Objective To investigate the changes of 8 lipid biomarkers,4 complement biomarkers and albu-min(ALB)in serum of patients with colorectal cancer(CRC)and their value in CRC screening.Methods A total of 120 newly diagnosed CRC patients in Renji Hospital Affiliated to Shanghai Jiaotong University School of Medicine from August 2022 to January 2024 were selected as the CRC group,and 110 healthy subjects were selected as the healthy control(HC)group.A total of 8 lipid biomarkers including total cholesterol(TC),tri-glyceride(TG),high density lipoprotein cholesterol(HDL-C),low density lipoprotein cholesterol(LDL-C),apolipoprotein(Apo)A1,ApoA2,ApoB and ApoE,4 complement biomarkers including complement C3(C3),complement C4(C4),complement C1q(C1q)and complement C1 inhibitor(C1INH),3 intestinal tumor markers including carcinoembryonic antigen(CEA),carbohydrate antigen(CA)125,CA19-9,and ALB levels were detected in serum of each group.Independent sample t test and Mann-Whitney U test were used for com-parison between groups,and stepwise Fisher discriminant algorithm was used to fit each marker to establish a screening model.Receiver operating characteristic curve was used to analyze the diagnostic efficacy of each marker and the model.Results The serum levels of ApoA1,ApoA2,HDL-C,TC and ALB in CRC group were lower than those in HC group(P<0.05),while the serum levels of C1INH,C4 and CEA were higher than those in HC group(P<0.05).Among the single biomarkers,ALB had the highest diagnostic efficiency,the area under the curve(AUC)was 0.909,the sensitivity was 77.50%,and the specificity was 94.55%.The AUC of the screening model composed of ApoA2,C1INH and ALB was 0.978,the sensitivity was 91.67%,and the specificity was 98.86%.The diagnostic efficacy was higher than any single biomarker.Conclusion ApoA2,C1INH and ALB are abnormally expressed in the serum of CRC patients.The screening model composed of ApoA2,C1INH and ALB can provide reference for CRC screening and clinical auxiliary diagnosis.

Objective Port-wine stains are a kind of dermatological disease of congenital capillary malformation.Based on the biological characteristics of port-wine stains and the advantages of microneedle transdermal administration,we intend to construct a nanodrug co-loaded with rapamycin(RPM),an anti-angiogenesis drug,and photochlor(HPPH),a photosensitizer,and integrate the nanodrug with dissolvable microneedles(MN)to achieve anti-angiogenesis and photodynamic combination therapy for port-wine stains.Methods First,RPM and HPPH co-loaded nanoparticles(RPM-HPPH NP)were prepared by the emulsification solvent-volatilization method,and its ability to generate reactive oxygen species(ROS)was investigated under 660 nm laser irradiation.Mouse hemangioendothelioma endothelial cells(EOMA)were used as the subjects of the study.The cellular uptake behaviors were examined by fluorescence microscopy and flow cytometry.The cytotoxicity effects of RPM-HPPH NP with or without 660 nm laser irradiation on EOMA cells were examined by MTT assays(with free RPM serving as the control).Then,hyaluronic acid(HA)dissolvable microneedles loaded with RPM-HPPH NP(RPM-HPPH NP@HA MN)were obtained by compounding the nanodrug with HA dissolvable microneedle system through the molding method.The morphological characteristics and mechanical properties of RPM-HPPH NP@HA MN were investigated by scanning electron microscope and electronic universal testing machine.The penetration ability of RPM-HPPH NP@HA MN on the skin of nude mice was evaluated by trypan blue staining and H&E staining experiment.Results The RPM-HPPH NP prepared in the study had a particle size of 150 nm and generated large amounts of ROS under laser irradiation.At the cellular level,RPM-HPPH NP was taken up by EOMA cells in a time-dependent manner.The cytotoxicity of RPM-HPPH NP was higher than that of free RPM with or without laser irradiation.Under laser irradiation,RPM-HPPH NP exhibited stronger cytotoxic effects and the difference was statistically significant(P＜0.05).The height of the needle tip of RPM-HPPH NP@HA MN was 600 μm and the mechanical property of a single needle was 0.75048 N.Trypan blue staining and HE staining showed that pressing on the microneedles could produce pores on the skin surface and penetration of the stratum corneum.Conclusion RPM-HPPH NP@HA MN can deliver RPM-HPPH NP percutaneously to the lesion tissue and realize the synergistic treatment of port-wine stains with anti-angiogenic therapy and photodynamic therapy,providing a new strategy for the construction of nanodrug-loaded microneedle delivery system and the clinical treatment of port-wine stains.

Objective: To investigate the significance of monitoring imatinib mesylate (IM) plasma concentrations in patients with gastrointestinal stromal tumor (GIST). Methods: A retrospective descriptive study was carried out. Inclusion criteria: (1) patients with GIST confirmed by postoperative pathology or puncture pathology receiving maintenance therapy of IM; (2) administration of same dose of IM for at least 4 weeks (achieving steady - state plasma concentration). Patients who had severe organ dysfunction, received IM generics, or received IM simultaneously with other drugs significantly affecting IM pharmacokinetic were excluded. A total of 185 patients at the GIST Clinic of Renji Hospital, Shanghai Jiaotong University School of Medicine from August 2018 to May 2019 were enrolled, including 114 males (61.6%) and 71 females (38.4%) with a median age of 60 years old (range, 30-89 years), and 63 advanced cases. Patients receiving preoperative or postoperative adjuvant therapy were given IM 400 mg QD; patients with KIT exon 9 mutation or with disease progression during IM 400 mg QD treatment were given IM 600 mg QD. If the patient had adverse reactions such as myelosuppression during the medication, IM would be reduced or given BID per day. The peripheral venous blood was collected (22 to 24 hours after the last dose for patients who took IM QD and 2 hours before the first dose per day for those who took IM BID). IM plasma concentration was measured through high performance liquid chromatography coupled with tandem mass spectrometry (HPLC-MS/MS). Correlation analysis between IM plasma concentration results and clinical data was performed using linear regression analysis. Results: A total of 241 stable blood samples of IM plasma concentration from 185 patients were finally collected. The IM plasma concentrations were significantly different between the doses of 300 mg/d and 400 mg/d [(942.4±433.5) μg/L vs. (1340.0±500.1) μg/L, t=6.317, P<0.001], and between 400 mg/d and 600 mg/d [(1340.0±500.1) μg/L vs. (2188.0±875.5) μg/L, t=3.557, P=0.004]. Among the blood samples of 57 patients receiving IM 300 mg/d, the IM plasma concentration of the advanced patients was significantly lower than that of the non-advanced patients [(795.6±225.8) μg/L vs. (992.2±484.4) μg/L, t=2.088, P=0.042]. Among the 137 blood samples of patients receiving IM 400 mg/d, the IM plasma concentration was higher in patients aged >60 years than those aged ≤60 years [(1461.0±595.3) μg/L vs. (1240.0±380.9) μg/L, t=2.528, P=0.013] and the IM plasma concentration of cases with diarrhea was significantly lower than that of those without diarrhea [(745.8±249.6) μg/L vs. (1382.0±486.9) μg/L, t=6.794, P<0.001]. Gender, primary location, surgical procedure, mutated gene, mutation type, or time of administration was associated with IM plasma concentration no matter in patients taking IM doses of 400 mg/d or 300 mg/d (all P>0.05). Regression analysis showed that body mass (P=0.004 and P=0.019), body mass index (P=0.016 and P=0.042), and body surface area (P=0.007 and P=0.028) were all negatively correlated with IM plasma concentrations in patients taking IM doses of 300 mg/d and 400 mg/d. Within the 137 patients who received a fixed oral dose of 400 mg/d IM, 17 patients received oral 200 mg BID, whose IM plasma drug concentration was not significantly different compared with that of 120 patients who received 400 mg IM QD [(1488.0±408.3) μg/L vs. (1319.0±509.7) μg/L, t=1.307, P=0.193]. Conclusions Monitoring IM plasma concentration is significant throughout the whole process of management of GIST patients receiving IM treatment. In particular, regular monitoring IM plasma concentration and developing appropriate treatment strategies can bring better therapeutic benefits for patients with low doses, diarrhea, advanced condition and older age.

Objective To investigate the significance of monitoring imatinib mesylate (IM) plasma concentrations in patients with gastrointestinal stromal tumor (GIST). Methods A retrospective descriptive study was carried out. Inclusion criteria: (1) patients with GIST confirmed by postoperative pathology or puncture pathology receiving maintenance therapy of IM; (2) administration of same dose of IM for at least 4 weeks (achieving steady?state plasma concentration). Patients who had severe organ dysfunction, received IM generics, or received IM simultaneously with other drugs significantly affecting IM pharmacokinetic were excluded. A total of 185 patients at the GIST Clinic of Renji Hospital, Shanghai Jiaotong University School of Medicine from August 2018 to May 2019 were enrolled, including 114 males (61.6%) and 71 females (38.4%) with a median age of 60 years old (range, 30?89 years), and 63 advanced cases. Patients receiving preoperative or postoperative adjuvant therapy were given IM 400 mg QD;patients with KIT exon 9 mutation or with disease progression during IM 400 mg QD treatment were given IM 600 mg QD. If the patient had adverse reactions such as myelosuppression during the medication, IM would be reduced or given BID per day. The peripheral venous blood was collected (22 to 24 hours after the last dose for patients who took IM QD and 2 hours before the first dose per day for those who took IM BID). IM plasma concentration was measured through high performance liquid chromatography coupled with tandem mass spectrometry (HPLC?MS/MS). Correlation analysis between IM plasma concentration results and clinical data was performed using linear regression analysis. Results A total of 241 stable blood samples of IM plasma concentration from 185 patients were finally collected. The IM plasma concentrations were significantly different between the doses of 300 mg/d and 400 mg/d [(942.4± 433.5) μg/L vs. (1340.0±500.1) μg/L, t=6.317, P<0.001], and between 400 mg/d and 600 mg/d [(1340.0± 500.1) μg/L vs. (2188.0 ± 875.5) μg/L, t=3.557, P=0.004]. Among the blood samples of 57 patients receiving IM 300 mg/d, the IM plasma concentration of the advanced patients was significantly lower than that of the non?advanced patients [(795.6±225.8) μg/L vs. (992.2±484.4) μg/L, t=2.088, P=0.042]. Among the 137 blood samples of patients receiving IM 400 mg/d, the IM plasma concentration was higher in patients aged>60 years than those aged≤60 years [(1461.0±595.3) μg/L vs. (1240.0±380.9) μg/L, t=2.528, P=0.013] and the IM plasma concentration of cases with diarrhea was significantly lower than that of those without diarrhea [(745.8 ± 249.6) μg/L vs. (1382.0 ± 486.9) μg/L, t=6.794, P<0.001]. Gender, primary location, surgical procedure, mutated gene, mutation type, or time of administration was associated with IM plasma concentration no matter in patients taking IM doses of 400 mg/d or 300 mg/d (all P>0.05). Regression analysis showed that body mass (P=0.004 and P=0.019), body mass index (P=0.016 and P=0.042), and body surface area (P=0.007 and P=0.028) were all negatively correlated with IM plasma concentrations in patients taking IM doses of 300 mg/d and 400 mg/d. Within the 137 patients who received a fixed oral dose of 400 mg/d IM, 17 patients received oral 200 mg BID, whose IM plasma drug concentration was not significantly different compared with that of 120 patients who received 400 mg IM QD [(1488.0±408.3) μg/L vs. (1319.0±509.7) μg/L, t=1.307, P=0.193]. Conclusions Monitoring IM plasma concentration is significant throughout the whole process of management of GIST patients receiving IM treatment. In particular, regular monitoring IM plasma concentration and developing appropriate treatment strategies can bring better therapeutic benefits for patients with low doses, diarrhea, advanced condition and older age.

Objective To investigate the significance of monitoring imatinib mesylate (IM) plasma concentrations in patients with gastrointestinal stromal tumor (GIST). Methods A retrospective descriptive study was carried out. Inclusion criteria: (1) patients with GIST confirmed by postoperative pathology or puncture pathology receiving maintenance therapy of IM; (2) administration of same dose of IM for at least 4 weeks (achieving steady?state plasma concentration). Patients who had severe organ dysfunction, received IM generics, or received IM simultaneously with other drugs significantly affecting IM pharmacokinetic were excluded. A total of 185 patients at the GIST Clinic of Renji Hospital, Shanghai Jiaotong University School of Medicine from August 2018 to May 2019 were enrolled, including 114 males (61.6%) and 71 females (38.4%) with a median age of 60 years old (range, 30?89 years), and 63 advanced cases. Patients receiving preoperative or postoperative adjuvant therapy were given IM 400 mg QD;patients with KIT exon 9 mutation or with disease progression during IM 400 mg QD treatment were given IM 600 mg QD. If the patient had adverse reactions such as myelosuppression during the medication, IM would be reduced or given BID per day. The peripheral venous blood was collected (22 to 24 hours after the last dose for patients who took IM QD and 2 hours before the first dose per day for those who took IM BID). IM plasma concentration was measured through high performance liquid chromatography coupled with tandem mass spectrometry (HPLC?MS/MS). Correlation analysis between IM plasma concentration results and clinical data was performed using linear regression analysis. Results A total of 241 stable blood samples of IM plasma concentration from 185 patients were finally collected. The IM plasma concentrations were significantly different between the doses of 300 mg/d and 400 mg/d [(942.4± 433.5) μg/L vs. (1340.0±500.1) μg/L, t=6.317, P<0.001], and between 400 mg/d and 600 mg/d [(1340.0± 500.1) μg/L vs. (2188.0 ± 875.5) μg/L, t=3.557, P=0.004]. Among the blood samples of 57 patients receiving IM 300 mg/d, the IM plasma concentration of the advanced patients was significantly lower than that of the non?advanced patients [(795.6±225.8) μg/L vs. (992.2±484.4) μg/L, t=2.088, P=0.042]. Among the 137 blood samples of patients receiving IM 400 mg/d, the IM plasma concentration was higher in patients aged>60 years than those aged≤60 years [(1461.0±595.3) μg/L vs. (1240.0±380.9) μg/L, t=2.528, P=0.013] and the IM plasma concentration of cases with diarrhea was significantly lower than that of those without diarrhea [(745.8 ± 249.6) μg/L vs. (1382.0 ± 486.9) μg/L, t=6.794, P<0.001]. Gender, primary location, surgical procedure, mutated gene, mutation type, or time of administration was associated with IM plasma concentration no matter in patients taking IM doses of 400 mg/d or 300 mg/d (all P>0.05). Regression analysis showed that body mass (P=0.004 and P=0.019), body mass index (P=0.016 and P=0.042), and body surface area (P=0.007 and P=0.028) were all negatively correlated with IM plasma concentrations in patients taking IM doses of 300 mg/d and 400 mg/d. Within the 137 patients who received a fixed oral dose of 400 mg/d IM, 17 patients received oral 200 mg BID, whose IM plasma drug concentration was not significantly different compared with that of 120 patients who received 400 mg IM QD [(1488.0±408.3) μg/L vs. (1319.0±509.7) μg/L, t=1.307, P=0.193]. Conclusions Monitoring IM plasma concentration is significant throughout the whole process of management of GIST patients receiving IM treatment. In particular, regular monitoring IM plasma concentration and developing appropriate treatment strategies can bring better therapeutic benefits for patients with low doses, diarrhea, advanced condition and older age.