRT), and previous carbapenem exposure were associated with CPKP infection. Higher albumin concentration and use of cephalosporins after diagnosis were strong prognostic factors for crude 28-day mortality. Further, high APACHE II score, CRRT, use of carbapenems after diagnosis, and bacteremia were risk factors for crude in-hospital mortality. CPKP isolates showed clonal spread and were resistant to most antibiotics, resulting in higher financial burden. Critical illness was associated with increased mortality.

Epidemiological characteristics and genetic structure of linezolid-resistant Enterococcus faecalis.

OBJECTIVES: The aim of this study was to investigate the mechanism of linezolid resistance and evaluate the risk factors for linezolid-resistant Enterococcus faecalis (LZR-Efa) infections. METHODS: A total of 730 E. faecalis isolates were collected, and whole-genome sequencing and bioinformatics analysis were performed. Meanwhile, risk factors related to linezolid resistance were analyzed by binary logistic regression. RESULTS: Twenty-six LZR-Efa were isolated from various clinical samples, and 24 isolates were multidrug resistant. Four isolates were daptomycin nonsusceptible, while all LZR-Efa were susceptible to vancomycin. Thirteen different sequence types (STs) were identified, and the most prevalent type was ST16 (23.1%). The genes dfrE, lsaA, and emeA were identified in all isolates. A total of 23 E. faecalis were positive for optrA gene, and six amino acids mutations were identified among 18 LZR-Efa in OptrA. The 23S rRNA mutation was found in 16 LZR-Efa isolates. However, the presence of cfr was not identified. Furthermore, there were 41 virulence genes detected, and 10 genes (ace, bopD, cpsA, cpsB, ebpB, ebpC, efaA, fss1, fss2, and srtC) were found in all isolates. A total of nine isolates were positive for multiple virulent factors (ace, asa1, cylA, efaA, esp, and gelE). There was no difference in the number of virulence factors among different specimens (P=0.825). It is of note that all patients had not been prescribed linezolid or traveled abroad previously. Moreover, previous use of carbapenems was a risk factor for LZR-Efa infections. CONCLUSION: The main trends of LZR-Efa, with lower level of resistance, were sporadic mainly in the department of surgery. optrA and 23S rRNA were the main resistance mechanisms. In addition, carbapenems use was an independent predictor of LZR-Efa infections.

Intrathecal Pump Implantation in the Cisterna Magna for Treating Intractable Cancer Pain.

A 54-year-old male patient with postoperative axillary lymph node, intrapulmonary, intracranial, and cervical spine metastases of left liver cancer was suffering from severe, persistent, and pricking pain in the right dorsal shoulder and right arm since 3 months. The drug dose of the fentanyl transdermal patch was gradually increased after admission and an adjuvant analgesic was also included, but neither treatment alleviated the pain. It was gradually alleviated after intramedullary analgesic infusion through intrathecal pump implantation in cistern magna. Terminally ill patients often have the desire to spend their remaining time at home, which however becomes a challenge in the face of refractory pain. At present, no palliative chemoradiation or ablative or stimulant neurosurgical options are available to manage pain in cancer patients. Based on the findings of this report, we concluded that an intramedullary drug infusion system can have a significant analgesic effect in patients with cervical metastasis and refractory cancer pain.