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 provide valuable insights for the adjustment of anti-infectious regimens， identification of adverse reactions， and individualized pharmaceutical care in patients with critically severe scrub typhus. METHODS Clinical pharmacists actively participated in the pharmaceutical care process for a patient with severe scrub typhus leading to mixed shock undergoing continuous renal replacement therapy and extracorporeal membrane oxygenation. Initially， the patient received meropenem （1 g， q12 h， ivdrip）， in combination with doxycycline （0.1 g， q12 h， po）， which was later switched to meropenem （1 g， q8 h， ivdrip） along with omacycline （100 mg， qd， ivdrip） due to impaired gastrointestinal function. However， as the patient’s condition progressively deteriorated and the infection became uncontrolled， the clinical pharmacists recommended that the clinicians adjust the anti-infective regimen to meropenem （2 g， q8 h， ivdrip） combined with tigecycline （100 mg for first dose； 50 mg， q12 h for maintenance； ivdrip）. The clinicians followed the advice of the clinical pharmacists. After treatment， the patient’s symptoms exhibited significant improvement， accompanied by a notable decrease in inflammatory markers， indicating that the infection had been successfully controlled. However， due to continuously increasing bilirubin levels， in order to reduce the risk of drug-induced liver injury， the clinicians changed tigecycline to azithromycin （0.5 g， qd， ivdrip） following the recommendation of the clinical pharmacists. RESULTS Ultimately， metagenomic next-generation sequencing of the bronchoalveolar lavage fluid and blood specimens indicated that Orientia tsutsugamushi had been completely eradicated in the patient. CONCLUSIONS Tigecycline may be a viable therapeutic choice for patients with severe scrub typhus. In the context of critically ill patients with scrub typhus， combining tigecycline with azithromycin might potentially enhance the efficacy in eliminating Orientia tsutsugamushi.

Objective To explore the pharmaceutical care clinical pharmacists provide for anti-infective therapy in patients undergoing continuous renal replacement therapy(CRRT)after lung transplantation.Methods The clinical pharmacist utilized a limited sampling strategy and participated in the entire anti-infective treatment process for an adult lung transplant recipient based on pharmacokinetic monitoring results.The CRRT duration was flexibly adjusted,the dosing regimen was optimized,and adverse drug reactions were monitored.Result The clinical pharmacist assisted the physician in optimizing the polymyxin B anti-infective therapy post-transplantation,leading to successful infection control and patient discharge.Conclusion Clinical pharmacists can conduct real-time drug concentration monitoring in lung transplant patients based on pharmacokinetic characteristics,develop individualized dosing regimens,and improve medication safety and efficacy during anti-infective therapy.

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 explore the pharmaceutical care clinical pharmacists provide for anti-infective therapy in patients undergoing continuous renal replacement therapy(CRRT)after lung transplantation.Methods The clinical pharmacist utilized a limited sampling strategy and participated in the entire anti-infective treatment process for an adult lung transplant recipient based on pharmacokinetic monitoring results.The CRRT duration was flexibly adjusted,the dosing regimen was optimized,and adverse drug reactions were monitored.Result The clinical pharmacist assisted the physician in optimizing the polymyxin B anti-infective therapy post-transplantation,leading to successful infection control and patient discharge.Conclusion Clinical pharmacists can conduct real-time drug concentration monitoring in lung transplant patients based on pharmacokinetic characteristics,develop individualized dosing regimens,and improve medication safety and efficacy during anti-infective therapy.

Taking chronic atrophic gastritis （CAG） as an example， the frontier technologies in data science have been introduced into the inheritance， innovation and development of traditional Chinese medicine （TCM）， providing reference for conducting real-world clinical research on specialized diseases of TCM. This paper put forward the construction of CAG data science system by elaborating the connotation of data science and its application value in TCM， and discussed the path to build CAG data science system， namely through "data acquisition-knowledge expression-knowledge reasoning" to establish CAG database， knowledge base and develop diagnosis platform differentiating diseases and syndromes. Besides， this paper analyzed the prospects of CAG data science in improving data governance ability and knowledge discovery efficiency， deepening the level of knowledge sharing， promoting interdisciplinary integration， and strengthening the integration process of industry， academia and research.

This paper summarized professor JIA Hongxiao's experience in treating cognitive impairments in schizophrenia patients upon five spirits stored in corresponding viscera theory. By elucidating the cognitive psychological connotation of the five spirits stored in corresponding viscera theory， it is proposed that the cognitive impairment of schizophrenia should be differentiated and treated based on the symptom characteristics of different cognitive domain impairments in schizophrenia. The key pathogenesis of impairments to cognitive domains such as information processing speed， executive control ability and will is kidney deficiency， liver hyperactivity， and heart spirit restlessness， for which the treatment is to boost the kidney and calm the liver， nourish the heart and calm the mind， using Shizhen Anshen Formula （石珍安神方） modifications. The main pathogenesis of memory and attention cognitive impairment is spleen-kidney depletion and lung corporeal soul failing to descend， for which it is suggested to fortify the spleen and supplement kidney， boost lung and direct qi downward using Jianpi Bushen Formula （健脾补肾方） modifications.

Objective:To investigate the occurrence and risk factors of intravenous polymyxin B-associated acute kidney injury (AKI) in patients with severe infection.Methods:Electronic medical records of patients with severe infection treated with intravenous polymyxin B during hospitalization in the First Affiliated Hospital, Sun Yat-sen University from October 2017 to October 2020 were collected and analyzed retrospectively. Patients with polymyxin B-induced acute kidney injury were screened out. The occurrence time, clinical stage, and outcome of AKI were statistically analyzed, and the incidence of polymyxin B-induced AKI and the cumulative incidence of AKI on the 3rd, 6th, 12th, and 15th days of administration were calculated. Patients were divided into AKI and non-AKI groups according to whether polymyxin B-associated AKI occurred. The clinical characteristics in patients of the 2 groups were compared. The risk factors of AKI were analyzed by multivariate logistic regression, and the odds ratio ( OR) and 95% confidence interval ( CI) were calculated. Results:A total of 311 patients were entered in the analysis, including 237 males (76.2%) and 74 (23.8%) females, with a median age of 58 (46, 70) years. Fifty-two patients (16.7%) developed polymyxin B-associated AKI, and the time from medication to onset of AKI was (4±2) days, ranging from 2 to 13 days. The cumulative incidence (%) of AKI and its 95 %CI on the 3rd, 6th, 12th, and 15th days of polymyxin B administration were 9.1(3.0-19.4), 15.4(7.9-25.2), 21.5(12.8-31.6), and 21.5(12.8-31.6), respectively. After developing AKI, polymyxin B was discontinued in 17 of 52 patients (32.7%), and 7 of them were given continuous renal replacement therapy (CRRT). The other 35 patients (53.8%) needed to continue medication because of the infection condition, and 25 of them were given CRRT and 10 received diuretics additionally. After the above treatments, 22 (42.3%) of 52 patients had Scr returning to normal, 6 patients (11.5%) were improved, 15 (28.9%) died due to primary diseases, and 9 (17.3%) were discharged under their own request. Multivariate logistic regression analysis showed that daily dose ≥150.0 mg ( OR=5.588, 95 %CI: 2.258-13.833, P<0.001) and high acute physiology and chronic health evaluation Ⅱ (APACHE-Ⅱ) score ( OR=1.063, 95 %CI: 1.021-1.106, P=0.003) were independent risk factors for polymyxin B-associated AKI. Conclusions:AKI may occur in a short time in patients with severe infection after intravenous administration of polymyxin B. The daily dose of polymyxin B ≥150.0 mg and high APACHE-Ⅱscore may increase the risk of AKI.

Objective:To investigate the occurrence and risk factors of intravenous polymyxin B-associated acute kidney injury (AKI) in patients with severe infection.Methods:Electronic medical records of patients with severe infection treated with intravenous polymyxin B during hospitalization in the First Affiliated Hospital, Sun Yat-sen University from October 2017 to October 2020 were collected and analyzed retrospectively. Patients with polymyxin B-induced acute kidney injury were screened out. The occurrence time, clinical stage, and outcome of AKI were statistically analyzed, and the incidence of polymyxin B-induced AKI and the cumulative incidence of AKI on the 3rd, 6th, 12th, and 15th days of administration were calculated. Patients were divided into AKI and non-AKI groups according to whether polymyxin B-associated AKI occurred. The clinical characteristics in patients of the 2 groups were compared. The risk factors of AKI were analyzed by multivariate logistic regression, and the odds ratio ( OR) and 95% confidence interval ( CI) were calculated. Results:A total of 311 patients were entered in the analysis, including 237 males (76.2%) and 74 (23.8%) females, with a median age of 58 (46, 70) years. Fifty-two patients (16.7%) developed polymyxin B-associated AKI, and the time from medication to onset of AKI was (4±2) days, ranging from 2 to 13 days. The cumulative incidence (%) of AKI and its 95 %CI on the 3rd, 6th, 12th, and 15th days of polymyxin B administration were 9.1(3.0-19.4), 15.4(7.9-25.2), 21.5(12.8-31.6), and 21.5(12.8-31.6), respectively. After developing AKI, polymyxin B was discontinued in 17 of 52 patients (32.7%), and 7 of them were given continuous renal replacement therapy (CRRT). The other 35 patients (53.8%) needed to continue medication because of the infection condition, and 25 of them were given CRRT and 10 received diuretics additionally. After the above treatments, 22 (42.3%) of 52 patients had Scr returning to normal, 6 patients (11.5%) were improved, 15 (28.9%) died due to primary diseases, and 9 (17.3%) were discharged under their own request. Multivariate logistic regression analysis showed that daily dose ≥150.0 mg ( OR=5.588, 95 %CI: 2.258-13.833, P<0.001) and high acute physiology and chronic health evaluation Ⅱ (APACHE-Ⅱ) score ( OR=1.063, 95 %CI: 1.021-1.106, P=0.003) were independent risk factors for polymyxin B-associated AKI. Conclusions:AKI may occur in a short time in patients with severe infection after intravenous administration of polymyxin B. The daily dose of polymyxin B ≥150.0 mg and high APACHE-Ⅱscore may increase the risk of AKI.

Objective:To analyze the immune response in mice after immunization with vaccine of rAd5F35-SIVenvT in combination with rMVA-SIVenvT to evaluate the efficacy of different immunization strategies.Methods:Two recombinant viruses were identified in vitro by PCR and Western blot. The BALB/c mice were immunized with homologous and heterologous immune strategies. The numbers of splenic lymphocytes secreting IFN-γ were measured by ELISPOT assay, meanwhile SIV gp120 antibody titer were measured by ELISA assay. Results:SIVenvT protein was expressed effectively by rAd5F35-SIVenvT and rMVA-SIVenvT in HEK293 cells. The specific immune response reached its peak at 4-week post first immunization, then decreased. SIV Env specific cellular immune response and SIV gp120 specific antibody could be detected at 4-16 weeks post first immunization. The specific cellular response was significant stronger in heterologous immunization group than homologous group at 4 week and 16 week. Furthermore, heterologous immunization induced significant higher titer of SIV gp120 antibody at 4 week than homologous group.Conclusions:Specific immune response induced by rAd5F35-SIVenvT in combination with rMVA-SIVenvT was stronger than homologous vector immunization. The results provided references for further study in nonhuman primates.