Chronic obstructive pulmonary disease (COPD) is the most common chronic respiratory disease around the world, and pharmacotherapy is the foremost treatment method currently. In recent decades, with the rapid development of bronchoscopic interventional therapy, endoscopic physical ablation technology presents a therapeutic effect in treating COPD, with few treatment-related side effects, showing excellent application prospects in treating COPD. Since ablation techniques in this field are emerging technologies with low patient acceptance, they are not widely used in the clinical treatment of COPD. This article reviews the development process of physical ablation techniques. Moreover, their current application status and the prospects in the field of COPD treatment are also summarized and analyzed. We hope to promote the application of physical ablation in the clinical treatment of COPD and provide practical references and a theoretical basis for the clinical treatment of COPD.

High partial pressure oxygen is widely used in the treatment of ischemic and hypoxic diseases and in diving.However,chronic inhalation of gas with high oxygen partial pressure can have a toxic effect on the body,that is,oxygen toxicity.The lung is one of the target organs where injury is the most pronounced and direct after exposure to high partial pressure oxygen.This article reviews the research progress in pathogenesis and diagnosis of pulmonary oxygen toxicity in the hope of providing a reference for related prevention and treatment.

Objective To investigate the ameliorative effect and potential mechanism of Cyclocaryae Paliuri Folium in sodium palmitate-induced lipid deposition in HepG2 cells.Methods The effect of sodium palmitate and lyophilized powder of Cyclocaryae Paliuri Folium on the viability of HepG2 cells was determined by the CCK-8 method to determine the subsequent dosage administered.The HepG2 cells were divided into blank group,model group,pioglitazone group and Cyclocaryae Paliuri Folium low-,medium-and high-dosage group,the lipid deposition model of HepG2 cells was established using 350 μmol/L sodium palmitate,the medication group were given pioglitazone and low-,medium-and high-dosage of Cyclocaryae Paliuri Folium(100,250,500 μg/mL)for 12 h respectively.The intracellular lipid deposition was observed by Nile red staining and BODIPY493/503 fluorescent probe staining,the content of TNF-α and IL-6 in supernatant of cell culture medium were detected by ELISA,Western blot was used to detect PI3K,Akt,sterol-regulatory element binding protein-1(SREBP-1),fatty acid synthase(FAS),Bcl-2,Bax protein expression,qPCR was used to detect the mRNA expression of adipose triglyceride lipase(ATGL)and CD36.Results Compared with the blank group,the lipid deposition of HepG2 cells in the model group increased,TNF-α and IL-6 contents in the supernatant of cell culture medium significantly increased(P<0.01),the protein expressions of p-PI3K,p-Akt,SREBP-1,FAS and Bax in cells significantly increased,while the protein expression of Bcl-2 significantly decreased(P<0.01),the mRNA expression of ATGL significantly decreased,and the mRNA expression of CD36 significantly increased(P<0.01).Compared with the model group,the intracellular lipid deposition of the pioglitazone group and Cyclocaryae Paliuri Folium groups improved to varying degrees,the contents of TNF-α and IL-6 in the cell supernatant decreased,the expressions of p-PI3K,p-Akt,SREBP-1,FAS and Bax proteins decreased,the expression of Bcl-2 protein increased,the expression of ATGL mRNA increased,and the expression of CD36 mRNA decreased,with statistical significance in pioglitazone group and Cyclocaryae Paliuri Folium high-dosage group(P<0.05,P<0.01).Conclusion Cyclocaryae Paliuri Folium may ameliorate sodium palmitate-induced lipid deposition in HepG2 model cells by modulating the PI3K/Akt/SREBP-1/FAS signaling pathway and affecting triacylglycerol metabolism.

Objective To investigate the ameliorative effect and potential mechanism of Cyclocaryae Paliuri Folium in sodium palmitate-induced lipid deposition in HepG2 cells.Methods The effect of sodium palmitate and lyophilized powder of Cyclocaryae Paliuri Folium on the viability of HepG2 cells was determined by the CCK-8 method to determine the subsequent dosage administered.The HepG2 cells were divided into blank group,model group,pioglitazone group and Cyclocaryae Paliuri Folium low-,medium-and high-dosage group,the lipid deposition model of HepG2 cells was established using 350 μmol/L sodium palmitate,the medication group were given pioglitazone and low-,medium-and high-dosage of Cyclocaryae Paliuri Folium(100,250,500 μg/mL)for 12 h respectively.The intracellular lipid deposition was observed by Nile red staining and BODIPY493/503 fluorescent probe staining,the content of TNF-α and IL-6 in supernatant of cell culture medium were detected by ELISA,Western blot was used to detect PI3K,Akt,sterol-regulatory element binding protein-1(SREBP-1),fatty acid synthase(FAS),Bcl-2,Bax protein expression,qPCR was used to detect the mRNA expression of adipose triglyceride lipase(ATGL)and CD36.Results Compared with the blank group,the lipid deposition of HepG2 cells in the model group increased,TNF-α and IL-6 contents in the supernatant of cell culture medium significantly increased(P<0.01),the protein expressions of p-PI3K,p-Akt,SREBP-1,FAS and Bax in cells significantly increased,while the protein expression of Bcl-2 significantly decreased(P<0.01),the mRNA expression of ATGL significantly decreased,and the mRNA expression of CD36 significantly increased(P<0.01).Compared with the model group,the intracellular lipid deposition of the pioglitazone group and Cyclocaryae Paliuri Folium groups improved to varying degrees,the contents of TNF-α and IL-6 in the cell supernatant decreased,the expressions of p-PI3K,p-Akt,SREBP-1,FAS and Bax proteins decreased,the expression of Bcl-2 protein increased,the expression of ATGL mRNA increased,and the expression of CD36 mRNA decreased,with statistical significance in pioglitazone group and Cyclocaryae Paliuri Folium high-dosage group(P<0.05,P<0.01).Conclusion Cyclocaryae Paliuri Folium may ameliorate sodium palmitate-induced lipid deposition in HepG2 model cells by modulating the PI3K/Akt/SREBP-1/FAS signaling pathway and affecting triacylglycerol metabolism.

OBJECTIVE To investigate the mechanism of the inhibitory effect of total flavonoids from Taraxacum mongolicum on high-fat diet-induced obesity in mice through modulation of intestinal flora.METHODS Twenty-four C57BL/6J mice were randomly divided into blank group,model group and T.mongolicum total flavonoid group,with 8 mice in each group.Except for the blank group,the other 2 groups were given a high-fat diet,while T mongolicum total flavonoid group was given T.mongolicum total flavonoid[400 mg/(kg·d)]intragastrically,once a day,for 8 consecutive weeks.During the experiment,the food intake of each group of mice was recorded.After the last medication,the body mass,fat weight,blood lipid level and pathological changes of liver and epididymal fat in mice were evaluated to observe the effect of T.mongolicum total flavonoid on the treatment of obesity in mice.The changes in abundance and structure of intestinal flora in mice were detected by amplicon sequencing;the effects of T.mongolicum total flavonoids on fat metabolism related genes were analyzed by qPCR.RESULTS Compared with model group,the body weight of mice in T.mongolicum total flavonoids group was decreased significantly(P＜0.05);the levels of total lipid cholesterol,triglycerides,and LDL cholesterol were all decreased significantly(P＜0.01),and the level of HDL cholesterol was increased significantly(P＜0.01);the fat indexes of inguinal white adipose tissue and epididymal white adipose tissue were significantly reduced(P＜0.05);significant improvement in hepatocellular steatosis and adipose cytopathy were significantly improved;mRNA expressions of COX7A1 and COX8B were significantly upregulated(P＜0.05).The results of bacterial colony detection showed that compared with the model group,there was a rising trend in the diversity of the bacterial colony in T.mongolicum total flavonoids group,and the Sobs index characterization and β diversity were increased significantly(P＜0.05).Relative abundances of Blautia,norank_f_Ruminococcaceae,Bilophila,Alistipes,classified_f_Ruminococcaceae,Parabacteroides,norank_f_Desulfovibrionaceae,Anaerotruncus were significantly up-regulated(P＜0.05),while those of Faecalibaculum,Erysipelatoclostridium,GCA-900066575,Tuzzerella,Lactobacillus,norank_f_norank_o_RF39,achnospiraceae_FCS020_group were significantly down-regulated(P＜0.05).CONCLUSIONS T.mongolicum total flavonoids can reduce body mass,fat weight and blood lipid levels,and repair the pathological damage to liver and epididymal fat in obese mice,which is related to improving intestinal flora disorders caused by high-fat diet.

Objective:To explore the feasibility of the tumor-targeted near infrared (NIR) fluorescent dye NIR-T for clearly and accurately delineating incisal edge of breast cancer.Methods:Firstly, the breast cancer xenograft subcutaneous tumor was established in BALB/c nude mice, and dye NIR-T was administrated intratumorally to evaluate the tumor-to-normal tissue (T/N) ratio of the incisal edge of breast tumor. Under the guidance of fluorescence signals, the tumor and peritumoral tissues were resected and collected respectively, and the accuracy of the tumor incisal edge delineated by NIR-T was evaluated by pathological analysis. Studies were further performed on fresh isolated human breast tumor tissues. After intratumoral injection of NIR-T, tumor and peritumoral tissues were collected with the guidance of fluorescence signals, and the accuracy of breast tumor incisal edge delineated by NIR-T was evaluated by pathological analysis.Results:Dye NIR-T was able to clearly delineate the incisal margin of subcutaneous breast tumor in BALB/c nude mice with a T/N ratio of up to 15, and was used to successfully guide the rapid resection of the tumor, and subsequent intraoperative pathological analysis confirmed that the tumor was absolutely removed; NIR-T could be used to clearly delineate the resection margin of breast tumors and its precision was determined to be 100% via pathological analysis.Conclusion:The tumor-targeted NIR fluorescent dye NIR-T was able to clearly and accurately delineate the resection margin of breast tumors, which would promote the precision of tumor resection and shorten the operation time.

Diabetic nephropathy(DN),a severe complication of diabetes,is widely recognized as a primary contributor to end-stage renal disease.Recent studies indicate that the inflammation triggered by Toll-like receptor 4(TLR4)is of paramount importance in the onset and progression of DN.TLR4 can bind to various ligands,including exogenous ligands such as proteins and polysaccharides from bacteria or vi-ruses,as well as endogenous ligands such as biglycan,fibrinogen,and hyaluronan.In DN,the expression or release of TLR4-related ligands is significantly elevated,resulting in excessive TLR4 activation and increased production of proinflammatory cytokines through downstream signaling pathways.This process is closely associated with the progression of DN.Natural compounds are biologically active products derived from natural sources that have advantages in the treatment of certain diseases.Various types of natural compounds,including alkaloids,flavonoids,polyphenols,terpenoids,glycosides,and polysaccharides,have demonstrated their ability to improve DN by affecting the TLR4 signaling pathway.In this review,we summarize the mechanism of action of TLR4 in DN and the natural compounds that can ameliorate DN by modulating the TLR4 signaling pathway.We specifically highlight the potential of compounds such as curcumin,paclitaxel,berberine,and ursolic acid to inhibit the TLR4 signaling pathway,which provides an important direction of research for the treatment of DN.

Objective To explore the effectiveness of Failure Modes and Effects Analysis(FMEA)in emergency man-agement of sudden incidents involving outpatient and emergency patients in general hospitals,to provide references for the optimi-zation of emergency response process for such incidents.Methods Based on FMEA,we identified and evaluated risks in the e-mergency response procedures for sudden incidents involving outpatient and emergency patients in general hospitals.Potential fail-ure modes were analyzed to identify key risks with a Risk Priority Number(RPN)greater than 125.Continuous quality improve-ment measures were implemented to control these risks,and the effectiveness of these controls was evaluated using chi-square tests for statistical analysis.Results A total of 16 risk points in 4 major areas were identified.After implementing continuous quality improvement measures,the RPNs of these high-risk points decreased to below 125,effectively controlling the potential risks.This intervention significantly improved the utilization rate of emergency equipment,the timely reporting rate of sudden in-cidents,the timely feedback rate of emergency response,with statistically significant differences(P＜0.01).Conclusion The application of FMEA to outpatient and emergency management of sudden incidents helps optimize the emergency response process,thus enhancing the emergency response capability of general hospitals and ensuring effective handling of such incidents.

Objective:We aimed to develop a novel visualized model based on nomogram to predict postoperative overall survival.Methods:This was a multicenter, retrospective, observational cohort study, including participants with histologically confirmed gastric and colorectal cancer who underwent radical surgery from 11 medical centers in China from August 1, 2015 to June 30, 2018. Baseline characteristics, histopathological data and nutritional status, as assessed using Nutrition Risk Screening 2002 (NRS 2002) score and the scored Patient-Generated Subjective Global Assessment, were collected. The least absolute shrinkage and selection operator regression and Cox regression were used to identify variables to be included in the predictive model. Internal and external validations were performed.Results:There were 681 and 127 patients in the training and validation cohorts, respectively. A total of 188 deaths were observed over a median follow-up period of 59 (range: 58 to 60) months. Two independent predictors of NRS 2002 and Tumor-Node-Metastasis (TNM) stage were identified and incorporated into the prediction nomogram model together with the factor of age. The model's concordance index for 1-, 3- and 5-year overall survival was 0.696, 0.724, and 0.738 in the training cohort and 0.801, 0.812, and 0.793 in the validation cohort, respectively.Conclusions:In this study, a new nomogram prediction model based on NRS 2002 score was developed and validated for predicting the overall postoperative survival of patients with gastric colorectal cancer. This model has good differentiation, calibration and clinical practicability in predicting the long-term survival rate of patients with gastrointestinal cancer after radical surgery.

Epimedin B(EB)is one of the main flavonoid ingredients present in Epimedium brevicornum Maxim.,a traditional herb widely used in China.Our previous study showed that EB was a stronger inducer of melanogenesis and an activator of tyrosinase(TYR).However,the role of EB in melanogenesis and the mechanism underlying the regulation remain unclear.Herein,as an extension to our previous investi-gation,we provide comprehensive evidence of EB-induced pigmentation in vivo and in vitro and eluci-date the melanogenesis mechanism by assessing its effects on the TYR family of proteins(TYRs)in terms of expression,activity,and stability.The results showed that EB increased TYRs expression through microphthalmia-associated transcription factor-mediated p-Akt(referred to as protein kinase B(PKB))/glycogen synthase kinase 3β(GSK3β)/β-catenin,p-p70 S6 kinase cascades,and protein 38(p38)/mitogen-activated protein(MAP)kinase(MAPK)and extracellular regulated protein kinases(ERK)/MAPK pathways,after which EB increased the number of melanosomes and promoted their maturation for melanogenesis in melanoma cells and human primary melanocytes/skin tissues.Furthermore,EB exerted repigmentation by stimulating TYR activity in hydroquinone-and N-phenylthiourea-induced TYR inhibitive models,including melanoma cells,zebrafish,and mice.Finally,EB ameliorated monobenzone-induced depigmentation in vitro and in vivo through the enhancement of TYRs stability by inhibiting TYR misfolding,TYR-related protein 1 formation,and retention in the endoplasmic reticulum and then by downregulating the ubiquitination and proteolysis processes.These data conclude that EB can target TYRs and alter their expression,activity,and stability,thus stimulating their pigmentation function,which might provide a novel rational strategy for hypopigmentation treatment in the pharmaceutical and cosmetic industries.