Inflammatory diseases are a group of disorders caused by abnormal activation of the immune system,including autoimmune diseases,chronic inflammatory bowel disease,metabolic inflammatory diseases,and periodontitis.The transcription factor purine rich box-1(PU.1)plays an important role in the development and progression of inflammatory diseases by regulating the development and differentiation of immune cells and related inflammatory signaling pathways.In recent years,studies have gradually revealed the cen-tral role of PU.1 in inflammatory response and highlighted its clinical application value as a potential therapeutic target.This article systematically summarizes the biological features and regulatory mechanisms of PU.1,explores its role in inflammatory response and common inflammatory diseases,and analyzes its clinical application strategies,in order to provide a reference for future research and clinical application.

Objective To investigate the effects of two driving pressure-based methods to set positive end-expiratory pressure on pulmonary mechanics and oxygenation in patients undergoing laparoscopic and thoracoscopic esophagectomy.Methods Sixty patients undergoing laparoscopic and thoracoscopic esophagectomy were divided into two groups(n=30 each):incremental group(group Ⅰ)and decremental group(group D).PEEP titration was performed in both groups during thoracoscopy and laparoscopy.Respiratory mechanics parameters,hemodynamic parameters,and blood gas analysis were collected for analysis before preoxygenation(T0),10 minutes after intuba-tion(T1),20 minutes after PEEP application for one-lung ventilation(T2),20 minutes after PEEP application for two-lung ventilation(T3),before extubation(T4),and 30 minutes after extubation(Ts).The postoperative pulmonary complications within 3 days and 7 days after operation,hospitalization duration,and costs were recorded.Results Compared with group Ⅰ,patients in group D showed higher oxygenation index and pulmonary compliance during surgery(P＜0.05).In both groups,driving pressure decreased and compliance increased after PEEP titration(P＜0.05).Conclusion Both driving pressure-guided incremental and decremental titration of individualized PEEP improved intraoperative respiratory mechanics in patients undergoing laparoscopic and thoracoscopic esopha-gectomy,and decremental titration was more effective in improving intraoperative respiratory mechanics and oxygenation in patients during operation.

Objective To investigate the regulatory effect of PU.1 on apoptosis resistance of aging macro-phages under in vitro inflammatory stimulation simulated by lipopolysaccharide(LPS)of Porphyromonas.Methods The expression of PU.1 in periodontitis gingival tissue and normal gingival tissue was analyzed by GEO database.Mouse macrophage cell line RAW264.7 was divided into control group,P.g-LPS group,H2O2 group and PU.1 inhibitor group.mRNA expression of senescence associated secretory phenotype(IL-6,IL-1β,TNF-α)and PU.1 were detected by RT-qPCR;The protein expressions of p21,p16,BAX,caspase-3,Bcl-2,Bcl-xl and PU.1 were detected by Western blot.The number of senescent cells was detected by senescence-associated-galactosidase(SA-β-gal)staining.The apoptosis rate was detected by flow cytometry.Results Compared with control group,the expression of p21,p16 protein and mRNA of IL-6,IL-1β and TNF-α were up-regulated in P.g-LPS group and H2O2 group,the number of senescent cells was increased,the expression of Bcl-2 and Bcl-xl was up-regulated,the expression of BAX and caspase-3 was decreased,and the apoptosis rate was decreased.Meanwhile,the mRNA and protein expression of PU.1 were increased(P<0.05).Compared with P.g-LPS group,mRNA and protein expression of PU.1 in PU.1 inhibitor group were down-regulated,Bcl-2 and Bcl-xl were down-regulated,BAX and caspase-3 expressions were increased,apoptosis rate was increased,the number of senescent cells was decreased,and mRNA levels of IL-6,IL-1β and TNF-α were decreased.The expression of p21 and p16 proteins were down-regulated.(P<0.05).Conclusion Under inflammatory stimulation in vitro,increased expression of PU.1 induced apoptosis resistance of aging macrophages,inhibition of PU.1 promoted apoptosis of aging macrophages,reduced the number of aging macrophages,and down-regulated the secretion of inflammatory factors.

Objective To investigate the effects of two driving pressure-based methods to set positive end-expiratory pressure on pulmonary mechanics and oxygenation in patients undergoing laparoscopic and thoracoscopic esophagectomy.Methods Sixty patients undergoing laparoscopic and thoracoscopic esophagectomy were divided into two groups(n=30 each):incremental group(group Ⅰ)and decremental group(group D).PEEP titration was performed in both groups during thoracoscopy and laparoscopy.Respiratory mechanics parameters,hemodynamic parameters,and blood gas analysis were collected for analysis before preoxygenation(T0),10 minutes after intuba-tion(T1),20 minutes after PEEP application for one-lung ventilation(T2),20 minutes after PEEP application for two-lung ventilation(T3),before extubation(T4),and 30 minutes after extubation(Ts).The postoperative pulmonary complications within 3 days and 7 days after operation,hospitalization duration,and costs were recorded.Results Compared with group Ⅰ,patients in group D showed higher oxygenation index and pulmonary compliance during surgery(P＜0.05).In both groups,driving pressure decreased and compliance increased after PEEP titration(P＜0.05).Conclusion Both driving pressure-guided incremental and decremental titration of individualized PEEP improved intraoperative respiratory mechanics in patients undergoing laparoscopic and thoracoscopic esopha-gectomy,and decremental titration was more effective in improving intraoperative respiratory mechanics and oxygenation in patients during operation.

Objective To investigate the regulatory effect of PU.1 on apoptosis resistance of aging macro-phages under in vitro inflammatory stimulation simulated by lipopolysaccharide(LPS)of Porphyromonas.Methods The expression of PU.1 in periodontitis gingival tissue and normal gingival tissue was analyzed by GEO database.Mouse macrophage cell line RAW264.7 was divided into control group,P.g-LPS group,H2O2 group and PU.1 inhibitor group.mRNA expression of senescence associated secretory phenotype(IL-6,IL-1β,TNF-α)and PU.1 were detected by RT-qPCR;The protein expressions of p21,p16,BAX,caspase-3,Bcl-2,Bcl-xl and PU.1 were detected by Western blot.The number of senescent cells was detected by senescence-associated-galactosidase(SA-β-gal)staining.The apoptosis rate was detected by flow cytometry.Results Compared with control group,the expression of p21,p16 protein and mRNA of IL-6,IL-1β and TNF-α were up-regulated in P.g-LPS group and H2O2 group,the number of senescent cells was increased,the expression of Bcl-2 and Bcl-xl was up-regulated,the expression of BAX and caspase-3 was decreased,and the apoptosis rate was decreased.Meanwhile,the mRNA and protein expression of PU.1 were increased(P<0.05).Compared with P.g-LPS group,mRNA and protein expression of PU.1 in PU.1 inhibitor group were down-regulated,Bcl-2 and Bcl-xl were down-regulated,BAX and caspase-3 expressions were increased,apoptosis rate was increased,the number of senescent cells was decreased,and mRNA levels of IL-6,IL-1β and TNF-α were decreased.The expression of p21 and p16 proteins were down-regulated.(P<0.05).Conclusion Under inflammatory stimulation in vitro,increased expression of PU.1 induced apoptosis resistance of aging macrophages,inhibition of PU.1 promoted apoptosis of aging macrophages,reduced the number of aging macrophages,and down-regulated the secretion of inflammatory factors.

Objective:Hypoxia is a common pathological phenomenon,usually caused by insufficient oxygen supply or inability to use oxygen effectively.Hydroxylated and methoxylated flavonoids have significant anti-hypoxia activity.This study aims to explore the synthesis,antioxidant and anti-hypoxia activities of 6-hydroxygenistein(6-OHG)and its methoxylated derivatives. Methods:The 6-OHG and its methoxylated derivatives,including 4',6,7-trimethoxy-5-hydroxyisoflavone(compound 3),4',5,6,7-tetramethoxyisoflavone(compound 4),4',6-imethoxy-5,7-dihydroxyisoflavone(compound 6),and 4'-methoxy-5,6,7-trihydroxyisoflavone(compound 7),were synthesized by methylation,bromination,methoxylation,and demethylation using biochanin A as raw material.The structure of these products were characterized by 1hydrogen-nuclear magnetic resonance spectroscopy(1H-NMR)and mass spectrometry(MS).The purity of these compounds was detected by high pressure chromatography(HPLC).The antioxidant activity in vitro was investigated by 1,1-diphenyl-2-picrylhydrazyl radical(DPPH)free radical scavenging assay.PC12 cells were divided into a normal group,a hypoxia model group,rutin(1×10-9-1×10-5 mol/L)groups,and target compounds(1×10-9-1×10-5 mol/L)groups under normal and hypoxic conditions.Cell viability was detected by cell counting kit-8(CCK-8)assay,the target compounds with excellent anti-hypoxia activity and the drug concentration at the maximum anti-hypoxia activity were screened.PC12 cells were treated with the optimal concentration of the target compound or rutin with excellent anti-hypoxia activity,and the cell morphology was observed under light microscope.The apoptotic rate was determined by flow cytometry,and the expressions of hypoxia inducible factor-1α(HIF-1α)and vascular endothelial growth factor(VEGF)were detected by Western blotting. Results:The structure of 6-OHG and its 4 methylated derivatives were correct,and the purity was all more than 97%.When the concentration was 4 mmol/L,the DPPH free radical removal rates of chemical compounds 7 and 6-OHG were 81.16%and 86.94%,respectively,which were higher than those of rutin,the positive control.The removal rates of chemical compounds 3,4,and 6 were all lower than 20%.Compared with the normal group,the cell viability of the hypoxia model group was significantly decreased(P<0.01).Compared with the hypoxia model group,compounds 3,4,and 6 had no significant effect on cell viability under hypoxic conditions.At all experimental concentrations,the cell viability of the 6-OHG group was significantly higher than that of the hypoxia model group(all P<0.05).The cell viability of compound 7 group at 1×10-7 and 1×10-6 mol/L was significantly higher than that of the hypoxia model group(both P<0.05).The anti-hypoxia activity of 6-OHG and compound 7 was excellent,and the optimal drug concentration was 1×10-6 and 1×10-7 mol/L.After PC12 cells was treated with 6-OHG(1×10-6 mol/L)and compound 7(1×10-7 mol/L),the cell damage was reduced,the apoptotic rate was significantly decreased(P<0.01),and the protein expression levels of HIF-1α and VEGF were significantly decreased in comparison with the hypoxia model group(both P<0.01). Conclusion:The optimized synthesis route can increase the yield of 6-OHG and obtain 4 derivatives by methylation and selective demethylation.6-OHG and compound 7 have excellent antioxidant and anti-hypoxia activities,which are related to the structure of the A-ring ortho-triphenol hydroxyl group in the molecule.

Flavonoids have been reported to possess significant pharmacological activities,such as antioxidant, anti-inflammatory and anticancer effects. However, the low solubility and low bioavailability limits their clinical application. Nanocrystal technology can solve the delivery problems of flavonoids by reducing particle size, increasing the solubility of insoluble drugs and improving their bioavailability. This article summaries nanosuspension preparation methods and the stabilizers for flavonoid nanocrystals, and reviews the drug delivery routes including oral, Injection and transdermal of flavonoid nanocrystals, to provide information for further research on nanocrystal delivery system of flavonoids.
Flavonoids/pharmacology* ; Pharmaceutical Preparations/chemistry* ; Biological Availability ; Nanoparticles/chemistry* ; Anti-Inflammatory Agents ; Particle Size

There is still a lack of sufficient evidence-based basis for the treatment of simple gaming disorder. The purpose of this paper is to review the research progress of gaming disorder intervention， in order to provide references for the treatment of patients with gaming disorder. With the development and popularization of the Internet， the adverse events caused by the pathological use of online games have attracted wide attention. At present， gaming disorder has been listed in the International Classification of Diseases， eleventh edition （ICD-11） by WHO. This paper reviewed the latest interventions measures about gaming disorder at home and abroad in the past decade， including psychological， pharmacological and physical intervention methods， and analyzed and summarized these intervention measures， so as to provide references for patients with gaming disorder to formulate a reasonable intervention plan.

Enamel formation is a complex physiological process that depends on the coordinated regulation of multiple mechanisms. This process is quite sensitive to various local and systemic interference factors. Therefore, during the long period from the embryonic stage to adolescence or even adulthood, various interference factors may lead to enamel developmental defects. Among them, early life is the most sensitive stage to environmental factors exposure, while it is also the critical period of enamel development of deciduous and permanent teeth. Environmental factors exposure during this period often leads to varying degrees of enamel development defects. In this review, we generalize the research progress of environmental factors affecting enamel developmental defects, summarize the potential mechanisms of environmental factors leading to enamel developmental defects, and conclude the clinical management strategies based on tertiary prevention. This work hopes to provide a theoretical basis for preventing abnormal teeth development from the critical time window of early life, propose eugenics health consultation and promote children ′s oral health management.

Malnutrition is a common complication of cancer patients, and solving nutrition problems is still one of the challenging tasks in clinical practice. The incidence of malnutrition in head and neck cancer patients during the peri-radiotherapeutic period is high, which is not only related to disease-mediated metabolic disorders, complications and psychological factors, but also associated with the toxic and side effects induced by radiotherapy. Malnutrition will reduce the tolerance, accuracy, and therapeutic effects of radiotherapy, which in turn lowers the quality of life and even adversely affects the prognosis of disease. Medical nutrition therapy can improve the nutritional status of the body, ensure smooth progress of radiotherapy, and improve the efficacy of comprehensive cancer treatment. It is necessary and urgent to deliver standardized nutrition therapy and management of head and neck cancer patients during the peri-radiotherapeutic period. Nutritional risk screening, nutritional assessment, and acute radiation injury assessment are required to develop an individualized nutrition treatment plan and make dynamic adjustment. In this article, relevant literature of nutrition therapy for head and neck radiotherapy at home and abroad was summarized, and the standardized nutrition therapy for head and neck cancer patients during the peri-radiotherapeutic period was reviewed.