Peri-articular lymphatic system and "Bi" theory of Chinese medicine in the pathogenesis and treatment of arthritis.

Rheumatoid arthritis (RA) and osteoarthritis (OA) are the two most common joint diseases, and they have characterization of synovial inflammation and cartilage destruction, associated with the accumulation of numerous catabolic mediators and inflammatory cells in the synovial space and surrounding soft tissues. How these factors are cleared and if the "clearance" process contributes to pathogenesis of arthritis are not known. Recently, we found the existence of the peri-articular lymphatic system in mouse joints. The blockade of lymphangiogenesis and lymphatic draining function accelerates while stimulation of lymphatic function attenuates the severity of joint tissue lesions in mouse models of RA and OA. More importantly, we noticed the similarity between the dysfunction of lymphatic drainage in arthritic joints and "Bi" theory of Chinese medicine (CM), and demonstrated that several Bi disease-treated herbal drugs directly affect the function of lymphatic endothelial cells. Here we review the advances about the interactions between joint inflammation and changes in the peri-articular lymphatic system and discuss our view of linking "Bi" theory of CM to lymphatic dysfunction in arthritis.

Effect of neoadjuvant chemotherapy combined with hyperthermic intraperitoneal perfusion chemotherapy on advanced gastric cancer.

Neoadjuvant and hyperthermic intraperitoneal chemotherapies have been shown to be effective in the treatment of resectable advanced gastric cancer. The aim of the present study was to investigate the clinical efficiency and security of neoadjuvant chemotherapy in combination with hyperthermic intraperitoneal chemotherapy for the treatment of postoperative advanced gastric cancer. A total of 192 patients diagnosed with advanced gastric cancer were randomly divided into the following four groups (n=48 per group): Control, neoadjuvant chemotherapy, hyperthermic intraperitoneal perfusion chemotherapy and joint groups. The joint group received neoadjuvant chemotherapy combined with hyperthermic intraperitoneal perfusion chemotherapy. Complications, adverse reactions, recurrence rates within 2 years and the 1- and 3-year survival rates following surgery were observed. No significant differences were observed in the occurrence rates of I-II degree myelosuppression, III-IV degree myelosuppression, I-II degree nausea or III-IV degree nausea and vomiting among the four groups (P>0.05). The median progression-free survival times were 26, 31, 33 and 28 months in the control, neoadjuvant chemotherapy, hyperthermic intraperitoneal perfusion chemotherapy and joint groups, respectively (P<0.001). Compared with the control group, the recurrence-free 2-year survival rate of the joint group was significantly lower (P=0.04). The difference among the median survival times of the four groups was statistically significant (P=0.001). The 1-year survival rate of the joint group was significantly higher when compared with the control group and the difference was statistically significant (P=0.03). However, no statistically significant difference was identified among the 1-year survival rates of the four groups (P>0.05). Compared with the control group, the 3-year survival rates of the other three groups were significantly higher (P<0.05). Therefore, the results of the present study indicated that neoadjuvant chemotherapy combined with hyperthermic intraperitoneal perfusion chemotherapy for the treatment of advanced gastric cancer is well tolerated and exhibits improved compliance and efficiency.

Incidence and risk of treatment-related mortality with anti-epidermal growth factor receptor monoclonal antibody in cancer patients: a meta-analysis of 21 randomized controlled trials.

BACKGROUND: Anti-epidermal growth factor receptor (EGFR) monoclonal antibodies (MoAbs) cetuximab and panitumumab have emerged as an effective targeted therapy in the treatment of cancer patients, but the overall incidence and risk of fatal adverse events (FAEs) associated with these agents is still unclear. METHODS: Databases from PubMed, Web of Science and abstracts presented at ASCO meeting up to May 31, 2013 were searched to identify relevant studies. Eligible studies included prospective randomized controlled trials evaluating MoAbs in cancer patients with adequate data on FAEs. Statistical analyses were conducted to calculate the summary incidence, odds ratio and 95% confidence intervals (CIs) by using either random effects or fixed effect models according to the heterogeneity of included studies. RESULTS: A total of 14,776 patients with a variety of solid tumors from 21 clinical trials were included in our analysis. The overall incidence of MoAbs associated FAEs was 1.7% (95%CI: 1.1-2.5%), and the incidence of cetuximab-related FAEs was higher than that of panitumumab (2.0% versus 0.9%). Compared with the controls, the use of MoAbs was associated with a significantly increased risk of FAEs, with an OR of 1.37 (95%CI: 1.04-1.81, p=0.024). Subgroup analysis based on EGFR-MoAbs drugs, phase of trials and tumor types demonstrated a tendency to increase the risk of FAEs, but the risk did not increase in breast cancer, esophagus cancer and phase II trials. CONCLUSIONS: With present evidence, the use of EGFR-MoAbs is associated with an increased risk of FAEs in patients with advanced solid tumors.

Immature mice are more susceptible to the detrimental effects of high fat diet on cancellous bone in the distal femur.

With the increasing prevalence of obesity among children and adolescents, it is imperative to understand the implications of early diet-induced obesity on bone health. We hypothesized that cancellous bone of skeletally immature mice is more susceptible to the detrimental effects of a high fat diet (HFD) than mature mice, and that removing excess dietary fat will reverse these adverse effects. Skeletally immature (5weeks old) and mature (20weeks old) male C57BL/6J mice were fed either a HFD (60% kcal fat) or low fat diet (LFD; 10% kcal fat) for 12weeks, at which point, the trabecular bone structure in the distal femoral metaphysis and third lumbar vertebrae were evaluated by micro-computed tomography. The compressive strength of the vertebrae was also measured. In general, the HFD led to deteriorations in cancellous bone structure and compressive biomechanical properties in both age groups. The HFD-fed immature mice had a greater decrease in trabecular bone volume fraction (BVF) in the femoral metaphysis, compared to mature mice (p=0.017 by 2-way ANOVA). In the vertebrae, however, the HFD led to similar reductions in BVF and compressive strength in the two age groups. When mice on the HFD were switched to a LFD (HFD:LFD) for an additional 12weeks, the femoral metaphyseal BVF in immature mice showed no improvements, whereas the mature mice recovered their femoral metaphyseal BVF to that of age-matched lean controls. The vertebral BVF and compressive strength of HFD:LFD mouse bones, following diet correction, were equivalent to those of LFD:LFD mice in both age groups. These data suggest that femoral cancellous metaphyseal bone is more susceptible to the detrimental effects of HFD before skeletal maturity and is less able to recover after correcting the diet. Negative effects of HFD on vertebrae are less severe and can renormalize with LFD:LFD mice after diet correction, in both skeletally immature and mature animals.