Kupffer cells (KCs), as residents and sentinels of the liver, are involved in the formation of hepatic fibrosis (HF). However, the biological functions of circular RNAs (circRNAs) in KCs to HF have not been determined. In this study, the expression levels of circRNAs, microRNAs, and messenger RNAs (mRNAs) in KCs from a mouse model of HF mice were investigated using microarray and circRNA-Seq analyses. circDcbld2 was identified as a candidate circRNA in HF, as evidenced by its up-regulation in KCs. Silver staining and mass spectrometry showed that Wtap and Igf2bp2 bind to cirDcbld2. The suppression of circDcbld2 expression decreased the KC inflammatory response and oxidative stress and inhibited hepatic stellate cell (HSCs) activation, attenuating mouse liver fibrogenesis. Mechanistically, Wtap mediated the N ⁶-methyladenosine (m6A) methylation of circDcbld2, and Igf2bp2 recognized m6A-modified circDcbld2 and increased its stability. circDcbld2 contributes to the occurrence of HF by binding miR-144-3p/Et-1 to regulate the inflammatory response and oxidative stress. These findings indicate that circDcbld2 functions via the m6A/circDcbld2/miR-144-3p/Et-1 axis and may act as a potential biomarker for HF treatment.

OBJECTIVE: Cassiae Semen (CS, Juemingzi in Chinese) is a widely used traditional Chinese medicine with a variety of pharmacological effects. This study aimed to investigate the potential therapeutic effects and molecular mechanisms of anthraquinones of CS (AQS) for adiposity. METHODS: The chemical components of the AQS were determined using high-performance liquid chromatography (HPLC). Network pharmacology analysis was used to predict potential anti-obesity targets of action for AQS. We constructed high fat with high sugar water diet-induced obese mice and observed their body weight and whole-body lipid metabolism to evaluate the efficacy of AQS in promoting lipid metabolism. Subsequently, the epidermal temperature at the brown adipose tissue (BAT) before and after cold stimulation was observed and the expression of lipid metabolism-related genes in the liver and BAT tissues was detected to clarify the mechanism of action of AQS. RESULTS: Network pharmacology analysis showed that AQS was involved in the regulation of liver and adipose tissue function under obesity. Pathological and biochemical results showed that AQS reduced lipid accumulation in the liver and adipose tissue induced by an unhealthy diet. With the increase of cold tolerance, the volume and weight of BAT were increased by AQS, suggesting that it regulated the body heat production dominated by BAT. After AQS treatment, the levels of genes related to uncoupling protein1 (UCP1)-mediated adaptive thermogenesis in BAT tissues and lipid metabolism in the liver were also increased, which further proved that AQS activated BAT function to promote lipid metabolism in the whole body. CONCLUSION This study revealed the pharmacological effects of AQS, thereby providing a scientific basis for regulating BAT thermogenesis and liver lipid metabolism to alleviate obesity and providing clues for further exploring the application of natural active ingredients in the treatment of metabolism-related diseases.

Objective:To explore the potential mechanism underlying IL-6 production through the TLR7 signaling pathway,which regulates Th17 cell differentiation in the context of Coxsackievirus B3(CVB3)-induced acute viral myocarditis(AVMC).Meth-ods:A total of 110 patients diagnosed with AVMC were admitted to Quanzhou First Hospital,Fujian between January 2020 and Janu-ary 2023,alongside 93 healthy volunteers.CD4+T cells were isolated from the subjects'blood,and the levels of CVB3 and the number of Th17 cells were assessed.Subsequently,CD4+T cells were infected with CVB3,and the levels of Th17 cells,IL-17,IL-21,and TNF-α were measured.After knockdown of TLR7 or treatment with TLR7 inhibitors,the differentiation of CVB3-infected CD4+T cells into Th17 cells was observed.Results:In comparison to healthy controls,AVMC patients exhibited elevated plasma levels of hsCRP,IL-17,IL-21,and TNF-α(P<0.05).The levels of CVB3 mRNA in CD4+T cells were also notably higher in AVMC patients compared to healthy controls(P<0.05).The mean viral titer in AVMC patients measured 230 PFU/ml,while no detectable virus was found in healthy volunteers(P<0.05).In CD4+T cells,the count of Th17 cells was significantly increased in AVMC patients compared to healthy volunteers(P<0.05).Moreover,the number of Th17 cells in peripheral blood CD4+T cells of AVMC patients showed a positive correlation with CVB3 virus titer(P<0.05).Following CVB3 infection,the number of Th17 cells increased compared with the control group(P<0.05),accompanied by elevated levels of IL-17,IL-21,and TNF-α in the supernatant(P<0.05).Knockdown of TLR7 and CVB3 infection in CD4+T cells significantly reduced the levels of Th17 cells(P<0.05),while the expression level of phosphorylated-activated TLR7 increased significantly after CVB3 infection of CD4+T cells compared to the control group(P<0.05).Treatment with the TLR7 inhibitor M5049 and CVB3 infection led to a significant decrease in Th17 cell levels(P<0.05).The secretion of IL-6 in CD4+T cells increased after CVB3 infection(P<0.05),and this increase was mitigated by TLR7 knockdown and CVB3 infection(P<0.05)as well as TLR7 inhibitor M5049 treatment and CVB3 infection(P<0.05).Conclusion:CVB3 activates TLR7 via phosphoryla-tion,prompting CD4+T cells to release IL-6 and undergo differentiation into Th17 cells.Consequently,TLR7 emerges as a promising therapeutic target for AVMC.

Background and Objectives: The Fractional Flow Reserve and Intravascular UltrasoundGuided Intervention Strategy for Clinical Outcomes in Patients with Intermediate Stenosis (FLAVOUR) trial demonstrated non-inferiority of fractional flow reserve (FFR)-guided percutaneous coronary intervention (PCI) compared with intravascular ultrasound (IVUS)-guided PCI. We sought to investigate the cost-effectiveness of FFR-guided PCI compared to IVUS-guided PCI in Korea. Methods: A 2-part cost-effectiveness model, composed of a short-term decision tree model and a long-term Markov model, was developed for patients who underwent PCI to treat intermediate stenosis (40% to 70% stenosis by visual estimation on coronary angiography).The lifetime healthcare costs and quality-adjusted life-years (QALYs) were estimated from the healthcare system perspective. Transition probabilities were mainly referred from the FLAVOUR trial, and healthcare costs were mainly obtained through analysis of Korean National Health Insurance claims data. Health utilities were mainly obtained from the Seattle Angina Questionnaire responses of FLAVOUR trial participants mapped to EQ-5D. Results: From the Korean healthcare system perspective, the base-case analysis showed that FFR-guided PCI was 2,451 U.S. dollar lower in lifetime healthcare costs and 0.178 higher in QALYs compared to IVUS-guided PCI. FFR-guided PCI remained more likely to be cost-effective over a wide range of willingness-to-pay thresholds in the probabilistic sensitivity analysis. Conclusions Based on the results from the FLAVOUR trial, FFR-guided PCI is projected to decrease lifetime healthcare costs and increase QALYs compared with IVUS-guided PCI in intermediate coronary lesion, and it is a dominant strategy in Korea.

Background and Objectives: The Fractional Flow Reserve and Intravascular UltrasoundGuided Intervention Strategy for Clinical Outcomes in Patients with Intermediate Stenosis (FLAVOUR) trial demonstrated non-inferiority of fractional flow reserve (FFR)-guided percutaneous coronary intervention (PCI) compared with intravascular ultrasound (IVUS)-guided PCI. We sought to investigate the cost-effectiveness of FFR-guided PCI compared to IVUS-guided PCI in Korea. Methods: A 2-part cost-effectiveness model, composed of a short-term decision tree model and a long-term Markov model, was developed for patients who underwent PCI to treat intermediate stenosis (40% to 70% stenosis by visual estimation on coronary angiography).The lifetime healthcare costs and quality-adjusted life-years (QALYs) were estimated from the healthcare system perspective. Transition probabilities were mainly referred from the FLAVOUR trial, and healthcare costs were mainly obtained through analysis of Korean National Health Insurance claims data. Health utilities were mainly obtained from the Seattle Angina Questionnaire responses of FLAVOUR trial participants mapped to EQ-5D. Results: From the Korean healthcare system perspective, the base-case analysis showed that FFR-guided PCI was 2,451 U.S. dollar lower in lifetime healthcare costs and 0.178 higher in QALYs compared to IVUS-guided PCI. FFR-guided PCI remained more likely to be cost-effective over a wide range of willingness-to-pay thresholds in the probabilistic sensitivity analysis. Conclusions Based on the results from the FLAVOUR trial, FFR-guided PCI is projected to decrease lifetime healthcare costs and increase QALYs compared with IVUS-guided PCI in intermediate coronary lesion, and it is a dominant strategy in Korea.

Objective To analyze the epidemiological characteristics of mumps in Guangxi from 2012 to 2024, and to provide a scientific basis for formulating prevention and control strategies. Methods Descriptive epidemiological methods were used to analyze the incidence data of mumps in Guangxi from 2012 to 2024. Results A total of 159 873 mumps cases were reported from 2012 to 2024 in Guangxi, with an average annual reported incidence of 25.41/100 000, and no death. Mumps occurred every month, with the peak incidence mainly concentrated in April to July and October to January of the next year. There were 96,118 male cases (29.43 /100 000), and 63 755 female cases (21.07 /100 000). The male to female ratio was 1.40:1, and the difference between male and female was significant (χ²=4 321.276，P＜0.05). The annual incidence of mumps showed a certain periodic change, with the incidence peak and trough alternating every 4 - 5 years. The majority of patients were under 15 years old, accounting for 85.32% of the total number of cases. The patients mainly included students, preschool children and scattered children. The highest average incidence was in Nanning City with 40 231 cases (42.08/100 000), and the lowest was in Qinzhou City with 3 466 cases (8.16/100 000). From 2012 to 2024, a total of 210 mumps outbreaks with 4 483 cases were reported in Guangxi. Conclusion The incidence of mumps in Guangxi from 2012 to 2024 shows a periodic change and obvious seasonality. People under 15 years old are the key group at risk of mumps. The prevention and control of the epidemic of mumps in schools and kindergartens should be strengthened. It is suggested to carry out long-term monitoring of mumps as well as immune effect research, and continue to maintain a high vaccination rate of 2 doses of mumps-containing vaccines.

Background and Objectives: The Fractional Flow Reserve and Intravascular UltrasoundGuided Intervention Strategy for Clinical Outcomes in Patients with Intermediate Stenosis (FLAVOUR) trial demonstrated non-inferiority of fractional flow reserve (FFR)-guided percutaneous coronary intervention (PCI) compared with intravascular ultrasound (IVUS)-guided PCI. We sought to investigate the cost-effectiveness of FFR-guided PCI compared to IVUS-guided PCI in Korea. Methods: A 2-part cost-effectiveness model, composed of a short-term decision tree model and a long-term Markov model, was developed for patients who underwent PCI to treat intermediate stenosis (40% to 70% stenosis by visual estimation on coronary angiography).The lifetime healthcare costs and quality-adjusted life-years (QALYs) were estimated from the healthcare system perspective. Transition probabilities were mainly referred from the FLAVOUR trial, and healthcare costs were mainly obtained through analysis of Korean National Health Insurance claims data. Health utilities were mainly obtained from the Seattle Angina Questionnaire responses of FLAVOUR trial participants mapped to EQ-5D. Results: From the Korean healthcare system perspective, the base-case analysis showed that FFR-guided PCI was 2,451 U.S. dollar lower in lifetime healthcare costs and 0.178 higher in QALYs compared to IVUS-guided PCI. FFR-guided PCI remained more likely to be cost-effective over a wide range of willingness-to-pay thresholds in the probabilistic sensitivity analysis. Conclusions Based on the results from the FLAVOUR trial, FFR-guided PCI is projected to decrease lifetime healthcare costs and increase QALYs compared with IVUS-guided PCI in intermediate coronary lesion, and it is a dominant strategy in Korea.

Background and Objectives: The Fractional Flow Reserve and Intravascular UltrasoundGuided Intervention Strategy for Clinical Outcomes in Patients with Intermediate Stenosis (FLAVOUR) trial demonstrated non-inferiority of fractional flow reserve (FFR)-guided percutaneous coronary intervention (PCI) compared with intravascular ultrasound (IVUS)-guided PCI. We sought to investigate the cost-effectiveness of FFR-guided PCI compared to IVUS-guided PCI in Korea. Methods: A 2-part cost-effectiveness model, composed of a short-term decision tree model and a long-term Markov model, was developed for patients who underwent PCI to treat intermediate stenosis (40% to 70% stenosis by visual estimation on coronary angiography).The lifetime healthcare costs and quality-adjusted life-years (QALYs) were estimated from the healthcare system perspective. Transition probabilities were mainly referred from the FLAVOUR trial, and healthcare costs were mainly obtained through analysis of Korean National Health Insurance claims data. Health utilities were mainly obtained from the Seattle Angina Questionnaire responses of FLAVOUR trial participants mapped to EQ-5D. Results: From the Korean healthcare system perspective, the base-case analysis showed that FFR-guided PCI was 2,451 U.S. dollar lower in lifetime healthcare costs and 0.178 higher in QALYs compared to IVUS-guided PCI. FFR-guided PCI remained more likely to be cost-effective over a wide range of willingness-to-pay thresholds in the probabilistic sensitivity analysis. Conclusions Based on the results from the FLAVOUR trial, FFR-guided PCI is projected to decrease lifetime healthcare costs and increase QALYs compared with IVUS-guided PCI in intermediate coronary lesion, and it is a dominant strategy in Korea.

Objective:To explore the potential mechanism underlying IL-6 production through the TLR7 signaling pathway,which regulates Th17 cell differentiation in the context of Coxsackievirus B3(CVB3)-induced acute viral myocarditis(AVMC).Meth-ods:A total of 110 patients diagnosed with AVMC were admitted to Quanzhou First Hospital,Fujian between January 2020 and Janu-ary 2023,alongside 93 healthy volunteers.CD4+T cells were isolated from the subjects'blood,and the levels of CVB3 and the number of Th17 cells were assessed.Subsequently,CD4+T cells were infected with CVB3,and the levels of Th17 cells,IL-17,IL-21,and TNF-α were measured.After knockdown of TLR7 or treatment with TLR7 inhibitors,the differentiation of CVB3-infected CD4+T cells into Th17 cells was observed.Results:In comparison to healthy controls,AVMC patients exhibited elevated plasma levels of hsCRP,IL-17,IL-21,and TNF-α(P<0.05).The levels of CVB3 mRNA in CD4+T cells were also notably higher in AVMC patients compared to healthy controls(P<0.05).The mean viral titer in AVMC patients measured 230 PFU/ml,while no detectable virus was found in healthy volunteers(P<0.05).In CD4+T cells,the count of Th17 cells was significantly increased in AVMC patients compared to healthy volunteers(P<0.05).Moreover,the number of Th17 cells in peripheral blood CD4+T cells of AVMC patients showed a positive correlation with CVB3 virus titer(P<0.05).Following CVB3 infection,the number of Th17 cells increased compared with the control group(P<0.05),accompanied by elevated levels of IL-17,IL-21,and TNF-α in the supernatant(P<0.05).Knockdown of TLR7 and CVB3 infection in CD4+T cells significantly reduced the levels of Th17 cells(P<0.05),while the expression level of phosphorylated-activated TLR7 increased significantly after CVB3 infection of CD4+T cells compared to the control group(P<0.05).Treatment with the TLR7 inhibitor M5049 and CVB3 infection led to a significant decrease in Th17 cell levels(P<0.05).The secretion of IL-6 in CD4+T cells increased after CVB3 infection(P<0.05),and this increase was mitigated by TLR7 knockdown and CVB3 infection(P<0.05)as well as TLR7 inhibitor M5049 treatment and CVB3 infection(P<0.05).Conclusion:CVB3 activates TLR7 via phosphoryla-tion,prompting CD4+T cells to release IL-6 and undergo differentiation into Th17 cells.Consequently,TLR7 emerges as a promising therapeutic target for AVMC.

Objective:To explore the differences in bacterial community structure between proximal colon cancer (PC), distal colon cancer (DC), and rectal cancer (RC), and the values of featured microbiota in differentiating PC with tumor markers.Methods:This case-control study enrolled 85 newly diagnosed colorectal cancer patients, including 22 PC, 15 DC and 48 RC patients, and 8 colorectal adenoma patients from May 2019 to July 2022 at the Department of General Surgery, Anyang Oncology Hospital. The blood and fecal samples were collected before surgery and then subjected to biochemical tests for tumor markers and 16S rDNA tests, respectively. SPSS (27.0.1) was applied to perform the t-test, one-way ANOVA, Mann-Whitney U test, Kruskal-Wallis H test, and Chi-Squared Test. Also, the receiver operating characteristic curve (ROC) was plotted on tumor markers and/or f_Bacteroidaceae with SPSS software .Results:All groups had significant differences in the CA125 ( F=3.543, P<0.05), CA72-4 ( F=3.596, P<0.05), and serum tumor-associated materials (TAM) levels ( F=5.787, P<0.01). In PC group, the levels of CA125 [PC vs RC, (36.84±6.30) kU/L vs (12.73±4.21) kU/L, P<0.01] and CA72-4 [PC vs RC, (45.56±10.86) kU/L vs (3.30±7.63) kU/L, P<0.01] were significantly higher than that of the RC group, while the level of TAM was remarkably elevated in PC group than in RC group [PC vs RC, (124.84±5.19) U/ml vs (102.44±3.63) U/ml, P<0.001] and CRA group [PC vs CRA, (124.84±5.19) U/ml vs (95.39±8.42) U/ml, P<0.01]. The LEfSe analysis showed that the featured microbiota in the PC group included f_Bacteroidaceae, f_Neisseriaceae, f_Clostridiaceae_1, f_Spirochaetaceae, and so on. The largest area under the ROC belonged to the combination of TAM and f_Bacteroidaceae, which reached 0.845 (95% CI 0.747-0.944), with sensitivity being 0.857 and specificity being 0.815. Conclusions:There is heterogeneity in gut microbiota composition among PC, DC, RC, and CRA. The combination of gut microbiota and tumor biomarkers demonstrated good differentiating effects in proximal colon cancers.