Objective:To explore the efficacy of adjusting the dose of imatinib dose in the context of therapeutic drug monitoring (TDM) in patients with gastrointestinal stromal tumors (GISTs) who are receiving adjuvant therapy after complete resection of their tumors.Methods:This was a descriptive study. Inclusion criteria were (1) complete surgical resection with a pathological diagnosis of GIST, (2) postoperative adjuvant therapy with imatinib and dosage adjustment, (3) multiple TDM of imatinib, and (4) complete clinical, pathological, and follow-up data. The data of 70 patients with GISTs treated at Union Hospital, Tongji Medical College, Huazhong University of Science and Technology between January 2015 and December 2023 were collected retrospectively. The study cohort comprised 15 (21.4%) men and 55 (78.6%) women of median age 60 years (range: 25–82). Of the eligible patients, 49 (70.0%) were at high-risk, 14 (20.0%) at intermediate-risk, six (8.6%) at low-risk, and one (1.4%) at very low risk. Patients were followed up by the gastrointestinal stromal tumor clinic every 2–3 months and their plasma concentrations of imatinib were checked. The dose was adjusted to 300 mg/d or 200 mg/d depending on whether they had had ≥ grade III adverse reactions, and whether the first plasma concentration of imatinib was ≥ 1,500 μg/L or between the expected range of 760 μg/L–1,100 μg/L. Studied indicators included adverse reactions, quality of life before and after dose adjustment, and overall survival and recurrence-free survival (RFS) after dose adjustment.Results:Before dose adjustment, all 70 patients received 400 mg of imatinib daily, with initial TDM values of 1,900 ± 568 μg/L, for a median duration of 8.3 months. After dose adjustment, 60 patients received 300 mg daily, with a TDM of 1,216 ± 350 μg/L, whereas 10 received 200 mg daily, with a TDM of 1,023 ± 269 μg/L. The median duration of treatment after dose adjustment was 23.4 months. Compared with those whose dosages were not adjusted, the incidence of bone marrow suppression was significantly lower (74.3% [52/70] vs. 51.4% [36/70], χ 2=9.202, P=0.010); as were the incidences of edema (95.7% [67/70] vs. 50.0% [35/70], χ 2=40.526, P<0.001); skin reactions (70.0% [49/70] vs. 32.9% [23/70), χ 2=22.495, P<0.001); and gastrointestinal reactions (38.6% [27/70] vs. 10.0% [7/70], χ 2=15.899, P<0.001) in those whose dosages were adjusted. The average total scores for physical health before and after dose adjustment were 76 ± 5 and 88 ± 4, respectively; whereas the mental health scores were 75 ± 6 and 89 ± 4, respectively. The median follow-up period was 36 months (range 6–126). During the first 3 years of follow-up, five high-risk patients with non-gastric GISTs developed recurrences. The 3-year overall survival rate was 100%, and the 3-year RFS rate was 92.8%, high-risk patients having a 3-year RFS rate of 89.8%. Conclusion:The adverse reactions and quality of life of GIST patients with severe adverse reactions to adjuvant imatinib therapy after complete resection can be mitigated by appropriately reducing the dosage of imatinib under the guidance of TDM.

Objective:To explore the efficacy of adjusting the dose of imatinib dose in the context of therapeutic drug monitoring (TDM) in patients with gastrointestinal stromal tumors (GISTs) who are receiving adjuvant therapy after complete resection of their tumors.Methods:This was a descriptive study. Inclusion criteria were (1) complete surgical resection with a pathological diagnosis of GIST, (2) postoperative adjuvant therapy with imatinib and dosage adjustment, (3) multiple TDM of imatinib, and (4) complete clinical, pathological, and follow-up data. The data of 70 patients with GISTs treated at Union Hospital, Tongji Medical College, Huazhong University of Science and Technology between January 2015 and December 2023 were collected retrospectively. The study cohort comprised 15 (21.4%) men and 55 (78.6%) women of median age 60 years (range: 25–82). Of the eligible patients, 49 (70.0%) were at high-risk, 14 (20.0%) at intermediate-risk, six (8.6%) at low-risk, and one (1.4%) at very low risk. Patients were followed up by the gastrointestinal stromal tumor clinic every 2–3 months and their plasma concentrations of imatinib were checked. The dose was adjusted to 300 mg/d or 200 mg/d depending on whether they had had ≥ grade III adverse reactions, and whether the first plasma concentration of imatinib was ≥ 1,500 μg/L or between the expected range of 760 μg/L–1,100 μg/L. Studied indicators included adverse reactions, quality of life before and after dose adjustment, and overall survival and recurrence-free survival (RFS) after dose adjustment.Results:Before dose adjustment, all 70 patients received 400 mg of imatinib daily, with initial TDM values of 1,900 ± 568 μg/L, for a median duration of 8.3 months. After dose adjustment, 60 patients received 300 mg daily, with a TDM of 1,216 ± 350 μg/L, whereas 10 received 200 mg daily, with a TDM of 1,023 ± 269 μg/L. The median duration of treatment after dose adjustment was 23.4 months. Compared with those whose dosages were not adjusted, the incidence of bone marrow suppression was significantly lower (74.3% [52/70] vs. 51.4% [36/70], χ 2=9.202, P=0.010); as were the incidences of edema (95.7% [67/70] vs. 50.0% [35/70], χ 2=40.526, P<0.001); skin reactions (70.0% [49/70] vs. 32.9% [23/70), χ 2=22.495, P<0.001); and gastrointestinal reactions (38.6% [27/70] vs. 10.0% [7/70], χ 2=15.899, P<0.001) in those whose dosages were adjusted. The average total scores for physical health before and after dose adjustment were 76 ± 5 and 88 ± 4, respectively; whereas the mental health scores were 75 ± 6 and 89 ± 4, respectively. The median follow-up period was 36 months (range 6–126). During the first 3 years of follow-up, five high-risk patients with non-gastric GISTs developed recurrences. The 3-year overall survival rate was 100%, and the 3-year RFS rate was 92.8%, high-risk patients having a 3-year RFS rate of 89.8%. Conclusion:The adverse reactions and quality of life of GIST patients with severe adverse reactions to adjuvant imatinib therapy after complete resection can be mitigated by appropriately reducing the dosage of imatinib under the guidance of TDM.

Objective:To evaluate the safety and feasibility of neoadjuvant chemotherapy (NACT) combined with radical surgery for elderly patients with locally advanced gastric cancer (LAGC).Methods:One hundred and fourty eight patients with LAGC after NACT and gastrectomy between 2012 and 2020 were retrospectively reviewed. They were divided into two groups: (1) <65 years old (111 cases) and (2) ≥65 years old (37 cases) and their clinicopathological and prognostic data were compared.Results:There was no significant difference between the two groups in the incidence of hematological complications such as anemia ( χ2=0.235, P=0.628), leukopenia ( χ2=0.613, P=0.434), neutropenia ( χ2=0.011, P=0.918) and thrombocytopenia ( χ2=0.253, P=0.615) and non-hematological complications such as nausea ( χ2=0.092, P=0.762), vomiting ( χ2=0.166, P=0.683), diarrhea ( χ2=0.015, P=0.902) and mucositis ( χ2=0.199, P=0.766) due to NACT. There were no statistical differences between the older patients and the younger in operation duration ( t=0.270, P=0.604), intraoperative bleeding ( t=1.140, P=0.250) and R 0 resection rate ( χ2=0.105, P=0.750). The incidence of postoperative complications was 25.2% and 37.8% in the younger patients and the olders ( χ2=2.172, P=0.141). Pleural effusion ( χ2=7.007, P=0.008) and pulmonary infection ( χ2=10.204, P=0.001) was significantly higher in the older patients than in the youngers. The 3-year progression-free survival rate ( t=0.494, P=0.482) and 3-year overall survival rate ( t=0.013, P=0.908) were comparable between the two groups. Conclusions:NACT combined with radical surgery is safe and effective in elderly patients with LAGC, except for higher perioperative pulmonary-related complications.

Objective To study the value of postmortem imaging on the diagnosis of intestinal perforation.Method Postmortem imaging(PMCT and PMCTA)data of 2 intestinal perforation deaths(and 4 controlled cases)were reviewed retrospectively.Diagnosing capacities of intestinal perforation by postmortem imaging method were further investigated.Results PMCT is sensitive in detecting the free air and liquid induced by intestinal perforation.PMCT can sometimes detect the gravity-dependent purulent secretions in the abdominopelvic cavity.PMCTA can visualize the extravasation of contrast agent from the perforation,which can be used to locate the accurate perforation region.Conclusion Postmortem imaging method(PMCT and PMCTA)is an important tool for the diagnosis of intestinal perforation,which can not only be used as a forensic diagnosis method,but is also useful to locate the perforation site before an forensic autopsy.

OBJECTIVE: To explore the genetic etiology of a child with lymphangiectasia and lymphedema. METHODS: DNA sample of the patient was extracted and subjected to whole exome sequencing. Suspected variants were verified by Sanger sequencing. RESULTS: The patient was found to carry compound heterozygote variants (c.521G>A and c.472C>T) of the CCBE1 gene, which were respectively inherited from his parents. CONCLUSION The compound heterozygote variants of the CCBE1 gene probably underlie the disease in this child.

Thanks to the process reengineering of appointment registration, outpatient doctor′s advice, payment and mobile Internet application system, multiple payment queues in outpatient service have been replaced by automatic book keeping of the information system. This reform, based on short message reminders and the credit mechanism, has effectively reduced queuing time in convenience of the outpatients.

OBJECTIVE: To identify potential mutations of the CLS gene in a Chinese pedigree affected with Coffin-Lowry syndrome. METHODS: Whole exome sequencing was applied to detect potential mutation in the proband, and the result was verified by Sanger sequencing. RESULTS: The proband was found to carry a c.966_967delAA (p.Arg323Thr fs*11) deletional mutation in the RPS6KA3 gene. The same mutation was also found in his mother. CONCLUSION The c.966_967delAA (p.Arg323Thr fs*11) deletional mutation of the RPS6KA3 gene probably underlies the disorder in this pedigree.
Asian Continental Ancestry Group ; China ; Coffin-Lowry Syndrome ; genetics ; Humans ; Mutation ; Pedigree ; Ribosomal Protein S6 Kinases, 90-kDa ; genetics ; Sequence Deletion

The research and development of the modules for outpatient medical advice prescriptions, mobile internet applications and order arrangement/delivery system, have established a procedure series for prescription, delivery, assessment, activation, settlement, order arrangement and distribution for patients of chronic diseases. These efforts can meet the long-term drug demands of such patients during their stable conditions, providing technology support for sustainable management and service for chronic disease patients.

Objective To study the therapeutic effect of anti-CD80 bivalent antibody on mouse lu-pus nephritis and to explore the possible molecular mechanism. Methods A mouse model of lupus nephritis was established through intraperitoneal injection of 0. 5 ml of pristine in female C57BL/6J mice. Appearance of urinary protein and significantly increased levels of peripheral antinuclear antibody ( ANA) and anti-doub-le-stranded DNA ( anti-dsDNA) antibody in the fourth month after injection indicated that the mouse model was established successfully. Then the mice were divided into two groups including anti-CD80 bivalent anti-body intervention group (injected with 200μg of anti-CD80 bivalent antibody at day 1, 3, 5, 8 and 15, fol-lowed by three times of injection with an interval of one month) and model group ( injected with the same protein using the same strategy). A normal control group was set up accordingly. Albustix test paper was used to monitor the dynamic changes in mouse urinary protein. Flow cytometry was used to analyze the acti-vation of immune-related cells in spleen. Levels of autoantibodies ( ANA and anti-dsDNA) and levels of IFN-γ and IL-4 in serum were detected by indirect immunofluorescence assay. Renal tissue samples were an-alyzed with hematoxylin and eosin ( HE) staining and immunocomplex ( IC) assay. Results Urinary pro-tein level of the anti-CD80 bivalent antibody intervention group was significantly lower than that of the model group (P<0. 05). Activated macrophages, dendritic cells, neutrophils and B cells in spleen tissues of the anti-CD80 bivalent antibody intervention group were significantly less than those of the model group ( P<0. 05), and the numbers of CD4+ and CD154+ T cells were significantly less than those of the model group (P<0. 05). Positive rates and titers of ANA and dsDNA in serum samples of the intervention group were lower than those of the model group (P<0. 05). Levels of IFN-γand IL-4 in serum samples of the interven-tion group were decreased as compared with those of the model group (P<0. 05). HE staining and immuno-fluorescence assay showed that glomerular inflammatory injury and necrosis were alleviated and kidney im-mune complex deposition was reduced after anti-CD80 bivalent antibody intervention. Conclusion Anti-CD80 bivalent antibody specifically binds to the CD80 molecule on antigen presenting cell surface, blocks the CD80/CD28 co-stimulatory signaling pathway and down-regulates the body′s immune response, which al-leviates and reverses the lupus-like nephritis-induced pathological damages in mice.

Objective: To investigate the serum lipidomic profile in patients with nonalcoholic fatty liver disease (NAFLD), and to analyze the lipid metabolism characteristics of NAFLD. Methods: The subjects were divided into control group (23 patients) and pathologically confirmed NAFLD group (42 patients), and ultra-high-performance liquid chromatography-tandem mass spectrometry was used to measure serum lipidomic metabolites. The partial least squares-discriminant analysis (PLS-DA) model was established to analyze the differences in lipid metabolism with reference to the univariate analysis. The t-test and Mann-Whitney U test were used for data analysis. Results: A total of 239 lipids were identified and qualitative and quantitative analyses were performed. The PLS-DA model (R2 = 0.753, Q2 = 0.456) and the univariate analysis showed that 77 lipids were metabolized differentially between the NAFLD group and the control group (VIP > 1, P < 0.05), including free fatty acid, phosphatidylcholine, phosphatidylethanolamine, phosphatidylinositol, lysophosphatidylcholine, lysophosphatidylinositol (LPI), choline plasmalogen (PlsCho), ethanolamine plasmalogen (PlsEtn), ceramide (Cer), sphingomyelin, and triglyceride (TG). Compared with the control group, the NAFLD group had significant increases in monounsaturated fatty acids (increased by 39%, t = -3.954, P < 0.05) and TGs (increased by 36%, Z = -2.662, P < 0.05), mainly TGs with low numbers of carbon atoms and unsaturated bonds, while there were reductions in TGs with high numbers of carbon atoms and unsaturated bonds. In addition, compared with the control group, the NAFLD group had significant increases in the levels of LPI (increased by 223%, t = -3.858, P < 0.05) and Cer (increased by 21%, t = -2.481, P < 0.05) and significant reductions in PlsCho (reduced by 18%, t = 3.184, P < 0.05) and PlsEtn (reduced by 20%, t = 2.363, P < 0.05). Conclusion There is a significant difference in lipid metabolism profile between NAFLD patients and healthy people, and a serum lipidomic analysis of NAFLD helps to further clarify the characteristics of lipid metabolism in patients with NAFLD.