Low back pain (LBP) is a common musculoskeletal symptom, which can be developed in multiple clinical diseases. It is widely recognized that intervertebral disc (IVD) degeneration (IVDD) is one of the leading causes of LBP. However, the pathogenesis of IVD-related LBP is still controversial, and the treatment means are also insufficient to date. In recent decades, the role of structure and function changes of sensory nervous system in the induction and the maintenance of LBP is drawing more and more attention. With the progress of IVDD, IVD cell exhaustion and extracellular matrix degradation result in IVD structural damage, while neovascularization, innervation and inflammatory activation further deteriorate the microenvironment of IVD. New nerve ingrowth into degenerated IVD amplifies the impacts of IVD-derived nociceptive molecules on sensory endings. Moreover, IVDD is usually accompanied with disc herniation, which could injure and inflame affected nerves. Under mechanical and pro-inflammatory stimulation, the pain-transmitting pathway exhibits a sensitized function state and ultimately leads to LBP. Hence, relevant pathogenic factors, such as neurotrophins, ion channels, inflammatory factors, etc., are supposed to serve as promising therapeutic targets for LBP. The purpose of this review is to comprehensively summarize the current evidence on 1) the pathological changes of sensory nervous system during IVDD and their association with LBP, and 2) potential therapeutic strategies for LBP targeting relevant pathogenic factors.

Trauma- or osteoarthritis-related cartilage damage resulted in functional decline of joints and heavy burden of public health. Recently, the reparative role of mesenchymal stem/progenitor cells (MSCs) in articular cartilage (AC) reconstruction is drawing more and more attention. To provide a review on (1) the locations and categories of joint-resident MSCs, (2) the regulation of chondrogenic capacities of MSCs, (3) the migratory approaches of MSCs to diseased AC and regulatory mechanisms. PubMed and Web of Science were searched for English-language articles related to MSC recruitment and migration for AC repair until June 2019. The presence of various MSCs in or around joints, the potential approaches to diseased AC` and the regenerative capacities of MSCs were reviewed. Various intra- and peri-articular MSCs, with inherent migratory potentials, are present in multiple stem cell niches in or around joints. The recruitment and migration of joint-resident MSCs play crucial roles in endogenous AC repair. Multiple recruiting signals, such as chemokines, growth factors, etc., emerge during the development of AC diseases and participate in the regulation of MSC mobilization. Motivated MSCs could migrate into cartilage lesions and then exert multiple reparative potentials, including extracellular matrix (ECM) reconstruction and microenvironment modulation. In general, AC repair based on endogenous MSC recruitment and migration is a feasible strategy, and a promising research field. Furthermore, endogenous AC repair mediated by native MSCs would provide new opportunities to efficient preventative or therapeutic options for AC diseases.

CXCL5 is a member of the CXC-type chemokine family, which has been found to play important roles in tumorigenesis and cancer progression. Recent studies have demonstrated that CXCL5 could serve as a potential prognostic biomarker for cancer patients. However, the prognostic value of CXCL5 is still controversial. We systematically searched PubMed, Embase and Web of Science to obtain all relevant articles investigating the prognostic significance of CXCL5 expression in cancer patients. Hazards ratios (HR) with corresponding 95% confidence intervals (CI) were pooled to estimate the association between CXCL5 expression levels with survival of cancer patients. A total of 15 eligible studies including 19 cohorts and 5070 patients were enrolled in the current meta-analysis. Our results demonstrated that elevated expression level of CXCL5 was significantly associated with poor overall survival (OS) (pooled HR 1.70; 95% CI 1.36–2.12), progression-free survival (pooled HR 1.65; 95% CI 1.09–2.49) and recurrence-free survival (pooled HR 1.49; 95% CI 1.15–1.93) in cancer patients. However, high or low expression of CXCL5 made no difference in predicting the disease-free survival (pooled HR 0.63; 95% CI 0.11–3.49) of cancer patients. Furthermore, we found that high CXCL5 expression was associated with reduced OS in intrahepatic cholangiocarcinoma (HR 1.91; 95% CI 1.31–2.78) and hepatocellular carcinoma (HR 1.87; 95% CI 1.55–2.27). However, there was no significant association between expression level of CXCL5 with the OS in lung cancer (HR 1.25; 95% CI 0.79–1.99) and colorectal cancer (HR 1.16; 95% CI 0.32–4.22, p = 0.826) in current meta-analysis. In conclusion, our meta-analysis suggested that elevated CXCL5 expression might be an adverse prognostic marker for cancer patients, which could help the clinical decision making process.

MLKL is the most important executor of necroptosis pathway. Recent studies have demonstrated that MLKL could serve as a potential prognostic biomarker for cancer patients. However, most studies reported so far are limited in discrete outcome and sample size. We systematically searched PubMed, Embase, Web of Science and CNKI to obtain all relevant articles about the prognostic value of abnormally expressed MLKL in patients with any type of tumor. Odds ratios or hazards ratios (HRs) with corresponding 95% confidence intervals (CIs) were pooled to estimate the association between MLKL expression and clinicopathological characteristics or survival of cancer patients. A total of 6 eligible studies with 613 cancer patients were enrolled in our meta-analysis. Our results demonstrated that decreased expression level of MLKL was significantly associated with poor overall survival (OS) (pooled HR 0.26, 95%CI 0.17–0.40, high/low) and event-free survival (EFS) (pooled HR 0.45, 95%CI 0.23–0.87, high/low) in cancer patients. Furthermore, subgroup analysis divided by type of cancer, sample size, follow-up time and Newcastle–Ottawa Scale (NOS) score showed consistent prognostic value. In addition, our analysis revealed that decreased expression level of MLKL was significantly associated with advanced tumor stage, more lymph node metastasis and older age. In conclusion, our meta-analysis suggested that decreased MLKL expression might be a convinced unfavorable prognostic factor that could help the clinical decision-making process.