ObjectiveThis paper aims to observe the role of Danlou tablet in treating coronary heart disease （CHD） with phlegm-stasis intermingling syndrome in minipigs by improving platelet function and explore the potential pharmacological mechanism of Danlou tablet in regulating platelet function by using proteomics technology. MethodsThirty Bama minipigs were randomly divided into a normal control group （6 pigs） and a high-fat diet group （24 pigs）. After 2 weeks of high-fat diet feeding， the high-fat diet group was randomly subdivided into a model group， an atorvastatin group （1 mg·kg^-1）， and Danlou tablet groups （0.6 g·kg^-1 and 0.3 g·kg^-1）. All groups continued to receive a high-fat diet for 8 weeks after the procedure. The normal control group was given a regular diet， underwent only coronary angiography， and did not receive an interventional injury procedure. The model group and each administration group were fed a high-fat diet. Two weeks later， they underwent a coronary angiography injury procedure. After the procedure， drugs were mixed into the feed every morning for 8 consecutive weeks， with the minipigs maintained on a continuous high-fat diet during this period. Quantitative proteomics technology was further used to study platelet proteins， and differential proteins were obtained by screening. Bioinformatics analysis was performed to analyze key regulatory proteins and biological pathways involved in the therapeutic effect of Danlou tablet on CHD with phlegm-stasis intermingling syndrome. ResultsCompared with the normal control group， the model group showed a significant increase in total cholesterol （TC）， triglyceride （TG）， high-density lipoprotein cholesterol （HDL-C）， and low-density lipoprotein cholesterol （LDL-C） of minipigs' serum （P<0.01）， a significant shortening in prothrombin time of （PT） （P<0.01）， a coagulation function index， and an increase in whole blood viscosity （P<0.01） and platelet aggregation rate （P<0.01）. Moreover， the platelet morphology was altered， and the contents of endothelin-1 （ET-1） and nitric oxide （NO） were significantly increased （P<0.01）. Hemodynamic parameters were obviously abnormal， including significantly decreased systolic blood pressure （SBP）， diastolic blood pressure （DBP）， mean arterial pressure （MAP）， left ventricular systolic pressure （LVSP）， and left ventricular maximal positive dp/dt （LV+dp/dt_max） （P<0.01）. Left ventricular maximal negative dp/dt （LV-dp/dt_max） was significantly increased （P<0.01）. Besides， there were myocardial cell hypertrophy， obvious edematous degeneration， massive interstitial inflammatory cell infiltration， high degree of fibrosis， and coronary endothelial atherosclerosis. TC and TG levels in minipigs' serum were significantly reduced in Danlou tablet groups with 0.6 g·kg^-1 and 0.3 g·kg^-1 （P<0.05， P<0.01）， compared with those in the model group. LDL-C was decreased in the Danlou tablet group with 0.6 g·kg^-1 （P<0.05）. The whole blood viscosity under low and high shear conditions was significantly reduced in the Danlou tablet group with 0.6 g·kg^-1 （P<0.05）. In groups with all doses of Danlou tablet， maximum aggregation rate （MAR） and average aggregation rate （AAR） were significantly decreased （P<0.05， P<0.01）， and platelets' morphological changes such as pseudopodia extension were reduced. ET-1 levels in the serum were significantly reduced. In the Danlou tablet group with 0.6 g·kg^-1， NO level in the serum was reduced （P<0.05）. In groups with all doses of Danlou tablet， DBP and MAP were significantly increased （P<0.05）. In the Danlou tablet group with 0.6 g·kg^-1， LVSP and LV+dp/dt_max were significantly increased （P<0.05， P<0.01）， and LV-dp/dt_max was significantly decreased （P<0.05）. In groups with all doses of Danlou tablet， edematous degeneration in myocardial tissue was milder， and coronary artery lesion degree was significantly alleviated. Compared with the normal control group， there were 94 differentially expressed proteins in the model group， including 81 up-regulated and 13 down-regulated proteins. Compared with the model group， the Danlou tablet group with 0.6 g·kg^-1 showed 174 differentially expressed proteins， including 100 up-regulated and 74 down-regulated proteins. A total of 30 proteins were reversed after Danlou tablet intervention. Bioinformatics analysis revealed that its pharmacological mechanism may exert anti-platelet activation， aggregation， and adhesion effects through biological pathways such as regulation of actin cytoskeleton， platelet activation pathway， Fcγ receptor-mediated phagocytosis， as well as proteins such as growth factor receptor-bound protein 2 （GRB2）， Ras-related C3 botulinum toxin substrate 2 （RAC2）， RAC1， and heat shock protein 90 alpha family class A member 1 （HSP90AA1）. ConclusionDanlou tablet can effectively reduce platelet activation and aggregation， exerting a good therapeutic effect on CHD with phlegm-stasis intermingling syndrome in minipigs. Its pharmacological mechanism may involve regulating biological pathways such as actin cytoskeleton and platelet activation pathway， as well as proteins like GRB2， RAC2， RAC1， and HSP90AA1， thereby exerting a pharmacological effect in anti-platelet activation， aggregation， and adhesion.

ObjectiveTo investigate the effects and underlying mechanisms of Xiaozheng Zhitong Paste （XZP） on bone cancer pain （BCP）. MethodsThirty female BALB/c mice were randomly divided into five groups： a Sham group， a BCP group， a BCP+low-dose XZP group， a BCP+high-dose XZP group， and a BCP+high-dose XZP + protease-activated receptor 2 （PAR2） agonist GB-110 group. BCP mice model was constructed by injecting Lewis lung carcinoma cells into the femoral cavity of the right leg， which was followed by being treated with XZP for 21 d. After 21 d， the mice were sacrificed. Nissl staining was used to evaluate the survival of spinal cord neurons. Immunofluorescence staining was conducted to localize ionized calcium-binding adapter molecule 1 （Iba1） and neuronal nuclear antigen （NeuN） in spinal cord tissue， thereby assessing microglial activation and neuronal survival. Enzyme-linked immunosorbent assay （ELISA） was employed to measure the levels of interleukin-1β （IL-1β）， tumor necrosis factor-α （TNF-α）， interleukin-6 （IL-6）， transforming growth factor-β （TGF-β）， interleukin-4 （IL-4）， and interleukin-10 （IL-10） in spinal cord tissue. Real-time quantitative polymerase chain reaction （Real-time PCR） was used to detect mRNA expression levels associated with M1/M2 polarization of microglia. Western blot analysis was performed to examine the expression of proteins related to microglial polarization as well as those involved in the PAR2/nuclear factor kappa B （NF-κB）/NOD-like receptor protein 3 （NLRP3） signaling pathway in the spinal cord. ResultsCompared with the Sham group， the spinal cord neurons were damaged， the number of Nissl-positive spinal cord neurons in the spinal cord tissue was significantly reduced （P<0.01）， and the rate of NeuN-positive cells was significantly decreased （P<0.01）. The spinal cord microglia were activated， the inflammatory level of the spinal cord tissue was enhanced， and Iba1 staining was significantly enhanced （P<0.01）. The levels of IL-1β， TNF-α， IL-6， TGF-β， IL-4 and IL-10 were significantly increased （P<0.01）. The mRNA expressions of IL-1β， TNF-α and inducible nitric oxide synthase （iNOS） were significantly increased （P<0.01）， and the expression of PAR2， NLRP3， ASC and NF-κB p65 proteins in the spinal cord tissue of the BCP mice was significantly enhanced （P<0.01）. Compared with the BCP group， high-dose XZP treatment significantly increased the number of Nissl-positive spinal cord neurons in the BCP mice （P<0.01）， significantly enhanced the rate of NeuN-positive cells in the spinal cord tissue， and significantly weakened Iba1 staining （P<0.01）. In addition， the levels of IL-1β， TNF-α， and IL-6 were significantly decreased， while the levels of TGF-β， IL-4， and IL-10 were significantly increased （P<0.05， P<0.01）. The mRNA expression levels of IL-1β， TNF-α， and iNOS were decreased， whereas those of cluster of differentiation 206 （CD206）， arginase-1 （Arg-1）， and YM1/2 were significantly increased （P<0.05， P<0.01）. Low-dose and high-dose XZP treatment significantly decreased the expression of PAR2， NLRP3， ASC， and NF-κB p65 proteins in the spinal cord tissue （P<0.05， P<0.01）. These effects could all be significantly eliminated by the PAR2 agonist GB-110. ConclusionXZP can mitigate BCP in mice， which may be achieved through blocking the activated PAR2/NF-κB/NLRP3 pathway.

Pain， as one of the most common symptoms in cancer patients， seriously affects the survival quality of patients. The three-step pain relief program currently used in clinical practice cannot completely relieve pain in cancer patients and is accompanied by many problems. From the perspective of Jueyin syndrome in traditional Chinese medicine （TCM）， this paper believed that the core pathogenesis of cancer pain was declined healthy Qi and cold and heat in complexity， and used Wumeiwan as the main formula with modification according to syndrome for clearing the upper， warming the lower part of the body， and harmonizing the cold and heat. It can regulate the pathological environment of deficiency， cold， stasis， toxicity， and heat， and restore the physiological function of Yang transforming Qi while Yin constituting form， so as to prevent， relieve， and even eliminate cancer pain， having achieved good clinical efficacy. It can not only help cancer patients relieve pain， but also control tumor and eliminate tumor， achieving a dual benefit of pain relief and tumor suppression. It gives full play to the characteristics and advantages of syndrome differentiation and treatment in TCM， and expands the scope of ZHANG Zhongjing's treatment for Jueyin syndrome， which provides ideas for the clinical diagnosis and treatment of cancer pain from the perspective of deficiency-excess in complexity and cold and heat in complexity.

Objective To analyze the differences of free and esterified oxo-eicosatetraenoic acids (oxo-ETEs) in blood cells and plasma from arterial and venous blood in hemodialysis (HD) patients. Methods Arterial and venous blood samples from 12 patients with end-stage renal disease (ESRD) before and after HD treatment at Charité – Universitätsmedizin Berlin, Germany, from June to December 2020 were collected. The esterified and free oxo-ETEs derived from arachidonic acid in blood cells and plasma were measured by high performance liquid chromatography-tandem mass spectrometry (HPLC-MS/MS). Results Neither esterified nor free oxo-ETEs in blood cells displayed significant arteriovenous differences before and after HD. HD predominantly affected the metabolic levels of esterified and free oxo-ETEs in plasma. HD reduced the arteriovenous differences of esterified 12-oxo-ETE, free 15-oxo-ETE, and free 5-oxo-ETE in plasma, while raised the arteriovenous differences of esterified 15-oxo-ETE. Conclusions The oxo-ETEs in blood cells are relatively well-stabilized responding to HD treatment, whereas arteriovenous differences of free and esterified oxo-ETEs in plasma are present and active in response to HD treatment, potentially contributing to the cardiovascular disease.

Objective : To investigate the effects of resveratrol(Res) on fibroblast-like synoviocytes(FLS) in patients with rheumatoid arthritis(RA), and to explore the possible mechanism of Res inhibiting the release of inflammatory factors from FLS. Methods : FLS from RA patients were culturedin vitroand treated with different concentrations of Res(0, 20, 40, 80, 160, 320 μmol/L). The viability of FLS cells was detected by CCK-8 assay after 12 and 24 h. The contents of inflammatory factor interleukin-6(IL-6) and tumor necrosis factor-α(TNF-α) in cell supernatant were detected by ELISA. The expression levels of cyclic guanosine monophosphate-adenosine monophosphate synthase(cGAS) and stimulator of interferon gene(STING) were measured by Western blot; After lentivirus infection with FLS caused the cells to overexpress cGAS, the cells were divided into Control group(blank control), cGAS group(cGAS overexpression), Res+cGAS group(Res 160 μmol/L+cGAS overexpression) and Res group(Res 160 μmol/L). The expression level of STING protein in cells of each group was determined by Western blot, the viability of FLS cells in each group was detected by CCK-8, and the contents of inflammatory factor IL-6 and TNF-α in the supernatant of cells of each group were detected by ELISA method. Results : The results of CCK-8 experiment showed that under 40, 80, 160 μmol/L Res treatment, FLS viability decreased significantly after 24 h compared with blank control group(P<0.01). ELISA results showed that the contents of IL-6 and TNF-α in cell supernatant were also significantly decreased after treatment with Res of 40, 80 and 160 μmol/L(P<0.01). Meanwhile, Western blot results showed that Res could significantly decrease the protein expression levels of STING and cGAS in FLS cells after treatment of 40, 80 and 160 μmol/L(P<0.05,P<0.01). Compared with the Control group, the expression level of STING protein in FLS increased after overexpression of cGAS(P<0.05); compared with the Res group, the content of inflammatory factors in the supernatant of FLS and the expression level of STING protein in FLS significantly increased after overexpression of cGAS(P<0.01,P<0.05). Conclusion The appropriate concentration of Res can inhibit the release of inflammatory cytokines in FLS cells, which may be related to the blocking of cGAS-STING signaling pathway.

ObjectiveTo explore the mechanism by which the ethanol extract of Epimedium brevicornu （EEBM） intervenes in mesenchymal adipose-derived stem cells （ADSCs） to delay aging in castrated rats. MethodsForty-five 3-month-old SPF female SD rats were ovariectomized and randomly divided into model group， ADSCs treatment group， and ADSCs groups treated with low， medium， and high concentrations of EEBM （1， 50， 100 μg·L^-1）， referred to as the AE low， medium， and high concentration groups， with 9 rats in each group. After tail vein injection of 200 μL of the corresponding stem cell suspension， aging-related indicators including cyclin-dependent kinase inhibitor （p21）， tumor suppressor gene （p53）， interleukin-6 （IL-6）， interleukin-8 （IL-8）， superoxide dismutase （SOD）， malondialdehyde （MDA）， B-cell lymphoma-2 （Bcl-2）， Bcl-2-associated X protein （Bax）， cysteine-aspartic acid protease-3 （Caspase-3）， and lipofuscin were measured using enzyme-linked immunosorbent assay （ELISA） and Western blot. ResultsCompared with the model group， the IL-6 content in the AE low， medium， and high concentration groups was significantly decreased （P<0.05）. Lipofuscin， MDA， and IL-8 levels in the ADSCs treatment group and AE low， medium， and high concentration groups were significantly reduced （P<0.01）， while SOD content was significantly increased （P<0.05， P<0.01）. Compared with the ADSCs treatment group， lipofuscin and IL-8 levels in the AE low， medium， and high concentration groups were significantly reduced （P<0.05， P<0.01）. The MDA content was significantly decreased in the AE medium concentration group （P<0.01）. Compared with the model group， protein levels of p21， p53， Bax， and Caspase-3 in the ADSCs treatment group and AE low， medium， and high concentration groups were significantly reduced （P<0.05， P<0.01）， while the Bcl-2 protein level was significantly increased （P<0.01）. Compared with the ADSCs treatment group， protein levels of p21， p53， Bax， and Caspase-3 in the AE low， medium， and high concentration groups were significantly reduced （P<0.05， P<0.01）， and the Bcl-2 protein level in the AE low concentration group was significantly increased （P<0.01）. ConclusionThe results of this experiment show that EEBM-treated ADSCs or ADSCs may delay aging in castrated rats by inhibiting cell apoptosis， reducing cell cycle inhibitors and pro-inflammatory factors， enhancing antioxidant capacity， and reducing oxidative reactions. Moreover， EEBM-treated ADSCs demonstrate stronger anti-aging effects than ADSCs alone. This study provides experimental evidence supporting the clinical use of EEBM to intervene in ADSCs and delay aging.

AIM: To explore the control effects of wearing orthokeratology lens for 1 a on adolescent myopia patients with different diopters.METHODS: Prospective non-randomized controlled study. A total of 120 adolescent myopic patients(224 eyes), with an average age of 11.00±2.08 years old, who were fitted with orthokeratology lenses in the optometry department of our hospital from November 2022 to May 2023 were collected. There were 3 groups according to the spherical equivalent, including 86 eyes in the group of -0.50--2.00 D, 99 eyes in the group -2.25--4.00 D, and 39 eyes in group -4.25--6.00 D. Patients were followed up for 1 a to observe the changes of uncorrected visual acuity, axial length, corneal curvature, corneal central thickness and corneal endothelial cells density in the three groups after wearing lens for 1 a.RESULTS:A total of 113 cases(212 eyes)were followed up for 1 a, including 82 eyes in the group of -0.50--2.00 D, 95 eyes in the group of -2.25--4.00 D, and 35 eyes in the group of -4.25--6.00 D. There was no statistical difference in corneal central thickness and corneal endothelial cell density among the three groups of patients after wearing lens for 1 a(all P>0.05). Uncorrected visual acuity was significantly improved, and flat kerotometry(FK)and steep kerotometry(SK)were significantly flatter(both P<0.01). Furthermore, the growth of axial length in the three groups of patients after wearing lens for 1 a was 0.21±0.26, 0.13±0.21 and 0.09±0.10 mm, respectively(P<0.05). There were differences between the -0.50--2.00 D group and the -2.25--4.00 D group and -4.25--6.00 D group(P=0.028, 0.010), and there were no differences between the -2.25--4.00 D group and the -4.25--6.00 D group(P=0.344).CONCLUSION:It is safe and effective for young myopia patients to wear orthokeratology lenses, which can prevent the non-benign growth of the axial length and effectively delay the development of myopia, and the myopia control effect is better especially for myopia patients of above -2.0 D.

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.

ObjectiveMicrotube associated protein-2 （MAP-2）， alpha-tubulin （α-tubulin）， and synaptophysin （SYP） are important proteins in neuronal signal communication. This paper observed the effects of modified Zhigancao Tang on the expression of serum α-Synuclein （α-Syn） and its oligomers， MAP-2， α-tubulin， and SYP of patients with liver and kidney deficiency of Parkinson's disease （PD）， analyzed their correlation， and evaluated the therapeutic effect of modified Zhigancao Tang in patients with liver and kidney deficiency of PD based on α-Syn transmission pathway mediated by neuronal communication in vivo. MethodsA total of 60 patients with PD who met the inclusion criteria were randomly divided into a treatment group （30 cases） and a control group （30 cases）. Both groups were treated on the basis of PD medicine， and the treatment group was treated with modified Zhigancao Tang. Both groups were treated for 12 weeks. The changes in UPDRS score， TCM syndrome score， and expression of serum α-Syn and its oligomers， MAP-2， α-tubulin， and SYP were observed before and after 12 weeks of treatment in each group. The correlation between the above-mentioned serum biological indexes and the levels of serum α-Syn and its oligomers was analyzed. ResultsAfter treatment， the TCM syndrome score， UPDRS score， UPDRS-Ⅱ score， and UPDRS-Ⅲ score of the treatment group were significantly decreased （P<0.05， P<0.01）. The UPDRS score， UPDRS-Ⅱ score， and UPDRS-Ⅲ scores in the treatment group were significantly decreased compared with those in the control group after treatment （P<0.05）. After treatment， the total effective rate of the control group was 63.3% （19/30）， and that of the treatment group was 86.7% （26/30）. The clinical effect of the observation group was better than the control group （Z=-2.03， P<0.05）. The total effective rate of the observation group was better than that of the control group， and the difference was statistically significant （χ²=5.136， P<0.05）. After treatment， the oligomer level of serum α-Syn and MAP-2 level in the treatment group were significantly decreased （P<0.05， P<0.01）. The levels of serum α-Syn and its oligomers， as well as α-tubulin in the treatment group， were significantly decreased compared with those in the control group after treatment （P<0.05， P<0.01）. Serum α-Syn was correlated with serum MAP-2 and α-Syn oligomer in patients with PD （P<0.05， P<0.01） but not correlated with serum SYP . Serum α-Syn oligomers of patients with PD were correlated with serum MAP-2 and α-tubulin （P<0.05， P<0.01） but not correlated with serum SYP level. Serum SYP of patients with PD was correlated with serum MAP-2 （P<0.05）. ConclusionModified Zhigancao Tang has a therapeutic effect on patients with liver and kidney deficiency of PD by inhibiting the production of α-Syn oligomers and intervening α-Syn microtubule transport pathway in vivo.

Shengyutang is a famous classical formula of tonic， which is made from Siwutang with Ginseng Radix et Rhizoma and Astragali Radix. It is included in the Catalogue of Ancient Famous Classical Formulas（The First Batch）. Based on the Principles of Key Information Research of Ancient Famous Classical Formulas， this paper used bibliometrics to sort out and research the key information of Shengyutang in the aspects of history， composition， origin and processing， dosage， decocting method， efficacy and indications. After research， it has been found that this formula was first recorded in Lanshi Micang written by LI Dongyuan during the Jin dynasty， composed of Rehmanniae Radix， Rehmanniae Radix Praeparata， Chuanxiong Rhizoma， Ginseng Radix et Rhizoma， Astragali Radix and Angelicae Sinensis taproot. The name of the formula passed down through generations was relatively unified， with clear origins and veins. In later generations， this formula was the mainstream， and adjustments were made to the dosage and composition according to the indication. In the formula， Astragalus membranaceus var. mongholicus was selected as the origin of Astragali Radix， and the origins of other medicinal materials were consistent with the 2020 edition of Chinese Pharmacopoeia. Except for Rehmanniae Radix Praeparata， the other medicinal materials were made from raw products， and the dosage form was boiled powder. According to the measurement standard in the Jin dynasty， the recommended usage and dosage were 1.24 g of Rehmanniae Radix， Rehmanniae Radix Praeparata， Chuanxiong Rhizoma， Ginseng Radix et Rhizoma each， 2.07 g of Astragali Radix and Angelicae Sinensis taproot each， crushed into coarse particles that pass through the 4 mesh sieve but can't pass through the 10 mesh sieve， added 1 200 mL of water and boiled to 300 mL， and removed the residue. Shengyutang has the functions of tonifying Qi and blood， and blood intake， treating various sores， and restlessness and insomnia caused by excessive blood flow. In ancient times， this formula was widely used in the treatment of surgical sores， gynecological diseases， deficiency syndrome， etc. In modern clinical practice， it is mostly used to treat gynecological， neurological， musculoskeletal， hematological diseases caused by Qi and blood deficiency. In this paper， the key information of Shengyutang was researched by reviewing relevant ancient literature， in order to provide reference for the modern application and development of this formula.