OBJECTIVE To investigate the improvement effect and potential mechanism of Qingxue xiaozhi jiangtang formula on insulin resistance （IR） in type 2 diabetes mellitus （T2DM） rats. METHODS T2DM rat model was established by intraperitoneal injection of 30 mg/kg streptozotocin combined with high-fat and high-sugar diet. The rats were randomly divided into normal control group， model group， Qingxue xiaozhi jiangtang formula low-dose and high-dose groups （6.525， 13.05 g/kg， calculated by raw material） and metformin group （positive control， 0.18 g/kg）， with 8 rats in each group. Administration groups were given relevant medicine intragastrically； normal control group and model group were given constant volume of normal saline intragastrically， once a day， for consecutive 6 weeks. Body mass and fasting blood glucose （FBG） were determined， and oral glucose tolerance test was conducted. Serum fasting insulin （FINS） level was measured to calculate the insulin resistance index （HOMA-IR） and insulin sensitivity index （ISI）. Additionally， the level of serum lipids， liver function， oxidative stress indicators and inflammatory factors were assessed. The phosphorylation levels of kinase R-like endoplasmic reticulum kinase （PERK） and forkhead box O1 （FOXO1） protein in liver tissue of rats were determined. RESULTS Compared with model group， the body weight， ISI， the levels of high-density lipoprotein cholesterol and superoxide dismutase were increased significantly in Qingxue xiaozhi jiangtang formula high-dose group and metformin group （P＜0.05）； FBG， blood glucose level at 120 minutes of glucose loading， area under the curve of glucose， FINS， HOMA-IR， low-density lipoprotein cholesterol， total cholesterol， triglyceride， alanine transaminase， aspartate transaminase， alkaline phosphatase， malondialdehyde， interleukin-6， tumor necrosis factor-α， and C-reactive protein levels were significantly reduced （P＜ Δ0.05）； the pathological damage of liver tissue had significantlyimproved， and the phosphorylation levels of PERK and FOXO1 proteins in liver tissue were significantly decreased （P＜0.05）. CONCLUSIONS Qingxue xiaozhi jiangtang formula can regulate glucose and lipid metabolism， inflammation factor and oxidative stress levels， and alleviate insulin resistance in T2DM rats. Its mechanism of action may be related to the inhibition of the PERK/FOXO1 signaling pathway.

OBJECTIVE To optimize the simmering technology of Rheum palmatum from Menghe Medical School and compare the difference of chemical components before and after processing. METHODS Using appearance score， the contents of gallic acid， 5-hydroxymethylfurfural （5-HMF）， sennoside A+sennoside B， combined anthraquinone and free anthraquinone as indexes， analytic hierarchy process （AHP）-entropy weight method was used to calculate the comprehensive score of evaluation indicators； the orthogonal experiment was designed to optimize the processing technology of simmering R. palmatum with fire temperature， simmering time， paper layer number and paper wrapping time as factors； validation test was conducted. The changes in the contents of five anthraquinones （aloe-emodin， rhein， emodin， chrysophanol， physcion）， five anthraquinone glycosides （barbaloin， rheinoside， rhubarb glycoside， emodin glycoside， and emodin methyl ether glycoside）， two sennosides （sennoside A， sennoside B）， gallic acid and 5-HMF were compared between simmered R. palmatum prepared by optimized technology and R. palmatum. RESULTS The optimal processing conditions of R. palmatum was as follows: each 80 g R. palmatum was wrapped with a layer of wet paper for 0.5 h， simmered on high heat for 20 min and then simmered at 140 ℃， the total simmering time was 2.5 h. The average comprehensive score of 3 validation tests was 94.10 （RSD＜1.0%）. After simmering， the contents of five anthraquinones and two sennosides were decreased significantly， while those of 5 free anthraquinones and gallic acid were increased to different extents； a new component 5-HMF was formed. CONCLUSIONS This study successfully optimizes the simmering technology of R. palmatum. There is a significant difference in the chemical components before and after processing， which can explain that simmering technology slows down the relase of R. palmatum and beneficiate it.

Diabetic kidney disease (DKD) is a common microvascular complication of diabetes. "Internal heat leading to zheng" is the core pathogenesis of DKD, while "glucose toxicity" is transformed from subtle substances through "internal heat" and the cementation of various pathological products, which is pivotal to the transformation of diabetes to DKD. "Glucose toxicity" is characterized by deep and widespread heat, caused by various pathological factors, and its sticky nature makes it difficult to resolve, which can cause severe damage to the kidney collaterals. In the early stage of "glucose toxicity", it is yang pathogen, which can be transformed into yin pathogen in the later stage with disease progression. In clinical practice, treatment should be based on disease staging, with attention on grasping the pathogenesis of "internal heat leading to zheng" and identifying the nature of "glucose toxicity". During the diabetic period, clearing heat is the primary method, often using modified Yueju Pill and Dachaihu Decoction. In the early stage of DKD, treatment primarily focuses on clearing and penetrating latent heat to treat DKD, aiming to prevent toxic heat from transitioning from qi to blood. The approach emphasizes clearing heat and re-penetrating, detoxification, and re-clearing, often using a self-made modified Qingre Xiaozheng Decoction. In the middle and late stages of DKD, the focus shifts to clearing heat, eliminating zheng, strengthening vital qi, and dispelling turbidity, with commonly used treatments including the self-made modified Xiezhuo Xiaozheng Formula, Jingui Shenqi Pill, and Zhenwu Decoction.

ObjectiveTo explore the effects of astragalin （AST） on autophagy and apoptosis of astrocytes in the L_4-5 dorsal horn of the spinal cord in mice with inflammatory pain induced by complete Freund's adjuvant （CFA）. MethodsTwenty-four male C57BL/6 mice， aged six months， were randomly assigned to four groups： control group， saline group， CFA model group， and CFA+AST group， six mice in each group. The inflammatory pain model was established by injection of 10 µL CFA into the right lateral malleolus fossa. The saline group were injected with an equal amount of normal saline at the same site. The inflammatory pain mice in CFA+AST group were further treated with AST （60 mg/kg） intraperitoneally once a day for 21 consecutive days. Multiplex immunofluorescence staining was used to detect the coexpression of autophagy-related factors including ATG 12 and Beclin-1， apoptosis-related factors including Cleaved-Caspase3 and Caspase9， and the astrocyte marker such as GFAP in the L_4-5 spinal dorsal horn of the mice in each group. Western blot was used to examine the protein expression levels of autophagy-related proteins（ATG12， Beclin-1） and apoptosis-related proteins（Caspase 3， Caspase 9） in the L_4-5 spinal dorsal horn of mice. ResultsImmunofluorescent staining showed that in the L_4-5 dorsal horn of the spinal cord， the fluorescence intensity of ATG12 （P<0.000 1） and Beclin-1 （P<0.000 1） was significantly increased， while that of Cleaved-Caspase 3 （P<0.001） and Caspase 9 （P<0.000 1） was decreased in the CFA+AST group when compared to the CFA model group. Furthermore， AST could inhibit the activation of astrocytes. Western blot further confirmed that AST significantly upregulated the expression of ATG12 （P<0.000 1） and Beclin-1 （P<0.000 1） in the L_4-5 spinal cord of CFA mice， and downregulated the expression of Caspase 3 （P<0.01） and Caspase 9 （P<0.001）. ConclusionsAST promotes autophagy of astrocytes and inhibits their apoptosis in the L_4-5 spinal dorsal horn of CFA mice.

BACKGROUND:Autophagy has become a rapidly developing research hotspot in the biomedical fields.Many researchers are actively exploring the molecular regulatory mechanism of autophagy in a variety of diseases.However,the role of autophagy in hair growth is still unknown. OBJECTIVE:To review the current research progress and application value of autophagy in hair growth and regeneration,to understand the role of autophagy in hair growth,to explore the pathogenesis of autophagy in pathological hair loss,and to provide new ideas for the study of drugs for hair loss. METHODS:Using"hair follicle growth,hair growth,hair regeneration,autophagy associated proteins,autophagy activity,autophagy associated genes,autophagy"as Chinese search terms and"hair growth,hair follicle,hair regeneration,autophagy"as English search terms,PubMed and CNKI databases were searched.The research progress on autophagy,hair growth and the role of autophagy in hair growth in and outside China in recent years was reviewed and summarized.Articles incompatible with the subject content of the paper were excluded.Finally,78 articles were included for the result analysis. RESULTS AND CONCLUSION:(1)Autophagy is a normal metabolic process in eukaryotes with complex molecular mechanisms and functional properties,which is beneficial to cell survival and cell death.(2)Alopecia-related diseases are associated with changes in autophagy activity,which can regulate hair growth cycle.Knockout or overexpression of autophagy-related genes can change the state of hair growth.Multiple autophagy related signaling pathways have been found to be related to hair follicle growth.Activators or inhibitors of autophagy can be used to treat or prevent hair loss.

OBJECTIVE To systematically evaluate the efficacy and safety of the four most common cell therapies， namely purified CD34+ （PCCs）， bone marrow mononuclear cells （BMMNCs）， bone marrow mesenchymal stem cells （BMMSCs） and peripheral blood mononuclear cells （PBMNCs） in the treatment of critical limb ischemia （CLI）. METHODS PubMed， Scopus， Embase， Cochrane Central Register of Controlled Trials （CENTRAL） and Web of Science databases were searched from the establishment of each database to June 2023 to collect randomized controlled trials （RCTs） comparing the efficacy and safety of four different cell therapies， namely PCCs， BMMNCs， BMMSCs and PBMNCs， with other cell therapies or standard therapy （ST） in the treatment of CLI. The outcomes indexes included amputation rate， ankle-brachial index （ABI）， transcutaneous oxygen partial pressure （TCPO2）， ulcer healing rate， pain-free walking distance （PFWD） and angiogenesis. After data extraction from clinical studies that met the inclusion criteria， the RoB 2.0 tool was used to assess the risk of bias， and Stata 15.0 software was used for statistical analysis. RESULTS Meta-analysis included 22 studies， involving 1 318 patients. The treatment groups involved 4 types of cell therapies， namely PCCs，BMMNCs， BMMSCs， and PBMNCs. Network meta-analysis showed that the amputation rates of the four cell therapies groups were lower than that of ST group， and only the difference in PBMNCs group was statistically significant（P＜0.05）. Four cell interventions were better than ST in improving ABI （P＜0.05）， and BMMNCs had the most significant effect on improving ABI. PBMNCs and BMMNCs groups had statistically significant differences in improving TCPO2， compared with ST group and BMMSCs group （P＜0.05）. Four cell interventions were better than ST in improving ulcer healing rate， among which BMMNCs group had no statistical difference with ST group （P＞0.05）； ulcer healing rates of the other three groups were higher than that of ST group （P＜0.05）， and those of PBMNCs and BMMSCs groups were significantly higher than that of BMMNCs group （P＜ 0.05）. BMMSCs group had a significantly better effect on improving the PFWD of patients than the ST group after transplantation， with statistical significance （P＜0.05）， but there was no significant difference in PBMNCs and BMMNCs groups compared with ST group （P＞0.05）. The three cell therapies of BMMSCs， BMMNCs and PBMNCs had a significantly better effect on angiogenesis than the ST group， and the BMMSCs group had a significantly better effect than the BMMNCs and PBMNCs groups， with statistical significance （P＜0.05）. CONCLUSIONS The four cell therapies can improve the prognosis of CLI patients to varying degrees. PBMNCs show the lowest amputation rate after transplantation and have the most significant effect on improving TCPO2 and improving the ulcer healing rate. BMMNCs possess the most significant effect on improving ABI. BMMSCs represent obvious advantages in PFWD and angiogenesis.

Objective To investigate the role of lncSIL in transforming growth factor-β1(TGF-β1)-induced alveo-lar epithelial interstitial transformation(EMT)and its related signaling pathways.Methods Western blot was used to detect the effect of lncSIL silencing on the expression of E-cadherin(E-cad),alpha-smooth muscle actin(α-SMA)and Collagen I(Col I)in the process of EMT induced by TGF-β1.LncSIL interacting proteins were ana-lyzed by RNA pulldown.Western blot was used to detect the effect of overexpression or silencing of lncSIL on the expression of its target gene enhancer of zeste homolog 2(EZH2)and its downstream factors P21 and cyclin-de-pendent kinase 6(CDK6).Flow cytometry was used to analyze the effect of lncSIL on cell cycle progression.Re-sults After lncSIL silencing,the expression of α-SMA and Col I increased,the expression of E-cad decreased.RNA pulldown assay showed that EZH2 was the target protein that interacted with lncSIL,and the expression of EZH2 increased after silencing lncSIL,the expression of EZH2 downstream gene P21 decreased,CDK6 increased.Flow cytometry showed that the number of cells in S phase significantly increased.When lncSIL was overexpressed,the expression of EZH2 and CDK6 was down-regulated,the expression of P21 was up-regulated,and the number of S phase cells significantly decreased.Conclusion LncSIL inhibits TGF-β1-induced alveolar epithelial cell mesen-chymal transition by negatively regulating EZH2/P21/CDK6 signaling pathway to inhibit cell cycle progression.

Radiotherapy can cause functional and morphological changes in the brain tissues of patients with primary or metastatic malignant brain tumors, leading to radiation-induced brain injury. However, the pathogenesis of radiation-induced brain injury has not yet been unanimously determined, and its research advances and treatment protocols are yet to be elucidated and improved. In this study, we explore the pathogenesis of radiation-induced brain injury from the perspective of vascular injury, inflammatory reactions, neuronal dysfunction, glial cell injury, and gut microbiota and reviewed the advances in research on its treatment and prevention. The purpose is to provide a reference and theoretical basis for the research and clinical diagnosis and treatment of radiation-induced brain injury.

Objective: To investigate the impact of childhood traumatic experiences on individual risktaking decisions in early adulthood using functional nearinfrared spectroscopy (fNIRS), so as to provide the reference for clarifying the brain mechanisms underlying the impact of childhood trauma on individual risky decision. Methods: From December 2023 to March 2024, 28 children with childhood trauma experiences (trauma group) and 32 healthy college students (control group) were selected from Jining Medical University by a combination of stratified descent and convenient sampling methods. All subjects participated in the Iowa Game task fNIRS scanning. The brain activation, functional connectivity, graph theory properties (degree centrality, betweenness centrality, and local efficiency), and Receiver Operating Characteristic (ROC) analysis were performed by using preprocessing fNIRS data. Results: Compared with control group, trauma group showed significantly fewer choice times in the inferior deck (Z=-0.88), and showed significantly decreased activation levels in the right frontalpolar (Z=-2.59), as well as showed significant decreased functional connectivity between left dorsolateral prefrontal and in right dorsolateral prefrontal (Z=-3.78), and between left dorsolateral prefrontal cortex and the right frontal pole (Z=-3.68)(P<0.05). The central index of right inferior frontal gyrus in the trauma group was higher than that in the control group, while the central index of left and right dorsolateral frontal lobes was lower than that in the control group (Z=2.13, -2.53, -2.12, P<0.05). The centrality index of the right inferior frontal gyrus in the trauma group was higher than that in the control group (Z=2.47, P<0.05). The local efficiency indicators of the right inferior frontal gyrus, left and right frontal pole in the trauma group were higher than those in the control group (Z=2.51, 2.17, 2.53, P<0.05). The results of the ROC curve analysis showed that the local efficiency achieved the highest area under the curve (AUC=0.68). Conclusions Young adults with childhood trauma experience tend to choose lower loss, and the frontal pole shows a lack of activation in the whole process of risk decision performance. The abnormalities in the brain connectivity and network properties might be the neural basis of excessive defense mechanisms that childhood trauma leads to risky decisions.

OBJECTIVE To elucidate the mechanisms responsible for the inhibitory effects of limonene on the proliferation of non-small cell lung cancer(NSCLC) by non-targeted metabolomics and additional approaches. METHODS The CCK-8 assay was utilized to evaluate the inhibitory effects of limonene on NSCLC A549 cell viability and to ascertain the IC50. In vitro experiments, encompassing colony formation, flow cytometry, iron content assessment, and mitochondrial staining, were conducted to assess the anti-lung cancer and iron-induced cell death effects of limonene. Metabolomic analysis was employed to identify potential pathways influenced by limonene, and Western blotting was carried out to validate pivotal proteins within these pathways. RESULTS In comparison to the control group, the limonene-treated group demonstrated a significant, dose-dependent reduction in A549 cell proliferation and colony formation. Optical microscopy revealed cellular detachment and pronounced changes in cellular morphology following exposure to limonene. Limonene induced apoptosis in A549 cells and arrested them in the G0-G1 phase of the cell cycle. Confocal microscopy unveiled diminished mitochondrial fluorescence and an augmented intracellular iron content, indicative of the classical phenomenon of ferroptosis. Metabolomic investigations unveiled divergent metabolic pathways, including glutathione(GSH) metabolism, arginine biosynthesis, D-glutamine and D-glutamate metabolism, as well as cysteine and methionine metabolism, with many of them intricately linked to intracellular GSH synthesis. Western blotting experiments underscored a marked reduction in the levels of SLC40A1, SLC7A11(xCT), and GPX4 proteins within the cells post-limonene treatment. CONCLUSION Limonene may induce ferroptosis in lung cancer cells by reducing GSH synthesis and increasing Fe2+ levels.