Objective:To explore the optimal duration of preoperative imatinib therapy in patients with locally advanced gastrointestinal stromal tumors (GIST) in order to optimize surgical timing and long-term survival benefits.Methods:A total of 171 patients with locally advanced GIST who received preoperative imatinib therapy and subsequent surgical resection between November 2012 and October 2024 at Fujian Cancer Hospital and Union Hospital of Fujian Medical University were retrospectively analyzed. Patients were divided into three groups according to the duration of preoperative imatinib treatment: short-term (≤6 months, n=50), intermediate-term (7-12 months, n=87), and long-term (>12 months, n=34). Imaging response, pathological efficacy, recurrence-free survival (RFS), and overall survival (OS) were compared among the groups. Univariate and multivariate Cox regression analyses were used to identify the optimal treatment duration. Results:The median duration of preoperative imatinib therapy was 9 (6, 12) months. After treatment, the average maximum tumor diameter decreased from (10.37±5.74) cm to (6.99±4.34) cm, with an average shrinkage of 31.5%. The objective response rates in the short-, intermediate-, and long-term groups were 50.0% (25/50), 58.6% (51/87), and 52.9% (18/34), respectively; high-grade pathological response rates were 28.0% (14/50), 37.9% (33/87), and 29.4% (10/34), with no statistically significant differences among groups (all P>0.05). With a median follow-up of 46 months, 39 patients experienced recurrence and 20 died. The intermediate-term group had 3- and 5-year RFS rates of 87.1% and 79.6%, respectively, significantly better than those of the short-term group (75.5% and 55.5%, P=0.004). The long-term group had 3- and 5-year RFS rates of 85.3% and 75.5%, which were between the other two groups, but not significantly different (all P>0.05). For OS, the intermediate-term group had 3- and 5-year rates of 97.3% and 92.7%, superior to the short-term group (84.4% and 72.4%, P=0.007), while the long-term group (88.2% and 79.4%) showed no significant advantage (all P>0.05). Stratified analysis revealed that among non-gastric primary tumor patients with c-Kit exon 11 mutations, partial response on imaging, or postoperative imatinib ≤24 months, the intermediate-term group had significantly better RFS and OS than the short-term group (all P<0.05), but had no differences compared to the long-term group ( P>0.05). Multivariate Cox regression analysis indicated that preoperative imatinib duration was not an independent factor for RFS ( P>0.05), but treatment for 7-12 months was an independent protective factor for OS ( HR=0.275, 95% CI: 0.089-0.851, P=0.025), while prolonging therapy beyond 12 months conferred no additional OS benefit ( P>0.05). Conclusions:In patients with locally advanced GIST, preoperative imatinib therapy for 7-12 months yielded the most favorable prognosis, with significantly improved RFS and OS compared to ≤6 months of treatment. Extending preoperative therapy beyond 12 months did not provide additional survival benefit.

Objective:To explore the optimal duration of preoperative imatinib therapy in patients with locally advanced gastrointestinal stromal tumors (GIST) in order to optimize surgical timing and long-term survival benefits.Methods:A total of 171 patients with locally advanced GIST who received preoperative imatinib therapy and subsequent surgical resection between November 2012 and October 2024 at Fujian Cancer Hospital and Union Hospital of Fujian Medical University were retrospectively analyzed. Patients were divided into three groups according to the duration of preoperative imatinib treatment: short-term (≤6 months, n=50), intermediate-term (7-12 months, n=87), and long-term (>12 months, n=34). Imaging response, pathological efficacy, recurrence-free survival (RFS), and overall survival (OS) were compared among the groups. Univariate and multivariate Cox regression analyses were used to identify the optimal treatment duration. Results:The median duration of preoperative imatinib therapy was 9 (6, 12) months. After treatment, the average maximum tumor diameter decreased from (10.37±5.74) cm to (6.99±4.34) cm, with an average shrinkage of 31.5%. The objective response rates in the short-, intermediate-, and long-term groups were 50.0% (25/50), 58.6% (51/87), and 52.9% (18/34), respectively; high-grade pathological response rates were 28.0% (14/50), 37.9% (33/87), and 29.4% (10/34), with no statistically significant differences among groups (all P>0.05). With a median follow-up of 46 months, 39 patients experienced recurrence and 20 died. The intermediate-term group had 3- and 5-year RFS rates of 87.1% and 79.6%, respectively, significantly better than those of the short-term group (75.5% and 55.5%, P=0.004). The long-term group had 3- and 5-year RFS rates of 85.3% and 75.5%, which were between the other two groups, but not significantly different (all P>0.05). For OS, the intermediate-term group had 3- and 5-year rates of 97.3% and 92.7%, superior to the short-term group (84.4% and 72.4%, P=0.007), while the long-term group (88.2% and 79.4%) showed no significant advantage (all P>0.05). Stratified analysis revealed that among non-gastric primary tumor patients with c-Kit exon 11 mutations, partial response on imaging, or postoperative imatinib ≤24 months, the intermediate-term group had significantly better RFS and OS than the short-term group (all P<0.05), but had no differences compared to the long-term group ( P>0.05). Multivariate Cox regression analysis indicated that preoperative imatinib duration was not an independent factor for RFS ( P>0.05), but treatment for 7-12 months was an independent protective factor for OS ( HR=0.275, 95% CI: 0.089-0.851, P=0.025), while prolonging therapy beyond 12 months conferred no additional OS benefit ( P>0.05). Conclusions:In patients with locally advanced GIST, preoperative imatinib therapy for 7-12 months yielded the most favorable prognosis, with significantly improved RFS and OS compared to ≤6 months of treatment. Extending preoperative therapy beyond 12 months did not provide additional survival benefit.

To expand the single-dose duration over which noninvasive clinical and preclinical cancer imaging can be conducted with high sensitivity, and well-defined spatial and temporal resolutions, a facile strategy to prepare ultrasmall nanoparticulate X-ray contrast media (nano-XRCM) as dual-modality imaging agents for positron emission tomography (PET) and computed tomography (CT) has been established. Synthesized from controlled copolymerization of triiodobenzoyl ethyl acrylate and oligo(ethylene oxide) acrylate monomers, the amphiphilic statistical iodocopolymers (ICPs) could directly dissolve in water to afford thermodynamically stable solutions with high aqueous iodine concentrations (>140 mg iodine/mL water) and comparable viscosities to conventional small molecule XRCM. The formation of ultrasmall iodinated nanoparticles with hydrodynamic diameters of ca. 10 nm in water was confirmed by dynamic and static light scattering techniques. In a breast cancer mouse model, in vivo biodistribution studies revealed that the ⁶⁴Cu-chelator-functionalized iodinated nano-XRCM exhibited extended blood residency and higher tumor accumulation compared to typical small molecule imaging agents. PET/CT imaging of tumor over 3 days showed good correlation between PET and CT signals, while CT imaging allowed continuous observation of tumor retention even after 10 days post-injection, enabling longitudinal monitoring of tumor retention for imaging or potentially therapeutic effect after a single administration of nano-XRCM.

Objective:To explore the association of DNA methylation with immune response to hepatitis B (HepB) vaccine in Han nationality children from Guangxi province.Methods:A total of 263 children aged 8-9 months who had completed HepB immunization program were recruited from three hospitals in Guangxi province by using unmatched case-control method. Children with the HepB surface antibody concentration(Anti -HBs)<100 mIU/ml was set as the case group and ≥100 mIU/ml as the control group. Multiplex PCR and heavy sulfite sequencing were used to treat the samples. Illumina platform was used for high-throughput DNA methylation sequencing of IFNG gene target regions and CpG sites. Unconditional logistic regression was used to analyze the association between cytosine-phospho-guanosine DNA methylation at 18 loci of IFNG gene and HepB immune response level. Results:There were 104 children in the case group and 159 in the control group. The median ( Q1, Q3) level of anti -HBs in two groups were 62.34 (30.06, 98.88) mIU/ml and 1 089.10 (710.35, 1 233.45) mIU/ml. The methylation levels of IFNG_1 gene 44 and 93 locus in the case group were higher than those in the control group ( P<0.05). The unconditional logistic regression model showed that the DNA methylation level of IFNG_1 gene at 44 ( OR=1.18, 95% CI: 1.03-1.35) and 93 ( OR=1.21, 95% CI: 1.07-1.38) locus was associated with the HepB response level. Conclusion:The changes of DNA methylation at locus 44 and 93 of IFNG_1 gene may be relevant factors affecting the response level of HepB in Han nationality children from Guangxi province.

Objective:To explore the association of DNA methylation with immune response to hepatitis B (HepB) vaccine in Han nationality children from Guangxi province.Methods:A total of 263 children aged 8-9 months who had completed HepB immunization program were recruited from three hospitals in Guangxi province by using unmatched case-control method. Children with the HepB surface antibody concentration(Anti -HBs)<100 mIU/ml was set as the case group and ≥100 mIU/ml as the control group. Multiplex PCR and heavy sulfite sequencing were used to treat the samples. Illumina platform was used for high-throughput DNA methylation sequencing of IFNG gene target regions and CpG sites. Unconditional logistic regression was used to analyze the association between cytosine-phospho-guanosine DNA methylation at 18 loci of IFNG gene and HepB immune response level. Results:There were 104 children in the case group and 159 in the control group. The median ( Q1, Q3) level of anti -HBs in two groups were 62.34 (30.06, 98.88) mIU/ml and 1 089.10 (710.35, 1 233.45) mIU/ml. The methylation levels of IFNG_1 gene 44 and 93 locus in the case group were higher than those in the control group ( P<0.05). The unconditional logistic regression model showed that the DNA methylation level of IFNG_1 gene at 44 ( OR=1.18, 95% CI: 1.03-1.35) and 93 ( OR=1.21, 95% CI: 1.07-1.38) locus was associated with the HepB response level. Conclusion:The changes of DNA methylation at locus 44 and 93 of IFNG_1 gene may be relevant factors affecting the response level of HepB in Han nationality children from Guangxi province.

Objective:To investigate the efficacy and safety of three-dimensional navigation template assisted osteotomy for fracture malunion of lateral condyle of humerus in children.Methods:Eighteen children with ma-lunion of fracture of lateral condyle of humerus were treated in Southern Medical University Third Affiliated Hospital from August 2012 to December 2019 and analyzed retrospectively.Among them, 12 cases were treated with routine ope-ration: according to CT reconstruction and empirical osteotomy during the operation, the location of deformity was analyzed.Six cases were treated with navigation template assisted osteotomy: according to the CT data of bilateral elbow joints, a three-dimensional bone model was established, and the coronal and sagittal deformities of the distal humerus were evaluated by comparing the images of the distal humerus of the affected side with the distal humerus of the healthy side, so as to determine the best plane of osteotomy and the target position of reduction.The preoperative simulation was carried out on the computer, and the osteotomy navigation template and reduction navigation template were designed.The navigation template was printed out with a 3D printer.During the operation, the osteotomy was corrected with the assistance of navigation template, and the broken end of osteotomy was fixed with hollow screw and fixed with 80 degree flexion plaster.The X-ray films of the two groups were reexamined regularly after operation.The amount of intraoperative blood loss, operation time, incidence of postoperative complications (necrosis of humeral head and trochlea, delayed ulnar nerve paralysis, and bone nonunion) and the recovery of flexion and the extension function of elbow joint were observed in the 2 groups.Results:The elbow joint activity of all children basically returned to normal, the orthopedic site of osteotomy achieved bony healing, and the orthopedic effects were satisfactory.All the 18 cases were followed up for 6-24 months (mean 15 months). According to the postoperative Dhillon score, the navigation template group was excellent in 1 case and better in 5 cases, while in the routine group, 11 cases were batter and 1 case was fair.There were no significant differences in Dhillon score between the 2 groups after operation ( P>0.05). There were no significant differences in the range of the motion of elbow joint between the 2 groups ( P>0.05). In the comparison of operation time and intraoperative blood loss, the navigation template group [(200.0±24.2) min, (85.0±10.9) mL]was better than the routine group[(232.0±20.1) min, (139.1±18.3) mL](all P<0.001). Conclusions:The application of three-dimensional humerus reconstruction and mirror image contrast to evaluate the distal humerus deformity of the affected side, and the design of osteotomy and reduction navigation template auxiliary operation can restore the normal anatomical structure of elbow joint to the greatest extent.Accurate correction, and the function of elbow joint recover well after operation, which optimizes the operation procedure, improves the safety and effectiveness of the operation.

Objective:To explore the application value of artificial intelligence-assisted diagnosis system for TBS report in cervical cancer screening.Methods:A total of 16 317 clinical samples and related data of cervical liquid-based thin-layer cell smears, which were obtained from July 2020 to September 2020, were collected from Southern Hospital, Guangzhou Huayin Medical Inspection Center, Shenzhen Bao′an People′s Hospital(Group) and Changsha Yuan′an Biotechnology Co., Ltd. The TBS report artificial intelligence-assisted diagnosis system of cervical liquid-based thin-layer cytology jointly developed by Southern Medical University and Guangzhou F. Q. PATHOTECH Co., Ltd. based on deep learning convolution neural network was used to diagnose all clinical samples. The sensitivity,specificity and accuracy of both artificial intelligence-assisted diagnosis system and cytologists using artificial intelligence-assisted diagnosis system were analyzed based on the evaluation standard(2014 TBS). The time spent by the two methods was also compared.Results:The sensitivity of artificial intelligence-assisted diagnosis system in predicting cervical intraepithelial lesions and other lesions (including endometrial cells detected in women over 45 years old and infectious lesions) under different production methods, different cytoplasmic staining and different scanning instruments was 92.90% and 83.55% respectively, and the specificity of negative samples was 87.02%, while that of cytologists using artificial intelligence-assisted diagnosis system was 99.34%, 97.79% and 99.10%, respectively. Moreover, cytologists using artificial intelligence-assisted diagnosis system could save about 6 times of reading time than manual.Conclusions:Artificial intelligence-assisted diagnosis system for TBS report of cervical liquid-based thin-layer cytology has the advantages of high sensitivity, high specificity and strong generalization. Cytologists can significantly improve the accuracy and work efficiency of reading smears by using artificial intelligence-assisted diagnosis system.

This paper is to report the exploration of the activation of Rho/ROCK signal pathway in 5-HT-induced proliferation of rat pulmonary artery smooth muscle cells (PASMCs) and the inhibitory effect of m-Nis on this pathway. PASMCs were cultured with the explant technique. MTT assay was used to explore the proliferation of PASMCs after 5-HT treated for different time and the intervening effect of m-Nis. RT-PCR and Western blot were used respectively to explore the mRNA expression of RhoA, ROCK1 and the protein expression of p-MYPT1 in 5-HT-treated PASMCs and intervening effect of m-Nis. The results of MTT assay suggested that 5-HT (1 µmol · L(-1)) treatment for 12-72 h significantly induced the proliferation of rat PASMCs (P<0.05 or P < 0.01), which were inhibited by m-Nis (1 x 10(-5), 1 x 10(-6), l x 10(-7), 1 x10(-8) mol · L(-1)) in dose-dependent manners (P < 0.05 or P < 0.01). Similarly, the mRNA expression of RhoA, ROCK1 and the protein expression of p-MYPT1 were also inhibited by m-Nis in different degrees (P < 0.05 or P < 0.01). Thus, the results of this study suggested that Rho/ROCK pathway played an important role in 5-HT-induced proliferation of rat PASMCs, m-Nis inhibited 5-HT-induced proliferation obviously, which may be related to the blockage of Rho/ROCK signal pathway.

ObjectiveTo investigate the application value of 3D visualization technology in precise hepatectomy for complex liver tumors in infants.MethodsClinical data of 16 infants undergoing precise hepatectomy for complex liver tumors with 3D visualization technology in the Afifliated Hospital of Qingdao University between June 2012 and January 2015 were retrospectively studied. Among the 16 infants, 10 were boys and 6 were girls with the age ranging from 22 d to 3 years old and the median of 1 year and 2 months old. Twelve patients were with giant tumors involving the corresponding porta hepatis and four patients were with primary tumor at porta hepatis. The informed consents of all infants were obtained from their parents and the local ethical committee approval had been received. The infants were examined by 64-slice spiral CT. The scanning data were imported into the computer-aided surgery system (Higemi) to perform 3D reconstruction and to compute remnant liver volume and remnant-standard liver volume ratio (RSLVR). The preoperative plan of precise hepatectomy was formulated according to the 3D reconstruction images.ResultsAfter Higemi 3D reconstruction, the intrahepatic vasculature, including the distribution, branching and spatial conformation of portal vein, hepatic artery and hepatic veins were clearly displayed. The anatomic spatial relationships between the lesions and the surrounding vascular structures could be observed at any angle, and lesions could be located and assessed accurately. The preoperative 3D reconstruction results were in accordance with the intraoperative ifndings. Sixteen infants underwent hepatectomy successfully according to the preoperative plan. The median RSLVR was 44.7% (21.1%-78.4%), the duration of operation was 145 (90-230) min, the intraoperative blood loss was 60 (3-100) ml and the rate of blood transfusion was 38% (6/16). One infant with giant tumor in the right liver lobe developed disseminated intravascular coagulation and died although active treatment. The other 15 infants had no complication and were discharged successfully.ConclusionFor complex liver tumors of infants, 3D visualization technology can assess the tumors accurately before surgery and help to make the optimum surgical plan, which makes hepatectomy for complex liver tumors of infants more precise, safe and effective.

Objective To establish an animal model of calpastatin ( CAST) transgenic mice by inserting the full hu-man CAST into the genome of C57BL/6J mice.Methods Recombinant transgenic vector pRP .EX3d-EF1A-CAST-IRES-eGFP was constructed by Gateway technology .It was injected into the fertilized eggs from C 57BL/6J mice.The injected eggs were transplanted into the oviduct of pseudopregnant mice .Tail DNA PCR screening was performed to identify the positive founder mice.The expressions of CAST mRNA and protein in tissues of the transgenic mice were detected by RT -PCR and Western blotting.Results Ninty eggs were transplanted into the oviducts of 3 recipients.The transplantation success rate was 100%.23 viable offsprings were born from the recipients .Tail DNA PCR screening showed that two of the offsprings were positive transgenic mice .The positive rate of transgenic mice was 9%.RT-PCR assay revealed that CAST mRNA ex-pressions were present in the heart , liver, kidney, lung, spleen, brain and skeletal muscle of the transgenic mice .Addition-ally, the CAST protein expression was significantly increased in the transgenic mice .Conclusion CAST transgenic mice have been successfully established and provide a good animal model support for further studies on the CAST function .