Background The positive rate of work-related musculoskeletal disorders (WMSDs) among coal mine workers remains high, which seriously affects the quality of life of the workers. Objective To estimate the prevalence of WMSDs among coal miners in Shanxi Province and analyze their influencing factors. Methods From May to December 2023, 2315 coal miners from a coal mine enterprise inShanxi Province were selected by convenience sampling, and the self-administered Basic Situation Survey Scale, Musculoskeletal Disorders Questionnaire, Effort-Reward Imbalance Questionnaire, and Pittsburgh Sleep Quality Scale were used to evaluate general demographic characteristics, work organization characteristics, living habits, sleep quality, occupational stress, and occurrence of WMSDs symptoms and the corresponding absences (sickness absence) in past 1 year. The positive rate and absenteeism rate of WMSDs were caculated, and Pearson's chi-square test was used for identify influencing factors of WMSDs, and finally a binary logistic regression method was used to further studying the factors. Results A total of 2577 questionnaires were distributed in this survey, and 2315 valid questionnaires were recovered, with an effective recovery rate of 89.9%. The positive rate of WMSDs symptoms was 48.7% (1127/2315), the absenteeism rate due to WMSDs was 22.6% (523/2315), and the waist (17.5%), neck (11.7%), and knee (9.0%) were the most common areas presenting WMSDs symptoms. The results of logistic regression showed that compared with ≤10 years of service, the risk of WMSDs was higher for those with > 20 years of service (OR=2.167, 95%CI: 1.419, 3.311). Compared with the daily working time of ≤8 h, the risk of WMSDs was higher for those >8 h daily working time (OR=1.463, 95%CI: 1.211, 1.767). A higher risk of WMSDs was reported in workers with moderate labor intensity (OR=1.247, 95%CI: 1.009, 1.542) or heavy labor intensity (OR=1.570, 95%CI: 1.215, 2.027) than those with light labor intensity. The higher the education level (OR _{high school and technical secondary school}=1.866, 95%CI: 1.435, 2.425; OR _{junior college/bachelor degree or above}=1.953, 95%CI: 1.445, 2.639), the higher the risk of WMSDs. The risk of WMSDs was higher in workers reporting smoking (OR=1.225, 95%CI: 1.021, 1.470) or alcohol consumption (OR=1.345, 95%CI: 1.122, 1.612). The risk of WMSDs in coal miners with high occupational stress (OR=1.229, 95%CI:1.030, 1.466) or those with sleep disorders (OR=3.616, 95%CI:2.824, 4.629) was higher than that in workers with low occupational stress or no sleep disorders respectively. Conclusion The positive rate of WMSDs among coal mine personnel in Shanxi Province is high, and education level, length of service, daily working hours, smoking, alcohol consumption, labor intensity, sleep disorders, and occupational stress are influencing factors for WMSDs.

ObjectiveTo study the effects of applying different microbial fertilizers on the growth and rhizosphere soil environment of Codonopsis pilosula and provide a theoretical basis for ecological cultivation of this medicinal plant. MethodsSeven groups were designed， including CK （no application of microbial fertilizer）， T1 （Trichoderma longibrachiatum fertilizer）， T2 （Bacillus subtilis fertilizer）， T3 （Trichoderma viride fertilizer）， T4 （compound microbial fertilizer）， T5 （C. pilosula stems and leaves fermented with compound microbial fertilizer）， and T6 （Scutellaria baicalensis stems and leaves fermented with T. viride fertilizer）. The physiological indicators， yield， and quality of C. pilosula and the physicochemical properties， enzyme activities， and microbial diversity in the rhizosphere soil of different fertilizer treatments were measured. ResultsGroup T1 showed slight decreases in soluble protein content （SPC） and superoxide dismutase （SOD）. Groups T2-T6 showed increases in physiological indicators such as proline （Pro）， soluble solids content （SSC）， SPC， catalase （CAT）， and peroxidase （POD） and a decrease in malondialdehyde （MDA） in C. pilosula leaves. All the fertilizer treatments increased the yield of C. pilosula and the total polysaccharide content in the roots. T1， T2， T3， T4， and T5 increased the total flavonoid content in the roots. Meanwhile， T4 increased the total saponin content in the roots. All the fertilizer treatments reduced the pH and increased the electric conductivity （EC）， soil organic matter （SOM）， and alkaline nitrogen （AN） in the soil. T2 and T5 increased the available phosphorus （AP）， and T3， T4， T5， and T6 increased the available potassium （AK） in the soil. All the fertilizer treatments increased the activities of urease， sucrase， and CAT in the soil. Except that T1 decreased the bacterial diversity in the soil， other fertilizer treatments significantly increased bacterial and fungal diversity in the soil. Different fertilizer treatments significantly affected the composition of bacterial and fungal communities in the soil. At the phylum level， the dominant bacterial phyla included Proteobacteria， Acidobacteriota， and Bacteroideta， and the dominant fungal phyla were Ascomycota， Mortierellomycota， and unclassified_fungi in the rhizosphere soil of C. pilosula after bacterial fertilizer treatment. At the genus level， unclassified Gemmatimonadaceae， Sphingomonas， and unclassified Vicinamibacteraceae were the dominant bacterial genera， while unidentified， unclassified Fungi， and unclassified Sordariomycetes were the dominant fungal genera in the rhizosphere soil. The results of redundancy analysis indicated that the main physicochemical factors affecting changes of microbial communities in the rhizosphere soil of C. pilosula were pH， EC， AK， AN， AP， and soil organic matter （SOM） in the soil. The correlation heatmap showed that Bryobacter had significantly positive correlations with EC， AK， and AN. There was a significantly negative correlation between Fusarium and SOM. In summary， applying an appropriate amount of microbial fertilizer can promote the growth and improve the rhizosphere soil environment of C. pilosula. ConclusionThe compound microbial fertilizer and the C. pilosula stems and leaves fermented with compound microbial fertilizer can improve the soil nutrients， growth， development， yield， and quality of C. pilosula， and thus they can be applied to the artificial cultivation of C. pilosula.

ObjectiveTo study the effects of applying different microbial fertilizers on the growth and rhizosphere soil environment of Codonopsis pilosula and provide a theoretical basis for ecological cultivation of this medicinal plant. MethodsSeven groups were designed， including CK （no application of microbial fertilizer）， T1 （Trichoderma longibrachiatum fertilizer）， T2 （Bacillus subtilis fertilizer）， T3 （Trichoderma viride fertilizer）， T4 （compound microbial fertilizer）， T5 （C. pilosula stems and leaves fermented with compound microbial fertilizer）， and T6 （Scutellaria baicalensis stems and leaves fermented with T. viride fertilizer）. The physiological indicators， yield， and quality of C. pilosula and the physicochemical properties， enzyme activities， and microbial diversity in the rhizosphere soil of different fertilizer treatments were measured. ResultsGroup T1 showed slight decreases in soluble protein content （SPC） and superoxide dismutase （SOD）. Groups T2-T6 showed increases in physiological indicators such as proline （Pro）， soluble solids content （SSC）， SPC， catalase （CAT）， and peroxidase （POD） and a decrease in malondialdehyde （MDA） in C. pilosula leaves. All the fertilizer treatments increased the yield of C. pilosula and the total polysaccharide content in the roots. T1， T2， T3， T4， and T5 increased the total flavonoid content in the roots. Meanwhile， T4 increased the total saponin content in the roots. All the fertilizer treatments reduced the pH and increased the electric conductivity （EC）， soil organic matter （SOM）， and alkaline nitrogen （AN） in the soil. T2 and T5 increased the available phosphorus （AP）， and T3， T4， T5， and T6 increased the available potassium （AK） in the soil. All the fertilizer treatments increased the activities of urease， sucrase， and CAT in the soil. Except that T1 decreased the bacterial diversity in the soil， other fertilizer treatments significantly increased bacterial and fungal diversity in the soil. Different fertilizer treatments significantly affected the composition of bacterial and fungal communities in the soil. At the phylum level， the dominant bacterial phyla included Proteobacteria， Acidobacteriota， and Bacteroideta， and the dominant fungal phyla were Ascomycota， Mortierellomycota， and unclassified_fungi in the rhizosphere soil of C. pilosula after bacterial fertilizer treatment. At the genus level， unclassified Gemmatimonadaceae， Sphingomonas， and unclassified Vicinamibacteraceae were the dominant bacterial genera， while unidentified， unclassified Fungi， and unclassified Sordariomycetes were the dominant fungal genera in the rhizosphere soil. The results of redundancy analysis indicated that the main physicochemical factors affecting changes of microbial communities in the rhizosphere soil of C. pilosula were pH， EC， AK， AN， AP， and soil organic matter （SOM） in the soil. The correlation heatmap showed that Bryobacter had significantly positive correlations with EC， AK， and AN. There was a significantly negative correlation between Fusarium and SOM. In summary， applying an appropriate amount of microbial fertilizer can promote the growth and improve the rhizosphere soil environment of C. pilosula. ConclusionThe compound microbial fertilizer and the C. pilosula stems and leaves fermented with compound microbial fertilizer can improve the soil nutrients， growth， development， yield， and quality of C. pilosula， and thus they can be applied to the artificial cultivation of C. pilosula.

Prescription optimization is a crucial aspect in the study of traditional Chinese medicine （TCM） compounds. In recent years， the introduction of mathematical methods， data mining techniques， and artificial neural networks has provided new tools for elucidating the compatibility rules of TCM compounds. The study of TCM compounds involves numerous variables， including the proportions of different herbs， the specific extraction parts of each ingredient， and the interactions among multiple components. These factors together create a complex nonlinear dose-effect relationship. In this context， it is essential to identify methods that suit the characteristics of TCM compounds and can leverage their advantages for effective application in new drug development. This paper provided a comprehensive review of the cutting-edge optimization experimental design methods applied in recent studies of TCM compound compatibilities. The key technical issues， such as the optimization of source material selection， dosage optimization of compatible herbs， and multi-objective optimization indicators， were discussed. Furthermore， the evaluation methods for component effects were summarized during the optimization process， so as to provide scientific and practical foundations for innovative research in TCM and the development of new drugs based on TCM compounds.

ObjectiveTo explore the mechanism by which Zuoguiwan improves the pancreas development in the gestational diabetes mellitus （GDM） model by observing the effects of Zuoguiwan on the expression of key regulatory factors in different stages of pancreas development. MethodsPregnant Wistar rats were randomly assigned into blank， model， insulin detemir （20 U·kg^-1） and Zuoguiwan （1.89 g·kg^-1） groups （n=18）. GDM was induced by peritoneal injection of streptozotocin on day 6.5 （E6.5d） in the embryonic stage， and the blank group was given an equal volume of sodium citrate buffer. The modeling performance was assessed by measuring the blood glucose of pregnant rats. Except the blank group and model group， pregnant rats in other groups were administrated with corresponding drugs from E9.5d to delivery. The random blood glucose of pregnant rats was monitored， and the embryos and offspring rats were measured for the length and weighed on E12.5d， E18.5d and day 21 after birth （B21d）. The Lee's index of rats on B21d was calculated. Enzyme-linked immunosorbent assay （ELISA） was employed to measure the fasting insulin （FINS） levels of B22d rats and the Homeostasis Model Assessment for Insulin Resistance （HOMA-IR） was calculated. The serum levels of aspartate aminotransferase （AST）， alanine aminotransferase （ALT）， total bilirubin （TBIL）， total cholesterol （CHO）， triglyceride （TG）， high-density lipoprotein cholesterol （HDL）， and low-density lipoprotein cholesterol （LDL） in E18.5d pregnant rats and B22d offspring were determined. The pathological changes in the pancreas of E12.5d， E18.5d and B22d rats were observed by hematoxylin-eosin （HE） staining. Western blot was used to determine the protein levels of pancreatic duodenal homeobox 1 （Pdx1）， pancreas-specific transcription factor 1a （Ptf1a）， and sex-determining region Y-box protein 9 （Sox9） in the pancreas of E12.5d embryos， Pdx1， Nkx2 homeobox 2 （Nkx2.2）， and hairy and enhancer of split-1 （Hes1） in the pancreas of E18.5d embryos， and Pdx1， v-maf musculoaponeurotic fibrosarcoma oncogene homolog A （Mafa）， and NK transcription factor-related homeobox gene family 6 locus 1 （Nkx6.1） in the pancreas of B22d rats. ResultsCompared with the blank group， the model group showed elevated blood glucose levels in pregnant rats on B0d， E9.5d， E12.5d， E15.5d， and E18.5d （P<0.05， P<0.01）， decreased body weight and body length （P<0.01） and increased Lee's index in the offspring. In addition， the B22d offspring showed rising levels of FBG， FINS， HOMA-IR， AST， and TG （P<0.01）， a declined level of HDL （P<0.01）， and pancreatic acinous cells with edema and loose arrangement. The pregnant rats on E18.5d exhibited raised levels of ALT， AST， and TG （P<0.05， P<0.01） in the pancreas and a declined level of HDL （P<0.05）. The E12.5d embryos showed up-regulated protein levels of Pdx1， Sox9， and Ptf1a in the pancreas （P<0.01） and the E18.5d embryos exhibited down-regulated protein levels of Pdx1， Nkx2.2， and Hes1 in the pancreas （P<0.01）. The protein levels of Pdx1， Nkx6.1， and Mafa in the pancreas of B22d offspring were down-regulated （P<0.01）. Compared with the model group， the insulin group exhibited lowered blood glucose in pregnant rats on B0d， E15.5d， and E18.5d （P<0.05， P<0.01）. The offspring in all treatment groups showcased increased body weight and body length （P<0.01） and decreased Lee's index. The B22d offspring exhibited declined levels of FBG， FINS， and HOMA-IR in the insulin group （P<0.01） and lowered levels of FBG and HOMA-IR in the Zuoguiwan group （P<0.01）. The B22d offspring in all the treatment groups showed reduced levels of ALT， AST， TBIL， CHO， TG， and LDL， a raised level of HDL， and alleviated edema of pancreatic acinous cells. The pregnant rats on E18.5d demonstrated declined levels of TG and ALT （P<0.05， P<0.01） and an elevated level of HDL （P<0.05）. The pancreas of E12.5d embryos presented down-regulated protein levels of Pdx1 and Sox9 and an up-regulated protein level of Ptf1a in the insulin group （P<0.05）. The pancreas of E12.5d embryos in the Zuoguiwan group presented down-regulated protein levels of Pdx1， Sox9， and Ptf1a （P<0.01）. All the treatment groups showed up-regulated protein levels of Pdx1， Nkx2.2， and Hes1 in the pancreas of E18.5d embryos （P<0.01） and Pdx1， Nkx6.1， and Mafa in the pancreas of B22d embryos （P<0.05， P<0.01）. ConclusionZuoguiwan can promote the growth and development and ameliorate the pathological changes in the pancreas of the offspring of GDM model by regulating the expression of Pdx1 pathway-related regulatory factors in different stages of pancreas development.

Myocardial ischemia-reperfusion injury （MIRI） is a major complication following coronary revascularization. Studies indicate that its pathophysiological mechanisms of MIRI are closely associated with oxidative stress， iron overload， inflammatory responses， and lipid peroxidation. Oxidative stress refers to an imbalance in redox homeostasis under pathological conditions， characterized by the abnormal accumulation of reactive oxygen species （ROS）， which disrupts the dynamic balance between pro-oxidant systems and antioxidant defense networks. In recent years， traditional Chinese medicine （TCM） has demonstrated unique advantages in the prevention and treatment of MIRI due to its multi-target and multi-pathway antioxidant properties. Research reveals that TCM primarily exerts protective effects against oxidative stress-induced MIRI by regulating signaling pathways such as nuclear factor erythroid 2-related factor 2 （Nrf2）， adenosine monophosphate-activated protein kinase （AMPK）， phosphatidylinositol 3-kinase/protein kinase B （PI3K/Akt）， nuclear factor kappa-B （NF-κB）， Janus kinase 2/signal transducer and activator of transcription 3 （JAK2/STAT3）， and protein kinase C beta Ⅱ/nicotinamide adenine dinucleotide phosphate oxidase 2/reactive oxygen species （PKCβⅡ/NOX2/ROS）. This article reviews recent literature on TCM monomers， compound formulas， and their active components， which alleviate oxidative stress to prevent and treat MIRI by modulating the aforementioned signaling pathways. It summarizes a concise overview of the molecular mechanisms by which oxidative stress-related signaling pathways lead to MIRI， discusses how TCM regulates these pathways to reduce oxidative stress-induced MIRI， and explores clinical application prospects and research challenges， aiming to provide a theoretical reference for the research and clinical management of MIRI.

OBJECTIVE To study the effects of peripheral blood-derived exosomes （Exo） intervened by Naozhenning （NZN） on injury of neuron cells HT22 induced by microglia BV-2 cells. METHODS Wistar rats were selected to prepare peripheral blood- derived Exo intervened by NZN （66.83 g/kg）， referred to as NZN-Exo； peripheral blood-derived Exo intervened by normal saline and piracetam （PLXT， 1.62 g/kg） were prepared using the same method， denoted as KB-Exo and PLXT-Exo respectively， and all Exo were subsequently identified. Meanwhile， BV-2 cells were stimulated with 1 μg/mL lipopolysaccharide （LPS） to prepare LPS- stimulated supernatant， and non-LPS-stimulated supernatant was prepared following the same protocol. HT22 cells were divided into four groups: KB-Exo group （treated with non-LPS-stimulated supernatant+KB-Exo）， model group （treated with LPS-stimulated supernatant+KB-Exo）， PLXT-Exo group （treated with LPS-stimulated supernatant+PLXT-Exo）， and NZN-Exo group （treated with LPS-stimulated supernatant+NZN-Exo）， with the concentration of the corresponding Exo in all groups being 50 μg/mL. After 24 hours of culture， the proliferation of HT22 cells was detected by the CCK-8 assay and EdU assay； the apoptosis of HT22 cells was detected； the microstructure of HT22 cells was observed； the contents of interleukin-1β （IL-1β）， IL-10， nuclear factor-κB （NF- κB）， and tumor necrosis factor-α （TNF-α） in HT22 cells were measured， as well as the expression levels of TNF-α， NOD-like receptor thermal protein domain associated protein 3 （NLRP3）， Caspase-1， B-cell lymphoma-2（ Bcl-2）， and Bcl-2-associated X protein （Bax）. RESULTS KB-Exo， PLXT-Exo and NZN-Exo were successfully prepared， and all Exo exhibited typical cup-shaped contours and membrane-enclosed characteristics. Compared with KB-Exo group， model group showed significantly decreased cell proliferation rates （detected by CCK-8 and EdU）， intracellular IL-10 levels， and Bcl-2 protein expression levels （P＜0.05）； while the cell apoptosis rate， intracellular levels of IL-1β， TNF-α， and NF-κB， as well as the expression levels of NLRP3， TNF-α， Caspase-1， and Bax proteins were significantly increased （P＜0.05）. Additionally， in the model group， the cells showed volume swelling， incomplete cell membrane， nucleolar rupture， significant swelling and deformation of mitochondria， and severe vacuolization. Compared with model group， the above quantitative indicators in the PLXT-Exo group and NZN-Exo group were significantly reversed （P＜0.05）， with large and round cell nuclei， intact nuclear membranes， and reduced mitochondrial vacuolization. CONCLUSIONS Peripheral blood-derived Exo intervened by naozhenning can alleviate the injury of neuronal cells HT22 by inhibiting inflammatory responses and cell apoptosis.

Objective:To investigate the expression levels of miRNA-21 (miR-21) and miRNA-330 (miR-330) in serum exosomes of non-small cell lung cancer (NSCLC) patients with brain metastases, and the correlation of the two with the prognosis of patients.Methods:A prospective cohort study was conducted. A total of 125 NSCLC patients who were admitted to the Affiliated People's Hospital of Shandong First Medical University from March 2021 to September 2022 were prospectively selected, and the brain metastasis was determined by CT, contrast-enhanced magnetic resonance imaging of the head, or surgical pathology. The NSCLC patients were divided into the metastatic group (58 cases) and the non-metastatic group (67 cases) according to whether they had brain metastases, and 50 patients with benign lung diseases and 50 healthy subjects who underwent physical examination in the same period were selected as benign group and healthy control group respectively. Serum samples were collected from all subjects (including patients' pre-treatment samples), the exosomes were extracted, and real-time fluorescence quantitative polymerase chain reaction was used to determine the relative expression of miR-21 and miR-330 in exosomes at the transcriptional level, and electrochemiluminescence immunoassay was used to detect the levels of serum tumor markers [neuron-specific enolase (NSE), carcinoembryonic antigen (CEA), squamous cell carcinoma antigen (SCCA)]. The levels of miR-21 and miR-330 in serum exosomes and serum tumor markers in the 4 groups were compared, and the correlation between miR-21 and miR-330 in serum exosomes of NSCLC patients with brain metastases before treatment and the correlation between miR-21, miR-330 and serum tumor markers were analyzed by Pearson method. Using brain metastases identified by CT, contrast-enhanced magnetic resonance imaging of the head or surgical pathology as the gold standard, the receiver operating characteristic (ROC) curves were drawn to determine the occurrence of brain metastases in NSCLC patients based on the levels of miR-21, miR-330 and their combination in the serum exosomes before treatment. NSCLC patients were divided into the poor prognosis group and the good prognosis group according to whether or not they died of tumor during the follow-up period, and the clinical characteristics and levels of miR-21 and miR-330 in serum exosomes before treatment were compared between the two groups. The independent influencing factors of death due to tumor in NSCLC patients were analyzed by multivariate logistic regression.Results:Among 125 NSCLC patients, 68 (54.4%) were male and 57 (45.6%) were female; the age was (63±5) years old, ranging from 49 to 82 years old; 89 patients (71.2%) were adenocarcinoma and 36 patients (28.8%) were squamous cell carcinoma. The transcriptional level relative expression of miR-21 in serum exosomes of healthy control group, benign group, non-metastatic group and metastatic group increased sequentially, the transcriptional level relative expression of miR-330 decreased sequentially, the protein concentrations of NSE, CEA and SCCA increased sequentially, and the differences between each two groups were statistically significant (all P<0.001). Pearson correlation analysis showed that in the serum exosomes of NSCLC patients with brain metastases before treatment, miR-21 was positively correlated with serum NSE, CEA and SCCA levels ( r values were 0.641, 0.785 and 0.612, respectively; P values were 0.015, 0.011 and 0.019, respectively), miR-330 in the serum exosomes before treatment was negatively correlated with serum NSE, CEA, and SCCA levels ( r values were -0.612, -0.689 and -0.587, respectively; P values were 0.016, 0.021 and 0.013, respectively), and miR-21 was positively correlated with miR-330 in the serum exosomes before treatment ( r = -0.529, P = 0.023). ROC curve analysis showed that the area under the curve of miR-21, miR-330 and their combination in serum exosomes before treatment for determining the occurrence of brain metastases in NSCLC patients were 0.861 (95% CI: 0.792-0.931), 0.894 (95% CI: 0.840-0.947) and 0.906 (95% CI: 0.849-0.963), and the differences were statistically significant (all P < 0.001). The optimal cut-off value of miR-21 relative expression was 1.625, and the corresponding sensitivity and specificity were 77.4% and 71.5%, respectively; the optimal cut-off value of miR-330 was 0.611, and the corresponding sensitivity and specificity were 81.1% and 74.9%, respectively; the sensitivity and specificity when the two were combined to reach the optimal cut-off value were 84.5% and 73.8%, respectively. NSCLC patients were followed up for a median time of 19 months (95% CI: 17-21 months), and 23 cases (18.4%) died due to the tumor during the follow-up period. The proportions of patients with age ≥60 years old, clinical stage Ⅲ-Ⅳ and brain metastases and the relative expression of miR-21 in serum exosomes before treatment in the poor prognosis group were higher than those in the good prognosis group, the relative expression of miR-330 in the serum exosomes before treatment was lower than that in the good prognosis group, and the differences were all statistically significant (all P < 0.05). Multivariate logistic regression analysis showed that the high age (≥60 years old vs. <60 years old, OR = 3.750, 95% CI: 1.191-11.806, P = 0.024), late clinical stage (stage Ⅲ-Ⅳ vs. stage Ⅰ-Ⅱ, OR = 4.667, 95% CI: 1.303-16.716, P = 0.018), brain metastasis (with metastasis vs. non-metastasis, OR = 2.573, 95% CI: 1.008-6.611, P = 0.049), and elevated relative expression of miR-21 in serum exosomes before treatment ( OR = 2.585, 95% CI: 1.198-6.152, P = 0.008) were the independent risk factors for death due to tumor in NSCLC patients, and elevated relative expression of miR-330 in serum exosomes before treatment was an independent protective factor for death due to tumor ( OR = 0.821, 95% CI: 0.715-0.954, P < 0.001). Conclusions:miR-21 level is high and miR-330 level is low in serum exosomes of NSCLC patients with brain metastases before treatment, and there is a negative correlation between them, and they are closely related to various serum tumor markers of NSCLC patients with brain metastases and NSCLC patients' prognosis; the combination of the two may predict the occurrence status of brain metastases in NSCLC.

OBJECTIVE To explore the mechanism of Naozhenning granules in regulating mitochondrial energy metabolism in hippocampal tissue of multiple cerebral concussion （MCC） model rats. METHODS SPF grade Wistar rats were used to prepare MCC models using the “free fall impact method”. The successfully modeled rats were divided into model group， piracetam group， and Naozhenning granule low-dose， medium-dose and high-dose groups， and a normal group was also set up， with 8 rats in each group. Rats in each treatment group orally administered corresponding drugs at doses of 0.324 g/kg for the piracetam group and 2.25， 4.5 and 9 g/kg for the Naozhenning granule low-dose， medium-dose and high-dose groups； the normal group and model group were given equal volumes of normal saline； once a day， for 14 consecutive days. The motor exploration ability， learning and memory ability of rats were tested； the adenosine triphosphate （ATP） content in the hippocampal tissue of rat was detected； the changes in the mitochondrial structure of hippocampal tissue was observed； the fluorescence intensity of mitochondrial dynamin- related protein 1 （Drp1）， mitochondrial fission protein 1 （Fis1）， mitochondrial fusion 1 （Mfn1）， and optic atrophy protein 1 （Opa1） were detected in the hippocampal tissue of rat； the protein expression levels of peroxisome proliferator activated receptor gamma coactivator-1α（PGC-1α）， nuclear respiratory factor-1（NRF-1），mitochondrial transcription factor A（TFAM）， Wnt-3a，β-catenin in hippocampal tissue of rat were detected. RESULTS Compared with the normal group， the total exercise distance， number of central grid entries， number of upright positions， new object recognition index， mitochondrial ATP content， fluorescence intensity of Mfn1 and Opa1， the protein expression levels of PGC-1α、NRF-1、TFAM、Wnt-3a、 β-catenin in the model group were significantly reduced （P＜0.01）， while the rest time and fluorescence intensity of Drp1 and Fis1 in hippocampal tissue were significantly increased （P＜0.01）. The results of transmission electron microscopy showed that the mitochondria in the hippocampal tissue were significantly swollen， with a large number of broken and reduced cristae， and some mitochondria had myeloid changes in the membrane. Compared with the model group， the levels/contents of the above indicators in rats of each administration group showed varying degrees of reversal， and most of the differences were statistically significant （P＜0.05 or P＜0.01）； the degree of mitochondrial swelling in the hippocampal tissue was reduced， with a small amount of broken and reduced cristae， fuzzy fractures appeared in local areas of the rough endoplasmic reticulum. CONCLUSIONS Naozhenning granules can improve the motor exploration， learning and memory abilities of MCC model rats， repair neuronal damage， and exert neuroprotective effects. Its mechanism may be related to activating Wnt/β-catenin signaling pathway，maintaining the balance of mitochondrial division and fusion，and promoting mitochondrial biosynthesis.

OBJECTIVE To investigate the effects of Setaria italica extract on improving insomnia model mice and to explore its potential mechanisms. METHODS The mice were randomly assigned into blank group， model group， positive control group （diazepam， 2.6 mg/kg）， and S. italica extract low-dose， medium-dose and high-dose groups （1.2， 2.4， 4.8 g/kg）， with 10 mice in each group. Except for the blank group， all other groups received intraperitoneal injection of para-chlorophenylalanine （PCPA） to establish the insomnia model. After modeling， the blank group and model group were given a constant volume of normal saline intragastrically， and administration groups were given relevant medicine intragastrically， with a volume of 0.01 mL/g， once a day， for 7 consecutive days. After the administration， the open-field test was conducted to observe the praxiological changes of mice， and to determine the levels of 5-hydroxytryptamine （5-HT） and 5-hydroxyindoleacetic acid （5-HTAA） in the hippocampal tissue， as well as the contents of 5-HT， brain-derived neurotrophic factor （BDNF）， interleukin-2 （IL-2）， IL-6， B-cell lymphoma-2 （Bcl- 2）， and Bcl-2-associated X protein （Bax） in the serum. The expression of phosphoinositide 3-kinase/protein kinase B/nuclear factor- κB （PI3K/Akt/NF-κB） signaling pathway related protein was determined in the hippocampus of mice. RESULTS Compared with the model group， the total exercise time of mice in S. italica extract high-dose group was significantly prolonged， but the total rest time was significantly shortened （P＜0.01）； the number of standing times and modification times were significantly reduced （P＜ 0.01）. The contents of 5-HT， BDNF， and Bcl-2 in serum， and Bcl-2/Bax were significantly increased， while the contents of IL-2， IL-6， and Bax were significantly reduced （P＜0.05 or P＜ 0.01）. The content of 5-HTAA in the hippocampal tissue and 202104010910029）；the phosphorylation levels of PI3K and Akt proteins were increased significantly， while the phosphorylation level of NF-κB p65 protein was decreased significantly （P＜0.05）.CONCLUSIONS High-dose of S. italica extract demonstrates significant therapeutic effects on insomnia in mice， and the mechanism of which may be associated with the regulation of PI3K/Akt/NF-κB signaling pathway.