BACKGROUND:The effect of advanced glycation end products (AGEs) on bone resorption is controversial. Our previous study has shown that bone resorption is significantly inhibited when AGEs present with pre-osteoclast cells RAW 264.7, while the effect of AGEs on osteoclastic acidification remains unknown. OBJECTIVE:To investigate the effect of AGEs on osteoclastic acidification and the underlying mechanism. METHODS:RAW 264.7 cells were induced by RANKL (15μg/L;normal group) to generate osteoclasts, and AGEs (50-400 mg/L;experimental group) or bovine serum albumin (100 mg/L;control group) were added at the beginning of the induction. The effect of AGEs on bone resorption was evaIuated by anaIyzing the area of bone resorption on the Osteo Assay Surface plates, and the effect of AGEs on osteoclastic acidification was evaluated by acridine orange staining. Furthermore, the expression levels of V-ATPase a3 and CIC-7 were detected to investigate the underlying mechanism. RESULTS AND CONCLUSION:The bone resorption area in the AGEs group was significantly decreased compared with the normal group (P<0.05). Acridine orange staining reveaIed that the red fluorescence (620 nm) intensity in the AGEs group was significantly decreased compared with the normal group (P<0.05), and this inhibitory effect became obvious with the increase of AGEs concentration. Immunocytochemistry, western blot assay and PCR findings showed that the expression levels of V-ATPase a3 and CIC-7 in the AGEs group were decreased significantly compared with the normal group (P<0.05). To conclude, AGEs exert inhibitory effect on osteoclastic acidification, probably by inhibiting the expression of V-ATPase a3 and CIC-7.

BACKGROUND:The effects of advanced glycation end products (AGEs) on osteoclast-induced bone resorption is controversial and the underlying mechanisms remain unclear. Most of the studies indicate that AGEs can enhance bone resorption, while some othersshowthe opposite effects.
OBJECTIVE:To investigate the effects of AGEs on osteoclast-induced inorganicmatrixdissolution and organic componentdegradation and the underlying mechanisms.
METHODS:RAW 264.7 cels were induced to generate osteoclasts,and AGEs (50-400 μg/mL) or control-bovine serum albumin (100 μg/mL) was added since the beginning of the induction. The effect of AGEs on bone resorption was evaluated by analyzing the area of resorption pits on the Osteo Assay Surface plates and the expression of cathepsin K. Furthermore, the number of tartrate-resistant acid phosphatase (TRAP)-positive multinucleated cels, nuclei per osteoclasts and the expression of integrinανβ3were detected.
RESULTS AND CONCLUSION:The area of resorption pits and expression of cathepsin K in AGEs groups were significantly decreased compared withthecontrol group, and this inhibiting effect became more obvious with the increase of AGEs concentration. TRAP staining also showed that number of TRAP-positivemultinucleated celsand nuclei per osteoclast were significantly reduced in an AGE dose-dependent manner. Quantitative PCR revealed that the expression of integrin ανβ3decreased significantly with the extension of AGEs incubation time. These data indicate that AGEs can exert inhibitory effects on organic and inorganicmatrixdegradation induced by osteoclasts. The underlying mechanism may be involved in the inhibitory effects of AGEs on directed differentiation and cel fusion of osteoclast precursor cels, and migration and adhension of osteoclasts.

Objective:To investigate the therapeutic potential of therapeutic plasma exchange (TPE) combined with continuous venovenous hemofiltration (CVVH) in the treatment of children with severe sepsis and multiple organ dysfunction syndrome (MODS).Methods:It was a prospective randomized controlled study (RCT) involving 70 children with severe sepsis and MODS admitted to Anyang Maternal and Child Health Hospital from February 2019 to February 2023.According to random number table method, they were randomly divided into combination group (35 cases) and CVVH group (35 cases). Patients in the CVVH group were treated with CVVH alone, and those in the combination group were treated with TPE combined with CVVH.The antibiotic use time of the two groups was recorded and compared by the t test.The prothrombin time (PT), thrombin time (TT), partial prothrombin time (APTT), fibrinogen (FIB), and serum levels of interleukin (IL)-1β, IL-6, tumor necrosis factor-α (TNF-α), high mobility group protein B1 (HMGB1), Toll-like receptor 4 (TLR4) and soluble receptor (sFLT) levels before treatment and 48 h and 72 h after treatment were compared by the repeated measurement ANOVA for the overall comparison at multiple time points, and LSD- t test for pair-wise comparison.The 28-day survival of the two groups was recorded and compared by the Chi- square test. Results:The PT, TT and APTT at 48 h and 72 h after treatment were significantly lower in the combination group than those of CVVH group (all P<0.05). The FIB at 48 h[(2.15±0.42) g/L vs.(1.84±0.31) g/L]and 72 h after treatment [(2.89±0.27) g/L vs.(2.49±0.20) g/L]were significantly higher in the combination group than those of CVVH group (all P<0.05). The duration of antibiotic use in the combination group was significantly shorter than that of CVVH group [(11.33±1.16) d vs.(13.54±1.92) d, t=5.828, P<0.05]. Serum levels of IL-1β, IL-6 and TNF-α at 48 h and 72 h were significantly lower in the combination group than those of CVVH group (all P<0.05). Serum levels of HMGB1, TLR4 and sFLT at 48 h and 72 h were significantly lower in the combination group than those of CVVH group (all P<0.05). The 28-day survival of the combination group was significantly higher than that of CVVH group (94.29% vs.77.14%, χ2=4.200, P=0.040). Conclusions:TPE combined with CVVH can improve the coagulation function and inflammatory factor levels in children with severe sepsis and MODS, which may achieve therapeutic objectives by regulating the levels of HMGB1, TLR4 and sFLT, and improve the short-term prognosis.

Cholangiocarcinoma is a malignant tumor originating from the bile duct epithelium, with the increasing incidence year by year. Its early symptoms are atypical and the diagnosis rate is low. Most of the patients are already in advanced stage when they are diagnosed, losing the best surgery period. Currently, the conservative treatments for unresectable extrahepatic cholangiocarcinoma include stent placement, radiofrequency ablation, radiotherapy and chemotherapy, targeted and immunotherapy and other systemic treatments. But due to the high malignancy of biliary tract tumors, the tendency to develop drug resistance and the limited population benefited from the emerging treatment modalities, we urgently need to explore new treatment strategies to break this bottleneck. As a new treatment for cholangiocarcinoma, photodynamic therapy has attracted much attention for its clinical application and therapeutic effects. In this paper, we summarize the principles of photodynamic therapy, the combination of photodynamic and other therapeutic modalities, especially the combination of photodynamic with emerging immune and targeted therapies, and describe the current hotspot directions of photodynamic therapy research at home and abroad to provide reference for clinical treatment and research.