ObjectiveTo investigate the possible mechanism of Wenyang Shengji Ointment （温阳生肌膏， WSO） in the treatment of diabetic wounds with yin syndrome. MethodsA total of 24 SD rats were randomly divided into a group （n=6） and modeling group （n=18）. The modeling group rats were fed with high-fat diet for 14 days and then were injected intraperitoneally with streptozotocin to induce diabetic model. After steroid injection， full-thickness skin defects were created on the back of the rats to establish a diabetic wound with yin syndrome model. The normal group was fed with regular diet， and full-thickness skin defects were created surgically on the back of the rats. The 18 successfully modeled rats were further divided into three groups， the model group， the WSO group， and the Beifuxin （Recombinant Bovine Basic Fibroblast Growth Factor Gel， BX） group， 6 rats in each group. The WSO group was given the ointment to the wound， the Beifuxin group was givne BX gel， and the normal group and model group was disinfected and treated with saline. All groups had their dressings changed once daily for 14 days. Wound healing was recorded on days 0， 3， 7， and 14， and the wound healing rate was calculated on day 3， 7， and 14. On day 14 after treatment， HE staining was performed to observe the pathological morphology of the wound tissue. Western Blot was used to detect the relative protein levels of hypoxia-inducible factor 1 alpha （HIF-1α） and vascular endothelial growth factor （VEGF）. Immunofluorescence was used to measure the fluorescence intensity of HIF-1α in the wound tissue， and ELISA was used to detect the methylglyoxal （MGO） content in the wound tissue. ResultsCompared with the normal group， the model group showed poor wound healing on day 3， 7， and 14， with a low wound healing rate （P＜0.01）. HE staining showed scab coverage on the wound， with inflammatory cell infiltration and disorganized collagen arrangement. The relative protein levels of VEGF were significantly reduced， while the relative protein levels of HIF-1α and the MGO content significantly increased （P＜0.01）， and the fluorescence intensity of HIF-1α was enhanced. Compared to the model group， the WSO group and Beifuxin group showed better wound healing on day 3， 7， and 14， with an increased wound healing rate （P＜0.01）. The wound tissue showed clear and complete epithelial structure， reduced inflammatory cells， mature granulation tissue， and organized collagen arrangement. MGO content was significantly reduced （P＜0.01）. The relative protein levels of HIF-1α and VEGF both significantly increased in the WSO group， while only VEGF increased in the Beifuxin group （P＜0.05 or P＜0.01）. Compared with the Beifuxin group， the WSO group had a thicker epidermal layer， prominent collagen formation， significantly increased HIF-1α fluorescence expression， reduced MGO content in the wound tissue， and higher relative protein levels of HIF-1α （P＜0.05）. ConclusionWSO can reduce the accumulation of MGO in diabetic wound tissue with yin syndrome and activate the HIF-1α/VEGF pathway， which could be one of the mechanisms for promoting wound healing.

Hydrogen-rich water (HRW) shows excellent antibacterial, anti-inflammatory, antioxidant, and wound-healing properties and plays a positive role in the treatment of various diseases, such as brain injury, kidney injury, and periodontitis. Current studies found that HRW can inhibit periodontopathogenic biofilm formation, inhibit oral connective tissue and bone tissue destruction, and show anti-inflammatory and antioxidant properties in periodontitis. Additionally, HRW can alleviate periodontal tissue damage by inhibiting oxidative stress and up-regulating the expression of antioxidant enzymes, such as glutathione peroxidase and superoxide dismutase. HRW exerts anti-inflammatory effects by regulating the nuclear factor erythroid 2-related factor 2 and mitogen-activated protein kinase pathways, which are closely associated with inflammation. Additionally, HRW inhibits the expression of inflammatory cytokines, such as interleukins, inhibits the growth and proliferation of bacterial plaque biofilms, and down-regulates glycosyltransferases and glucan-binding proteins to prevent bacterial adhesion and subsequent development of periodontitis. Furthermore, HRW has a positive effect on the expression of various cell growth factors, α-smooth muscle actin, and type I collagen, which promotes wound healing. Current clinical studies have demonstrated the biological safety of HRW (to a certain extent) and reported no adverse reactions. However, most studies on HRW in oral diseases are preclinical in vivo and in vitro studies. Therefore, further clinical studies are required to validate the therapeutic significance and optimal therapeutic regimen of HRW in human periodontitis. This article aims to review the therapeutic role and the underlying mechanisms of HRW in periodontitis.

OBJECTIVE To establish fingerprint， chemical pattern recognition and multi-component quantification analysis of Sanzi powder， and evaluate its quality. METHODS HPLC method was adopted. The fingerprints of 15 batches of Sanzi powder were established by using the Similarity Evaluation System for Chromatographic Fingerprint of Traditional Chinese Medicine （2012 edition）. Cluster analysis， principal component analysis and orthogonal partial least squares-discriminant analysis were also conducted. The variable importance in projection （VIP） value greater than 1 was used as the index to screen the differential markers， and the contents of the differential markers were determined by the same HPLC method. RESULTS A total of 21 common peaks in the HPLC fingerprints of 15 batches of Sanzi powder were calibrated， and the similarities of them were 0.994- 0.999； 6 common peaks were identified， including gallic acid （peak 3）， garminoside （peak 10）， corilagin （peak 11）， chebulinic acid （peak 16）， ellagic acid （peak 18）， crocin Ⅰ （peak 19）. According to the results of cluster analysis， YKD2024LH005，No.YKD2023LH062） principal component analysis and orthogonal partial least squares-discriminant analysis， 15 batches of samples could be clustered into two categories： S1， S5， S7， S9， S14 were clustered into one category； S2-S4， S6， S8， S10-S13， S15 were clustered into one category. VIP values of 11 differential components such as corilagin， chebulinic acid and ellagic acid were higher than 1. Among 15 batches of samples， the contents of corilagin， chebulinic acid and ellagic acid ranged 2.667-5.152， 9.506- 13.522， 0.891-1.811 mg/g. CONCLUSIONS Established HPLC fingerprint and multi-component quantification analysis of Sanzi powder are rapid and simple， and can be used for quality evaluation of Sanzi powder by combining with chemical pattern recognition. Eleven components such as corilagin， chebulinic acid and ellagic acid are differential markers affecting the quality of Sanzi powder.

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 investigate the awareness of radon exposure hazards among non-uranium miners in Chongqing, China. Methods A survey was conducted among 177 male miners from eight non-uranium metal mines in Chongqing to collect data on basic information, personal habits, and the rate of radon awareness. Factors affecting radon awareness were analyzed using chi-square test and logistic regression model. Results The awareness rate of radon among miners was 23.73%. The chi-square test indicated significant difference in the radon awareness rate among miners with different levels of education (χ² = 10.28, P < 0.05), while there was no significant difference across different ages, years of work, labor relations, job categories, and types of miners (P > 0.05). Binary logistic regression analysis showed that a college (junior college) or higher level of education, a high school level of education, and working in mines were factors affecting the radon awareness among miners (χ² = 4.030, 9.150, 11.776, P < 0.05). Conclusion Miners lack awareness of radon, and there is an urgent need to strengthen education and propaganda regarding the hazards of radon.

AIM: To explore the factors influencing heart rate(HR)changes during small incision lenticule extraction(SMILE)surgery by monitoring HR trends at different time points of the procedure.METHODS: Prospective cohort study. A total of 69 patients who underwent SMILE surgery at the Laser Vision Correction Center of Xi'an No.1 Hospital from April to May 2024 were enrolled. Before the surgery, patients completed the State Anxiety Inventory(S-AI, questions 1-20)to assess their preoperative anxiety scores related to the next day's surgery. Baseline HR was recorded using medical pulse oximeter, and real-time HR was recorded during patient positioning, lenticule scanning, lenticule separation and extraction, and the application of postoperative eye drops.RESULTS: The HR during patient positioning was 83.61±13.87 bpm, which was significantly different from the baseline HR(77.52±10.88 bpm), HR during lenticule separation and extraction(75.54±12.52 bpm), and HR during postoperative eye drop application(76.65±10.54 bpm; all P<0.001). When stratified by median age, older patients(>26 years)had the HR during lenticule separation and extraction 76.27±9.93 bpm, which differed from the HR at positioning(84.82±14.10 bpm)and at lens scanning(82.76±13.72 bpm; all P<0.005). Stratified by gender, the HR of male patients at positioning was the highest(85.31±16.61 bpm), which differed significantly from the baseline HR(78.26±12.63 bpm), HR during lenticule separation and extraction(77.14±14.59 bpm), and HR during postoperative eye drop application(77.11±12.49 bpm; all P<0.005). There was no correlation between HR during positioning and preoperative anxiety scores(r=0.124, P=0.418).CONCLUSION: HR changes during SMILE surgery vary with different procedural stages, peaking during patient positioning and reaching the lowest point during lenticule separation and extraction. Older patients showed higher HR during positioning, and male patients exhibited higher HR during positioning.

In recent years, gastrointestinal stromal tumors (GIST) have increased incidence and mortality, and most GIST is caused by the activation mutation of the c-KIT gene. Therefore, c-KIT has become a promising therapeutic target of GIST. At present, the drugs approved for the treatment of GIST including imatinib, sunitinib, regorafenib and ripretinib, are mostly prone to developing resistance and accompanied by various degrees of adverse reactions. Therefore, there is an urgent need to develop new c-KIT inhibitors to solve the problem of resistance. In this study, we investigated the anti-tumor effect of a novel c-KIT inhibitor PN17-1 on gastrointestinal stromal tumor GIST-882 cells in vitro. We found that PN17-1 significantly inhibited the proliferation, colony formation and migration ability of GIST-882 cells, and significantly downregulated the protein expression levels of p-c-KIT and its downstream signals p-AKT, p-STAT5 and p-ERK in GIST-882 cells. In addition, PN17-1 induced apoptosis in GIST-882 cells, and the apoptosis may be mainly related to the mitochondrial-dependent endogenous pathway. In conclusion, the novel c-KIT inhibitor PN17-1 is a promising anti-GIST drug, and this study provides new ideas for further development of c-KIT inhibitors in the future.

Eight compounds were isolated and purified from the ethyl acetate part of 70% acetone extract of Rehmannia glutinosa by various chromatographic techniques such as silica gel, MCI gel CHP-20, ODS, Toyopearl HW-40C, combined with TLC and semi-preparative HPLC. Their structures were elucidated by modern spectroscopy techniques (NMR, MS, UV, IR), and identified as neomartynoside A (1), osmanthuside B₆ (2), martynoside (3), isomartynoside (4), (E)-p-hydroxycinnamic acid (5), caffeic acid (6), ferulic acid (7), and methyl caffeate (8). Compound 1 is a new phenylethanol glycoside, which was identified as neomartynoside A. Compound 2 was isolated from Rehmannia glutinosa for the first time. In addition, compounds 2, 6 and 7 significantly increased relative glucose consumption, showing potential hypoglycemic activity.

ObjectiveTo observe the effects of Hei Xiaoyaosan on the learning and memory abilities of Alzheimer's disease model mice （APP/PS1 mice）， and to explore its mechanism through the inflammatory cascade mediated by nucleotide-binding oligomerization domain-like receptor family pyrin domain-containing 3 （NLRP3）/cysteine aspartate-specific protease （Caspase-1）/gasdermin D （GSDMD） signaling pathway. MethodsSPF-grade 4-month-old APP/PS1 mice were randomly divided into the model group， MCC950 group， and Hei Xiaoyaosan high-， medium-， and low-dose groups. C57BL/6J mice were used as the blank group. After 7 days of adaptive feeding， mice in each group were intervened. The Hei Xiaoyaosan high-， medium-， and low-dose groups were given corresponding doses by gavage （25.79， 12.90， 6.45 g·kg^-1·d^-1）， the MCC950 group was intraperitoneally injected with 10 mg·kg^-1·2 d^-1， and the blank group received the same volume of physiological saline by gavage. After 90 days of intervention， the learning and memory abilities were assessed using the Y maze and Morris water maze tests. The structural changes of hippocampal neurons were observed by hematoxylin-eosin （HE） staining. The expression of amyloid precursor protein （APP） in the hippocampal CA3 region was detected by immunohistochemistry. Enzyme-linked immunosorbent assay （ELISA） was used to measure the levels of interleukin （IL）-10， IL-18， and IL-1β in the hippocampus. Western blot was applied to detect the protein expression of NLRP3， Caspase-1， GSDMD， and GSDMD-N in the hippocampus. Immunofluorescence was used to detect the co-localization of GSDMD-N and ionized calcium-binding adapter molecule-1 （Iba-1） in the hippocampus. Results① In the Y maze test， compared with the blank group， the spontaneous alternation rate of the model group was significantly reduced （P<0.01）. Compared with the model group， the spontaneous alternation rate in the Hei Xiaoyaosan high- and low-dose groups was significantly increased （P<0.01）. ② In the Morris water maze test， during the 1-4 days of the location navigation test， the escape latency time of mice decreased with the extension of training time. On day 4， compared with the blank group， the model group showed a significantly increased escape latency （P<0.05）. Compared with the model group， the MCC950 group and the Hei Xiaoyaosan low-dose group showed significantly reduced escape latency （P<0.05）. In the spatial exploration experiment， compared with the blank group， the number of platform crossings in the model group was significantly reduced （P<0.01）. Compared with the model group， the Hei Xiaoyaosan low-dose group showed significantly increased platform crossings （P<0.05）. ③ HE staining showed that， compared with the blank group， the hippocampal CA3 cells of the model group were damaged， arranged loosely and irregularly， swollen， with unclear boundaries， and the nuclei were pyknotic and deeply stained. MCC950 and all doses of Hei Xiaoyaosan improved the hippocampal CA3 cell damage in APP/PS1 mice to varying degrees. ④ Immunohistochemical results indicated that， compared with the blank group， the expression of APP in the hippocampal CA3 region was significantly increased in the model group （P<0.01）. MCC950 and all doses of Hei Xiaoyaosan could reduce the expression of APP in the hippocampal CA3 region of APP/PS1 mice （P<0.01）. ⑤ ELISA results showed that the levels of IL-18 and IL-1β in the hippocampus of mice in the model group were significantly increased， and IL-10 levels were significantly reduced （P<0.01）. Compared with the model group， the IL-18 levels in the MCC950 group and the Hei Xiaoyaosan medium- and low-dose groups were significantly reduced （P<0.01）. IL-1β levels in the hippocampus of the MCC950 group and Hei Xiaoyaosan high-， medium-， and low-dose groups were significantly decreased （P<0.01）. The IL-10 levels in the hippocampus of the MCC950 group and the Hei Xiaoyaosan medium- and low-dose groups were increased （P<0.05， P<0.01）. ⑥ Western blot results showed that compared with the blank group， the protein levels of NLRP3， Caspase-1， GSDMD， and GSDMD-N in the hippocampus of the model group were significantly elevated （P<0.01）. Compared with the model group， the content of NLRP3 and Caspase-1 in the hippocampus of the treated groups was decreased （P<0.05， P<0.01）. The content of GSDMD in the hippocampus of the Hei Xiaoyaosan high-， medium-， and low-dose groups was reduced （P<0.05， P<0.01）， and the content of GSDMD-N in the hippocampus of the Hei Xiaoyaosan medium- and low-dose groups was decreased （P<0.05， P<0.01）. ⑦ Immunofluorescence results showed that， compared with the blank group， the co-expression of GSDMD-N and Iba-1 in the hippocampus of the model group was significantly increased （P<0.01）. Compared with the model group， the co-expression of GSDMD-N and Iba-1 in the treated groups was significantly reduced （P<0.01）. ConclusionHei Xiaoyaosan may regulate the NLRP3/Caspase-1/GSDMD signaling pathway to affect the release of inflammatory factors， alleviate neuroinflammation，improve hippocampal histopathological changes，and improve learning and memory deficits，thus providing potential therapeutic benefits for Alzheimer's disease.