ObjectiveTo investigate the role and mechanism of Go-Ichi-Ni-San complex subunit 1 （GINS1） in the progression of hepatocellular carcinoma （HCC） and the development of chemotherapy resistance. MethodsThe tumor database GEPIA2 was used to analyze the differential expression of GINS1 between HCC patients and healthy individuals， and pathological tissue samples were collected from 40 HCC patients who were admitted to The Affiliated Tumor Hospital of Xinjiang Medical University and the First Affiliated Hospital of Xinjiang Medical University from May 2017 to January 2021. Immunohistochemical staining was used to measure the difference in the expression of GINS1 between HCC tissue and corresponding adjacent tissue， and the correlation between the expression level of GINS1 and the clinical TNM stage of HCC was analyzed. Western blot was also used to measure the difference in the expression of GINS1 between HCC Huh7/Hep3B/Li-7/MHCC97H cell lines and normal human QSG7701 hepatocytes. The method of lentivirus transfection was used to establish the MHCC97H cell line with stable GINS1 knockdown and its negative control cell line. CCK-8 assay and colony formation assay were used to measure cell proliferative capacity； scratch assay was used to measure cell migration ability； Transwell assay was used to measure cell invasion ability； cells were treated with oxaliplatin to measure their sensitivity to chemotherapy drugs. Nude mice were used to establish a tumor-bearing model and observe the effect of GINS1 knockdown on the growth of HCC in vivo. Western Blot was used to measure the expression levels of the proteins associated with the Notch pathway and the JAK/STAT pathway. The cells were treated with the Notch receptor agonist Jagged-1 to analyze the association between GINS1 and the Notch/JAK/STAT pathway. The independent-samples t test was used for comparison of continuous data between two groups； a one-way analysis of variance was used for comparison between multiple groups， and the least significant difference t-test was used for further comparison between two groups. ResultsThe expression of GINS1 was upregulated in HCC patients， HCC tissue， and HCC cell lines （all P<0.05）， and the expression level of GINS1 was positively correlated with the clinical TNM stage of HCC （r=0.822， P=0.011）. Compared with the negative control cells， the GINS1-knockdown MHCC97H cells showed significant reductions in proliferation， migration， and invasion activities （all P<0.01） and a significantly enhanced sensitivity to oxaliplatin （P<0.01）. Compared with the nude mice in the control group， GINS1 knockdown caused significant inhibition of tumor weight and volume in vivo in nude mice （all P<0.001）. Compared with the negative control cells， the GINS1-knockdown MHCC97H cells showed significant reductions in the expression levels of Notch1， Notch3， p-JAK2， and p-STAT3 （all P<0.05）， while there were no significant differences in the overall expression levels of JAK2 and STAT3 （P>0.05）. After Jagged-1 treatment， the GINS1-knockdown MHCC97H cells showed significant increases in proliferation， migration， and invasion activities and a significant reduction in sensitivity to oxaliplatin， as well as significant increases in the levels of p-JAK2 and p-STAT3 （all P<0.05）. ConclusionGINS1 is upregulated in HCC and can promote HCC progression and chemotherapy resistance through the Notch/JAK2/STAT3 pathway.

Objective:To explore the dosimetric characteristics of proton and photon radiotherapy in the treatment of breast cancer.Methods:Four female breast cancer patients who needed radiotherapy at Shandong Cancer Hospital and Institute from January 2024 to May 2024 were selected as the research subjects. The target area ranges of 4 patients were left-sided breast cancer with lymph node involvement, left-sided breast cancer with lymph node involvement and internal mammary node, right-sided breast cancer with lymph node involvement and internal mammary node and synchronous bilateral breast cancer. Intensity modulated proton therapy (IMPT) and intensity modulated radiation therapy (IMRT) plans were designed respectively based on the prescribed dose in the target area and the limits of organs at risk (tomotherapy plan for bilateral breasts). The conformity index (CI), homogeneity index (HI), gradient index (GI) and organs at risk doses were evaluated. The dosimetric characteristics of IMPT and photon radiotherapy were compared.Results:Both IMPT and photon radiotherapy plans of the 4 breast cancer cases met the clinical dose requirements. The HI value of IMPT plans (0.10-0.14) was comparable to that of photon radiotherapy plans (0.10-0.12), and the average CI of the photon radiotherapy plans was 0.10 higher than that of the IMPT plans, and the average GI was 0.55 lower than that of the IMPT plans. The D mean of ipsilateral lung and heart of IMPT was lower, especially in the low-dose area (V 0-3), which was significantly lower than the photon radiotherapy plans, D mean of ipsilateral lung was reduced by 12.2%, 6.1%, 16.1% and 34.8%, respectively, D mean of heart was reduced by 47.2%, 57.0%, 72.4% and 83.0%, respectively. The ipsilateral lung V 20 of IMPT was not lower than photon radiotherapy plans (unilateral breast: IMPT was 30.0%-34.0%, IMRT was 29.0%-35.9%) . Conclusions:IMPT significantly reduces the D mean to the ipsilateral lung and heart while ensuring dose coverage of the target in breast cancer, preventing more volume of surrounding normal tissues from being irradiated. However, IMPT does not show much more advantage than photon radiotherapy plans in the ipsilateral lung V 20.

OBJECTIVE:To optimize the formulation of Roxatidine acetate hydrochloride(ROX)sustained-release tablets. METHODS:ROX sustained-release tablets were prepared by direct powder compression method. Central composite design-response surface methodology was used to optimize the formulation with composite index of 1,4,8 h in vitro accumulative release rate as index,using mass ratio of lactose/microcrystalline cellulose(MCC)(m/m),ethyl cellulose(EC)amount and HPMC amount as factors. Validation test was also conducted. RESULTS:The optimal formulation was as follows as ROX 75 mg,lactose 45 mg, MCC 91 mg,EC 65 mg,HPMC 124 mg,micropowder silica gel 2 mg. 1,4,8 h in vitro accumulative release rates of prepared sustained-release tablets were(30.7 ± 0.5)%,(65.8 ± 0.7)%,(89.4 ± 0.6)%,respectively. Related errors of them to predicted value were 0.6%,0.8%,1.2%,respectively. CONCLUSIONS:ROX sustained-release tablets are prepared successfully,and sustained-release effect is consisted with the expected effect.

Objective To explore absorption kinetics of roxatidine acetate hydrochloric (ROX) in intestine of rats.Methods The absorption kinetics and permeability of ROX under different concentrations and different intestinal segments were investigated by double wavelength spectrophotometry via the in situ perfusing method in rats.Results There was no significant difference in Ka of ROX under different concentrations.The absorption rate in rats descended in order of duodenum,jejunum,ileum and colon [(3.87±0.12)×10-2,(2.53±0.18)×10-2,(1.43-±0.10)×10-2,(0.91±0.15)×10-2 · h-1].Conclusion The absorption of ROX in intestine complies with the passive transport mechanism and first order kinetics.ROX is well absorbed in thewhole intestine.

Objective This study was designed to investigate the prognostic implications of the intertumoral heterogeneity of molecular phenotype in multifocal and multicentric breast cancer ( MMBC ) . Methods The clinical and follow-up data of 146 patients with MMBC from Jan.2009 to Dec.2009 treated in Tumor Hospital Affiliated to Zhengzhou University were retrospectively analyzed .We used Kaplan-Meier curves to compare the survivals of patients who had tumors with molecular phenotypic heterogeneity and patients who had multifocal homogeneous tumors in molecular phenotype , and the survivals of patients who had heterogeneous tumor type and grade and who had homogeneous tumor type and grade .The corresponding hazard ratio was calculated by Cox proportional-hazards regression .Results Intertumoral heterogeneity in histological type and grade of multiple breast cancer was detected in 16 of 146 patients (11.0%) and in 10 of 146 patients( 6.8%), respectively.Interfocal heterogeneous molecular phenotype of multiple breast cancer was detected in 24 of 146 patients ( 16.4%) .There was no significant difference in 5-year disease-free survival in multifocal cancer patients who had heterogeneous histological type and grade and who had homogeneous type and grade tumors (75.0%vs.77.3%, P=0.808).Multifocal cancers patients who had heterogeneous tumorsin molecular phenotype compared with those with homogeneous tumors in molecular phenotype had worse 5-year disease-specific survival (78 .7%vs.58.3%,P =0.037) , and had a greater risk of recurrence( HR=2.130, 95%CI=1.027-4.420; P=0.042).Phenotyping the additional cancer foci influenced the therapeutic decision in up to 16 patients (11 .0%) .Conclusoi ns Multifocal breast cancer patients who had heterogeneous tumors in molecular phenotype have a statistically significantly shorter disease-free survival.Phenotyping the additional cancer foci and managing with proper therapeutic decision may reduce the risk of recurrence or metastasis , and improve the outcomes of the patients .

Objective This study was designed to investigate the prognostic implications of the intertumoral heterogeneity of molecular phenotype in multifocal and multicentric breast cancer ( MMBC ) . Methods The clinical and follow-up data of 146 patients with MMBC from Jan.2009 to Dec.2009 treated in Tumor Hospital Affiliated to Zhengzhou University were retrospectively analyzed .We used Kaplan-Meier curves to compare the survivals of patients who had tumors with molecular phenotypic heterogeneity and patients who had multifocal homogeneous tumors in molecular phenotype , and the survivals of patients who had heterogeneous tumor type and grade and who had homogeneous tumor type and grade .The corresponding hazard ratio was calculated by Cox proportional-hazards regression .Results Intertumoral heterogeneity in histological type and grade of multiple breast cancer was detected in 16 of 146 patients (11.0%) and in 10 of 146 patients( 6.8%), respectively.Interfocal heterogeneous molecular phenotype of multiple breast cancer was detected in 24 of 146 patients ( 16.4%) .There was no significant difference in 5-year disease-free survival in multifocal cancer patients who had heterogeneous histological type and grade and who had homogeneous type and grade tumors (75.0%vs.77.3%, P=0.808).Multifocal cancers patients who had heterogeneous tumorsin molecular phenotype compared with those with homogeneous tumors in molecular phenotype had worse 5-year disease-specific survival (78 .7%vs.58.3%,P =0.037) , and had a greater risk of recurrence( HR=2.130, 95%CI=1.027-4.420; P=0.042).Phenotyping the additional cancer foci influenced the therapeutic decision in up to 16 patients (11 .0%) .Conclusoi ns Multifocal breast cancer patients who had heterogeneous tumors in molecular phenotype have a statistically significantly shorter disease-free survival.Phenotyping the additional cancer foci and managing with proper therapeutic decision may reduce the risk of recurrence or metastasis , and improve the outcomes of the patients .