Objective To investigate the pharmacokinetic(PK)profile of ripretinib in patients with advanced gastrointestinal stromal tumors(GISTs)in real-world settings.Methods The PK data of eight advanced GIST patients treated with ripretinib and the steady-state trough concentration(Cmin)blood samples of 54 advanced GIST patients treated with ripretinib were collected from November 2023 to March 2025 at the First Affiliated Hospital of Sun Yat-sen University.A validated liquid chromatography-tandem mass spectrometry method was used to quantify ripretinib and DP-5439 concentrations.The PK profiles of ripretinib were characterized.Cmin was compared across various dosages.The correlations among PK parameters of ripretinib and DP-5439,and clinical features impacting PK were explored.Results All patients reached Cmin approximately 24 hours post-dose for ripretinib and DP-5439.The median time to maximum con-centration(Tmax)for both ripretinib and DP-5439 was 3.16 hours.The steady-state Cmin,maximum plasma concentration(Cmax),and area under the plasma concentration-time curve from 0 to 24 hours(AUC0-24 h)of ripretinib,DP-5439,and their combined total were found to be highly correlated(all r>0.85,all P<0.05).In patients receiving 150 mg once-daily(n=44),the median Cmin(range)was 381.66(40.90-1 045.48)ng/mL for ripretinib,589.08(25.28-1 168.11)ng/mL for DP-5439,and 998.00(66.18～2 381.48)ng/mL for total,with coeffi-cients of variation(CVs)of 59.4%,57.2%,and 53.6%.In the 300 mg group(n=11),the median Cmin(range)was 1 024.51(251.36-2 030.51)ng/mL for ripretinib,1 122.34(111.54-2 682.57)ng/mL for DP-5439,and 1 924.58(404.37-4 766.08)ng/mL for total,with CVs of 59.5%,57.3%,and 54.8%.Univariate analysis showed that no significant correlation was found between age or BMI and the dose-corrected Cmin of ripretinib and DP-5439(all P>0.05),and the median dose-corrected Cmin of ripretinib and DP-5439 was slightly lower in male patients than in female patients(P<0.05).In the multiple linear regression analysis,male patients were observed to have a lower median dose-cor-rected Cmin of DP-5439 than female patients(P=0.024),but no statistical difference was found in that of ripretinib(P>0.05).Conclusions In advanced GIST patients receiving ripretinib,ripretinib and DP-5439 reached Cmin 24 hours post-dose,just before the next administra-tion.The ripretinib,DP-5439,and total Cmin showed significant correlations with their AUC0-24 h,which indicated that Cmin could serve as an indicator of ripretinib exposure.The PK features of ripretinib in advanced GIST patients exhibit significant inter-individual variability.

Objective:To analyze the clinical characteristics,diagnosis and treatment of pediatric myocardial infarction (MI) patients with coronary artery lesions (CAL) after Kawasaki disease (KD).Methods:Clinical data including baseline characteristics, KD and CAL information, clinical symptoms at MI onset, electrocardiogram (ECG) and imaging findings, MI treatment, and clinical outcomes of 41 MI patients with CAL after KD admitted to the Children′s Hospital of Fudan University from January 2017 to August 2024 were analyzed retrospectively.Results:(1) Demographic characteristics: a total of 41 patients were included (36 males and 5 females). The age at MI was 4.6 (2.3, 5.7) years, and time from KD onset to MI was 397 (50, 1 095) d. (2) Treatment of acute KD: only 15 patients (37%) received standard initial treatment within 10 days of KD onset with intravenous immunoglobulin 2 g/kg. The other 26 cases (63%) received non-standard treatment or no treatment. (3) Treatment of CAL before MI: the time from KD onset to CAL was 14 (10, 116) d, with CAL not identified before MI onset in 15 patients. Among the 26 cases diagnosed with CAL prior to MI, 9 cases received only single or dual antiplatelet drug, of which 7 cases received oral dipyridamole. The remaining 16 cases received antiplatelet drug combined with warfarin, but only 1 case achieved the target international standardized ratio of 1.5-2.5. Out of all 41 cases, only 1 case (2%) received standard antithrombotic treatment before MI onset. (4) Clinical symptoms of MI: at MI onset, 32 patients presented with different clinical symptoms, with typical MI symptoms such as chest tightness, chest pain, precordial discomfort in 18 cases, and cardiopulmonary arrest accompanied by syncope or convulsions in 10 cases. Other non-specific symptoms included abdominal pain, nausea, vomiting and pallor. Nine patients were asymptomatic and were found to have silent MI on follow-up. (5) ECG and imaging findings: ECG showed ST-T changes in 33 cases, and abnormal Q waves, and arrhythmias in the remaining patients; echocardiography indicated coronary artery aneurysm with thrombosis in 27 cases, reduced left ventricular ejection fraction in 18 cases, abnormal wall motion in 15 cases, and ventricular aneurysm in 3 cases. Thirty-seven patients underwent coronary angiography and (or) multi-slice spiral CT angiography, with 39 occluded vessels and 3 severe stenosis (≥75%), all of which were caused by giant aneurism with thrombus formation. (6) Treatment of MI: of the 32 patients with acute MI, 9 patients received successful cardiopulmonary resuscitation, 7 patients received intravenous thrombolysis, and 1 patient underwent percutaneous coronary balloon angioplasty. All of these patients received dual antiplatelet drugs and low-molecular-weight heparin at therapeutic doses following MI treatment. Sixteen patients received coronary artery bypass graft (CABG) treatment, all of which were successful. (7) Outcomes: the follow-up time was 994 (215, 1 832) d. Thirty-one patients showed improvement, 5 patients experienced disease progression or no change, 1 patient died, and 4 patients were lost to follow-up.Conclusions:MI in children with CAL after KD often occurs within 1 year after the onset of KD. MI can present with atypical clinical symptoms in children. CABG is the main treatment option in children severe CAL after KD who developed MI.

Objective To investigate the pharmacokinetic(PK)profile of ripretinib in patients with advanced gastrointestinal stromal tumors(GISTs)in real-world settings.Methods The PK data of eight advanced GIST patients treated with ripretinib and the steady-state trough concentration(Cmin)blood samples of 54 advanced GIST patients treated with ripretinib were collected from November 2023 to March 2025 at the First Affiliated Hospital of Sun Yat-sen University.A validated liquid chromatography-tandem mass spectrometry method was used to quantify ripretinib and DP-5439 concentrations.The PK profiles of ripretinib were characterized.Cmin was compared across various dosages.The correlations among PK parameters of ripretinib and DP-5439,and clinical features impacting PK were explored.Results All patients reached Cmin approximately 24 hours post-dose for ripretinib and DP-5439.The median time to maximum con-centration(Tmax)for both ripretinib and DP-5439 was 3.16 hours.The steady-state Cmin,maximum plasma concentration(Cmax),and area under the plasma concentration-time curve from 0 to 24 hours(AUC0-24 h)of ripretinib,DP-5439,and their combined total were found to be highly correlated(all r>0.85,all P<0.05).In patients receiving 150 mg once-daily(n=44),the median Cmin(range)was 381.66(40.90-1 045.48)ng/mL for ripretinib,589.08(25.28-1 168.11)ng/mL for DP-5439,and 998.00(66.18～2 381.48)ng/mL for total,with coeffi-cients of variation(CVs)of 59.4%,57.2%,and 53.6%.In the 300 mg group(n=11),the median Cmin(range)was 1 024.51(251.36-2 030.51)ng/mL for ripretinib,1 122.34(111.54-2 682.57)ng/mL for DP-5439,and 1 924.58(404.37-4 766.08)ng/mL for total,with CVs of 59.5%,57.3%,and 54.8%.Univariate analysis showed that no significant correlation was found between age or BMI and the dose-corrected Cmin of ripretinib and DP-5439(all P>0.05),and the median dose-corrected Cmin of ripretinib and DP-5439 was slightly lower in male patients than in female patients(P<0.05).In the multiple linear regression analysis,male patients were observed to have a lower median dose-cor-rected Cmin of DP-5439 than female patients(P=0.024),but no statistical difference was found in that of ripretinib(P>0.05).Conclusions In advanced GIST patients receiving ripretinib,ripretinib and DP-5439 reached Cmin 24 hours post-dose,just before the next administra-tion.The ripretinib,DP-5439,and total Cmin showed significant correlations with their AUC0-24 h,which indicated that Cmin could serve as an indicator of ripretinib exposure.The PK features of ripretinib in advanced GIST patients exhibit significant inter-individual variability.

Objective:To analyze the clinical characteristics,diagnosis and treatment of pediatric myocardial infarction (MI) patients with coronary artery lesions (CAL) after Kawasaki disease (KD).Methods:Clinical data including baseline characteristics, KD and CAL information, clinical symptoms at MI onset, electrocardiogram (ECG) and imaging findings, MI treatment, and clinical outcomes of 41 MI patients with CAL after KD admitted to the Children′s Hospital of Fudan University from January 2017 to August 2024 were analyzed retrospectively.Results:(1) Demographic characteristics: a total of 41 patients were included (36 males and 5 females). The age at MI was 4.6 (2.3, 5.7) years, and time from KD onset to MI was 397 (50, 1 095) d. (2) Treatment of acute KD: only 15 patients (37%) received standard initial treatment within 10 days of KD onset with intravenous immunoglobulin 2 g/kg. The other 26 cases (63%) received non-standard treatment or no treatment. (3) Treatment of CAL before MI: the time from KD onset to CAL was 14 (10, 116) d, with CAL not identified before MI onset in 15 patients. Among the 26 cases diagnosed with CAL prior to MI, 9 cases received only single or dual antiplatelet drug, of which 7 cases received oral dipyridamole. The remaining 16 cases received antiplatelet drug combined with warfarin, but only 1 case achieved the target international standardized ratio of 1.5-2.5. Out of all 41 cases, only 1 case (2%) received standard antithrombotic treatment before MI onset. (4) Clinical symptoms of MI: at MI onset, 32 patients presented with different clinical symptoms, with typical MI symptoms such as chest tightness, chest pain, precordial discomfort in 18 cases, and cardiopulmonary arrest accompanied by syncope or convulsions in 10 cases. Other non-specific symptoms included abdominal pain, nausea, vomiting and pallor. Nine patients were asymptomatic and were found to have silent MI on follow-up. (5) ECG and imaging findings: ECG showed ST-T changes in 33 cases, and abnormal Q waves, and arrhythmias in the remaining patients; echocardiography indicated coronary artery aneurysm with thrombosis in 27 cases, reduced left ventricular ejection fraction in 18 cases, abnormal wall motion in 15 cases, and ventricular aneurysm in 3 cases. Thirty-seven patients underwent coronary angiography and (or) multi-slice spiral CT angiography, with 39 occluded vessels and 3 severe stenosis (≥75%), all of which were caused by giant aneurism with thrombus formation. (6) Treatment of MI: of the 32 patients with acute MI, 9 patients received successful cardiopulmonary resuscitation, 7 patients received intravenous thrombolysis, and 1 patient underwent percutaneous coronary balloon angioplasty. All of these patients received dual antiplatelet drugs and low-molecular-weight heparin at therapeutic doses following MI treatment. Sixteen patients received coronary artery bypass graft (CABG) treatment, all of which were successful. (7) Outcomes: the follow-up time was 994 (215, 1 832) d. Thirty-one patients showed improvement, 5 patients experienced disease progression or no change, 1 patient died, and 4 patients were lost to follow-up.Conclusions:MI in children with CAL after KD often occurs within 1 year after the onset of KD. MI can present with atypical clinical symptoms in children. CABG is the main treatment option in children severe CAL after KD who developed MI.

Objective To compare the EC50 of Propofol for inhibiting intubation response. Methods 80 cases un-derwent tracheal intubation general anesthesia, all patients were randomly divided into two groups. The general situ-ation between the two groups showed no significant difference. Except for Propofol, other anesthesia drugs infusion method and dosage were the same. Sequential determination the EC50 of Propofol which for inhibiting intubation re-sponse of each groups by up-and-down. Propofol target concentration of the first patient was set to 4 μg/ml, and ad-justed according to intubation stress response disappeared or not, concentration of two adjacent patients with ratio of 1.2. Results A group inhibited the cardiovascular responses of Propofol EC50 and 95%CI was 5.19 μg/ml (95%CI:4.88 ~ 5.50 μg/ml). B group inhibited the cardiovascular responses of Propofol EC50 and 95 %CI was 4.15μg/ml (95%CI:3.80~4.40μg/ml). The EC50 and 95% confidence interval of the B group were significantly lower than those of the A group ( P< 0.05). The MAP and HR at T2 were higher than that of T1 in each group ( P< 0.05), and the MAP and HR of observe group were lower than that of control group ( P< 0.05). The MAP and HR at T3 were lower than that of T1 in control group ( P< 0.05), but there were no significant deference in observe group ( P> 0.05).Conclusion The EC50 and 95% confidence interval of Propofol for inhibiting intubation response under photopic laryngoscopes was significant lower than those of under direct laryngoscopes, the circulation during period of induc-tion and intubation was more stable.

Objective To investigate the feasibility of Narcotrend-guided application of small dose of dexmedetomidine ( DEX) for sedation during combined spinal-epidural anesthesia for elderly patients. Methods Fifty cases of ASA II or Ⅲelderly patients were randomly divided into treatment group and control group (25 patients of each group). After combined spinal-epidural anesthesia, both groups received continuous intravenous infusion of DEX, at 0. 4 μg·kg-1 in 10 min, and then the rate was lowered to 0. 4 μg·kg-1 per hour. For the treatment group, infusion rate was adjusted to reach a Narcotrend Index (NTI) of 75-85, and for the control group, infusion rate was adjusted to reach an OAA/S score of level 3-4. MAP, HR, RR, SpO2 , NTI and OAA/S score were recorded at the beginning of DEX treatment ( t0 ) , 10 min ( t1 ) , 20 min ( t2 ) , 30 min ( t3 ) , and 60 min ( t4 ) after the beginning of DEX treatment, and at the end of surgery ( t5 ) . The incidence rates of adverse events including bradycardia, hypotension, low oxygenation, and respiratory depression were also recorded. The patients were followed up until 24 h after surgery to record loss of memory about the surgical events. Results In comparison with t0 , NTI and MAP of both groups significantly decreased at t1-t5(P<0. 01). Comparison between the two groups showed no difference in MAP at each time point, and NTI of treatment group was higher than that of control group at t2-t5(P<0. 05). In comparison with t0, OAA/S of both groups significantly decreased at t1-t5(for t1, P<0. 05;for t2-t5, P<0. 01). Comparison between the two groups showed no difference in OAA/S at each time point (P>0. 05). Follow-up at 24 h after surgery observed total amnesia in 72. 0% of DEX group patients and in 76. 0% of the control group, without significant difference (P>0. 05). Conclusion Sedating elderly patients undergoing spinal-epidural anesthesia with DEX under the guidance of Narcotrend is safe and feasible, and the patients can be sedated properly.

Objective To investigate the postoperative epidural analgesia and adverse reactions in total abdominal hysterectomy with dezocine and ropivacaine.Methods Sixty elective transabdominal hysterectomy patients with American Society of Anesthesiologists (ASA) Ⅰ-Ⅱ grade were randomly divided into two groups,dezocine group and morphine group,there were 30 cases in each group.Dezocine group:dezocine (6 mg) + 0.75％ ropivacaine hydrochloride(20 ml) + saline dilution,diluted to 100 ml.Morphine group:morphine(6 mg) + 0.75 ％ hydrochloride ropivacaine (20 ml) + saline dilution,diluted to 100 ml,for postoperative epidural analgesia.Both two groups were adopted in LCP mode with a loading dose:dezocine group,dezocine(2 mg) +saline dilution,diluted to 5 ml; morphine group,morphine (2 mg) + saline dilution,diluted to 5 ml.Continuous infusion of 2 ml/h,a bolus dose of 2 ml,and a lockout interval of 15 min.The analgesia duration was 48 h.Visual analogue scales (VAS) evaluation was employed to assess the analgesic effect,and the postoperative epidural analgesia adverse reaction were also recorded.Results The analgesic effect was both satisfied in the two groups.Comparing the VAS scores postoperative at different time point (4 h,8 h,12 h,24 h,36 h,48 h),dezocine group(2.7 ± 0.4,2.5 ± 0.6,2.2 ± 0.5,1.5 ± 0.5,1.3 ± 0.5,1.1 ± 0.3) were slightly lower than morphine group (2.8 ± 0.5,2.6 ± 0.7,2.3 ± 0.6,1.6 ± 0.7,1.5 ± 0.6,1.2 ± 0.4),but the difference was not significant (within the group:F =2414.96,P ＜ 0.01 ; between the group:F =0.63,P ＞ 0.05 ; interactive:F =2.42,P ＞0.05).Comparison of VAS scores at different time points after operation in two groups,the difference was not statistically significant; And within the group,there was not,the difference was not significant at the time point at 12,24,36,48 h compare to postoperative at 4 h (P ＜ 0.01).the Adverse reaction like nausea and vomiting,skin itching occur rate is lower in dezocine group (3.3 ％ (1/30),0 (0/30)) than that of in morphine group(26.7％ (8/30),20.0％ (6/30)),and there were signficant differences between the two groups (P =0.026,0.024,P ＜ 0.05).Conclusion Dezocine composed with ropivacaine is safe and effective,and with few adverse reactions in total abdominal hysterectomy postoperative epidural analgesia,it is worth of widely use in clinical.