OBJECTIVE To study the pharmacokinetic characteristics of antidepressant active components from Jiaotai pills in healthy subjects. METHODS Eight healthy subjects （3 males and 5 females） were recruited and given a single oral dose of 8.55 g of Jiaotai pills. Venous blood samples were collected before administration （0 h） and at intervals from 0.25 to 36.0 hours post- administration. After treating the plasma samples with protein precipitation， the blood concentrations of the antidepressant active ingredients （coptisine， berberine， magnoflorine， and palmatine） in Jiaotai pills were determined using liquid chromatography- tandem mass spectrometry （LC-MS/MS） method. DAS 2.0 software was employed to calculate the pharmacokinetic parameters of healthy subjects [half-life （t1/2）， peak concentration （cmax）， time to peak concentration （tmax）， area under the concentration-time curve （AUC）， and mean residence time （MRT）] using a non-compartmental model. RESULTS After healthy subjects took Jiaotai pills， the drug-time curve of the four antidepressant active ingredients conforms to a two-compartment model and tmax values were similar， with all reaching peak blood concentrations within 2.00 to 4.00 hours post-administration. However， the t1/2 and MRT of coptisine and berberine were significantly longer than that of magnoflorine and palmatine. There were also significant differences in the AUC and cmax among the four antidepressant active ingredients， with magnoflorine exhibiting markedly higher AUC0-t and cmax compared to the other three components. CONCLUSIONS In this study，LC-MS/MS is used to analyze the pharmacokinetic characteristics of the antidepressant active ingredients from Jiaotai pills in healthy subjects， can provide valuable references for the clinical application of Jiaotai pills.

ObjectiveThis paper aims to find the identified and validated clinical biomarker data building upon a clinical study of early-phase phase Ⅱ and investigate the correlation analysis of Huanglian Jiedu Wan on syndrome improvement and clinical biomarkers in the treatment of "excess heat-toxicity" based on a machine learning model. Additionally， the effective prediction of clinical biomarker values for the main symptoms of the "excess heat-toxicity" syndrome was assessed. MethodsA total of 229 patients meeting the inclusion criteria for "excess heat-toxicity" syndrome were randomly divided into the Huanglian Jiedu Wan group and the placebo group. Syndrome score transition matrices were constructed for the Huanglian Jiedu Wan group and the placebo group based on three main symptoms of "excess heat-toxicity" syndrome， such as oral ulcers， sore throat， and gum swelling and pain. Data from the patients with these three syndromes were also integrated for an overall analysis. The corresponding syndrome score transition matrices were further constructed to visualize symptom change trends of the patients in the two groups via heatmaps. Based on the identified and validated clinical biomarkers related to inflammation， oxidative stress， and energy metabolism in the early phase， Spearman correlation analysis was employed to analyze and evaluate the associations between clinical biomarkers and syndrome improvement. Key clinical biomarkers reflecting the effect of Huanglian Jiedu Wan were screened through the comparison of differences between groups. An extreme gradient boosting （XGBoost） algorithm was used to develop a prediction model for main symptom classification， with classification performance evaluated through 10-fold cross-validation. Feature importance analysis was applied to identify variables with the greatest contribution to the prediction result. ResultsThe syndrome transition matrix results indicated that the Huanglian Jiedu Wan group showed a superior effect to the placebo group in improving oral ulcers， sore throat， and overall symptoms， with significant effects observed especially in sore throat and overall symptom analyses （P<0.01）. Spearman correlation analysis revealed that several clinical biomarkers positively correlated with "excess heat-toxicity" syndrome and its main symptom improvement， were also called "heat-related biomarkers"， including succinic acid， α-ketoglutaric acid， glycine， lactic acid， adenosine monophosphate （AMP）， tumor necrosis factor-α （TNF-α）， interferon-γ （IFN-γ）， interleukin-1β （IL-1β）， interleukin-4 （IL-4）， interleukin-6 （IL-6）， interleukin-8 （IL-8）， interleukin-10 （IL-10）， and so on. Conversely， clinical biomarkers negatively correlated with symptom severity， were also called "heat-clearing related biomarkers" after administration of Huanglian Jiedu Wan， including malic acid， fumaric acid， cis-aconitic acid， adrenocorticotropic hormone （ACTH）， IL-1β， IL-4， IL-8， succinic acid， and citric acid. The XGBoost classification model using all 52 biomarkers as variables achieved an average test accuracy of 0.754 and an average F1 score of 0.777. Feature importance analysis identified the scores of glutamic acid in saliva and IL-6 were the highest in all the variables， with importance scores of 0.081 and 0.080， respectively. After screening out 14 key variables and optimizing the parameters， model performance improved to an average accuracy of 0.758 and an F1 score of 0.798. Feature importance analysis further determined that the glutamic acid in saliva and IL-6 showed obvious changes after screening the variables， confirming the good syndrome prediction ability of the model constructed by these key clinical biomarkers. ConclusionThis study systematically elucidates the correlation between syndrome improvement and clinical biomarkers of Huanglian Jiedu Wan in the treatment of "excess heat-toxicity" syndrome. An XGBoost classification model based on key clinical biomarkers is successfully established， achieving effective prediction of the symptoms related to the "excess heat-toxicity" syndrome such as oral ulcers and sore throat and providing a new insight for objective identification of traditional Chinese medicine syndromes.

ObjectiveThis paper aims to find the identified and validated clinical biomarker data building upon a clinical study of early-phase phase Ⅱ and investigate the correlation analysis of Huanglian Jiedu Wan on syndrome improvement and clinical biomarkers in the treatment of "excess heat-toxicity" based on a machine learning model. Additionally， the effective prediction of clinical biomarker values for the main symptoms of the "excess heat-toxicity" syndrome was assessed. MethodsA total of 229 patients meeting the inclusion criteria for "excess heat-toxicity" syndrome were randomly divided into the Huanglian Jiedu Wan group and the placebo group. Syndrome score transition matrices were constructed for the Huanglian Jiedu Wan group and the placebo group based on three main symptoms of "excess heat-toxicity" syndrome， such as oral ulcers， sore throat， and gum swelling and pain. Data from the patients with these three syndromes were also integrated for an overall analysis. The corresponding syndrome score transition matrices were further constructed to visualize symptom change trends of the patients in the two groups via heatmaps. Based on the identified and validated clinical biomarkers related to inflammation， oxidative stress， and energy metabolism in the early phase， Spearman correlation analysis was employed to analyze and evaluate the associations between clinical biomarkers and syndrome improvement. Key clinical biomarkers reflecting the effect of Huanglian Jiedu Wan were screened through the comparison of differences between groups. An extreme gradient boosting （XGBoost） algorithm was used to develop a prediction model for main symptom classification， with classification performance evaluated through 10-fold cross-validation. Feature importance analysis was applied to identify variables with the greatest contribution to the prediction result. ResultsThe syndrome transition matrix results indicated that the Huanglian Jiedu Wan group showed a superior effect to the placebo group in improving oral ulcers， sore throat， and overall symptoms， with significant effects observed especially in sore throat and overall symptom analyses （P<0.01）. Spearman correlation analysis revealed that several clinical biomarkers positively correlated with "excess heat-toxicity" syndrome and its main symptom improvement， were also called "heat-related biomarkers"， including succinic acid， α-ketoglutaric acid， glycine， lactic acid， adenosine monophosphate （AMP）， tumor necrosis factor-α （TNF-α）， interferon-γ （IFN-γ）， interleukin-1β （IL-1β）， interleukin-4 （IL-4）， interleukin-6 （IL-6）， interleukin-8 （IL-8）， interleukin-10 （IL-10）， and so on. Conversely， clinical biomarkers negatively correlated with symptom severity， were also called "heat-clearing related biomarkers" after administration of Huanglian Jiedu Wan， including malic acid， fumaric acid， cis-aconitic acid， adrenocorticotropic hormone （ACTH）， IL-1β， IL-4， IL-8， succinic acid， and citric acid. The XGBoost classification model using all 52 biomarkers as variables achieved an average test accuracy of 0.754 and an average F1 score of 0.777. Feature importance analysis identified the scores of glutamic acid in saliva and IL-6 were the highest in all the variables， with importance scores of 0.081 and 0.080， respectively. After screening out 14 key variables and optimizing the parameters， model performance improved to an average accuracy of 0.758 and an F1 score of 0.798. Feature importance analysis further determined that the glutamic acid in saliva and IL-6 showed obvious changes after screening the variables， confirming the good syndrome prediction ability of the model constructed by these key clinical biomarkers. ConclusionThis study systematically elucidates the correlation between syndrome improvement and clinical biomarkers of Huanglian Jiedu Wan in the treatment of "excess heat-toxicity" syndrome. An XGBoost classification model based on key clinical biomarkers is successfully established， achieving effective prediction of the symptoms related to the "excess heat-toxicity" syndrome such as oral ulcers and sore throat and providing a new insight for objective identification of traditional Chinese medicine syndromes.

ObjectiveTo investigate the mechanism of salt processing of Psoraleae Fructus （PF） through modern analytical techniques and biotechnology， focusing on its effects related to hepatotoxicity and anti-osteoporosis activity. MethodsThe zebrafish model was utilized to evaluate the impact of PF and salt-processed Psoraleae Fructus （SPF） on the hepatotoxicity （using 134.17 ， 178.89， 268.34 mg·L^-1 as low， medium， and high dose groups of PF， 135.04， 180.06， 270.08 mg·L^-1 as low， medium， and high dose groups of SPF， respectively） and anti-osteoporotic activity （using 33.54 ， 67.08 and 134.17 mg·L^-1 as low， medium， and high dose groups of PF， 33.76， 67.52， 135.04 mg·L^-1 as low， medium， and high dose groups of SPF， respectively）， which was using alizarin red skull staining of zebrafish as an indicator of different batches of PF. The specific dosage of a batch of PF was taken as an example. Then ultra-performance liquid chromatography-quadrupole-time of flight-mass spectrometry（UPLC-Q-TOF-MS） analysis was employed to identify the chemical composition of PF before and after salt processing， and PCA， OPLS-DA， and independent sample t-test were used to elucidating the compositional changes associated with the effects of salt processing on hepatotoxicity and anti-osteoporosis activity. ResultsUnder specific conditions， PF induced notable hepatotoxicity in zebrafish while simultaneously demonstrating protective effect against prednisolone-induced osteoporosis. In comparison to PF， SPF showed alleviated hepatotoxicity while retaining significant anti-osteoporosis activity. UPLC-Q-TOF-MS analysis revealed that after salt processing， the overall chemical composition of PF showed a downward trend， with 69 components showing a decrease in content， represented by psoralen， and 13 components showing an increase， represented by 4′-O-methyl psoralen B. Further multivariate statistical analysis revealed 11 key differential components before and after salt processing of PF， including psoralen and bakuchiol. ConclusionSalt processing effectively diminishes hepatotoxicity without impairing therapeutic efficacy against osteoporosis of PF， which may be related to the compositional changes before and after salt processing of PF and provides key evidence to reveal the scientific significance of salt processing of PF.

Objective To compare the clinical efficacy of intraoperative intravenous tirofiban versus preoperative loading dose dual antiplatelet therapy in the acute phase LVIS stent-assisted coil embolization treatment for ruptured wide-necked intracranial aneurysms.Methods Patients with acutely ruptured,wide-neck intracranial aneurysms underwent LVIS stent-assisted coil embolization in the Department of Neurosurgery at Heze Municipal Hospital were retrospectively and consecutively enrolled from January 2017 to June 2023.According to the Chinese expert consensus on antiplatelet therapy for intracranial aneurysms,patients were divided into two groups based on the types of antiplatelet therapy they received:the loading-dose dual antiplatelet therapy(DAPT)group and the tirofiban group.Baseline and clinical data were collected and compared between the two groups,including age,sex,hypertension,diabetes mellitus,coronary artery disease,history of cerebral hemorrhage,preoperative Hunt-Hess grade,maximum aneurysm diameter,aneurysm neck width,and aneurysm location.Perioperative ischemic and hemorrhagic complications were collected and compared between the two groups.Perioperative ischemic complications included:intraoperative stent thrombosis(defined as filling defects in the parent artery,and,occlusion of the parent artery or stented branch during the procedure),and symptomatic ischemic infarction within 24 h postoperatively(confirmed by imaging with corresponding neurological deficits).Perioperative hemorrhagic complications included:intraoperative rupture of the target aneurysm(contrast extravasation or acute hemorrhage during embolization)and intracranial hemorrhage within 24 h postoperatively(new or worsened subarachnoid hemorrhage or intraparenchymal hemorrhage on CT).Clinical outcomes at 90 days were collected via telephone or outpatient follow-up,and evaluated using favorable prognosis defined as modified Rankin scale(mRS).A mRS score of 0-2 were defined as favorable prognosis and 3-6 as poor prognosis.Six-month postoperative imaging follow-up were collected,angiographic outcomes were categorized into four groups based on comparison with immediate post-embolization results:complete occlusion,total absence of contrast filling in the aneurysm sac;improved,reduced contrast filling;stable,unchanged contrast filling;and,recurrence,increased contrast filling.Results Totals of 108 patients with intracranial aneurysms treated by LVIS stent-assisted coiling were enrolled,with 30 males and 78females,aged32-75years(median age63[50,66]years).Among the108cases,55cases were assigned into the DAPT group,and 53 cases were included in the tirofiban group.(1)No statistically significant differences were observed between the tirofiban group and the DAPT group in baseline and clinical characteristics(all P＞0.05).(2)All patients underwent successful LVIS stent-assisted coiling,with a technical success rate of 100%.The total perioperative ischemic complications were 12.0%(13/108),including 4.6%(5/108)intraoperative stent thrombosis and 7.4%(8/108)symptomatic ischemic infarction within 24h after surgery.The total perioperative hemorrhagic complications rate was 1.9%(2/108),including 1 case of intraoperative aneurysm rupture and 1 case of postoperative intracranial hemorrhage within24h.92.6%(100/108)of the patients exhibited favorable prognosis and 7.4%(8/108)showed poor prognosis at the 90-day follow-ups.78.7%(85/108)of the patients accomplished at 6-month imaging follow-ups,the complete occlusion ratio was 94.1%(80/85)and the recurrence ratio was 2.4%(2/85).(3)The overall perioperative ischemic complication rates were 13.2%(7/53)in the tirofiban group and 10.9%(6/55)in the DAPT group,with no statistically significant difference(P=0.720).Intraoperative stent thrombosis occurred more frequently in the DAPT group(9.1%[5/55]vs.0,P=0.025),while symptomatic ischemic infarction within 24 h post-procedure was lower in the DAPT group(1.8%[1/55]vs.13.2%[7/53],P=0.028).The hemorrhagic complications occurred only in the DAPT group,with a rate of 3.6%(2/55),while no events observed in the tirofiban group.At the 90-day follow-up,the proportion of patients with favorable outcomes was 94.3%(50/53)in the tirofiban group and 90.9%(50/55)in the DAPT group,with no statistically significant difference between the groups(P=0.754).Conclusions Both intraoperative intravenous tirofiban and preoperative loading-dose DAPT demonstrated comparable safety profile and favorable clinical efficacy in the acute-phase treatment of ruptured wide-necked intracranial aneurysms with LVIS stent-assisted coil embolization.The results require further validation through large-scale prospective studies.

Social robots play an important role in the field of medical companionship， providing services such as companion communication， drug monitoring， and rehabilitation guidance for the elderly and other subjects. However， social robots also pose the risk of deceiving medical users. Although certain forms of social robots’ deception can be used for therapeutic purposes， unethical deception can have adverse consequences for patients， doctors， and even society. These risks include causing patients to develop attachment disorders， violating their privacy， endangering their health， and even undermining the credibility of the healthcare system. Faced with the deception problem of social robots， starting from relational theory， medical artificial intelligence developers can conduct ethical regulation from the following two paths. First， social robots should be ethically programmed， including embedding programs for limiting benevolent lies， implementing informed consent principles， and ensuring information accuracy. Second， the deceptive behaviors of social robots should be controlled， requiring developers to take full-process supervision responsibility， design medical social robots that can supervise each other， and participate in formulating quality standards and evidence mechanisms for deception issues.

OBJECTIVE To investigate the anti-inflammatory effect of electroacupuncture in mice with chronic obstructive pul-monary disease(COPD)and its underlying mechanisms.METHODS Forty C57BL/6 mice were randomly divided into normal group,model group,electroacupuncture(EA)group,vagotomy group,and vagotomy+EA group,with 8 mice in each group.Except for the normal group,all groups were exposed to cigarette smoke for 12 weeks to establish a COPD model.After model establishment,the vagotomy group and the vagotomy+EA group underwent left cervical vagotomy before EA.EA treatment was performed at the Feishu(BL13)and Zusanli(ST36)acupoints once daily for 20 minutes for a total of 14 days.After EA,the pulmonary ventilation function of the mice was detected by a pulmonary function analysis system;lung tissue pathology was observed by HE staining;the levels of inter-leukin(IL)-6,tumor necrosis factor-α(TNF-α),IL-10,and transforming growth factor-β(TGF-β)in lung tissue were detected by ELISA;the expression of CD86 and CD206 proteins in lung tissue was detected by Western blot;the distribution of F4/80+CD86+(M1 type)and F4/80+CD206+(M2 type)cells in lung tissue was determined by flow cytometry;the expression of CD86 and CD206 in lung tissue was observed by immunofluorescence.RESULTS Compared with the normal group,the model group showed significantly decreased lung function(P<0.01),obvious lung pathological damage,increased M1 proportion,IL-6,TNF-α,CD86 content and expression(P<0.05,P<0.01),and decreased M2 proportion,IL-10,TGF-β,CD206 content and expression(P<0.01).Compared with the model group,the EA group showed varying degrees of improvement in lung function and pathology;the M1 proportion,IL-6,TNF-α,and CD86 were reduced(P<0.05,P<0.01),while the M2 proportion,IL-10,TGF-β,and CD206 were increased(P<0.05,P<0.01).The vagotomy group showed worsened lung function and pathology,increased IL-6,TNF-α,and CD86 content and expression(P<0.05,P<0.01),and decreased IL-10,TGF-β,and CD206 content and expression(P<0.05,P<0.01).Compared with the EA group,the vagotomy+EA group showed increased M1 proportion,IL-6,TNF-α,and CD86 content and expression(P<0.01),and decreased M2 proportion,IL-10,TGF-β,and CD206 content and expression(P<0.05,P<0.01).CONCLUSION EA at Feishu(BL13)and Zusanli(ST36)acupoints can improve lung function and pulmonary inflammation in COPD mice,promoting the polarization of alveolar macrophages from M1 to M2,which is mediated by the vagus nerve.

OBJECTIVE To investigate the anti-inflammatory effect of electroacupuncture in mice with chronic obstructive pul-monary disease(COPD)and its underlying mechanisms.METHODS Forty C57BL/6 mice were randomly divided into normal group,model group,electroacupuncture(EA)group,vagotomy group,and vagotomy+EA group,with 8 mice in each group.Except for the normal group,all groups were exposed to cigarette smoke for 12 weeks to establish a COPD model.After model establishment,the vagotomy group and the vagotomy+EA group underwent left cervical vagotomy before EA.EA treatment was performed at the Feishu(BL13)and Zusanli(ST36)acupoints once daily for 20 minutes for a total of 14 days.After EA,the pulmonary ventilation function of the mice was detected by a pulmonary function analysis system;lung tissue pathology was observed by HE staining;the levels of inter-leukin(IL)-6,tumor necrosis factor-α(TNF-α),IL-10,and transforming growth factor-β(TGF-β)in lung tissue were detected by ELISA;the expression of CD86 and CD206 proteins in lung tissue was detected by Western blot;the distribution of F4/80+CD86+(M1 type)and F4/80+CD206+(M2 type)cells in lung tissue was determined by flow cytometry;the expression of CD86 and CD206 in lung tissue was observed by immunofluorescence.RESULTS Compared with the normal group,the model group showed significantly decreased lung function(P<0.01),obvious lung pathological damage,increased M1 proportion,IL-6,TNF-α,CD86 content and expression(P<0.05,P<0.01),and decreased M2 proportion,IL-10,TGF-β,CD206 content and expression(P<0.01).Compared with the model group,the EA group showed varying degrees of improvement in lung function and pathology;the M1 proportion,IL-6,TNF-α,and CD86 were reduced(P<0.05,P<0.01),while the M2 proportion,IL-10,TGF-β,and CD206 were increased(P<0.05,P<0.01).The vagotomy group showed worsened lung function and pathology,increased IL-6,TNF-α,and CD86 content and expression(P<0.05,P<0.01),and decreased IL-10,TGF-β,and CD206 content and expression(P<0.05,P<0.01).Compared with the EA group,the vagotomy+EA group showed increased M1 proportion,IL-6,TNF-α,and CD86 content and expression(P<0.01),and decreased M2 proportion,IL-10,TGF-β,and CD206 content and expression(P<0.05,P<0.01).CONCLUSION EA at Feishu(BL13)and Zusanli(ST36)acupoints can improve lung function and pulmonary inflammation in COPD mice,promoting the polarization of alveolar macrophages from M1 to M2,which is mediated by the vagus nerve.

Objective To compare the clinical efficacy of intraoperative intravenous tirofiban versus preoperative loading dose dual antiplatelet therapy in the acute phase LVIS stent-assisted coil embolization treatment for ruptured wide-necked intracranial aneurysms.Methods Patients with acutely ruptured,wide-neck intracranial aneurysms underwent LVIS stent-assisted coil embolization in the Department of Neurosurgery at Heze Municipal Hospital were retrospectively and consecutively enrolled from January 2017 to June 2023.According to the Chinese expert consensus on antiplatelet therapy for intracranial aneurysms,patients were divided into two groups based on the types of antiplatelet therapy they received:the loading-dose dual antiplatelet therapy(DAPT)group and the tirofiban group.Baseline and clinical data were collected and compared between the two groups,including age,sex,hypertension,diabetes mellitus,coronary artery disease,history of cerebral hemorrhage,preoperative Hunt-Hess grade,maximum aneurysm diameter,aneurysm neck width,and aneurysm location.Perioperative ischemic and hemorrhagic complications were collected and compared between the two groups.Perioperative ischemic complications included:intraoperative stent thrombosis(defined as filling defects in the parent artery,and,occlusion of the parent artery or stented branch during the procedure),and symptomatic ischemic infarction within 24 h postoperatively(confirmed by imaging with corresponding neurological deficits).Perioperative hemorrhagic complications included:intraoperative rupture of the target aneurysm(contrast extravasation or acute hemorrhage during embolization)and intracranial hemorrhage within 24 h postoperatively(new or worsened subarachnoid hemorrhage or intraparenchymal hemorrhage on CT).Clinical outcomes at 90 days were collected via telephone or outpatient follow-up,and evaluated using favorable prognosis defined as modified Rankin scale(mRS).A mRS score of 0-2 were defined as favorable prognosis and 3-6 as poor prognosis.Six-month postoperative imaging follow-up were collected,angiographic outcomes were categorized into four groups based on comparison with immediate post-embolization results:complete occlusion,total absence of contrast filling in the aneurysm sac;improved,reduced contrast filling;stable,unchanged contrast filling;and,recurrence,increased contrast filling.Results Totals of 108 patients with intracranial aneurysms treated by LVIS stent-assisted coiling were enrolled,with 30 males and 78females,aged32-75years(median age63[50,66]years).Among the108cases,55cases were assigned into the DAPT group,and 53 cases were included in the tirofiban group.(1)No statistically significant differences were observed between the tirofiban group and the DAPT group in baseline and clinical characteristics(all P＞0.05).(2)All patients underwent successful LVIS stent-assisted coiling,with a technical success rate of 100%.The total perioperative ischemic complications were 12.0%(13/108),including 4.6%(5/108)intraoperative stent thrombosis and 7.4%(8/108)symptomatic ischemic infarction within 24h after surgery.The total perioperative hemorrhagic complications rate was 1.9%(2/108),including 1 case of intraoperative aneurysm rupture and 1 case of postoperative intracranial hemorrhage within24h.92.6%(100/108)of the patients exhibited favorable prognosis and 7.4%(8/108)showed poor prognosis at the 90-day follow-ups.78.7%(85/108)of the patients accomplished at 6-month imaging follow-ups,the complete occlusion ratio was 94.1%(80/85)and the recurrence ratio was 2.4%(2/85).(3)The overall perioperative ischemic complication rates were 13.2%(7/53)in the tirofiban group and 10.9%(6/55)in the DAPT group,with no statistically significant difference(P=0.720).Intraoperative stent thrombosis occurred more frequently in the DAPT group(9.1%[5/55]vs.0,P=0.025),while symptomatic ischemic infarction within 24 h post-procedure was lower in the DAPT group(1.8%[1/55]vs.13.2%[7/53],P=0.028).The hemorrhagic complications occurred only in the DAPT group,with a rate of 3.6%(2/55),while no events observed in the tirofiban group.At the 90-day follow-up,the proportion of patients with favorable outcomes was 94.3%(50/53)in the tirofiban group and 90.9%(50/55)in the DAPT group,with no statistically significant difference between the groups(P=0.754).Conclusions Both intraoperative intravenous tirofiban and preoperative loading-dose DAPT demonstrated comparable safety profile and favorable clinical efficacy in the acute-phase treatment of ruptured wide-necked intracranial aneurysms with LVIS stent-assisted coil embolization.The results require further validation through large-scale prospective studies.

OBJECTIVE To investigate the effects of osthole(OST)on skin wound healing and angiogenesis in rats by regulating the sonic hedgehog(SHH)signaling pathway.METHODS Full-layer skin defect wound model rats were established and then randomly separated into Model group,OST low-dose,medium-dose and high-dose groups(OST-L group,OST-M group,OST-H group,20,30,40 mg/kg OST),high-dose OST+SHH inhibitor cyclopamide group(OST-H+cyclopamide group,40 mg/kg OST+10 mg/kg cyclopamide),with 12 rats in each group.Another 12 rats were selected as the control group.The wound healing of rats on 1,7 and 14 days of administration was observed,and the wound healing rate of rats in each group was measured.The pathological changes and collagen deposition in rat wound tissue were observed;the levels of angiopoietin-1(Ang-1)and basic fibroblast growth factor(bFGF)in wound tissue of rats were detected;the relative expressions of vascular endothelial growth factor A(VEGFA)and vascular endothelial growth factor receptor-2(VEGFR-2)mRNA were also detected in wound tissue of rats;the protein expressions of VEGFA,VEGFR-2,SHH and glioma-associated oncogene homolog-1(GLI1)were determined in wound tissue of rats.RESULTS Compared with Model group,the healing rate of skin wound,relative expression of collagen protein,the levels of Ang-1 and bFGF,the mRNA and protein expressions of VEGFA and VEGFR-2,and the protein expressions of SHH and GLI1 were all significantly increased in OST-M and OST-H groups(P＜0.05).The wound tissue underwent significant re-epithelialization,with reduced inflammatory cell infiltration and granulation tissue edema,and an increase in the number of new blood vessels.SHH inhibitor cycloparamide weakened the promoting effects of OST on skin wound healing and angiogenesis in rats.CONCLUSIONS OST may promote skin wound healing and angiogenesis in rats by activating the SHH signaling pathway.