This paper comprehensively discusses on the potential neurobiological mechanisms of acupuncture in the treatment of tobacco dependence， focusing on three important aspects， including acupuncture's regulation of tobacco dependence behavior， effects of acupuncture on withdrawal syndrome， and the role of acupuncture in preventing relapse. It is found that acupuncture can inhibit drug-seeking behavior by regulating the reward pathway and related neurons， such as dopamine， thus modulating tobacco dependence behavior. It also alleviates withdrawal symptoms by improving the oral environment of smokers and reducing negative emotions after quitting. Furthermore， acupuncture can prevent relapse by decreasing brain network activity related to smoking cravings and improving cognitive brain functions like addiction memory. Currently， research on the specific neurobiological mechanism of acupuncture in treating tobacco dependence and the involved neural circuits is limited. Future research directions are proposed， including the evaluation of clinical effects， exploration of specific therapeutic mechanisms， investigation of brain pathology， and strengthening the exploration of brain functions. Additionally， combining modern technologies to clarify the neural circuits involved in acupuncture intervention will provide a basis for acupuncture treatment of tobacco addiction.

Background At present, the treatment of silicosis is still limited, and no method is available to cure the disease. miRNAs are involved in the process of fibrosis at the transcriptional level by directly degrading target gene mRNA or inhibiting its translation. However, how miR-130a-3p regulates silicosis fibrosis has not been fully elucidated yet. Objective To investigate whether miR-130a-3p promotes epithelial-mesenchymal transition (EMT) by inhibiting peroxisome proliferators-activated receptors gamma (PPAR-γ), thereby pro-moting the process of silicotic fibrosis. To identify effective new targets for the treatment of silicotic fibrosis. Methods (1) Animal experiments: C57BL/6J mice were intratracheally injected with a one-time dose of 10 mg silica suspension (dissolved in 100 μL saline) as positive lung exposure. A silicosis model group was established 28 d after the exposure. A control group was injected with the same amount of normal saline into the trachea. Hematoxylin-eosin staining and Sirius red staining were used to observe the pathological changes and collagen deposition in lung tissues respectively. Realtime fluorescence-based quantitative polymerase chain reaction (RT-qPCR) was used to assay the expression of miR-130a-3p and PPAR-γ mRNA in lung tissues. Western blotting was used to detect the protein expression of PPAR-γ, transforming growth factor (TGF)-β1, E-cadherin, α-smooth muscle actin (α-SMA), and Collagen Ⅰ in lung tissues. (2) Cells experiments: Mouse lung epithelial cells (MLE-12) were induced with 5 µg·L⁻¹ TGF-β1 for different time (0, 12, 24, 48 h). RT-qPCR was used to detect the expression of miR-130a-3p and PPAR-γ mRNA in cells. The binding relationship between miR-130a-3p and PPAR-γ mRNA was verified by dual luciferase reporter gene assay. MLE-12 cells were stimulated by 5 µg·L⁻¹ TGF-β1 after transfection of miR-130a-3p inhibitor, and Western blotting was used to measure the protein expression of PPAR-γ, E-cadherin, and α-SMA in the TGF-β1-induced cells. Results In the silicosis model group, the alveolar septum was widened and the pulmonary nodules were formed. The Sirius red staining collagen deposition in pulmonary nodules indicated that a silicosis fibrosis model was successfully established. The expressions of TGF-β1, α-SMA, and Collagen Ⅰ proteins were increased, and the expressions of E-cadherin and PPAR-γ proteins were decreased in lung tissues of the silicosis group, compared with the control group (P<0.05 or P<0.01). The expression of miR-130a-3p was increased and the expression of PPAR-γ mRNA was decreased in lung tissues of the silicosis model (P<0.01). The expression of miR-130a-3p was significantly increased, while the expression of PPAR-γ mRNA was decreased in the TGF-β1 induced MLE-12 cells (P<0.05 or P<0.01). The dual luciferase reporter assay showed a direct relationship between miR-130a-3p and PPAR-γ mRNA in MLE-12 cells. The transfection of miR-130a-3p inhibitor in the TGF-β1 induced MLE-12 cells inhibited the decrease of PPAR-γ and E-cadherin proteins, and the increase of α-SMA protein in the MLE-12 cells induced by TGF-β1 (P<0.05 or P<0.01). Conclusion miR-130a-3p promotes the development of silicosis fibrosis by targeting PPAR-γ to increase pulmonary EMT.

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.

BACKGROUND:Magnetic resonance imaging is the gold standard for the diagnosis of osteonecrosis of femoral head,and previous methods of predicting osteonecrosis of femoral head collapse based on magnetic resonance images mostly require the combined assessment of coronal and sagittal images.However,osteonecrosis of femoral head tends to occur bilaterally,most hospitals perform bilateral hip magnetic resonance imaging scans during clinical examinations,but the bilateral hip scans can only view coronal and cross-sectional images,and it is difficult to obtain sagittal images,which affects the assessment of the risk of collapse.Therefore,it is of clinical value to establish a method to assess the risk of early osteonecrosis of femoral head collapse by applying the images that can be obtained after bilateral hip magnetic resonance scanning. OBJECTIVE:To establish a method of applying coronal and cross-sectional images of bilateral hip magnetic resonance imaging to assess the risk of osteonecrosis of femoral head collapse. METHODS:The medical records of 111 patients(181 hips)with early-stage osteonecrosis of femoral head diagnosed at the outpatient clinic of Honghui Hospital Affiliated to Xi'an Jiaotong University from October 2017 to October 2019 were retrospectively analyzed.They were categorized into collapsed and non-collapsed groups according to the femoral head collapse at the final follow-up,with 69 hips in the collapsed group and 112 hips in the non-collapsed group.The angle of necrotic range on the images of median coronal plane,transverse plane or one level above and below it was measured on the magnetic resonance imaging system.The sum of the two angles of necrotic angle on the coronal and transverse planes was used as the combined necrotic angle.The average of the three combined necrotic angles of each hip was taken to get the average combined necrotic angle of each hip.Finally,the correlation between the three combined necrotic angles and the average combined necrotic angle with the collapse of osteonecrosis of femoral head was analyzed,and the specificity and sensitivity of the four combined necrotic angles in predicting collapse were evaluated by using receiver operating characteristic curves. RESULTS AND CONCLUSION:(1)Totally 69 hips(38.1%)had femoral head collapse at the last follow-up and were included in the collapsed group;112 hips(61.9%)did not have progression of collapse and were included in the non-collapsed group.(2)The difference between the collapsed group and the non-collapsed group in terms of Association Research Circulation Osseous(ARCO)stage was significant(P<0.001).The difference in age,body mass index,follow-up time,gender distribution,side of onset,and causative factors was not significant(P>0.05).(3)The results of independent samples t-test suggested that all four combined necrotic angles were significantly correlated with collapse(P<0.000 1);and the differences in combined necrotic angles between the collapsed group and the non-collapsed group of ARCO stage I and the two groups of ARCO stage II were all significant(P<0.000 1).(4)In the analysis of the receiver operating characteristic,the area under the curve of the average combined necrotic angle was greater than that of the combined necrotic angle on the lower level of the median,the middle level,and the upper level of the median.(5)The average combined necrotic angle had a higher accuracy in the prediction of collapse than the lower level of the median,the middle level,and the upper level of the combined necrotic angle.(6)It is concluded that the accuracy of the average combined necrotic angle in predicting the risk of osteonecrosis of femoral head collapse is higher,and the clinical practicability is stronger,so we can consider using this method to predict the risk of osteonecrosis of femoral head collapse.

The shaoyang meridian is an important pivot between the internal organs and meridians system， with the functions of regulating qi and blood， balancing yin and yang， and coordinating the ascending and descending movement of qi. Dysfunction of the shaoyang pivot can lead to spleen and kidney deficiency， impaired liver and gallbladder qi regulation， and stagnation of qi and blood. It is believed that the onset and progression of Crohn's disease are closely related to shaoyang pivot dysfunction， with the core pathogenesis characterized by shaoyang disharmony， spleen deficiency， dampness retention， and blood stasis. Based on this understanding， the treatment principle centers on harmonizing the shaoyang pivot， supplemented by methods such as warming and nourishing the spleen and stomach， tonifying shaoyang， and soothing the liver and benefiting the gallbladder. Acupuncture is employed to target key acupoints along the shaoyang meridian to restore its regulatory functions， improve spleen and stomach transformation and transportation， facilitate liver and gallbladder qi flow， and promote the circulation of qi and blood. This provides a practical therapeutic approach for acupuncture-based treatment of Crohn's disease.

Objective: This study investigated the value of multiparametric MRI (mpMRI) in predicting Gleason score (GS) upgrading and downgrading in radical prostatectomy (RP) compared with presurgical biopsy. Materials and Methods: Clinical and mpMRI data were retrospectively collected from 219 patients with prostate disease between January 2015 and December 2021. All patients underwent systematic prostate biopsy followed by RP. MpMRI included conventional diffusion-weighted and dynamic contrast-enhanced imaging. Multivariable logistic regression analysis was performed to analyze the factors associated with GS upgrading and downgrading after RP. Receiver operating characteristic curve analysis was used to estimate the area under the curve (AUC) to indicate the performance of the multivariable logistic regression models in predicting GS upgrade and downgrade after RP. Results: The GS after RP was upgraded, downgraded, and unchanged in 92, 43, and 84 patients, respectively. The AUCs of the clinical (percentage of positive biopsy cores [PBCs], time from biopsy to RP) and mpMRI models (prostate cancer [PCa] location, Prostate Imaging Reporting and Data System [PI-RADS] v2.1 score) for predicting GS upgrading after RP were 0.714 and 0.749, respectively. The AUC of the combined diagnostic model (age, percentage of PBCs, tPSA, PCa location, and PIRADS v2.1 score) was 0.816, which was larger than that of the clinical factors alone (P < 0.001). The AUCs of the clinical (age, percentage of PBCs, ratio of free/total PSA [F/T]) and mpMRI models (PCa diameter, PCa location, and PI-RADS v2.1 score) for predicting GS downgrading after RP were 0.749 and 0.835, respectively. The AUC of the combined diagnostic model (age, percentage of PBCs, F/T, PCa diameter, PCa location, and PI-RADS v2.1 score) was 0.883, which was larger than that of the clinical factors alone (P < 0.001). Conclusion Combining clinical factors and mpMRI findings can predict GS upgrade and downgrade after RP more accurately than using clinical factors alone.

The role of acetylated apurinic/apyrimidinic endonuclease 1/redox factor 1 (APE1/Ref-1) in ovarian cancer remains poorly understood. Therefore, this study aimed to investigate the combined effect of recombinant human APE1/Ref-1 (rhAPE1/Ref-1) and aspirin (ASA) on two ovarian cancer cells, PEO-14, and CAOV3.The viability and apoptosis of ovarian cancer cells treated with rhAPE1/Ref-1 or ASA were assessed. Our results demonstrated that ASA induced rhAPE1/Ref-1 acetylation and widespread hyperacetylation in PEO-14 cells. Additionally, co-treatment with rhAPE1/Ref-1 and ASA substantially reduced cell viability and induced PEO-14 cell apoptosis, not CAOV3, in a dose-dependent manner. ASA increased the expression and membrane localization of the receptor for advanced glycation endproducts (RAGEs). Acetylated APE1/Ref-1 showed enhanced binding to RAGEs. In contrast, RAGE knockdown reduced cell death and poly(ADP-ribose) polymerase cleavage caused by rhAPE1/Ref-1 and ASA combination treatment, highlighting the importance of the APE1/Ref-1-RAGE interaction in triggering apoptosis. Moreover, combination treatment with rhAPE1/Ref-1 and ASA effectively induced apoptosis in 3D spheroid cultures of PEO-14 cells, a model that better mimics the tumor microenvironment. These results demonstrate that acetylated APE1/Ref-1 and its interaction with RAGE is a potential therapeutic target for ovarian cancer. Thus, the combination of ASA and APE1/Ref-1 may offer a promising new strategy for inducing cancer cell death.

Liver fibrosis is a chronic liver injury resulting from factors like viral hepatitis, autoimmune hepatitis, non-alcoholic steatohepatitis, fatty liver disease, and cholestatic liver disease. Liver transplantation is currently the gold standard for treating severe liver diseases. However, it is limited by a shortage of donor organs and the necessity for lifelong immunosuppressive therapy. Mesenchymal stem cells (MSCs) can differentiate into various liver cells and enhance liver function when transplanted into patients due to their differentiation and proliferation capabilities. Therefore, it can be used as an alternative therapy for treating liver diseases, especially for liver cirrhosis, liver failure, and liver transplant complications. However, due to the potential tumorigenic effects of MSCs, researchers are exploring a new approach to treating liver fibrosis using extracellular vesicles (exosomes) secreted by stem cells. Many studies show that exosomes released by stem cells can promote liver injury repair through various pathways, contributing to the treatment of liver fibrosis. In this review, we focus on the molecular mechanisms by which stem cell exosomes affect liver fibrosis through different pathways and their potential therapeutic targets. Additionally, we discuss the advantages of exosome therapy over stem cell therapy and the possible future directions of exosome research, including the prospects for clinical applications and the challenges to be overcome.

Objective: This study investigated the value of multiparametric MRI (mpMRI) in predicting Gleason score (GS) upgrading and downgrading in radical prostatectomy (RP) compared with presurgical biopsy. Materials and Methods: Clinical and mpMRI data were retrospectively collected from 219 patients with prostate disease between January 2015 and December 2021. All patients underwent systematic prostate biopsy followed by RP. MpMRI included conventional diffusion-weighted and dynamic contrast-enhanced imaging. Multivariable logistic regression analysis was performed to analyze the factors associated with GS upgrading and downgrading after RP. Receiver operating characteristic curve analysis was used to estimate the area under the curve (AUC) to indicate the performance of the multivariable logistic regression models in predicting GS upgrade and downgrade after RP. Results: The GS after RP was upgraded, downgraded, and unchanged in 92, 43, and 84 patients, respectively. The AUCs of the clinical (percentage of positive biopsy cores [PBCs], time from biopsy to RP) and mpMRI models (prostate cancer [PCa] location, Prostate Imaging Reporting and Data System [PI-RADS] v2.1 score) for predicting GS upgrading after RP were 0.714 and 0.749, respectively. The AUC of the combined diagnostic model (age, percentage of PBCs, tPSA, PCa location, and PIRADS v2.1 score) was 0.816, which was larger than that of the clinical factors alone (P < 0.001). The AUCs of the clinical (age, percentage of PBCs, ratio of free/total PSA [F/T]) and mpMRI models (PCa diameter, PCa location, and PI-RADS v2.1 score) for predicting GS downgrading after RP were 0.749 and 0.835, respectively. The AUC of the combined diagnostic model (age, percentage of PBCs, F/T, PCa diameter, PCa location, and PI-RADS v2.1 score) was 0.883, which was larger than that of the clinical factors alone (P < 0.001). Conclusion Combining clinical factors and mpMRI findings can predict GS upgrade and downgrade after RP more accurately than using clinical factors alone.