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 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 safety and feasibility of bilateral axillo-breast approach （BABA） robot in the operation of thyroid cancer in obese women. Methods:The clinical data of 81 obese female patients who underwent da Vinci robotic thyroid cancer surgery（robotic group） at the Department of Thyroid and Breast Surgery, PLA 960 Hospital from May 2018 to December 2021 were retrospectively analyzed and compared with the clinical data of 106 obese female thyroid cancer patients who underwent open surgery（open group） during the same period. The age, body mass index（BMI）, mean time of surgery, mean postoperative drainage, tumor diameter, postoperative tumor stage, number of lymph node dissection in the central and lateral cervical regions, number of positive lymph nodes in the central and lateral cervical regions, postoperative cosmetic outcome satisfaction score, mean postoperative hospital stay and postoperative complications of all patients were counted. The results were analyzed using SPSS 26.0 statistical software, and the count data were compared using the χ² test, and the measurement data were compared using the t test. Results:All patients completed the operation successfully, and there was no conversion in the robot group, postoperative pathological results were all composed of papillary thyroid carcinoma. The operation time in the robot group was（144.62±36.38） min, which was longer than that in the open group（117.06±18.72） min（P<0.05）. The average age of the robot group was（40.25±9.27） years, which was lower than that of the open group（49.59±8.70） years（P<0.05）. The satisfactory score of cosmetic effect in the robot group（9.44±0.65） was higher than that in the open group（5.23±1.07）（P<0.05）. There was no significant difference in tumor diameter, BMI, average postoperative drainage, temporary hypoparathyroidism and recurrent laryngeal nerve injury, number of central and lateral cervical lymph node dissection, number of positive lymph nodes in the central and lateral cervical regions, and average postoperative hospital stay between the two groups. There was no permanent hypoparathyroidism and recurrent laryngeal nerve injury in both groups. Conclusion:The application of BABA pathway robot in thyroid cancer surgery in obese women is safe and feasible, and the cosmetic effect is better after operation.
Humans ; Female ; Adult ; Middle Aged ; Robotics/methods* ; Retrospective Studies ; Recurrent Laryngeal Nerve Injuries ; Thyroidectomy/methods* ; Carcinoma, Papillary/surgery* ; Thyroid Neoplasms/pathology* ; Neck Dissection ; Treatment Outcome

Objective Conduct routine microbiological monitoring of laboratory rats and mice from vendors to provide an important basis for the scientific management of laboratory animal facility and ensure the reliability of relevant experimental data obtained from laboratory animals.Methods Taking the Department of Laboratory Animal Science of Fudan University as an example, between April 2021 and April 2023, rats and mice purchased from 7 vendors were sampled for microbiological quality according to the principle of simple random sampling on the arrival days of animal delivery. Then, surveillance tests were conducted to examine the microbiological contaminations according to the national standards of SPF laboratory animals.Results The total qualified rate was 80.36%, with 52.63% in SD rat, 82.76% in inbred mice, 86.67% in outbred mice and 86.36% in immunodeficient mice in details. The most frequent bacteria isolated were Staphylococcus aureus, Pseudomonas aeruginosa, Klebsilla pneumoniae and Rodentibacter heylii, and their detection rates were 10.76%, 3.16%, 2.53% and 0.63%, respectively. Serological assays demonstrated the highest prevalence for virus was Sendai virus, and the detection rate was 2.53%. In addition to the pathogens those must be excluded from SPF rodents, Entamoeba muris and Enterobacter spp. were also detected in inbred mice, and Klebsiella oxytoca was detected in immunodeficient mice, with the detection rates of 1.15%, 2.30% and 4.55%, respectively.Conclusion There are certain incidences of pathogen infections in laboratory rats and mice from vendors, and an efficient microbiological monitoring of laboratory animals should be implemented in animal facilities, in order to eliminate pathogen infections in laboratory animals, which is required for improving the accuracy of research results and protecting the occupational health of laboratory animal practitioners as well.

Schizophrenia (SCZ) is a highly destructive and complex psychiatric disorder illness, accompanied by a variety of positive and negative symptoms along with cognitive impairment, which brings a heavy social burden. Elucidation of the pathogenesis and therapeutic development is challenging because the complex interplay between genetic risk factors and environmental factors in essential neurodevelopmental processes. Therefore, preparing appropriate animal models can help people better understanding the neurobiological basis of SCZ and provide theoretical basis for finding new treatments. In order to provide reference for the application and improvement of SCZ animal models, this commentary reviewed several main modeling methods for animal models of SCZ, including neurodevelopmental models, drug-induced animal models, and genetic models, and the behavioral evaluation, histological analysis and possible molecular mechanisms of SCZ animal models were also outlined.

Objective To observe the effect of anti NRP-1 b1/b2 monoclonal antibody (NRP-1mAb) on migration and invasion of gastric cancer cell line BGC-823, and to explore the possible mechanism. Methods NRP-1mAb was prepared in the laboratory, and the purity of antibody was detected by flow cytometry. The different concentrations of NRP-1mAb were added into the culture medium of gastric cancer cell line BGC-823. The migration and invasion of cells after 12 hours was observed by using Transwell method. The phosphorylation of related signal proteins after NRP-1mAb was detected by Western blot analysis. Results When NRP-1mAb prepared by patented technology had the effects on BGC-823 cells after 12 hours, the number of migration and invasion of BGC-823 cells was reduced. The number of cells through the basement membrane in the control group (blank) and the administration group (NRP-1mAb 25, 100, 400 μg / ml) were 167 ± 9, 138 ± 5, 98 ± 5, 36 ± 4, respectively (F = 22.6, P< 0.01); the number of cells through the filtration membrane were 231 ± 40,224 ± 19,176 ± 26,124 ± 34,respectively(F=26.63,P<0.01). There were statistically significant differences between the administered group and the control group at 100 and 400 μg/ml (all P< 0.001). High concentration of NRP-1mAb (100 μg/ml) decreased the phosphorylation level of Akt after 10 minutes' function on gastric cancer cells. However, it was difficult to detect phosphorylated Akt after 30 minutes. Conclusion NRP-1mAb may inhibit the migration and invasion of gastric cancer cell line BGC-823 by decreasing the phosphorylation of Akt, which is positively correlated with the concentration.

Objectvi e To investigate whether promoting gap junctions may contribute to the radiosensi-tivity in triple negative breast cancer( TNBC)cells.Methods HCC70(triple-negative),MCF-7(ER-posi-tive)or SK-BR3(HER2-positive )cells were transfected with pcDNA/5 -Cx43 expression plasmid using liposome 2000.The transfected cells were treated with various doses of radiation(0,5,10,15 Gy),and the level of Cx43 protein was determined by Western blot and the cell connectivity was determined by fluorescent tracer technique. Cell proliferation inhibition,clone formation ability and apoptosis were detected using MTT,clone formation assay, AnnexinV-FITC/PI double staining and flow cytometer,respectively.Results The level of Cx43 protein signifi-cantly increased in HCC 70 -Cx43 ,MCF-7 -Cx43 and SK-BR3 -Cx43 cells.After transfection the cells were treated with various doses of radiation,level of Cx43protein was gradually enhanced in dose dependent fashion .The re-sults form fluorescent tracer technique showed that fluorescence intensity was gradually elevated with increase of radiation doses.Cell viability and clone formation ability were decreased gradually in dose dependent manner in HCC70-Cx43 ,MCF-7 -Cx43 and SK-BR3-Cx 43 cells.Unexpectedly,the inhibitive effect of proliferation ability and clone formation ability in HCC70 -Cx43 cell was higher than in MCF-7 -Cx43 and SK-BR3 -Cx43 cells under same conditions.The results from AnnexinV-FITC/PI and flow cytometer showed that apoptosis rate was enhanced gradually accompanying with increase of radiation doses.Conclu sion Enhancing the function of cell gap junc-tions promoted radiosensitivity of breast cancer cells,particularly in TNBC cells.Radiation can strengthen cell gap junctions in breast cancer cell and cytotoxicity of TNBC cell can be enhanced by both synergistic effects.

Toll-like receptor 5 (TLR5) is responsible for the recognition of bacterial flagellin in vertebrates. In the present study, the first TLR5 gene in duck was cloned. The open reading frame (ORF) of duck TLR5 (dTLR5) cDNA is 2580 bp and encodes a polypeptide of 859 amino acids. We also cloned partial sequences of myeloid differentiation factor 88, 2'-5'-oligoadenylate synthetase (OAS), and myxovirus resistance (Mx) genes from duck. dTLR5 mRNA was highly expressed in the bursa of Fabricius, spleen, trachea, lung, jejunum, rectum, and skin; moderately expressed in the muscular and glandular tissues, duodenum, ileum, caecum, and pancreas; and minimally expressed in the heart, liver, kidney, and muscle. DF-1 or HeLa cells transfected with DNA constructs encoding dTLR5 can activate NF-kappaB leading to the activation of interleukin-6 (IL-6) promoter. When we challenged ducks with a Herts33 Newcastle disease virus (NDV), mRNA transcription of the antiviral molecules Mx, Double stranded RNA activated protein kinase (PKR), and OAS was up-regulated in the liver, lung, and spleen 1 and 2 days post-inoculation.
2',5'-Oligoadenylate Synthetase/genetics/metabolism ; Animals ; Cell Line ; *Cloning, Molecular ; Ducks ; Gene Expression Regulation/*physiology ; Humans ; Immunity, Innate ; Myeloid Differentiation Factor 88/genetics/metabolism ; Myxovirus Resistance Proteins/genetics/metabolism ; Newcastle Disease/metabolism ; Newcastle disease virus/classification ; RNA, Messenger/genetics/metabolism ; Species Specificity ; Toll-Like Receptor 5/genetics/*metabolism

Objective This study is to explore the differences in the curative effect of intra -abdominal infusion between Recombinant mutant human tumor necrosis factor and Dendritic cell -Cytokine induced killer . Methods We selected 48 advanced gastric cancer patients with ascites .Those patients were randomized into two groups:DC-CIK group and rmhTNF group .After one month treatment ,we observed the adverse events both two groups,and evaluated the clinical beneficial responses ,the responsive rate ,the tumor indicators′level,the immune indexes and the time of tumor progression .Results In the DC-CIK group,the RR and the CBR were 83.3%and 66.67%,respectively;while in the rmhTNF group,they were 58.33%and 75%,respectively.The difference between two groups was statistically significant (P<0.05).Only CA724 decreased after treatment in two groups (P=0.015).There were no significant differences of tumor markers between the two groups before and after treatment(P>0.05).The ratios of CD3 +、CD4 +、NK cells distinctly increased after treatment (P<0.05),but the ratio of CD8 +cell was no obvious difference in DC -CIK group(P=0.551);The ratio of NK cells increased obviously after treatment(P=0.027),but the ratios of CD3 +and CD4+were similar as previous in rmhTNF group(P>0.05).One year follow-up of the time to progression(TTP)was 7.1 months in DC-CIK group,and 5.8 months in TNF group,which was statistically significant (P=0.02).Conclusion Both rmhTNF and DC-CIK can improve the efficacy for the patients with malignant ascites caused by gastric cancer .However ,DC-CIK immunotherapy shows better active effect on improvement of specific immune function .