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: Hepatitis B surface antigen (HBsAg) loss is seldom achieved with nucleos(t)ide analog (NA) therapy in chronic hepatitis B patients but may be enhanced by switching to finite pegylated-interferon (Peg-IFN) alfa-2a. We assessed HBsAg loss with 48- and 96-week Peg-IFN alfa-2a in chronic hepatitis B patients with partial response to a previous NA. Methods: Hepatitis B e antigen (HBeAg)-positive patients who achieved HBeAg loss and hepatitis B virus DNA < 200 IU/mL with previous adefovir, lamivudine or entecavir treatment were randomized 1:1 to receive Peg-IFN alfa-2a for 48 (n = 153) or 96 weeks (n = 150). The primary endpoint of this study was HBsAg loss at end of treatment. The ClinicalTrials.gov identifier is NCT01464281. Results: At the end of 48 and 96 weeks' treatment, 14.4% (22/153) and 20.7% (31/150) of patients, respectively, who switched from NA to Peg-IFN alfa-2a cleared HBsAg. Rates were similar irrespective of prior NA or baseline HBeAg seroconversion. Among those who cleared HBsAg by the end of 48 and 96 weeks' treatment, 77.8% (14/18) and 71.4% (20/28), respectively, sustained HBsAg loss for a further 48 weeks. Baseline HBsAg < 1 500 IU/mL and week 24 HBsAg < 200 IU/mL were associated with the highest rates of HBsAg loss at the end of both 48- and 96-week treatment (51.4% and 58.7%, respectively). Importantly, extending treatment from 48 to 96 weeks enabled 48.3% (14/29) more patients to achieve HBsAg loss. Conclusion Patients on long-term NA who are unlikely to meet therapeutic goals can achieve high rates of HBsAg loss by switching to Peg-IFN alfa-2a. HBsAg loss rates may be improved for some patients by extending treatment from 48 to 96 weeks, although the differences in our study cohort were not statistically significant. Baseline and on-treatment HBsAg may predict HBsAg loss with Peg-IFN alfa-2a.

Objective To compare risk factors and bacterial etiology in patients with early-onset versus late-onset ventilator-associated pneumonia (VAP) in intensive care unit (ICU).Methods This prospective cohort study enrolled mechanically ventilated patients hospitalized for more than 48 hours in the first affiliated hospital,China Medical University from Jan 2012 to Jun 2016.Subjects were classified by ventilator status:early-onset VAP (＜ 5 d ventilation,E-VAP) or late-onset VAP (≥ 5 d ventilation,L-VAP).Potential risk factors and pathogen were evaluated.Results A total of 4 179 patients in adult ICU were screened,3 989 (95.5％) of whom were mechanically ventilated,962 patients with mechanical ventilation time ≥ 48 h.VAP developed in 142 patients.E-VAP and L-VAP had different potential risk factors based on statistical analysis.Independent risk factors for E-VAP included male (OR =1.825,95％ CI 1.006-3.310),chronic obstructive pulmonary disease (COPD;OR =3.746,95％ CI 1.795-7.818),emergency intubation (OR =1.932,95％ CI 1.139-3.276),aspiration (OR =3.324,95％ CI 1.359-8.130).Whereas independent risk factors for L-VAP were coma (OR =2.335,95％ CI 1.300-4.194),renal dysfunction (OR =0.524,95％ CI O.290-O.947),emergency intubation (OR =2.184,95％ CI 1.334-3.574).Mortality in E-VAP and L-VAP group were both higher than the non-VAP group[30.2％(19/63)vs 19.8％ (162/820),P=0.044;29.1％ (23/79) vs 19.8％(162/820),P=0.046].The pathogens isolated from early-onset versus late-onset VAP were not significantly different between groups,which the most common ones were acinetobacter baumannii,pseudomonas aeruginosa and klebsiella pneumoniae.Conclusion E-VAP and L-VAP have different risk factors,however related pathogens are similar.Different specific preventive strategies are suggested based on different onset of VAP.

OBJECTIVE To investigate the protective effects and mechanism of diterpene ginkgolides meglumine injection (DGMI) against oxidative stress induced by oxygen-glucose deprivation (OGD) in SH-SY5Y cells. METHODS SH-SY5Y cells were divided into five groups: normal control, model control (OGD group) and drug(25 mg · L- 1) administration groups including DGMI group, extract of ginkgo biloba leaves injection group (EGBLI) and lactones ginkgo biloba injection group (LGBI). The cells suffered from oxygen-glucose deprivation (OGD) for 4 h, followed by reoxygenation with drugs for 6 h. Then, cell viabilities were detect using CCK-8 assays, reactive oxygen species (ROS) levels using fluorescence probe DCFH-DA and superoxide dismutase (SOD) activities using WST-1 test. Western blotting was used to detected protein levels of hemeoxygenase-1(HO-1), NAD(P)H, quinone oxidore?ductase l (Nqo1), protein kinase B (Akt), phosphorylated Akt (p-Akt), nuclear factor-E2-related factor2 (Nrf2) and phosphorylated Nrf2 (p-Nrf2). The cells were induced by OGD for 4 h, followed by reoxygen?ation and DGMI for 1 h, combined with different concentrations of PI3K inhibitor (LY294002) (at the final concentration of 12.5, 25 and 50 μmol · L-1) before the protein levels of AKT, p-AKT, Nrf2 and p-Nrf2 were detected by Western blotting. RESULTS SH-SY5Y cells induced by OGD for 4 h resulted in an increase in ROS(P<0.01), but a decrease in cell viabilities(P<0.01), SOD activities(P<0.01), and antioxidant protein levels ( Akt, p-Akt, Nrf2, p-Nrf2, HO-1 and Nqo1) (P<0.01). Compared with OGD group, treatment with reoxygenation and drugs (DGMI,EGBLI and LGBI respectively) for 6 h resulted in a decrease in ROS (P<0.01), but an increase in cell viabilities, SOD activities and antioxidant protein levels of p-Nrf2, HO-1, Nqo1 and p-Akt(P<0.05,P<0.01). DGMI group showed the best efficiently. Moreover, after OGD for 4 h, compared with DGMI group, combining reoxygenation and DGMI with LY294002 for 1 h resulted in a concentration-dependent inhibition of the protein levels of p-AKT and p-Nrf2(P<0.01). CONCLUSION DGMI 25 mg · L-1 can inhibit oxidative stress in SH-SY5Y cells induced by OGD by increasing the activity and expression of Nrf2 through PI3K/Akt pathway, which may be one of the mechanisms by which DGMI protects neurons from stroke.

Aim To investigate the protective effects of Diterpene Ginkgolides Meglumine Injection(DGMI)on SY5 Y cells damaged by oxygen-glucose deprivation and its functional mechanisms.Methods After 4 h of OGD,the cells were treated with 25 mg·L-1 drugs for 1 h.Subsequently,cell viabilities were measured by cell counting kit-8(CCK-8 kit)and cell apoptosis was measured by flow cytometric analysis.Furthermore, the mitochondrial membrane potential was detected by rhodamine123 staining.The levels of phospho-p38, phospho-p53,Bcl-2,Bax and cleaved caspase-9/3 were evaluated by western blot.Results DGMI signif-icantly increased the cell viabilities of SY5 Y cells dam-aged by OGD,and reduced OGD-elicited dissipation of mitochondrial membrane potential and cell apoptosis. Furthermore,DGMI also reduced p-p38,p-p53,Bax/Bcl-2 ratio,cleaved caspase-9 and cleaved caspase-3. Conclusion DGMI shows good neuroprotective effects on SY5 Y cells after oxygen-glucose deprivation.The underlying mechanisms may be associated with the sup-pression of p38/p53/Bcl-2 /caspase-9/caspase-3 sig-naling pathway.

Objective To evaluate the application value of arcuate fasciculus diffusion tensor imaging (DTI) combined with neuronavigation in epilepsy surgery. Methods A retrospective analysis of 24 patients with refractory epilepsy, admitted to our hospital from March 2011 to March 2014, was performed; the epileptic foci of these patients were adjacent to the language functional areas conformed by imaging before operation. Surgical resection was performed with the help of arcuate fasciculus of DTI, diffusion tensor fiber tracking (DT-FT) combined with neuronavigation. The surgical efficacy and language function of the patients were evaluated by Engel classification and Verbal Behavior Assessment Scale (VerBAS) at postoperative follow-up. Results During the follow-up from 12 to 47 months, according to Engel classification, in 7 patients with foci adjacent to Broca area, Engel grade I was achieved in 3, Engel grade II in 3 and Engel grade Ⅲ in one; and in 17 patients with foci adjacent to Wernicke area, seizure control was as follows: Engel grade I was noted in 13, Engel grade II in 2 and Engel grade III in 2. No perpetual language dysfunction after operation was noted in all the patients. Conclusion Arcuate fasciculus DTI combined with intraoperative neuronavigation has very high application value in the epilepsy surgery.

OBJECTIVETo analyze the literature on power frequency electric field testing data and to propose views and suggestions for current testing.

METHODSThe literature on power frequency electric field testing data published in the previous years was searched to identify 306 articles involving 193 valid testing data. Mann-Whitney test and Wilcoxon W test were used for analyzing the testing data.

RESULTSThe classification of data was carried out according to one quarter of occupational exposure limit (1.25 kV/m), one half of the exposure limit (2.5 kV/m), and the exposure limit (5 kV/m). The structure of testing data showed a significant difference between the non-power facility group and the power facility group (P<0.05).

CONCLUSIONAs occupational hazard factors, the radiation exposure from power frequency electric field is extensive. However, the power frequency electric field testing data in actual workplaces except high-voltage power facilities are far less than the occupational exposure limit with little harmfulness. There is a phenomenon of excessive testing at present.

Objective To evaluate the clinical effect of functional neuronavigation combined with intra-operative magnetic resonance imaging (iMRI) in resection of symptomatic occipital lobe epilepsy.Methods Sixteen patients with symptomatic occipital lobe epilepsy,admitted to our hospital from January 2011 to April 2012,were involved in present study.All patients underwent surgical operation assisted by functional neuronavigation.Before the operation,MRI scanning,imaging fusing,scope of lesion excision describing,and operative approach designing were performed successively.Three-D reconstructed navigation plan was integrated into neuronavigation system and used by combining with functional neuronavigation under microscope during the surgical procedure.And,the iMRI was performed in five of them; the operative plan of the residuary lesion was redesigned accordingly.After the operation,the regular clinical and iconography follow-up were in progress.Results The functional neuronavigation was successfully completed.The lesions,posterior central gyrus and pyramidal tracts were projected into operation microscope.The lesions were precisely excised,and the posterior central gyrus and pyramidal tracts were protected effectively.The last iMRI indicated that the range of resection was coincided with the pro-operative plan.During the follow-up of 12-24 months,11 patients were found to be completely seizure-free or with only aura (Engel I),and 5 patients had only rare seizure (Engel Ⅱ,fewer than three seizures per year).Nine patients appeared visual field defect without hemiparalysis or hemianesthesia.Conclusion Functional neuronavigation combined with iMRI is a safe and reliable technique for perfect resection of symptomatic occipital lobe epilepsy and reduction of normal brain functions by precisely locating lesions and important functional structures.

To compare the regulation effects by different promoters on bovine prolactin gene expression in different cell lines, three recombinant bovine prolactin expression vectors were constructed using different promoters, i.e., CMV promoter, bovine prolactin gene promoter and goat beta-casein gene promoter, respectively named pCMV, pPRLP and pP1A3, which were transfected into two cell lines, mouse pituitary tumor cell strain (AtT20) and mouse mammary epithelial cell strain (HC11), respectively. RT-PCR and real-time RT-PCR were used to investigate the expression level of the above three vectors in both cell lines, pCMV vector was effectively expressed in both cell lines, pPRLP vector had a similar expression level to that of pCMV in both cell lines, pP1A3 was expressed in HC11 but not in AtT20. pP1A3 was tissue-specific to mammary gland, pPRLP was able to express with a significant level in pituitary and mammary glands, while its tissue-specific characteristics in other tissues need further investigation.
Animals ; Cattle ; Cell Line ; Cell Line, Tumor ; Epithelial Cells ; cytology ; Gene Expression Regulation ; Genetic Vectors ; Mice ; Pituitary Neoplasms ; pathology ; Prolactin ; biosynthesis ; genetics ; Promoter Regions, Genetic ; Transfection