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 of Schisandrae Chinensis Fructus lignans on schizophrenia induced by dizocilpine maleate （MK-801） in mice and to clarify its mechanism. MethodsMale mice of 4-6 weeks old were randomized into blank， model， positive drug， and low-， medium-， and high-dose （40， 80， 160 mg·kg^-1， respectively） Schisandrae Chinensis Fructus lignans groups. The blank group was administrated with distilled water， and the other groups were injected with 0.5 mg·kg^-1 MK-801 to induce schizophrenia symptoms. Meanwhile， risperidone was injected at 0.2 mg·kg^-1 in the positive drug group， and mice in the intervention groups were injected with corresponding drugs for 14 consecutive days. The behavioral changes of mice were observed by autonomous activity test， open field test， forced swimming test， and water maze test. The levels of dopamine （DA） and 5-hydroxytryptamine （5-HT） in the brain and tumor necrosis factor-α （TNF-α） and nuclear factor-κB （NF-κB） in peripheral blood were quantified by enzyme-linked immunosorbent assay （ELISA）. The changes in the prefrontal lobe of mice were observed by hematoxylin-eosin staining， and the changes of the hippocampal tissue were observed by Nissl staining. The protein levels of silencing information regulatory factor 1 （SIRT1） and forkhead box protein O3a （FoxO3a） in the hippocampus of mice were determined by Western blot. ResultsCompared with the model group， low， medium， and high doses of Schisandrae Chinensis Fructus lignans reduced the total number of autonomous activities， total distance in the open field test， immobile time in the forced swimming test， and levels of TNF-α and NF-κB in peripheral blood （P<0.05）， while increasing the number of platform crossings in the water maze test and DA and 5-HT levels in the brain tissue （P<0.05）. Compared with the model group， risperidone and low， medium， and high doses of Schisandrae Chinensis Fructus lignans improve the neural cell morphology in the CA1 region， with full cells in neatly dense arrangement and exhibiting clear membrane boundary. Schisandrae Chinensis Fructus lignans inhibited the expression of SIRT 1 and FoxO3a in the hippocampus （P<0.05）. ConclusionTo sum up， Schisandrae Chinensis Fructus lignans may improve the behavior of schizophrenic mice by activating the SIRT1/FoxO3a signaling pathway to exert neuroprotective effects.

OBJECTIVE To investigate the mechanism of Shenling baizhu san （SLBZS） in ameliorating ulcerative colitis （UC）. METHODS Mice were randomly divided into normal group， model group， and low-， medium-， high-dose SLBZS groups （3， 6， 12 g/kg）， with 10 mice in each group. Except for the normal group， mice in other groups were given free access to 3% dextran sulfate sodium solution for 7 days to establish UC models. Simultaneously， mice in each group were intragastrically administered corresponding medicinal liquid or double-distilled water once a day for consecutive 7 days. After the last administration， the histopathological morphology of colon tissues was observed； the serum levels of inflammatory factors including tumor necrosis factor-α （TNF-α）， interleukin-1β （IL-1β） and IL-18 were detected； the total bile acid contents in liver， gallbladder and colon tissues were determined； the expression level of NOD-like receptor family pyrin domain-containing protein 3 （NLRP3） in colon tissues was tested. The expression levels of flora metabolism-related proteins [G protein-coupled receptor 41（GPR41），GPR43，farnesoid X receptor （FXR）， G protein-coupled bile acid receptor 1 （TGR5）， flavin-containing monooxygenase 3 （FMO3）， cytochrome P450 family 27 subfamily A member 1 （CYP27A1）， CYP7A1] in liver or colon tissues， as well as the proteins related to Toll-like receptor 4 （TLR4）/nuclear factor-κB （NF-κB）/NLRP3 inflammatory axis [TLR4， NF-κB， phosphorylated NF-κB （p-NF-κB）， myeloid differentiation factor 88 （MyD88）， NLRP3， apoptosis-associated speck-like protein containing a CARD （ASC）， caspase-1] in colon tissues were measured. RESULTS Compared with the model group， the colon tissue injury and inflammatory cell infiltration were alleviated in medium- and high-dose SLBZS groups. The serum levels of TNF-α， IL-1β and IL-18， total bile acid contents in liver and colon tissues， as well as the protein expression levels of FMO3 and CYP7A1 in liver tissues， TLR4， p-NF-κB， NF-κB， MyD88， NLRP3， ASC and caspase-1 in colon tissues were significantly decreased （P＜0.05）. Meanwhile， the total bile acid content in gallbladder， the protein expression levels of GPR41 and GPR43 in colon tissues， along with CYP27A1， FXR and TGR5 in liver tissues were significantly increased （P＜0.05）. CONCLUSIONS SLBZS may relieve colonic inflammatory injury and ameliorate UC by regulating the expression of flora metabolism-related proteins and inhibiting the abnormal activation of TLR4/NF-κB/NLRP3 inflammatory axis.

Objective To evaluate the effectiveness of preoperative immunosuppressive therapy combined with surgical intervention for Behçet's disease. Methods A retrospective study was conducted on Behçet's disease patients who underwent cardiovascular surgery at Guangdong Provincial People's Hospital from 2012 to 2021. Patients were divided into an immunosuppressive group and a non-immunosuppressive group based on whether they received immunosuppressive therapy before surgery. The complications and long-term survival rates of the two groups were analyzed. Results A total of 28 patients were included, among which 2 patients underwent reoperation, a total of 30 surgeries were performed, including 16 males (53.3%), and the age at diagnosis was 37 (31, 45) years. There were 15 surgeries in the immunosuppressive group and 15 surgeries in the non-immunosuppressive group. Compared with the non-immunosuppressive group, the incidence of complications during hospitalization in the immunosuppressive group was lower (13.3% vs. 53.3%, P=0.008). One patient died in hospital, and the rest were discharged and followed up, with a median follow-up time of 38.7 (15.1, 57.3) months, and there was no statistically significant difference in long-term survival rate between the two groups (73.3% vs. 93.3%, P=0.158). There was no statistical difference in the cumulative incidence of complications one month (20% vs. 53%, P=0.058) and one year (27% vs. 60%, P=0.065) after surgery between the immunosuppressive group and the non-immunosuppressive group, but there was a statistical difference in the cumulative incidence of complications three years after surgery (47% vs. 92%, P=0.002). Conclusion Surgical treatment can save lives in Behçet's disease patients with cardiovascular diseases, but the incidence of postoperative complications is high. Timely use of immunosuppressants before cardiovascular surgery can reduce the incidence of postoperative complications.

ObjectiveTo observe the analgesic efficacy and safety of Qihuang acupuncture theory combined with opioid analgesics in patients with moderate to severe cancer pain due to lung cancer. MethodsPatients with moderate to severe cancer pain from lung cancer were randomly divided into Qihuang acupuncture group and control group， with 33 cases in each group. The control group was treated with long-acting opioid analgesics at maintenance doses and supplementary analgesic medications as needed. In case of breakthrough pain， short-acting opioids were used for rescue. The Qihuang acupuncture group received Qihuang acupuncture treatment in addition to the treatment used in the control group， administered once every other day， with 3 sessions constituting one treatment course. The treatment duration for both groups was 5 days. The primary outcome was the change in pain intensity， measured using the numerical rating scale （NRS） before and after treatment， and the NRS change rate was calculated. Secondary endpoints included the daily NRS change rate， the Eastern Cooperative Oncology Group （ECOG） Performance Status （PS） score， the European Organization for Research and Treatment of Cancer Quality of Life Core Questionnaire （EORTC QLQ-C30） score， and the 24-hour equivalent hydrocodone sustained-release tablet dose. Laboratory tests， including routine blood， urine， stool， liver function， and kidney function， were performed before and after treatment. Adverse events were recorded throughout the trial. ResultsAll patients completed the trial， and both groups showed a decrease in average NRS scores and PS scores after treatment， with the Qihuang acupuncture group showing lower average NRS scores and PS scores than the control group （P＜0.05 or P＜0.01）. After treatment， the NRS change rate in the Qihuang acupuncture group was （0.42±0.17）， significantly higher than that in the control group （0.14±0.27， P＜0.01）. The daily NRS change rate during treatment was also higher in the Qihuang acupuncture group compared to the control group （P＜0.01）. The Qihuang acupuncture group showed an increase in overall health status and functional scores in the EORTC QLQ-C30， and a decrease in symptom scores for fatigue， nausea and vomiting， pain， dyspnea， insomnia， appetite loss， constipation， and financial difficulties. In contrast， overall health status and constipation scores in the control group increased， while scores of fatigue， nausea and vomiting， pain， and appetite loss decreased （P＜0.05 or P＜0.01）. After treatment， the 24-hour equivalent hydrocodone sustained-release tablet dose did not show significant difference in the Qihuang acupuncture group （P＞0.05）， while the control group showed a significant increase in the 24-hour dose （P＜0.01）. No significant abnormalities were observed in laboratory tests before and after treatment in either group. During the study， the incidence of nausea and vomiting as well as constipation in the Qihuang acupuncture group was both 3.03% （1/33）， while the incidence in the control group was 27.27% （9/33） and 36.36% （12/33）， respectively， with the Qihuang acupuncture group showing significantly lower incidence （P＜0.01）. No serious adverse reactions were observed in either group. ConclusionQihuang acupuncture therapy combined with opioid analgesics is more effective than using opioids alone in relieving pain in patients with moderate to severe cancer pain due to lung cancer. It can improve the patients' physical condition and quality of life， reduce the dose of opioid analgesics， and has good safety.

Non-small cell lung cancer (NSCLC) is a malignant tumor with a high global incidence rate, accounting for about 10.54% of all new cancer cases and posing a serious threat to human health. Due to significant individual variations in the efficacy of immunotherapy among NSCLC patients, it is necessary to identify accurate detection indicators to screen appropriate populations, monitor treatment efficacy, and assist in prognosis assessment. Programmed death-ligand 1 (PD-L1), as an immunosuppressive molecule expressed on the surface of tumor cells and various immune cell membranes, can serve as a "companion diagnostic" or "supplementary diagnostic" tool to guide clinical treatment decisions for metastatic NSCLC patients. Given that tumor tissue PD-L1 testing is an invasive procedure and its reliability is still under debate, the assessment of PD-L1 expression via liquid biopsies, such as circulating tumor cells, will play a significant role in predicting treatment response and prognosis in NSCLC patients.

Objective To explore and analyze the related factors of kinesiophobia in elderly patients with coronary heart disease (CHD) during cardiac rehabilitation exercise period, and to evaluate the effect of cognitive behavior therapy on improving kinesiophobia and promoting rehabilitation. Methods A total of 352 elderly patients with CHD admitted to the hospital were included from October 2023 to October 2024. Tampa Scale for Kinesiophobia-11 (TSK-11) was adopted to evaluate the kinesiophobia status. Patients with kinesiophobia were randomly grouped. Routine intervention (routine group, n=82) and cognitive behavior intervention (study group, n=82) were implemented respectively. The intervention effects were observed in both groups. Results Among the 352 patients, 46.59 % (164/352 ) of elderly patients with coronary heart disease had different degrees of kinesiophobia. The proportions of female, divorced/widowed, revascularization and family relationship disharmony and scores of Patient Health Questionnaire (PHQ9) and Generalized Anxiety Disorder Scale (GAD7) in patients with kinesiophobia were higher than those in patients without kinesiophobia (P<0.05) while the scores of General Self-Efficacy Scale (GSES) and Social Support Rating Scale (SSRS) were lower compared with those in patients without kinesiophobia (P<0.05). Logistic regression analysis found that female, divorced/widowed, family relationship disharmony, revascularization and scores of PHQ9, TSK-11, GAD7, GSES and SSRS were related to kinesiophobia (P<0.05). After intervention, the scores of TSK-11, PHQ9 and GAD7 in the study group were lower while the scores of GSES and SSRS, 6 min walking test distance, and cardiopulmonary exercise test peak oxygen uptake and anaerobic threshold were higher compared to the routine group (P<0.05). Conclusion The kinesiophobia in elderly patients with CHD during cardiac rehabilitation is related to gender, revascularization and psychosocial factors. Clinically, cognitive behavior intervention should be provided according to the situation and guided to carry out rehabilitation exercise regularly so as to promote improvement of cardiopulmonary function.

Objective To investigate the effects of Aconite decoction （AD） on the viability and polarization of murine RAW264.7 macrophages induced by lipopolysaccharide （LPS） or interleukin-4 （IL-4）. Methods Cytotoxicity of AD was assessed by the CCK-8 assay. RAW264.7 cells were polarized toward M1 phenotype by LPS or M2 phenotype by IL-4, followed by treatment with varying concentrations of AD. Macrophage polarization was analyzed by flow cytometry. Quantitative PCR was performed to measure mRNA expression of polarization-associated markers （IL-6, iNOS, Arg1, and Ym1）. ELISA was used to quantify secreted cytokines （TNF-α and IL-10）in the supernatant. Results At non-toxic concentrations, IL-6 and iNOS mRNA levels in LPS-stimulated cells were significantly upregulated while Arg1 and Ym1 expression in IL-4-treated groups were downregulated by AD. Concurrently, TNF-α secretion in LPS-induced M1 polarization was enhanced but IL-10 production in IL-4-induced M2 polarization was suppressed by AD. Conclusion AD could promote macrophage proliferation and viability, augments LPS-driven M1 polarization, and inhibit IL-4-mediated M2 polarization, which provided experimental evidence for the potential application of AD in tumor immunotherapy.

BACKGROUND:Gradient artificial bone repair scaffolds can mimic unique anatomical features in musculoskeletal tissues,showing great potential for repairing injured musculoskeletal tissues. OBJECTIVE:To review the latest research advances in gradient artificial bone repair scaffolds for tissue engineering in the musculoskeletal system and describe their advantages and fabrication strategies. METHODS:The first author of the article searched the Web of Science and PubMed databases for articles published from 2000 to 2023 with search terms"gradient,bone regeneration,scaffold".Finally,76 papers were analyzed and summarized after the screening. RESULTS AND CONCLUSION:(1)As an important means of efficient and high-quality repair of skeletal system tissues,gradient artificial bone repair scaffolds are currently designed bionically for the natural gradient characteristics of bone tissue,bone-cartilage,and tendon-bone tissue.These scaffolds can mimic the extracellular matrix of native tissues to a certain extent in terms of structure and composition,thus promoting cell adhesion,migration,proliferation,differentiation,and regenerative recovery of damaged tissues to their native state.(2)Advanced manufacturing technology provides more possibilities for gradient artificial bone repair scaffold preparation:Gradient electrospun fiber scaffolds constructed by spatially differentiated fiber arrangement and loading of biologically active substances have been developed;gradient 3D printed scaffolds fabricated by layered stacking,graded porosity,and bio-3D printing technology;gradient hydrogel scaffolds fabricated by in-situ layered injections,simple layer-by-layer stacking,and freeze-drying method;and in addition,there are also scaffolds made by other modalities or multi-method coupling.These scaffolds have demonstrated good biocompatibility in vitro experiments,were able to accelerate tissue regeneration in small animal tests,and were observed to have significantly improved histological structure.(3)The currently developed gradient artificial bone repair scaffolds have problems such as mismatch of gradient scales,unclear material-tissue interactions,and side effects caused by degradation products,which need to be further optimized by combining the strengths of related disciplines and clinical needs in the future.

Objective:This study investigated the independent risk factors for lymph node metastasis（LNM）in high-risk prostate cancer（HRPCa）patients undergoing robot-assisted radical prostatectomy（RARP），and constructed a nomogram model based on clinical data to improve the accuracy and clinical practicality of preoperative prediction of LNM.Methods:A retrospective analysis was conducted on the clinical data of 218 HRPCa patients who received RARP treatment at the First Medical Center of the PLA General Hospital from January 2020 to March 2025 as the modeling group. The age of the modeling group was（66.91±6.94）years old. 75 cases（34.40%）had a history of smoking，and 48 cases（22.02%）had a history of drinking. There were a body mass index（BMI）of 25.55（23.58，27.00）kg/m 2，a total prostate-specific antigen（tPSA）of 20.59（10.42，30.61）ng/ml，a free prostate-specific antigen（fPSA）of 1.87（1.04，3.26）ng/ml，a prostate volume（PV）of（41.19±21.00）ml，a prostate-specific antigen density（PSAD）of 0.52（0.30，0.84）ng/ml 2. Among the patients，60 cases（27.52%）had a preoperative biopsy Gleason score >8，and the percentage of positive biopsy cores（PPBC）was 50%（31%，80%）. Thirty-one patients（14.22%）were staged clinically as >T 2c. The diagnostic criteria for high-risk prostate cancer（HRPCa）were defined as meeting any one of the following：PSA >20 ng/ml，Gleason score on prostate biopsy ≥8，or clinical stage ≥T 3. Among the 218 patients in the modeling cohort，67 cases（30.73%）met two of the criteria，and 7 cases（3.21%）met all three criteria. All 218 patients underwent RARP，and based on postoperative pathology，they were divided into the LNM group and the non-LNM group. The relationship between the number of diagnostic criteria met and the occurrence of LNM was analyzed. An external validation cohort included 42 HRPCa patients who underwent RARP at the Third，Fifth Medical Centers of the PLA General Hospital between January 2023 and May 2025. Their mean age was（66.79±5.92）years. Eighteen patients（42.86%）had a smoking history，and nine（21.43%）had a history of alcohol consumption. The median BMI was 26.00（23.80，27.13）kg/m 2. The median tPSA level was 17.34（8.97，27.30）ng/ml. The median fPSA was 1.51（0.83，2.52）ng/ml，and the median PV was（35.57 ± 15.25）ml. The median PSAD was 0.57（0.23，0.87）ng/ml 2，and the median PPBC was 58%（36%，71%）. Three patients（7.14%）had a clinical stage >T 2c，and 12 patients（28.57%）had a Gleason score >8 on preoperative biopsy. Univariate and multivariate binary logistic regression analyses were used to identify independent risk factors for LNM，and a nomogram model was constructed based on these factors. The predictive performance of the model was evaluated using receiver operating characteristic（ROC）curves and calibration plots，and the model was validated in the external cohort. Result:According to postoperative pathology，45 patients were classified into the LNM group，and 173 into the non-LNM group. The probability of LNM increased proportionally with the number of diagnostic criteria met for HRPCa（meeting two criteria： OR = 4.762，95% CI 2.323-9.761， P < 0.01；meeting three criteria： OR = 10.667，95% CI 2.187-52.025， P=0.003）. Binary logistic regression analysis revealed that age（ OR=0.913，95% CI 0.859-0.971， P = 0.004），tPSA（ OR=1.039，95% CI 1.018-1.061， P<0.01），PPBC（ OR = 5.656，95% CI 1.101-29.056， P = 0.038），and clinical T stage（T 2c stage： OR=2.945，95% CI 0.888-9.769， P=0.077；>T 2c stage OR = 18.351，95% CI 4.790-70.306， P < 0.01）were independent risk factors for postoperative LNM in HRPCa patients after RARP. The ROC curve of the nomogram model based on these factors showed an area under the curve（AUC）of 0.853（95% CI 0.790-0.917）. In the external validation cohort，the nomogram achieved an AUC of 0.743（95% CI 0.556-0.929）. The calibration plots demonstrated good agreement between the predicted probabilities and actual observations. Conclusions:Age，tPSA，PPBC，and clinical T stage were independent predictors of postoperative LNM in HRPCa patients undergoing RARP. The greater the number of HRPCa diagnostic criteria met，the higher the likelihood of postoperative LNM. The nomogram developed in this study could effectively predict the risk of LNM in HRPCa patients after RARP.