Objective To investigate the effects of imatinib mesylate and sunitinib malate on the migration and invasion of gastroin-testinal stromal tumor(GIST)cells.Methods After identifying primary-cultured GIST cells,their morphology was characterized using atomic force microscopy(AFM).Changes in the expression of genes related to the PI3K/AKT signaling pathway were analyzed using quan-titative real-time PCR following drug treatments.Changes in the binding of related molecules were detected using AFM,and alterations in cell migration,invasive ability,and apoptosis were determined using scratch assay,Transwell assay,and flow cytometry,respectively.Results AFM imaging showed that pseudopods were flatly spread around the GIST cells,indicating characteristics consistent with easy metastasis.Administration of either imatinib or sunitinib significantly reduced the expression of genes related to the PI3K/AKT signaling pathway,the density of epidermal growth factor receptor(EGFR)on the surface of GIST cells,and molecular binding force with EGF.These changes were more pronounced with the combination treatment.Correspondingly,the invasive and migratory abilities of GIST cells were significantly reduced when either drug was administered alone and the inhibitory effect was more significant when the drugs were combined.Conclusion Both imatinib and sunitinib can significantly inhibit the expression of genes related to the PI3K/AKT signaling pathway,reduce the density of EGFR on the surface of GIST cells,and attenuate their molecular binding to EGF,thereby reducing the migration and invasion of GIST cells.However,the combination of these two drugs has a more significant effect.

OBJECTIVE To comparatively analyze tumor staging versus clinical staging in reimbursement scope restrictions under medical insurance for antineoplastic agents in order to better implement the medicare drug payment policy. METHODS Antineoplastic agents included in the National Basic Medical Insurance， Workers’ Compensation Insurance and Maternity Insurance Drug Catalogue （2024） （hereinafter referred to as the “Medical Insurance Catalog”） were used as research subject to compile and analyze reimbursement scope restrictions regarding tumor staging. By consulting clinical diagnosis and treatment guidelines and relevant literature， the tumor staging in reimbursement scope restrictions of the Medical Insurance Catalog was mapped and compared with clinical staging. RESULTS & CONCLUSIONS A total of 89 antineoplastic agents’ medical insurance payments had tumor staging. Among these， there were 86 western drugs （including 17 ordinary western drugs， 68 negotiated drugs， and 1 competitive drug） and 3 Chinese patent medicines （including 1 ordinary Chinese patent medicine and 2 negotiated drugs）. Non-small cell lung cancer involved the most restricted payment drugs， with 36 drugs. The tumor staging in reimbursement scope restrictions was mostly “metastatic” and “locally advanced”， involving 67 and 48 drugs respectively. Tumor staging in most reimbursement scope restrictions could correspond to the clinical staging of the tumor. However， mid-advanced esophageal cancer， unresectable gastrointestinal stromal tumors， unresectable locally advanced neuroendocrine tumors， locally advanced basal cell carcinoma， and unresectable neurofibromatosis type Ⅰ did not have a corresponding clinical staging mentioned in authoritative guidelines or high-quality clinical studies and need to be determined by the clinic according to the actual situation of the patient. Therefore， it is recommended that the interpretation of tumor staging in reimbursement scope restrictions should be accurately defined and standardized， so as to improve the accuracy of the drug payment policy in the actual implementation process.

Objective To observe the clinical and echocardiographic manifestations of Williams syndrome(WS).Methods Two children with WS were retrospectively enrolled,and 21 cases of WS in literature were reviewed,and clinical and echocardiographic manifestations of WS were observed.Results Clinical manifestations of 23 cases including 21 cases of"elf"face,8 cases of intellectual disability,7 cases of developmental delay,7 cases of inguinal hernia,6 cases of hypothyroidism,4 cases of hypercalcemia,3 cases of urinary system abnormalities(1 case of hydrocele,1 case of ureteral dilation and tortuosity,and 1 case of kidney stones),2 cases of behavioral abnormalities,2 cases of feeding difficulties,1 case of congenital hypertrophic pyloric stenosis,1 case of binocular esotropia,1 case of hyperbilirubinemia,and 1 case of corpus callosum dysplasia.Echocardiography showed cardiovascular malformations in all 23 cases,including 20 cases of supravalvular aortic stenosis(SVAS),18 cases of pulmonary artery stenosis(PAS)and 10 cases of other cardiovascular malformations.Conclusion WS presented multiple system abnormalities in clinic,and cardiovascular malformations,especially SVAS and PAS could often be detected with echocardiography.

Objective To examine the impact of different numbers of microsatellite markers on the analysis of population genetic diversity of Schistosoma japonicum, so as to provide insights into studies on the population genetic diversity of S. japonicum. Methods Oncomelania hupensis snails were collected from a wasteland in Gong’an County, Hubei Province, and 37 S. japonicum-infected O. hupensis snails were identified using the cercarial shedding method. A single cercaria released from each S. japonicum-infected O. hupensis snail was collected, and 10 cercariae were randomly collected from DNA extraction. Nine previously validated microsatellite loci and 15 additional microsatellite loci screened from literature review and the GenBank database and confirmed with stable amplification efficiency were selected as molecular markers. Genomic DNA from cercariae was subjected to three multiplex PCR amplifications of microsatellite markers with the Type-it Microsatellite PCR kit, and genotyped using capillary electrophoresis. The population genetic diversity of S. japonicum cercariae DNA was analyzed with observed number of alleles (Na), effective number of alleles (Ae), observed heterozygosity (Ho), expected heterozygosity (He), and polymorphism information content (PIC), and tested for Hardy-Weinberg equilibrium (HWE) and linkage disequilibrium (LD). To further investigate the impact of the number of microsatellite loci on the population genetic diversity of S. japonicum, the number of microsatellite markers was sequentially assigned from 1 to 24, and the mean and standard deviation of Na were calculated for S. japonicum populations at different locus numbers. In addition, the coefficient of variation (CV) of allelic number (defined as the ratio of the standard deviation to the mean) was determined, and the variation in Na with increasing microsatellite locus numbers was analyzed. Results Genomic DNA from 345 S. japonicum cercariae was selected for genotyping of 24 microsatellite markers, and all 24 microsatellite loci met linkage equilibrium (standardized linkage disequilibrium coefficient D′ < 0.7, r² < 0.3) and deviated from Hardy-Weinberg equilibrium (P < 0.001). The mean Na, Ae, Ho and He were 27.46 ± 2.18, 12.46 ± 0.95, 0.46 ± 0.03, and 0.91 ± 0.01 for 24 microsatellite loci in S. japonicum cercarial populations, respectively, and PIC ranged from 0.85 to 0.96, indicating high genome-wide representativeness of 24 microsatellite loci. The mean value of Na-Ae was higher in genotyping with 9 previously validated microsatellite loci (19.88 ± 8.43) than with all 24 loci (14.99 ± 8.09). As the number of microsatellite loci increased, the mean Na showed no significant variation; however, the standard deviation gradually decreased. Notably, if the locus number reached 18 or more, the variation in the standard deviation of Na remarkably reduced. In addition, the standard deviation of Na at 18 loci was less than 5% of the mean Na at 24 loci, with a CV of 4.6%. Conclusions The number of microsatellite loci significantly affects the population genetic diversity analysis of S. japonicum. Eighteen or more microsatellite loci are recommended for analysis of the population genetic diversity of S. japonicum under the current conditions of low-prevalence infection and unbalanced genetic distribution of S. japonicum.

Objective To investigate the levels and clinical significance of serum secreted frizzled related protein 5(SFRP5),soluble cell adhesion molecule-1(sICAM-1),and Fetuin-B in patients with type 2 diabetes mellitus(T2DM)complicated with metabolic syndrome(MS).Methods A total of 142 T2DM patients ad-mitted in the Jiamusi Hospital of Infectious Diseases from April 2021 to April 2023 were selected as the study subjects.T2DM patients were grouped into MS group(n=75)and non MS group(n=67)based on whether they had MS.Enzyme linked immunosorbent assay(ELISA)was applied to determine the expression levels of serum SFRP5,sICAM-1,and Fetuin-B.Logistic regression was applied to analyze and determine the influen-cing factors of complicated MS in T2DM patients.The diagnostic efficacy of SFRP5,sICAM-1,and Fetuin-B in T2DM patients with MS was analyzed by establishing receiver operating characteristic(ROC)curve.Results There were statistically significant differences in HDL-C and HOMA-IR between the MS group and the non MS group(P＜0.05).Compared with the non MS group,the serum SFRP5 level in the MS group de-creased(P＜0.05),while the sICAM-1 and Fetuin-B levels increased(P＜0.05).Logistic regression analysis showed that SFRP5 and HDL-C were protective factors for the development of MS in T2DM patients(P＜0.05),while sICAM-1,Fetuin-B,and HOMA-IR were risk factors for the development of MS in T2DM pa-tients(P＜0.05).The combination of serum SFRP5,sICAM-1 and Fetuin-B had the largest area under the curve in diagnosing MS in T2DM patients,and its evaluation efficacy was obviously better than that of the in-dividual diagnosis of serum SFRP5,sICAM-1,and Fetuin-B(Zcombination-SFRP5=2.466,P=0.014,Zcombination-SICAM-1=3.550,P＜0.001,Zcombination-Fetuin-B=3.697,P＜0.001).Conclusion The serum SFRP5 level in patients with T2DM complicated with MS decreases,while sICAM-1 and Fetuin-B levels increase.The combination of the three has a good effect in diagnosing complicated MS in T2DM patients.

Background:To compare the efficacy and safety of monthly administrations of gonadotropin releasing hormone (GnRH) agonists LY01005 and Zoladex ? in Chinese patients with premenopausal breast cancer. Methods:From October 2020 to November 2021, 188 premenopausal breast cancer patients were enrolled in 34 hospitals and randomized 1:1 to receive either LY01005 or Zoladex ? every 28 days for a total of three injections. All patients concomitantly received oral tamoxifen (TAM). The primary efficacy endpoint was cumulative probability of maintaining menopausal level [oestradiol (E2) ≤30 pg/ml] from day 29 to day 85. The second efficacy endpoint included changes in E2, luteinizing hormone (LH), and follicle-stimulating hormone (FSH) compared with the baseline. Pharmacokinetics (PK), pharmacodynamics (PD), and safety were analyzed. The study also evaluated the pharmacokinetic and pharmacodynamic characteristics of LY01005. Results:A total of 188 patients were randomised and 187 patients received either LY01005 or Zoladex ?. Cumulative probabilities of maintaining menopausal level (E2≤30 pg/ml) from day 29 to day 85 were 93.1% for LY01005 and 86.3% for Zoladex ?. The between-group difference was 6.8% (95% CI: -2.3%, 15.9%) and primary efficacy in the LY01005 group was not inferior to that in the Zoladex ? group. Changes in E2, LH, and FSH levels compared with the baseline were equivalent between the two groups (E2: 89.34% to 90.23% vs. 82.11% to 85.02%; LH: 88.89% to 95.52% vs. 89.70% to 97.02%; FSH: 75.36% to 80.85% vs.73.07% to 80.24%, respectively). After three consecutive doses of LY01005, the LH and FSH levels of the subjects showed a transient increase after the first dose, reached a peak on the second day and then started to decrease. The LH and FSH reached a lower level and remained at or below that level until the 85th day. Both treatments were well-tolerated. Conclusion:LY01005 is as effective as Zoladex ? in suppressing E2 to menopausal levels in Chinese patients with premenopausal breast cancer, with a similar safety profile.

Purpose To investigate the expression of chromogranin A(CgA)in gastroenteropancreatic neuroendo-crine neoplasms(GEP-NENs)and its relationship with clinicopathological features.Methods The clinicopathological data of GEP-NENs diagnosed in the Department of Pathology,Beijing Chao-yang Hospital,Capital Medical University from May 2011 to December 2024 were retrospectively analyzed.Immunohistochemical staining was applied to evaluate the expression of CgA,and the patients were divided into CgA(+)group and CgA(-)group.Differences in clinico-pathological features between the 2 groups were compared.Results The age of 229 patients ranged from 21 to 89 years,with an average age of 54.4 years.The most common primary site was the rectum(56.8％,130/229),fol-lowed by the stomach(16.6％,38/229),pancreas(14.4％,33/229),small intestine(6.1％,14/229),and colon(6.1％,14/229).There were 206 cases of single lesion and 23 cases of multiple lesions(number of tumors ≥2).There were 153 cases of G1(66.8％),29 cases of G2(12.7％),7 cases of G3(3.1％),and 40 cases of neuroendocrine carcinoma(NEC,17.5％).The positive rates of CgA in G1,G2,G3,and NEC groups were 37.2％,75.8％,71.4％,and 65.0％,respectively,with statistically significant differences(P＜0.001).The positive rates of CgA in T1,T2,T3,and T4 were 37.2％,83.3％,75.9％,and 57.7％,respectively,with statistically significant differences(P＜0.001).There were significant differences in age,vascular invasion,lymph node metasta-sis,and number of tumors between CgA(+)group and CgA(-)group(P＜0.001),but there was no significant difference in sex,tumor location,Syn,and CD56 expression between the two groups(P=0.595,P=0.098,P=0.173,P=0.557).Conclusion Immunohistochemical antibody CgA is a useful marker for GEP-NENs.CgA positiv-ity may be a poor prognostic factor for GEP-NENs patients.

Objective To observe the clinical and echocardiographic manifestations of Williams syndrome(WS).Methods Two children with WS were retrospectively enrolled,and 21 cases of WS in literature were reviewed,and clinical and echocardiographic manifestations of WS were observed.Results Clinical manifestations of 23 cases including 21 cases of"elf"face,8 cases of intellectual disability,7 cases of developmental delay,7 cases of inguinal hernia,6 cases of hypothyroidism,4 cases of hypercalcemia,3 cases of urinary system abnormalities(1 case of hydrocele,1 case of ureteral dilation and tortuosity,and 1 case of kidney stones),2 cases of behavioral abnormalities,2 cases of feeding difficulties,1 case of congenital hypertrophic pyloric stenosis,1 case of binocular esotropia,1 case of hyperbilirubinemia,and 1 case of corpus callosum dysplasia.Echocardiography showed cardiovascular malformations in all 23 cases,including 20 cases of supravalvular aortic stenosis(SVAS),18 cases of pulmonary artery stenosis(PAS)and 10 cases of other cardiovascular malformations.Conclusion WS presented multiple system abnormalities in clinic,and cardiovascular malformations,especially SVAS and PAS could often be detected with echocardiography.

Objective To investigate the effects of imatinib mesylate and sunitinib malate on the migration and invasion of gastroin-testinal stromal tumor(GIST)cells.Methods After identifying primary-cultured GIST cells,their morphology was characterized using atomic force microscopy(AFM).Changes in the expression of genes related to the PI3K/AKT signaling pathway were analyzed using quan-titative real-time PCR following drug treatments.Changes in the binding of related molecules were detected using AFM,and alterations in cell migration,invasive ability,and apoptosis were determined using scratch assay,Transwell assay,and flow cytometry,respectively.Results AFM imaging showed that pseudopods were flatly spread around the GIST cells,indicating characteristics consistent with easy metastasis.Administration of either imatinib or sunitinib significantly reduced the expression of genes related to the PI3K/AKT signaling pathway,the density of epidermal growth factor receptor(EGFR)on the surface of GIST cells,and molecular binding force with EGF.These changes were more pronounced with the combination treatment.Correspondingly,the invasive and migratory abilities of GIST cells were significantly reduced when either drug was administered alone and the inhibitory effect was more significant when the drugs were combined.Conclusion Both imatinib and sunitinib can significantly inhibit the expression of genes related to the PI3K/AKT signaling pathway,reduce the density of EGFR on the surface of GIST cells,and attenuate their molecular binding to EGF,thereby reducing the migration and invasion of GIST cells.However,the combination of these two drugs has a more significant effect.

Purpose To investigate the expression of chromogranin A(CgA)in gastroenteropancreatic neuroendo-crine neoplasms(GEP-NENs)and its relationship with clinicopathological features.Methods The clinicopathological data of GEP-NENs diagnosed in the Department of Pathology,Beijing Chao-yang Hospital,Capital Medical University from May 2011 to December 2024 were retrospectively analyzed.Immunohistochemical staining was applied to evaluate the expression of CgA,and the patients were divided into CgA(+)group and CgA(-)group.Differences in clinico-pathological features between the 2 groups were compared.Results The age of 229 patients ranged from 21 to 89 years,with an average age of 54.4 years.The most common primary site was the rectum(56.8％,130/229),fol-lowed by the stomach(16.6％,38/229),pancreas(14.4％,33/229),small intestine(6.1％,14/229),and colon(6.1％,14/229).There were 206 cases of single lesion and 23 cases of multiple lesions(number of tumors ≥2).There were 153 cases of G1(66.8％),29 cases of G2(12.7％),7 cases of G3(3.1％),and 40 cases of neuroendocrine carcinoma(NEC,17.5％).The positive rates of CgA in G1,G2,G3,and NEC groups were 37.2％,75.8％,71.4％,and 65.0％,respectively,with statistically significant differences(P＜0.001).The positive rates of CgA in T1,T2,T3,and T4 were 37.2％,83.3％,75.9％,and 57.7％,respectively,with statistically significant differences(P＜0.001).There were significant differences in age,vascular invasion,lymph node metasta-sis,and number of tumors between CgA(+)group and CgA(-)group(P＜0.001),but there was no significant difference in sex,tumor location,Syn,and CD56 expression between the two groups(P=0.595,P=0.098,P=0.173,P=0.557).Conclusion Immunohistochemical antibody CgA is a useful marker for GEP-NENs.CgA positiv-ity may be a poor prognostic factor for GEP-NENs patients.