Extensive evidence has demonstrated that glucagon-like peptide-1 receptor agonists (GLP-1RAs) can ameliorate obesity. Our previous studies revealed that (Ex-4)₂-Fc, a long-acting GLP-1RA we developed, depends on the leptin pathway to treat obesity. However, the mechanisms linking (Ex-4)₂-Fc and leptin resistance remain largely unclear. To address this question, we explored the mechanism of GLP-1RAs from the perspective of the gut microbiota, as increasing evidence indicates an important link between the gut microbiota and obesity. This study aimed to explore the potential role of the gut microbiota in the treatment of GLP-1RAs. We found that (Ex-4)₂-Fc treatment reshaped obesity-induced gut microbiota disturbances and substantially increased the abundance of Akkermansia muciniphila (Am). In addition, (Ex-4)₂-Fc did not respond well in antibiotic-treated (ATB) Obese mice. Subsequent studies have shown that this defect can be overcome by gavage with Am. In addition, we found that Am enhanced (Ex-4)₂-Fc therapy by producing the metabolite inosine. Inosine regulates the macrophage adenosine A2A receptor (A2A) pathway to indirectly reduce leptin levels in adipocytes Thus, elucidating the role of metabolites in regulating the leptin pathway will provide new insights into GLP-1RAs therapy and may lead to more effective strategies for guiding the clinical use of antidiabetic agents.

Objective To construct and validate a predictive model based on preoperative inflammatory biomarkers,and to evaluate its ability in predicting the prognosis of patients with unresectable hepatocellular carcinoma(HCC)after receiving transcatheter arterial chemoembolization(TACE).Methods A total of 544 patients with HCC,who received TACE as the initial treatment at six medical institutions between January 2007 and December 2020,were retrospectively collected.The patients were divided into training cohort(n=376)and validation cohort(n=168).LASSO algorithm and Cox regression analysis were used to screen out the independent influencing factors and to make modelling.The model was validated based on the discrimination,calibration and clinical applicability,and the Kaplan-Meier risk stratification curves were plotted to determine the prognostic differences between groups.The likelihood ratio chi-square value,R2 value,akaike information criterion(AIC)value,C-index and AUROC value of the model were calculated to determine its accuracy and efficiency.Results The training cohort and validation cohort had 376 participants and 168 participants respectively.Multivariate analysis indicated that BCLC,tumor size,number of tumor lesions,neutrophil and prognostic nutritional index(PNI)were the independent influencing factors for postoperative overall survival(OS),with all P being＜0.05;the BCLC grade,tumor size,number of tumor lesions,NLR,PNI and PS score were the independent influencing factors for progression-free survival(PFS),with all P being＜0.05.The C-indexes of the OS and PFS models were 0.735(95％ CI=0.708-0.762)and 0.736(95％ CI=0.711-0.761)respectively,and the external validation was 0.721(95％ CI=0.680-0.762)and 0.693(95％ CI=0.656-0.730)respectively.Ideal discrimination ability of the nomogram was exhibited in time-dependent C-index,time-dependent ROC,and time-dependent AUC.The calibration curves significantly coincided with the ideal standard lines,indicating that the model had high stability and low over-fitting level.Decision curve analysis revealed that there was a wider range of threshold probabilities and it could augment net benefits.The Kaplan-Meier curves for risk stratification indicated that the prognosis of patients varied dramatically between risk categories(P＜0.000 1).The Kaplan-Meier curves for risk stratification indicated that the prognosis of patients varied dramatically among different risk groups(P＜0.000 1).The likelihood ratio chi-square value,R2 value,AIC value,C-index and AUROC value of the model were better than those of other models commonly used in clinical practice.Conclusion The newly-developed prognostic nomogram based on preoperative inflammatory indicators has excellent accuracy as well as excellent prediction effect in predicting the prognosis of patients with unresectable HCC after receiving TACE,therefore,it can be used as an effective tool for guiding individualized treatment and for predicting prognosis.(J Intervent Radiol,2024,33:245-258)

Objective:In order to scientifically promote the selection of appropriate technology of traditional non-pharmacologi-cal,the value evaluation index system of traditional non-pharmacological technology was constructed in line with the characteristics of TCM based on the theory of health technology assessment and multi-criteria decision analysis.Methods:The evaluation index pool was initially formed through literature research,and then those indicators were further improved through semi-structured inter-views and Delphi method.Results:The value evaluation index was constructed with seven dimensions,including quality standard,safety,effectiveness,economy,inheritance and innovation,suitability and accessibility,which were subordinated by 17 second-level indicators and 33 third-level indicators.The questionnaire response rate was 100%.The group authority coefficient of 17 experts was 0.87,and the concentration and coordination degree of expert opinions of the first-level indicators were high.Conclusion:The index pool constructed in this study has high expert authority,good concentration and coordination of expert opinions,which needs to be verified by practical experience,which is of great significance for the value evaluation of traditional non-pharmacological technology.

Background: Microsporum canis is a zoonotic disease that can cause dermatophytosis in animals and humans. Objectives: In clinical practice, ketoconazole (KTZ) and other imidazole drugs are commonly used to treat M. canis infection, but its molecular mechanism is not completely understood.The antifungal mechanism of KTZ needs to be studied in detail. Methods: In this study, one strain of fungi was isolated from a canine suffering with clinical dermatosis and confirmed as M. canis by morphological observation and sequencing analysis.The clinically isolated M. canis was treated with KTZ and transcriptome sequencing was performed to identify differentially expressed genes in M. canis exposed to KTZ compared with those unexposed thereto. Results: At half-inhibitory concentration (½MIC), compared with the control group, 453 genes were significantly up-regulated and 326 genes were significantly down-regulated (p < 0.05). Quantitative reverse transcription polymerase chain reaction analysis verified the transcriptome results of RNA sequencing. Gene ontology enrichment analysis and Kyoto Encyclopedia of Genes and Genomes enrichment analysis revealed that the 3 pathways of RNA polymerase, steroid biosynthesis, and ribosome biogenesis in eukaryotes are closely related to the antifungal mechanism of KTZ. Conclusions The results indicated that KTZ may change cell membrane permeability, destroy the cell wall, and inhibit mitosis and transcriptional regulation through CYP51, SQL, ERG6, ATM, ABCB1, SC, KER33, RPA1, and RNP genes in the 3 pathways. This study provides a new theoretical basis for the effective control of M. canis infection and the effect of KTZ on fungi.

The oral direct-acting antiviral drug (DAA) offers tremendous opportunities to eliminate hepatitis C. We analyzed the market trends, price trends and global treatment progress of DAA drugs by reviewing the guidelines recommended by the World Health Organization for the treatment of hepatitis C, and discusses the current accessibility of DAA treatment and its influencing factors. The results show that WHO recommends the use of DAA for treatment of hepatitis C, but the price of DAA is expensive. Although some countries have taken measures to lower prices and improve accessibility, the advancement of DAA treatment has been unsatisfactory and coverage is still not high. In addition to price, factors such as strategy, health system, accessibility and service provision need to be considered, and public health methods should be adopted to promote DAA treatment to achieve the elimination of hepatitis C.

The oral direct-acting antiviral drug (DAA) offers tremendous opportunities to eliminate hepatitis C. We analyzed the market trends, price trends and global treatment progress of DAA drugs by reviewing the guidelines recommended by the World Health Organization for the treatment of hepatitis C, and discusses the current accessibility of DAA treatment and its influencing factors. The results show that WHO recommends the use of DAA for treatment of hepatitis C, but the price of DAA is expensive. Although some countries have taken measures to lower prices and improve accessibility, the advancement of DAA treatment has been unsatisfactory and coverage is still not high. In addition to price, factors such as strategy, health system, accessibility and service provision need to be considered, and public health methods should be adopted to promote DAA treatment to achieve the elimination of hepatitis C.

Objective: To investigate the effects and the potential mechanism of shikonin on rat random flaps. Methods: Seventy-two wistar male rats in grade SPF were randomly divided into negative control group, tetramethylpyrazine group (TMP group) or shikonin treatment group. The random skin flap sized 8 cm×2 cm, with a cephalic based pedicle, was performed on the back of the rat. Each group was administered accordingly by intraperitoneal injection once per day for 7 days: shikonin treatment group (1 mg/kg), TMP group (10 mg/kg) and control group (1 ml/kg). Morphological changes of skin flaps were observed by HE staining. The positive expression of iNOS and COX-2 in skin flap tissues after operation were detected by immunofluorescence staining. The serum contents of TNF-α and IL-6 were detected by ELISA. Results: Inflammatory cell infiltration and inflammatory reaction of flap was more severe in control group at different time points after operation. The number of inflammatory cells in shikonin treatment group and TMP group were significantly decreased, compared with controls (P<0.01). The decrease of the inflammatory cell numbers in shikonin treatment group was more significant. The proliferation of granulation tissue and fibroblast in skin flap was obvious, and the survival rates of the skin flap were significantly increased in shikonin treatment group and TMP group (both P<0.01). The numbers of iNOS or COX-2 positive cells in shikonin treatment group and TMP group were significantly decreased, when compared with controls (both P<0.01). Compared with TMP group, the numbers of iNOS and COX-2 positive cells in shikonin treatment group were significantly decreased (P<0.01 and P<0.05, respectively)in early period after operation. Compared with the control group, serum levels of TNF-α and IL-6 in shikonin treatment group and TMP group were significantly decreased (all P<0.01). The shikonin treatment group developed more significant reduce. Conclusions Shikonin can significantly improve inflammatory response of skin flap in rats, which might be related to inhibiting the expression of iNOS and COX-2, decreasing serum levels of TNF-α and IL-6 , and reducing the release of inflammatory cytokines .

A description of the intervention measures of the reform program for integrated care and payment in pilot areas,covering such diseases as chronic obstructive pulmonary disease and cerbral stroke.The reform aims at exploring impacts on both medical behaviors and medical costs.Authors of the paper hold that the practice of packaged ceiling payment for a single disease is a two-edged sword for clinical pathway management,and joint efforts by the government,medical insurers,medical workers and patients at large are required to regulate medical behaviors over time.They also see the total growth of medical costs as an objective rule,and the correct way out for optimal use of medical insurance funds is to focus on makeup of such costs.

Animals ; Drosophila Proteins ; genetics ; metabolism ; Drosophila melanogaster ; Memory ; physiology ; Mushroom Bodies ; cytology ; metabolism ; Proteins ; genetics ; metabolism

Objective From the perspective of health economics, to evaluate 23 pneumococcal polysaccharide vaccination programme among chronic obstructive pulmonary disease (COPD) patient. Methods In the pilot counties of the project of integrated care pathway for COPD patient (Hanbin district of Hanzhong city in Shanxi Province, Qianjian district of Qingqing city, Huandao district of Qindao city in Shangdong Province, Wen county of Jiaozuo city in Henan Province), information of insurance participants of New Rural Cooperative Medical System (NRCS) was collected by local NRCM information system, which included general information as well as records of medical care and medical fee. Nonprobability sampling method was applied to select a total of 860 objects, who were over 60 years old with local household registration, hospitalized within one recent year due to COPD acute exacerbation, and without vaccination of 23 voluntary pneumococcal polysaccharide vaccine within 3 years. A quasi-experimental design without control group was adopted. Objects were vaccinated with 23-valent pneumococcal polysaccharide vaccine from January to December in 2013, then were followed up from January in 2014 for one year. Data of effectiveness and medical cost was collected by self-designed questionnaire and (Chinese version). Paired rank sum test applied to test the difference of quality of life, number and direct medical cost of treatment (including outpatient treatment and hospitalization) due to COPD acute exacerbation, one year before and after intervention. The incremental cost-effectiveness ratio (ICER) and cost-benefit ratio (CBR) of the programme were calculated. Results By January 2014, eight hundred sixty objects were vaccinated. By January 2015, seven hundred eighty eight objects were followed up, with 72 cases withdrawed (8.4%). On average, COPD patients reduced 1.12±2.51 treatments due to acute exacerbation, including 0.28±2.09 outpatient treatments and 0.85±1.15 hospitalizations. Total medical cost was saved by 3 610.21 per capita yuan, including outpatient cost of 241.41 yuan and hospitalization cost of 269.82 yuan; Quality of life was gained by 0.03 QALY gain per capita. The ICER was dominant and CBR was 12.00. Conclusion COPD patients vaccinated with 23-valent pneumococcal polysaccharide vaccine within one year reduced treatments due to acute exacerbation. The vaccination was cost effective and cost saving , and we suggest the vaccine should be covered in the public health program or health insurance scheme in conditional region.