OBJECTIVE To compare the efficacy and safety of vedolizumab （VDZ） versus infliximab （IFX） in biologic-naive（Bio-naive） patients with moderate-to-severe active ulcerative colitis （UC）， and to analyze the factors influencing efficacy. METHODS Clinical data were retrospectively collected from Bio-naive patients with moderate-to-severe active UC who received treatment in the Department of Gastroenterology at Shanxi Provincial People’s Hospital from June 2023 to June 2024. Based on the type of biologic agent administered， the patients were divided into the IFX group （41 cases） and the VDZ group （30 cases）. Patients in the two groups received IFX （5 mg/kg） or VDZ （300 mg） for induction and maintenance of remission therapy. The two groups were compared regarding modified Mayo score， serological indicators （hemoglobin， albumin， platelet count， erythrocyte sedimentation rate， C-reactive protein）， combined medication， efficacy-related indexes （clinical response rate/remission rate， and endoscopic response rate/remission rate）， and the occurrence of adverse drug reactions （ADR）. Based on Logistic regression model， univariate and multivariate analyses were conducted to identify potential factors influencing clinical remission at week 14 and endoscopic remission at week 38. RESULTS There were no statistically significant differences in clinical response rate/remission rate， or endoscopic response rate/remission rate between the two groups at weeks 14 and 38 （ P ＞0.05）. However， at week 14 of treatment， the proportion of patients using concomitant corticosteroids in VDZ group was 26.67%， significantly higher than the 7.50% in IFX group （ P ＜0.05）. There was no statistical significance in the overall incidence of ADR between the two groups （ P ＞0.05）； all ADRs in the IFX group were grade 3 and led to treatment discontinuation （6 cases）， whereas ADR in the VDZ group was grade 2 and did not interrupt therapy （1 case）. Univariate and multivariate regression analyses revealed that disease type （relapsing） was significantly associated with clinical remission at week 14 of treatment， and a history of smoking was significantly associated with endoscopic remission at week 38 of treatment （the odds ratios were 0.08 for both， with 95% confidence intervals of 0.01-0.77 and 0.01-0.91 respectively， P ＜0.05）. CONCLUSIONS For Bio-naive patients with moderate-to-severe active UC， VDZ and IFX demonstrate comparable efficacy in inducing and maintaining clinical remission and promoting mucosal healing， as well as overall safety. Although IFX can achieve faster control of inflammation in the early stage of the disease， it causes more severe ADR. Disease type （relapsing） and smoking history are identified as independent negative predictors for short-term clinical remission and long-term endoscopic remission， respectively.

ObjectiveTo provide a basis for the establishment of an ideal animal model of allergic asthma by statistically analyzing the modeling characteristics and the selection of indicators of the available models. MethodsWe retrieved the relevant articles from China National Knowledge Infrastructure（CNKI）， VIP， Wanfang Data， SinoMed， and PubMed with "allergic asthma" as the keyword and the time interval from January 2019 to January 2024. Through integrating the literature and extracting data， we used Excel 2021 to create a personal database and sorted out the animal strains， genders， allergenic substances， modeling routes， and test indicators and methods. Excel 2021， Cytoscape 3.10.2， and SPSS Modeler 18.0 were then used to analyze the relevant characteristics of the animal models. ResultsA total of 418 articles were included in the database， and the comparative analysis showed that the most frequently used animal strain for modeling was BALB/c mice， and female animals were mostly used. The main modeling method was sensitization by intraperitoneal injection of ovalbumin （OVA）， which was combined with intranasal inhalation. The test indicators mainly included appearance signs， cellular analysis， lung histopathology， lung function indicators， and protein and gene expression in the lung. The test methods mainly involved pathological staining， enzyme-linked immunosorbent assay， immunohistochemistry， immunofluorescence， Western blot， and polymerase chain reaction（PCR） assays. ConclusionThere is no recognized modeling method or evaluation standard for the animal models of allergic asthma. Based on the results of data analysis， the OVA-induced allergic asthma model in BALB/c mice is recommended. The main criteria for evaluating the success of modeling are the general behavioral changes， the morphological changes of the airway and inflammatory cell infiltration in the lung tissue， the changes of pro-inflammatory and anti-inflammatory cytokines in the serum， and the alterations of inflammatory cells in the bronchoalveolar lavage fluid.

OBJECTIVE To explore the effect and mechanism of embryonic intervention with Zuogui pill on the glucose tolerance in offsprings of pregnant rats with gestational diabetes mellitus. METHODS Pregnant rats were randomly divided into blank group， model group， positive control group （insulin glargine）， Zuogui pill low-， medium- and high-dose groups （4.725， 9.45， 18.9 g/kg）. In addition to the blank group， streptozotocin was injected intraperitoneally to establish a gestational diabetes mellitus rat model. From day 6 to day 18 of pregnancy， each group was given relevant medicine and distilled water intragastrically， once a day. After 21 days of birth， the body weight and body length of offsprings were recorded， and the area under the curve （AUC） was calculated through a glucose tolerance test. After 22 days of birth， fasting blood glucose （FBG）， fasting insulin （FINS） levels in serum， insulin sensitivity index （ISI）， and homeostasis model assessment of insulin resistance （HOMA-IR） were measured， and the morphological structure of pancreatic tissue was observed. The protein spectrum of pancreatic tissue was analyzed by tandem mass tag-based proteomics， and protein and mRNA expression levels of apolipoprotein A1（ApoA1）， solute carrier family 27 member 1 （Slc27a1）， kininogen 1（Kng1） and sodium/potassium-transporting ATPase subunit alpha 2 （Atp1a2）， solute carrier family 7 member 5 （Slc7a5）， solute carrier family 3 member 2 （Slc3a2）， bile acid-coenzyme A： amino acid N- acyltransferase （Baat）， eukaryotic translation initiation factor 2 subunit gamma （Eif2s3） were detected. RESULTS Compared with the model group， the body weight， body length and ISI of offsprings in the positive control group and Zuogui pill medium-dose group were significantly increased （P＜0.05）， while the glucose tolerance and islet cell proliferation were significantly improved， and the AUC， FBG， FINS and HOMA-IR were significantly decreased （P＜0.05）. There were 88 potential target proteins for the embryonic intervention of Zuogui pill in offsprings of pregnant rats with gestational diabetes mellitus，involving multiple pathways such as peroxisome proliferator-activated receptor （PPAR）， cyclic guanosine monophosphate-protein kinase G （cGMP-PKG）， fat digestion and absorption， and bile secretion. The proteins closely related to glucose metabolism and insulin resistance mainly included ApoA1， Slc27a1， Kng1， Atp1a2， Slc7a5， Slc3a2， Baat， and Eif2s3. Among them， compared with the model group， protein and mRNA expressions of Slc7a5， Slc3a2， and Baat in the pancreatic tissues of pregnant rat offsprings in the Zuogui pill medium-dose group were significantly up-regulated （P＜0.05）； protein and mRNA expressions of ApoA1， Slc27a1， Kng1， Atp1a2 and Eif2s3 were all significantly down-regulated （P＜0.05）. CONCLUSIONS The intervention of Zuogui pill in the embryonic period on offsprings of pregnant rats with gestational diabetes mellitus can improve their blood glucose levels and pancreatic pathological morphology. The mechanism may be related to the upregulation of the expressions of Slc7a5， Slc3a2， and Baat and the down-regulation of ApoA1， Slc27a1， Kng1， Atp1a2 and Eif2s3 expressions in the PPAR， cGMP-PKG， fat digestion and absorption， and bile secretion pathways.

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 observe the effects of electroacupuncture (EA) at changbing fang (prescription for intestinal disease) on autophagy of colonic cells and gut microbiota in rats with ulcerative colitis (UC), and to explore the mechanism of EA in the treatment of UC. METHODS: Thirty-two SD male rats were randomly divided into a control group, a model group, an EA group and a sham-EA group, with 8 rats in each group. Except the control group, the UC rat model was established by free drinking of 5% dextran sulfate sodium solution for 7 days in the other groups. In the EA group, changbing fang was adopted, in which, EA was applied at "Tianshu" (ST25) and "Shangjuxu" (ST37), at disperse-dense wave and frequency of 10 Hz/50 Hz, for 20 min in each intervention. In the sham-EA group, shallow transcutaneous puncture was performed at the sites, 5 mm away from the points as the EA group, with the same parameters as the EA group. The intervention was delivered once daily for 3 consecutive days. The body weight was measured daily and the disease activity index (DAI) score was calculated before and after intervention. After intervention completion, the colon length was measured. Using HE staining, the colon morphology was observed and the score of colonic pathology was assessed. With ELISA adopted, the contents of tumor necrosis factor (TNF-α), interleukin (IL)-1β, IL-2 and IL-10 in the serum of the rats were detected. The ultrastructure of the colon tissue was observed under electron microscopy. Using Western blotting, the protein expression was detected for microtubule-associated protein 1 light chain 3 (LC3)Ⅱ, LC3Ⅰ, autophagy-related genes (ATG) 5, ATG12, sequestosome 1 (p62), phosphatidylinositol 3-kinase (PI3K), phosphorylated protein kinase B (p-AKT), protein kinase B (AKT), and phosphorylated mammalian target of rapamycin (p-mTOR), mammalian target of rapamycin (mTOR) in the colon tissue. The mRNA expression of PI3K, AKT and m-TOR in the colon tissue was detected by real-time fluorescence quantitative PCR. The 16S rRNA gene sequencing was used to analyze the structure of gut flora in the feces of rats. RESULTS: From day 1 to day 7, compared with the control group, the body weight decreased in the model group, EA group, and SEA group (P<0.05, P<0.01). From day 9 to day 10, the EA group showed an increase in body weight compared with the model group and SEA group (P<0.05, P<0.01). Before intervention, the DAI score in the model group, EA group, and SEA group was higher than the score of the control group, respectively (P<0.01). After intervention, the DAI score in the EA group was reduced compared with the model group and SEA group (P<0.01). Compared with the control group, in the model group, the colon length of rats was shorter (P<0.01); it showed the distorted crypts, thinner mucosal layer, reduced goblet cells, inflammatory cell infiltration and the disarranged histological structure; and the pathological score of the colon tissue increased (P<0.01); the serum contents of TNF-α and IL-1β increased (P<0.01), and those of IL-2 and IL-10 decreased (P<0.01). The structure of colon epithelial cells was disarranged, with cilia pelt off, and a large number of vacuoles in the cytoplasm; the mitochondria were swollen, with unclear structure and cristae partially disappeared; and few autophagosomes were observed. The value of LC3Ⅱ/LC3Ⅰand the protein expression of ATG5 and ATG12 in the colon tissues were reduced (P<0.01), the protein expression of p62 and PI3K, and the values of p-AKT/AKT, and p-mTOR/mTOR increased (P<0.01), and mRNA expression of PI3K, AKT and mTOR was elevated (P<0.01). The indexes of Chao1, Ace and Shannon decreased (P<0.01). At the phylum level, the relative abundance of Firmicutes decreased (P<0.05), that of Bacteroidetes and Proteobacteria increased (P<0.05, P<0.01). At the genus level, the relevant abundance of Lactobacillus decreased (P<0.05), while that of Lachnospiraceae_NK4A136_group and Phascolarctobacterium increased (P<0.01, P<0.05 ). Compared with the model group and SEA group, in the EA group, the colon length increased (P<0.01), the infiltration of inflammatory cells was reduced, the arrangement of intestinal epithelial cells was arranged regularly, with a small amount of shedding, and the pathological score of the colon tissue decreased (P<0.01). The serum contents of TNF-α and IL-1β decreased (P<0.01), and those of IL-2 and IL-10 increased (P<0.01). The colonic epithelial cells were arranged relatively, the morphology of organelles was basically normal, and autophagosomes were visible. The value of LC3Ⅱ/LC3Ⅰand the protein expression of ATG5 and ATG12 in colon tissue increased (P<0.01, P<0.05), the protein expression of p62 and PI3K, and the values of p-AKT/AKT, and p-mTOR/mTOR decreased (P<0.01); and mRNA expression of PI3K, AKT, m-TOR was reduced (P<0.01). The indexes of Chao1, Ace and Shannon increased (P<0.01). At the phylum level, the relative abundance of Firmicutes increased (P<0.01), while that of Bacteroidetes decreased (P<0.01). At the genus level, the relative abundance of Lactobacillus increased (P<0.05), whereas that of Lachnospiraceae_NK4A136_group decreased (P<0.01). When compared with the model group, the relative abundance of Proteobacteria decreased (P<0.05), and that of Phascolarctobacterium was reduced (P<0.05) in the EA group. CONCLUSION EA at changbingfang alleviates UC symptoms probably through inhibiting the PI3K/AKT/mTOR signaling pathway to regulate colonic autophagy and improve the intestinal flora.
Animals ; Electroacupuncture ; Colitis, Ulcerative/metabolism* ; Male ; Rats ; Gastrointestinal Microbiome ; Rats, Sprague-Dawley ; Colon/metabolism* ; Humans ; Autophagy ; Acupuncture Points ; Tumor Necrosis Factor-alpha/genetics* ; Interleukin-10/genetics*

Objective To propose a new method for mining compatibility rules of traditional Chinese medicine (TCM) formulation from the perspective of weighted projection of bipartite networks, and to predict the combination of new drugs to provide a basis for guiding the clinical treatment of acute nasopharyngitis. Methods Using the acute nasopharyngitis prescription data in the Traditional Chinese Medicine Integrated Database (TCMID) as the data source, a bipartite network is constructed by extracting the prescription and drug nodes.A drug network projection map was then obtained using weighted projection.Social network analysis was performed combined with weighted projection of bipartite networks, and compatibility rules of "Jun-Chen-Zuo-Shi" in TCM via hierachical cluster analysis based on Pearson correlation.Besides, link prediction was used for core drug prediction. Results The combination of bipartite network weighted projection and Pearson correlation for systematic clustering analysis played a significant role in the study of the compatibility rules of TCM prescriptions.In link prediction, 11 link prediction indicators were selected, and weighted and unweighted algorithms were distinguished.The final calculation showed that the area under the curve (AUC) of the weighted indicators were generally higher than that of the unweighted network.Among the weighted indicators, the indicator with the highest AUC index was the network resource allocation Index.A total of 7 groups of drug combinations were predicted, including Baitouweng-Maokezi, Anxixiang-Shijiaocao, Baihuacha-Fuzi, etc. Conclusion The bipartite network weighted projection method is practical and effective in revealing the compatibility rules of TCM and predicting drug combination.

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.

BackgroundSuicide ideation in adolescent inpatients with depression is a multi-factorial problem， and perceived stress is considered to be closely related to suicide ideation， while its mediating role in suicide ideation among adolescent inpatients with depression remains unclear. ObjectiveTo explore the mediating effect of psychological capital on the relationship between perceived stress and suicide ideation among adolescent inpatients with depression， so as to provide references for preventing the onset of suicide ideation in adolescent inpatients with depression. MethodsA sample of 585 adolescent patients who were hospitalized in Beijing Huilongguan Hospital from June 2021 to March 2023 and fulfilling the International Classification of Diseases， 10th edition （ICD-10） diagnostic criteria for depression were enrolled. All patients were evaluated using self-designed questionnaire， Chinese Perceived Stress Scale （CPSS）， Positive Psychological Capital Questionnaire （PPQ） and Beck Scale for Suicide Ideation-Chinese Version （BSI-CV）. Pearson correlation was used to assess the correlation among the scores of the above scales. Bootstrap method was employed to verify the mediating effect of psychological capital on the relationship between perceived stress and suicide ideation. ResultsCPSS score in adolescent inpatients with depression was positively correlated with BSI-CV score （r=0.375， P<0.01）， and CPSS score and BSI-CV score were negatively correlated with PPQ score （r=-0.481， -0.436， P<0.01）. Psychological capital played a significant yet a partial role in mediating the link between perceived stress and suicide ideation， with an indirect mediating effect value of 0.160 （95% CI： 0.178~0.373）， accounting for 30.42% of the total effect. ConclusionThe perceived stress of adolescent inpatients with depression can affect the onset of suicide ideation both directly and indirectly through psychological capital.

ObjectiveTo observe the possible mechanism of Dihuang Yinzi Decoction （地黄饮子） for improving cognitive dysfunction in Alzheimer's disease （AD） from the perspective of retina. MethodsForty-five APP/PS1 mice （AD model mice） were randomly divided into model group， Dihuang Yinzi Decoction group， and memantine group， with 15 mice in each group， while 15 wild-type C57BL/6J mice from the same litter were used as blank group. Mice in Dihuang Yinzi Decoction group were given Dihuang Yinzi Decoction 30.03 g/（kg·d） by gavage， mice in the memantine group were given memantine hydrochloride 6.1 mg/（kg·d） by gavage， and mice in the blank group and the model group were given normal saline 2 ml/（kg·d） by gavage for 4 consecutive weeks. Fasting blood glucose was measured weekly. After 4 weeks of intervention， oral glucose tolerance test （OGTT） and insulin tolerance test （ITT） were performed； Morris water maze was used to detect the changes in spatial memory ability of mice； glucose oxidase method was used to detect retinal glucose content of mice； enzyme-linked immunosorbent assay （ELISA） was used to detect serum and retinal insulin content of mice， and Homeostatic Model Assessment of insulin resistance （HOMA-IR） was calculated. Hematoxylin-eosin （HE） staining was performed to observe the histopathological changes in the retina， and the retinal thickness and ganglion cell number were counted； protein immunoblotting was performed to detect the retinal pathway-associated proteins ［insulin receptor substrate 1 （IRS1）， phosphorylated insulin receptor substrate 1 （pIRS1）， phosphatidylinositol-3-hydroxykinase （PI3K）， protein kinase B （Akt1）， phosphorylated protein kinase B （pAkt1）］ expression； retinal glucose transporter protein 4 （GLUT4） expression was detected by immunohistochemistry. ResultsCompared with the blank group， fasting blood glucose of mice in the model group at weeks 1， 2， 3， and 4， blood glucose and area under the curve （AUC） at different time point of OGTT and ITT test， fasting serum insulin， and HOMA-IR increased （P＜0.05， P＜0.01）； in the Morris water maze experiment， the escape latency increased from day 3 to day 5， and the number of crossing platforms， the percentage of target quadrant distance， and the percentage of target quadrant time decreased （P＜0.05， P＜0.01）； the outer nuclear layer of the retina became sparse， thinner， and the number of ganglion cells decreases （P＜0.01）； the expression level of retinal glucose increased， while the expression levels of insulin， pIRS1/IRS1， PI3K/β-Actin， pAkt1/Akt1， and GLUT4 proteins decreased （P＜0.01）. Compared with the model group， fasting blood glucose at week 4， blood glucose at each time point of the OGTT and ITT tests AUC decreased （P＜0.05， P＜0.01）， and fasting serum insulin and HOMA-IR decreased （P＜0.05） in Dihuang Yinzi Decoction group； In the Morris water maze test， the escape latency shortened on day 4 and day 5， number of platform crossings， target quadrant distance as a proportion of total distance， and target quadrant movement time as a proportion of total time decreased （P＜0.05， P＜0.01）； retinal pathological changes alleviated， and retinal thickness and ganglion cell number increased （P＜0.01）； retinal glucose content decreased， and retinal pIRS1/IRS1， PI3K/β-Actin， and GLUT4 protein expression elevated （P＜0.05 or P＜0.01）. ConclusionsDihuang Yinzi Decoction can improve cognitive dysfunction of Alzheimer's disease， which may be related to regulating retinal insulin content and insulin signaling pathway.

Objective To investigate the anti-fatigue effect of PTR-SeNPs in vivo by measuring the muscle relative length of hindlimb,load-bearing swimming time as well as serum and liver indexes of mice.Methods 48 male C57/BL6 mice were randomly assigned into 4 groups with 12 mice in each group,including vehicle control group(control group),swimming training exercise group(EC group)with vehicle treatment,swimming training exercise with low dose of PTR-SeNPs group(LPTR-SeNPs)and high dose of PTR-SeNPs group(HPTR-SeNPs).The mice were intragastrically administrated with normal saline in both control group and EC group,as well as 2.5 and 10 μmol/(kg·bw)PTR-SeNPs in LHPTR-SeNPs group,respectively,once per day for consecutively 21 days.After swimming training exercise,the muscle structures in the hind limb of mice were examined by magnetic resonance imaging.Furthermore,the burdened swimming time was measured,the serum content of blood lactic acid(BLA),urea nitrogen(BUN),alanine aminotransferase(ALT),glutamic oxalate aminotransferase(AST)and lactate dehydrogenase(LDH),as well as the hepatic level of glycogen(HG),malondialdehyde(MDA)and activity of catalase(CAT)and superoxide dismutase(SOD)were determined.Results Compared with the control group,the serum contents of BLA,BUN,ALT,AST and LDH in EC group(P<0.05 or P<0.01)and hepatic CAT in HPTR-SeNPs group(P<0.01)were significantly increased.The muscle relative length of hind limbs and the burdened swimming time were extended by HPTR-SeNPs markedly(P<0.05).There was no significant difference in MDA level in LHPTR-SeNPs group.Compared with EC group,the burdened swimming time of mice was significantly prolonged(P<0.01),the contents of BLA and BUN were obviously decreased in the HPTR-SeNPs group(P<0.05 or P<0.01),the level of HG was significantly increased in the LHPTR-SeNPs groups(P<0.05 or P<0.01),the serum content of ALT,AST and LDH were markedly decreased in the HPTR-SeNPs group(P<0.05 or P<0.01).Hepatic SOD activity was remarkably increased in LPTR-SeNPs group(P<0.05),the level of CAT was evidently increased(P<0.01)and AST was decreased(P<0.05)in the HPTR-SeNPs group.Conclusion PTR-SeNPs could improve the liver physiological function,increase glycogen storage,reduce the accumulation of metabolites and enhance the body's antioxidant capacity to ameliorate fatigue significantly,which could present the potential to be developed into health care products or drugs.