Objective To construct a glioma microfluidic chip model to simulate tumor microenvironment for evaluating the medicinal efficacy of anti-glioma traditional Chinese medicines. Methods Glioblastoma cells U251 were seeded into microfluidic chips with different culture modes, and the cell viability and tumour microenvironment within the constructed model were characterized. Fluorescence staining was used to evaluate the effects of the positive drugs temozolomide （TMZ） and docetaxel （DOC） on the cell activity and apoptosis within the model, which was applied to evaluate the medicinal efficacy of the extracts of the herb Scutellaria barbata on gliomas. Results The cells in the constructed U251 microfluidic chip model displayed high viability and were able to mimic the hypoxic microenvironment of tumor to a certain extent. The viability of the U251 cells in the microfluidic chips decreased with the increasing of the concentration of the positive drug, and the viability of the 3D cultured U251 cells was higher than that in the 2D condition （P<0.05）. The intracellular mitochondrial membrane potential decreased with the increasing of the concentration of the positive drug. And the 2 mg/ml Scutellaria barbata extract killed U251 cells to a certain extent and reduced the mitochondrial membrane potential of the cells in the model. Conclusion This study successfully constructed a microfluidic chip model of glioma that could effectively simulate the tumor microenvironment and rapidly evaluate the anti-tumor medicinal efficacy, which provided a new strategy for the medicinal efficacy evaluation and active components screening of anti-glioma traditional Chinese medicines.

ObjectiveTo observe the effect of Zishen Tiaogan prescription on the oxidative stress injury in the rat model of diminished ovarian reserve （DOR） and explore the role of the Kelch-like ECH-associated protein 1 （Keap1）/nuclear factor E₂-related factor 2 （Nrf2）/heme oxygenase-1 （HO-1） signaling pathway. MethodsForty-eight female SD rats were randomly assigned into a normal group （n=12） and a modeling group （n=36）. The rats in the modeling group received subcutaneous injection of galactose （350 mg·kg^-1） combined with immobilization stress daily. After 28 days of modeling， 6 rats in the normal group and 6 rats in the modeling group were sacrificed to examine the modeling results. The successfully modeled rats were assigned into model， estradiol valerate （0.09 mg·kg^-1）， and low-， medium-， and high-dose （6.39， 12.78， 25.56 g·kg^-1， respectively） Zishen Tiaogan prescription groups. The intervention lasted for 4 weeks with 6 animals per group. Hematoxylin-eosin staining was used to observe the estrous cycle and the pathological changes in the ovarian tissue. The ovarian index was calculated. Enzyme-linked immunosorbent assay was employed to measure the serum levels of sex hormones and oxidative stress-related indexes. Western blot and real-time PCR were employed to determine the protein and mRNA levels， respectively， of Nrf2， Keap1 and HO-1 in the ovarian tissue. The positive expression of superoxide dismutase 2 （SOD2） in the ovarian tissue was detected by immunohistochemistry （IHC）. ResultsCompared with the normal group， the model group showed reduced follicles in the ovary， loose arrangement of the follicle granule layer， declined levels of anti-Mullerian hormone （AMH） and estradiol （E₂） in the serum， elevated levels of luteinizing hormone （LH） and follicle-stimulating hormone （FSH） （P<0.01）， lowered levels of superoxide dismutase （SOD）， catalase （CAT）， and glutathione （GSH） （P<0.01）， and increased accumulation of malondialdehyde （MDA） （P<0.01）. In addition， the modeling led to up-regulated protein and mRNA levels of Keap1 （P<0.01）， the expression of Nrf2 and HO-1 protein was significantly decreased （P<0.01）， the mRNA expression of Nrf2 was significantly decreased （P<0.05）， the mRNA expression of HO-1 was significantly decreased （P<0.01）， in the ovarian tissue. Compared with model group， the estradiol valerate and low-， medium-， and high-dose Zishen Tiaogan prescription groups showed increases in the ovarian index （P<0.01） and serum E₂ and AMH levels （P<0.01）， declined levels of FSH and LH （P<0.01）， increased follicles in the ovary， elevated levels of SOD， CAT， and GSH， and reduced accumulation of MDA （P<0.05， P<0.01）. Furthermore， these groups showcased down-regulated protein and mRNA levels of Keap1 （P<0.01）， the expression of Nrf2 protein was significantly increased （P<0.01）， the expression level of HO-1 protein was increased （P<0.05，P<0.01）， and increased positive expression of SOD2 （P<0.01）. ConclusionZishen Tiaogan prescription can regulate the serum levels of hormones， down-regulate the expression of Keap1， up-regulate the expression of Nrf2， HO-1， and SOD2， enhance the antioxidant capacity， and reduce the peroxidation damage in the ovarian tissue to improve the ovarian reserve function in the rat model of DOR. High-dose Zishen Tiaogan prescription demonstrated the best effect and the mechanism is associated with the regulation of the Keap1/Nrf2/HO-1 pathway.

BackgroundMany studies have shown that patients with depressive disorder show impairments in prospective memory， while it is deemed necessary for facilitating their social reintegration， and the current research findings are inconsistent regarding the factors affecting prospective memory of patients with depressive disorder. ObjectiveTo explore the impact of target characteristics （emotional valence and salience） on prospective memory in patients with depressive disorder， so as to provide references for the training and recovery of prospective memory function in these patients. MethodsFrom January to December 2022， 53 patients with depressive disorder were recruited from the outpatient department of Inner Mongolia Autonomous Mental Health Center. Meanwhile， 45 healthy individuals were concurrently recruited from surrounding communities as control group. An experiment with a 2 （participant type： depressive disorder， healthy control） ×2 （target salience： salient， non-salient） ×3 （emotional valence： positive， neutral， negative） factorial design was conducted. The positive/neutral/negative emotional pictures from Chinese Affective Picture System （CAPS） were used for emotional stimulation. A dual-task experimental paradigm was adopted， and the response time and accuracy in prospective memory task and ongoing task were recorded for participants with different target characteristics. Results①In the prospective memory task， the main effect of participant type was statistically significant， with the depressive group showing lower accuracy （F=14.892， P<0.01） and longer response time （F=10.642， P=0.002） compared with control group. ② The main effect of target emotional valence on accuracy （F=7.575， P=0.001） and response time （F=3.196， P=0.044） in the prospective memory task was statistically significant. Simple effect analysis revealed that depressive group yielded a shorter response time and higher accuracy rate under negative conditions compared with positive and neutral conditions （P<0.05 or 0.01）. ③ The main effect of target salience on accuracy （F=6.659， P=0.012） and response time （F=10.106， P=0.002） in the prospective memory task was also statistically significant， with higher accuracy and shorter response time for salient targets compared with non-salient targets. ConclusionPatients with depressive disorder demonstrate preferential attention to and processing of negative stimuli in prospective memory tasks， while increasing target salience may facilitate spontaneous processing of prospective memory task in patients with depressive disorder. ［Funded by Inner Mongolia Health Commission Medical Health Science and Technology Project （number， 202202104）］

ObjectiveTo observe the effect of Zishen Tiaogan prescription on the oxidative stress injury in the rat model of diminished ovarian reserve （DOR） and explore the role of the Kelch-like ECH-associated protein 1 （Keap1）/nuclear factor E₂-related factor 2 （Nrf2）/heme oxygenase-1 （HO-1） signaling pathway. MethodsForty-eight female SD rats were randomly assigned into a normal group （n=12） and a modeling group （n=36）. The rats in the modeling group received subcutaneous injection of galactose （350 mg·kg^-1） combined with immobilization stress daily. After 28 days of modeling， 6 rats in the normal group and 6 rats in the modeling group were sacrificed to examine the modeling results. The successfully modeled rats were assigned into model， estradiol valerate （0.09 mg·kg^-1）， and low-， medium-， and high-dose （6.39， 12.78， 25.56 g·kg^-1， respectively） Zishen Tiaogan prescription groups. The intervention lasted for 4 weeks with 6 animals per group. Hematoxylin-eosin staining was used to observe the estrous cycle and the pathological changes in the ovarian tissue. The ovarian index was calculated. Enzyme-linked immunosorbent assay was employed to measure the serum levels of sex hormones and oxidative stress-related indexes. Western blot and real-time PCR were employed to determine the protein and mRNA levels， respectively， of Nrf2， Keap1 and HO-1 in the ovarian tissue. The positive expression of superoxide dismutase 2 （SOD2） in the ovarian tissue was detected by immunohistochemistry （IHC）. ResultsCompared with the normal group， the model group showed reduced follicles in the ovary， loose arrangement of the follicle granule layer， declined levels of anti-Mullerian hormone （AMH） and estradiol （E₂） in the serum， elevated levels of luteinizing hormone （LH） and follicle-stimulating hormone （FSH） （P<0.01）， lowered levels of superoxide dismutase （SOD）， catalase （CAT）， and glutathione （GSH） （P<0.01）， and increased accumulation of malondialdehyde （MDA） （P<0.01）. In addition， the modeling led to up-regulated protein and mRNA levels of Keap1 （P<0.01）， the expression of Nrf2 and HO-1 protein was significantly decreased （P<0.01）， the mRNA expression of Nrf2 was significantly decreased （P<0.05）， the mRNA expression of HO-1 was significantly decreased （P<0.01）， in the ovarian tissue. Compared with model group， the estradiol valerate and low-， medium-， and high-dose Zishen Tiaogan prescription groups showed increases in the ovarian index （P<0.01） and serum E₂ and AMH levels （P<0.01）， declined levels of FSH and LH （P<0.01）， increased follicles in the ovary， elevated levels of SOD， CAT， and GSH， and reduced accumulation of MDA （P<0.05， P<0.01）. Furthermore， these groups showcased down-regulated protein and mRNA levels of Keap1 （P<0.01）， the expression of Nrf2 protein was significantly increased （P<0.01）， the expression level of HO-1 protein was increased （P<0.05，P<0.01）， and increased positive expression of SOD2 （P<0.01）. ConclusionZishen Tiaogan prescription can regulate the serum levels of hormones， down-regulate the expression of Keap1， up-regulate the expression of Nrf2， HO-1， and SOD2， enhance the antioxidant capacity， and reduce the peroxidation damage in the ovarian tissue to improve the ovarian reserve function in the rat model of DOR. High-dose Zishen Tiaogan prescription demonstrated the best effect and the mechanism is associated with the regulation of the Keap1/Nrf2/HO-1 pathway.

Objective: To investigate the effect of targeted silencing of DNA methyltransferase 3A(DNMT3A) on collagen deposition, proliferation and migration activity of mouse lung fibroblasts(PFs). Methods: In order to ensure the proliferation and migration activity of primary fibroblasts, the lung tissues of neonatal C57 suckling mice were taken, PFs were extracted after being sheared, and the morphology was observed and identified under the microscope. PFs cells were activated by 5 ng/ml TGF-β1for 24 h after cell attachment, and DNMT3A silencing model was constructed by small interfering RNA; The experiment was divided into control group, TGF-β1group, TGF-β1+ siRNA-NC group and TGF-β1+ siRNA-DNMT3A group. The protein expressions of DNMT3A, α-smooth muscle actin(α-SMA) and Collagen Ⅰ were detected by Western blot; Real time quantitative reverse transcription polymerase chain reaction(RT-qPCR) was used to detect the mRNA expression changes ofDNMT3A,α-SMAandCollagenⅠ. The proliferation ability of PFs was detected by CCK-8 and EdU staining; the migration ability of PFs was detected by scratch test and Transwell migration test. Results: Compared with the control group, TGF-β1induced the increase of DNMT3A in the activated PFs cell group(P<0.01), the protein and mRNA levels of fibrosis and proliferation related indicators α-SMA and Collagen Ⅰ also increased(allP<0.05), and the proliferation and migration ability of PFs increased(allP<0.000 1). Compared with the siRNA-NC group, the protein expression levels of DNMT3A(P<0.000 1) and related indicators α-SMA(P<0.01) and Collagen Ⅰ(P<0.01) significantly decreased in the DNMT3A silencing group by Western blot, and the mRNA levels ofDNMT3A,α-SMAandCollagenⅠby RT-qPCR also decreased(allP<0.001), and the proliferation(P<0.01) and migration ability(P<0.05) of PFs cells decreased compared with the control group. Conclusion Silencing DNMT3A can inhibit the deposition of collagen and the proliferation of PFs. DNMT3A can promote the proliferation and migration of PFs, and then promote the activation of PFs and the development of pulmonary fibrosis. This process may be regulated by DNA methylation modification.

Background: and Purpose Ruptured intracranial aneurysms (RIA) are associated with a mortality rate of up to 40% in the Chinese population, highlighting the critical need for targeted treatment interventions for at-risk individuals. Although the impact of aldehyde dehydrogenase 2 (ALDH2) gene mutations on susceptibility to intracranial aneurysms (IA) is well documented, the potential connection between ALDH2 rs671 single-nucleotide polymorphism (SNP) and RIA remains unexplored. Given the increased prevalence of ALDH2 gene mutations among Chinese Han individuals, it is clinically relevant to investigate the link between ALDH2 rs671 SNP and IA rupture. Methods: A prospective study was conducted on 546 patients diagnosed with IA to investigate the association between ALDH2 rs671 SNP and the risk of IA rupture. Results: The ALDH2 rs671 SNP (ALDH2*2) was significantly more prevalent in patients with unruptured IA (UIA) than in those with RIA (32.56% vs. 18.58%, P=0.004). Multivariate logistic regression analysis revealed that people with the ALDH2 mutation (ALDH2*1/*2 and ALDH2*2/*2 gene type) had a significantly reduced odds ratio (OR=0.49; 95% confidence level [CI] 0.27–0.88; P=0.018) for RIAs. Age-specific subgroup analysis indicated that the ALDH2 mutation provided a stronger protective effect in individuals aged 60 years and above with IA compared to those under 60 years old (OR=0.38 vs. OR=0.52, both P<0.05). Conclusion The incidence of RIA was significantly higher in individuals with a normal ALDH2 gene (ALDH2*1/*1) than in those with an ALDH2 rs671 SNP (ALDH2*1/*2 or ALDH2*2/*2). ALDH2 rs671 SNP may serve as a protective factor against RIA in the Chinese Han population.

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 Purpose Ruptured intracranial aneurysms (RIA) are associated with a mortality rate of up to 40% in the Chinese population, highlighting the critical need for targeted treatment interventions for at-risk individuals. Although the impact of aldehyde dehydrogenase 2 (ALDH2) gene mutations on susceptibility to intracranial aneurysms (IA) is well documented, the potential connection between ALDH2 rs671 single-nucleotide polymorphism (SNP) and RIA remains unexplored. Given the increased prevalence of ALDH2 gene mutations among Chinese Han individuals, it is clinically relevant to investigate the link between ALDH2 rs671 SNP and IA rupture. Methods: A prospective study was conducted on 546 patients diagnosed with IA to investigate the association between ALDH2 rs671 SNP and the risk of IA rupture. Results: The ALDH2 rs671 SNP (ALDH2*2) was significantly more prevalent in patients with unruptured IA (UIA) than in those with RIA (32.56% vs. 18.58%, P=0.004). Multivariate logistic regression analysis revealed that people with the ALDH2 mutation (ALDH2*1/*2 and ALDH2*2/*2 gene type) had a significantly reduced odds ratio (OR=0.49; 95% confidence level [CI] 0.27–0.88; P=0.018) for RIAs. Age-specific subgroup analysis indicated that the ALDH2 mutation provided a stronger protective effect in individuals aged 60 years and above with IA compared to those under 60 years old (OR=0.38 vs. OR=0.52, both P<0.05). Conclusion The incidence of RIA was significantly higher in individuals with a normal ALDH2 gene (ALDH2*1/*1) than in those with an ALDH2 rs671 SNP (ALDH2*1/*2 or ALDH2*2/*2). ALDH2 rs671 SNP may serve as a protective factor against RIA in the Chinese Han population.

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:Dysfunction of macrophage efferocytosis can induce local and systemic inflammatory damage and is associated with a variety of obesity-related metabolic diseases.Moreover,compounds targeting efferocytosis have shown good therapeutic effects. OBJECTIVE:By reviewing the effects of obesity on macrophage efferocytosis,to analyze the key mechanism by which obesity inhibits efferocytosis,to summarize the research progress in compounds targeting efferocytosis to treat obesity-related metabolic diseases,so as to provide new ideas for fully understanding efferocytosis and its relationship with metabolic diseases,aiming to provide new strategies for disease prevention and treatment. METHODS:The English search terms were"efferocytosis,metabolism,obesity,obese,atherosclerosis,non-alcoholic steatohepatitis,neurodegeneration,tumor,osteoarthritis,diabetes,compound,medicine,treatment,"which were used for literature retrieval in PubMed and Web of Science.The Chinese search term was"efferocytosis,"which was used for literature retrieval in CNKI,VIP and WanFang datebases.Ninety-nine papers were finally included in the review analysis after a rigorous screening process. RESULTS AND CONCLUSION:In the process of efferocytosis,the"Find me"and"Eat me"processes involving a large number of apoptotic cell derived factors are mainly regulated by apoptotic cells.The efferocytosis factor involved in cytoskeletal remodeling and digestion are mainly derived from macrophages,which are crucial for efferocytosis activity.These results suggest that the"Find me"and"Eat me"factors mainly reflect the condition of apoptosis,and it is more scientific to select the expression of factors involved in cytoskeletal remodeling and digestion when evaluating the efferocytosis activity of macrophages.Obesity inhibits efferocytosis,and shows an inhibitory effect on most digestive factors,but has a stress-induced activation effect on most"Find me,""Eat me"and cytoskeletal recombination factors,which further indicates the decisive effect of digestive stage on efferocytosis and suggests that it is not reliable for some studies to evaluate the efferocytosis based on the increased expression of"Find me"and"Eat me"factors.Targeting cytokines in the digestive phase may be more effective when discussing future intervention strategies targeting macrophages efferocytosis.The efferocytosis activators of macrophages are effective in the treatment of various metabolic diseases,but the efferocytosis inhibitors in tumor tissue show good anticancer effects,suggesting that the role of efferocytosis should be rationally evaluated according to the characteristics of tissue inflammation.Efferocytosis is a relatively new concept proposed in 2003,with a short research history and complex efferocytosis factors.Current studies on obesity and efferocytosis only involve a tip of the iceberg and most of them are at a superficial level and a large number of scientific experiments are needed to further validate the mechanisms.