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.

Abstract: Objective To investigate the clinical types of children's tinea capitis and the distribution of fungal pathogens in Wuhan from 2011 to 2020, and to provide scientific basis for the prevention, diagnosis and treatment of children's tinea capitis. Methods Laboratory data of children with tinea capitis in outpatient and inpatient department of dermatology in Wuhan No.1 Hospital from January 2011 to December 2020 were collected. A total of 542 cases of pediatric tinea capitis were included, with 239 male cases and 303 female cases. Microscopic examination of fungi and culture identification were performed on the affected skin lesions of the children. Chi-square test was used to analyze the differences in pathogen spectrum of children with different age groups and clinical type. Results Among the pediatric tinea capitis patients, the age group with the highest prevalence was preschool children（3 to <7 years old), accounting for 48.52%（263/542). The top three pathogenic fungi were Trichophytes violaceum（49.26%, 267/542), Microsporum canis（31.55%, 171/542) and Trichophyton mentagrophytes （9.96%, 54/542). Trichophyton violaceum was the main pathogen in all ages, followed by Microsporum canis. The infection rate of Microsporum canis in children over 7 years old was lower than that in children under 7 years old, and the infection rate of Trichophyton rubrum in infants was higher than that in other ages. The distribution of Trichophytes violaceum, Trichophyton mentagrophytes, Nannizzia gypseum and Microsporum ferrugineum was uniform in all age groups. Trichophytes violaceum and Trichophyton tousurans mainly caused black-dot ringworm, Microsporum canis mainly caused tinea alba, Trichophyton mentagrophytes,Nannizzia gypseum and Trichophytonrubrum mainly caused kerion. Except for Microsporum ferrugineum, the composition ratios of other fungi species showed statistically significant differences among different clinical types of tinea capitis（P<0.05). Conclusions Preschool children are the most commonly affected age group by pediatric tinea capitis, and black-dot ringworm caused by Trichophytes violaceum is the main clinical type. Analysis of the high-riskage group, pathogenic fungi and clinical types of tinea capitis in children can enhance the understanding of its epidemiological characteristics, which is helpful for early diagnosis and targeted standardized treatment of pediatric tinea capitis.

Objective:To explore the clinical features of transplanted renal artery stenosis after pediatric donor kidneys in children.Methods:We retrospectively summarized the clinical data in five cases of transplanted renal artery stenosis undergoing deceased pediatric donor kidney transplantation from May 1, 2014 to June 30, 2021.Donor/receptor characteristics, diagnosis, treatment and prognosis were recorded.The median follow-up period was 29 months.The median age of five donors and recipients was 9 and 132 months respectively.En bloc renal allograft( n=2)and single kidney transplantation( n=3)were performed.End-to-side anastomosis was performed for renal arteries.The median diagnostic time of renal artery stenosis was 10(3-60)months post-transplantation.Except for one 3-year-old recipient with an earlier onset of stenosis, four stenotic cases during a rapid growth period had a maximal height increase of 30 cm post-transplantation.Three of them had a history of surgery at graft site, including previous kidney transplantation( n=1)and transplant urinary tract reconstruction( n=2). All five cases had hypertension and two showed an elevated serum level of creatinine.Ultrasound indicated a significantly elevated flow rate of >300 cm/s( n=4)and CTA/MRA indicated that the degrees of stenosis varied from 50% to 95%( n=5). Results:After balloon dilatation, stenosis either improved( n=2)or relapsed( n=2). Further stenting succeed( n=1)or failed( n=1). One case of stenosis was relieved partially after 6-month observation without any invasive treatment. Conclusions:As a serious complication, transplant renal artery stenosis is common after pediatric donor kidney transplantation.Too small size in donor kidney and rapid recipient growth may be specific risk factors.After diagnosis, balloon dilation is a preferred treatment.Stent placement should be cautiously employed.

Objective:To summarize the clinical outcomes of en-bloc kidney transplantation from small infant donors to adult recipients at a single center.Methods:A total of 22 en-bloc transplantations from pediatric donors to adult recipients were performed from July 2013 to October 2017 in Institute of Organ Transplantation Affiliated Tongji Hospital Tongji Medical College Huazhong University of Science. Clinical data were retrospectively analyzed. The average age of 22 donors was (2.9±1.7) months with an average weight of (4.9±1.4) kg and 15 of them were aged under 3 months. The average weight of 22 adult recipients was (46.3±5.6) kg and most recipients were female. The causes of early graft failure and recipient death were examined during follow-ups. The recipients with functioning grafts post-transplantation were divided into single kidney survival group and en-bloc kidney survival group based upon the occurrence of unilateral vascular thrombosis. Medium/long-term renal graft function was compared between two groups.Results:Early graft failure occurred in 4 recipients. The causes were bilateral renal vascular thrombosis ( n=2), renal rupture ( n=1) and multiple organ failure followed by death ( n=1). Eighteen recipients were discharged after a recovery of renal graft function. One case had a removal of bilateral renal grafts due to new-onset graft tumor and another two died from interstitial pneumonia and complicate systematic disorder respectively during follow-ups. Among the remaining 15 recipients, 10 achieved bilateral renal survival (median follow-up: 59 months) and 5 unilateral renal survival (median follow-up: 48 months). The average eGFR of bilateral renal survival group was significantly higher than that of unilateral renal survival group at Year 1 post-transplantation (95±27 vs 61±24 ml/min/1.73 m 2, P<0.05) while the gap narrowed at Year 3 and there was no statistical significance (95±21 vs 69±31 ml/min/1.73 m 2, P=0.12). Conclusions:Although en-bloc kidney transplantation from infant donors can expand organ donor pool, there is a higher risk of early graft failure and unilateral renal vascular thrombosis. Nevertheless, satisfactory renal transplant outcomes may be achieved in patients with unilateral renal graft survival.

Objective:To summarize the transplant outcomes of pediatric kidney transplantation at a single center and discuss probable measures of improving the outcomes.Methods:A total of 111 pediatric renal transplantation were performed from September 2002 to September 2019. They were divided into adult-donor group ( n=41) and pediatric-donor group ( n=70). Adult-donor group consisted of two subgroups based upon donor sources: living-donor group ( n=19) and deceased-donor group ( n=22). Pediatric-donor group consisted of two subgroups based upon surgical types: single kidney group ( n=48) and en bloc kidney group ( n=22). Clinical data and outcomes of grafts and recipients were retrospectively analyzed. Results:The average age of recipients was (15.6±1.9) years in adult-donor group. None developed delayed graft function (DGF) in living-donor group whereas 6 patients (27.3%) had DGF in deceased-donor group ( P<0.05). During a follow-up period of 22-181 months, 1-year and 5-year graft survivals were 100% vs 94.1% and 93.8% vs 94.1% in living-donor and deceased-donor groups respectively. There were no statistical differences. In pediatric-donor group, the age of donors was significantly lower in en bloc subgroup than that in single kidney subgroup (median: 0.5 vs 6 months, P<0.05). The age of recipients was similar between two subgroups: (9.5±5.3) years in single kidney group vs. 11.5± 1.8 years in en bloc kidney group. In addition, 7 cases of single kidney were transplanted for infant recipients aged under 1 year. Vascular thrombosis occurred in 3 patients (6.3%) of single kidney group, less than that in 5 patients (22.7%) of en bloc kidney group ( P=0.06). During a follow-up period of 4-54 months, 1-year and 2-year graft survivals were 85% and 80% in single kidney group whereas 75% and 70% in en bloc kidney group. However, there was no statistically significant difference. One-year survival was 98% in single kidney group and 95% in en bloc kidney group. Conclusions:For elder pediatric recipients, excellent kidney transplant outcomes may be achieved with grafts from adult donors. For pediatric kidney recipients, transplant outcomes can be further improved with careful assessments and cautious usage of small grafts, particularly those form neonatal donors.

Objective:To Investigate the correlation of eosinophil count and stroke-associated pneumonia (SAP) in patients with acute ischemic stroke.Methods:Patients with acute ischemic stroke within 24 h after onset admitted to the Department of Encephalopathy, Suzhou Integrated Traditional Chinese and Western Medicine Hospital from August 2016 to September 2018 were enrolled prospectively. Their general clinical data and eosinophil counts were collected. National Institutes of Health Stroke Scale (NIHSS) was used to assess the severity of stroke. Multivariate logistic regression analysis was used to determine the independent risk factors for SAP. Results:A total of 521 patients were enrolled, including 106 (20.35%) SAP. Univariate logistic analysis showed that SAP was associated with the classification of eosinophil count (odds ratio [ OR] 0.37, 95% confidence interval [ CI] 0.20-0.68; P=0.001), and tended to be associated with eosinophil count ( OR 0.08, 95% CI 0.01-1.01; P=0.051). Multivariate logistic regression analysis showed that both eosinophil count and eosinophil count classification were not the independent risk factors for SAP, and advanced age ( OR 1.077, 95% CI 1.045-1.109; P< 0.001), chronic obstructive pulmonary disease ( OR 6.931, 95% CI 1.295-37.106; P=0.024) and high baseline NIHSS score ( OR 1.148, 95% CI 1.003-1.314; P=0.045) were significantly independently associated with SAP. Conclusions:Eosinophil count was not an independent predictor of SAP in patients with acute ischemic stroke.

Objective:To explore the effects of direct antiviral agent (DAAs) on the frequency of peripheral blood mononuclear cells and their activating factors sCD14s and CD163 in patients with chronic hepatitis C.Methods:Data of 15 treatment-naive chronic hepatitis C patients and 10 healthy controls were collected. Patients with chronic hepatitis C were treated with DAAs for 12 weeks. Blood samples were collected at 0, 4 and 12 weeks respectively, and blood samples of healthy controls were used as controls. Flow cytometry was used to detect the frequency of classical CD14 ++CD16 - mononuclear cells and pro-inflammatory CD14 +CD16 + mononuclear cells in peripheral blood. Serum sCD14s and sCD163 were detected by enzyme-linked immunosorbent assay. The comparison between the two groups was performed by t-test. The comparison between multiple groups was performed by analysis of variance, and further pairwise comparison was performed by LSD-t test. Results:Prior DAAs treatment, peripheral blood CD14 +CD16 + mononuclear cell frequency (18.49% ± 1.54% vs. 10.65% ± 0.83%), serum sCD14s [(64 407.38 ± 5778.49) pg/ml vs. (28 370.76 ± 2 357.68 ) pg/ml] and sCD163 [(22 853.80 ± 4 137.61) pg/ml vs. (2 934.41 ± 223.31) pg/ml] were all higher than healthy controls ( P < 0.05), while the frequency of CD14 ++CD16 - mononuclear cells in peripheral blood was lower than healthy controls (59.14%±0.54% vs. 72.75%±1.31%, P < 0.01). During DAAs treatment, CD14 +CD16 + mononuclear cells frequency, serum sCD14 and sCD163 were all decreased significantly. After 12 weeks of treatment, CD14 +CD16 + mononuclear cells had decreased to nearly normal level (12.42% ± 1.60% vs. 10.65% ± 0.83%, P > 0.05), and serum sCD14 and scd163 were still higher than those of healthy controls [sCD14: (44 390.06 ± 3 330.17) pg / ml vs. (28 370.76 ± 2 357.68) pg/ml, Scd163: (11 494.79 ± 1 836.97) pg / ml vs. (2 934.41 ± 223.31) pg / ml, P < 0.01], while the frequency of CD14 ++CD16 -mononuclear cells had gradually increased during the course of treatment and neared healthy control level after 12 weeks of treatment. There was no statistically significant difference between the two groups (71.54) % ± 2.99% vs. 72.75% ± 1.31%, P > 0.05). Conclusion:DAAs therapy can reduce the activation of peripheral blood mononuclear cells in patients with chronic hepatitis C.

OBJECTIVETo investigate the effect of modified bone morphogenetic protein-2 polylactic acid nanospheres (BMP-2-PLA-Ns) sustained-release system on rabbit mandibular defect repair.

METHODSThe polylactic acid s nanospheres (PLA-Ns) and BMP-2-PLA-Ns were prepared by ultrasonic emulsification after graft polymerization. Forty-five rabbits were randomly divided into 3 groups: Blank group, PLA-Ns gel group(control group), and BMP-2-PLA-Ns gel group (experimental group). The rabbit mandibular defect models were established. The defect area of control group was implanted with PLA-Ns gel, meanwhile, the experimental group was implanted with BMP-2-PLA-Ns gel, the blank group experienced no special handling. Rabbits were killed in 1, 2, 4 weeks after operation and the iconography, hematine eosin(HE) staining and PCNA immunohistochemistry were used to detect the reparative effect on rabbit mandible defects.

RESULTSImage observation showed that bone defect repair in the experimental group was well and the shadow was not obvious. Better repair effect was seen compared with the control group and blank group. HE staining showed that the experimental group and the control group had a large number of neovascularization and secondary callus formation, callus in experimental group was obviously higher than that of control group and blank group. Immunohistochemical observation showed that the experimental group's PCNA positive chondrocytes were more than those in the control group and the blank group in the first 2 weeks; all groups of PCNA positive cells were rare in the fourth week, PCNA positive expression rate of the fourth week was lower than that of the first 2 weeks.

CONCLUSIONThe modified BMP-2-PLA-Ns sustained-release system promotes mandibular defect repair obviously.

Animals ; Bone Morphogenetic Protein 2 ; Delayed-Action Preparations ; Lactic Acid ; Mandible ; Nanospheres ; Polyesters ; Polymers ; Rabbits ; Reconstructive Surgical Procedures

Abstract: Objective To research the relationship between promoter polymorphism-438 A/G of thrombin-activatable fibrinolysis inhibitorgene (TAFI-438 A/G) and atherosclerotic cerebral infarction (ACI) in Chinese Han population. Methods TAFI-438A/G genotypes andtheir allele frequencies were identified with the polymerase chain reaction and restriction fragment length polymorphism (PCR-RFLP) in225 ACI patients and 184 healthy controls. Results There was no significant difference of TAFI-438A/G polymorphism between ACI groupand control group. Stratified by gender, in males, the incidence of A allele was 28.6% in ACI group, and 20.6% in control (P=0.039); of theAA genotype was 9.0% in ACI group, and 1.9% in control (P=0.019). But no significant difference was found in females. ConclusionTAFI-438A/G polymorphism is associated with the risk of ACI in males, that AA genotype may increase the risk of ACI.