Objective To investigate the effects of scribble planar cell polarity protein(SCRIB)on proliferation,apoptosis,and autophagy of glioblastoma(GBM)and elucidate its potential underlying mechanisms.Methods The expression level of SCRIB in GBM tissue was queried through the Biomarker Exploration of Solid Tumors(BEST)database.Lentivirus-mediated shRNA interference was employed to downregulate SCRIB expression in human glioblastoma cell lines U87 and U251,which were divided into negative control group(mock)and SCRIB shRNA interference groups(kd1 and kd2).SCRIB expression levels were detected using Western blotting(WB)and quantitative polymerase chain reaction(qPCR).EdU incorporation and cell apoptosis rates were detected by flow cytometry(FCM).CCK-8 assay was used to detect the proliferation vitality of U87 and U251 cells,and WB was used to detect the expression of proliferation-related proteins.Immunofluorescence(IF)staining was conducted to detect the expression of autophagy-related proteins LC3 and p62,followed by quantitative analysis across multiple fields.WB was also used to detect the expression levels of LC3,p62,and proteins in the JAK-STAT3 signaling pathway.Results Compared with that of normal tissues,SCRIB mRNA expression level was significantly upregulated in GBM tissues(P＜0.05).FCM results showed that EdU incorporation rates were significantly reduced(P＜0.001)while cell apoptosis rates were markedly increased(P＜0.001)in U87 and U251 cells with SCRIB knockdown.CCK-8 results indicated that compared with the mock group,the proliferation vitality of U87 and U251 cells in the SCRIB knockdown group was significantly downregulated(P＜0.001).IF staining showed that LC3 fluorescence aggregation was significantly enhanced(P＜0.001),while p62 fluorescence aggregation was significantly reduced(P＜0.001)in the SCRIB knockdown group.WB results showed that compared with the mock group,the protein expression levels of p27,LC3,p-JAK2 and p-STAT3 were upregulated,while C-Myc,Cyclin D1,MCM,PCNA and p62 were downregulated,with statistically significant differences(P＜0.05).Conclusion Downregulation of SCRIB may induce autophagy and apoptosis in glioblastoma cells by inhibiting the JAK-STAT3 signaling pathway,thereby suppressing cell proliferation.

Objective To investigate the effects of scribble planar cell polarity protein(SCRIB)on proliferation,apoptosis,and autophagy of glioblastoma(GBM)and elucidate its potential underlying mechanisms.Methods The expression level of SCRIB in GBM tissue was queried through the Biomarker Exploration of Solid Tumors(BEST)database.Lentivirus-mediated shRNA interference was employed to downregulate SCRIB expression in human glioblastoma cell lines U87 and U251,which were divided into negative control group(mock)and SCRIB shRNA interference groups(kd1 and kd2).SCRIB expression levels were detected using Western blotting(WB)and quantitative polymerase chain reaction(qPCR).EdU incorporation and cell apoptosis rates were detected by flow cytometry(FCM).CCK-8 assay was used to detect the proliferation vitality of U87 and U251 cells,and WB was used to detect the expression of proliferation-related proteins.Immunofluorescence(IF)staining was conducted to detect the expression of autophagy-related proteins LC3 and p62,followed by quantitative analysis across multiple fields.WB was also used to detect the expression levels of LC3,p62,and proteins in the JAK-STAT3 signaling pathway.Results Compared with that of normal tissues,SCRIB mRNA expression level was significantly upregulated in GBM tissues(P＜0.05).FCM results showed that EdU incorporation rates were significantly reduced(P＜0.001)while cell apoptosis rates were markedly increased(P＜0.001)in U87 and U251 cells with SCRIB knockdown.CCK-8 results indicated that compared with the mock group,the proliferation vitality of U87 and U251 cells in the SCRIB knockdown group was significantly downregulated(P＜0.001).IF staining showed that LC3 fluorescence aggregation was significantly enhanced(P＜0.001),while p62 fluorescence aggregation was significantly reduced(P＜0.001)in the SCRIB knockdown group.WB results showed that compared with the mock group,the protein expression levels of p27,LC3,p-JAK2 and p-STAT3 were upregulated,while C-Myc,Cyclin D1,MCM,PCNA and p62 were downregulated,with statistically significant differences(P＜0.05).Conclusion Downregulation of SCRIB may induce autophagy and apoptosis in glioblastoma cells by inhibiting the JAK-STAT3 signaling pathway,thereby suppressing cell proliferation.

OBJECTIVE To analyze the use and distribution characteristics of toxic traditional Chinese medicine decoction pieces in oncology outpatient department, and to provide data reference for the safe and rational use of toxic traditional Chinese medicine decoction pieces in clinical applications. METHODS The 838 prescriptions data of toxic traditional Chinese medicine from the Oncology Outpatient Department of The Second Affiliated Hospital of Anhui University of Traditional Chinese Medicine in 2022 were collected and made retrospective statistical analysis of patient gender, age, clinical diagnosis, variety of toxic traditional Chinese medicine, frequency of use, frequency of overdose, and combination use of toxic traditional Chinese medicine. RESULTS Among the 838 prescriptions of toxic Chinese herbal medicines, 22 toxic Chinese herbal medicines were involved, accounting for 81.48% of the hospital's toxic Chinese herbal medicines. The majority of prescriptions (217 cases, accounting for 25.89%) aged 50 to 60 years old. Most of the single prescriptions were concentrated in 11 to 15, and the toxic Chinese herbal decoction pieces were mainly used in various tumor diseases, digestive system diseases and gynecological diseases, etc. In addition to golden larch bank, ginkgo and centipede, the other toxic traditional Chinese medicines all had the overdose problem. 231 prescriptions of toxic traditional Chinese medicine were used in combination with≥2 , with 190 prescriptions of 2 ingredients being the most commonly used (accounting for 22.67%). There were 78 incompatibilities, most of which were the combination of Aconiti Lateralis Radix Praeparata and Pinelliae Rhizoma. It was used to treat chronic Atrophic gastritis, insomnia and depression. CONCLUSION Toxic traditional Chinese medicine decoction pieces are widely used in oncology department. However, the overdose phenomenon is serious, it is necessary to be aware of the potential risks of overdose and combination of toxic traditional Chinese medicine. Therefore, it is necessary to further strengthen drug management, promote rational application, and ensure patient medication safety.

OBJECTIVE: To explore the genetic basis for three Chinese patients with McCune-Albright syndrome (MAS). METHODS: Three children who had respectively presented at Shandong Provincial Hospital in April 2019 and Peking Union Medical College Hospital in August 2020 and May 2021 were selected as the research subjects. Peripheral blood samples of the probands and their family members were taken for the extraction of genomic DNA. Potential variants were screened by whole exome sequencing (WES), and candidate variants were validated by Sanger sequencing of the patients and their family members. RESULTS: The proband from family 1 was found to harbor a heterozygous c.601C>T (p.R201C) missense variant in exon 8 of the GNAS gene, whilst the probands from families 2 and 3 were both found to harbor a heterozygous c.602G>A (p.R201H) missense variant in exon 8 of the GNAS gene. Both variants were known to be pathogenic, and all probands were found to be mosaics for the corresponding variants but with various degrees. CONSLUSION WES can effectively diagnose MAS and other somatic genetic disorders. In this study, the combined WES and Sanger sequencing have verified the degree of mosaicisms of pathogenic variants in the three MAS patients, albeit no apparent correlation was found between the degree of mosaicisms and the phenotype of patients. Above finding has provided a basis for genetic counseling and prenatal diagnosis for the affected families.
Humans ; Mutation ; Fibrous Dysplasia, Polyostotic/genetics* ; East Asian People ; Exons ; Phenotype ; Pedigree

Objective:To compare the differences in population distribution and prognosis of patients with nasopharyngeal carcinoma (NPC) treated with intensity-modulated radiotherapy (IMRT) in T staging of the Union for International Cancer Control (UICC) 7th edition and UICC 8th edition, and to analyze the prognostic factors in patients with NPC.Methods:The clinicopathologic date of 184 patients with newly diagnosed NPC treated with IMRT at the Department of Radiation Oncology of Weifang People′s Hospital of Shandong Province from June 1, 2005 to December 31, 2017 were retrospectively analyzed. All patients were restaged according to the 7th and 8th edition of the UICC staging system. The distribution of T staging of patients in the two staging systems was analyzed, and the consistency of the two staging systems was compared using the Kappa consistency test. Kaplan-Meier method was used for survival analysis, and log-rank test was used to compare the prognostic differences among T stages. Cox regression model was used to analyze the prognostic factors of patients with NPC.Results:Of all 184 patients with NPC, stage T 1, T 2, T 3 and T 4 respectively accounted for 18.5% (34/184), 16.8% (31/184), 15.2% (28/184) and 49.5% (91/184) according to the 7th edition UICC staging system. However, stage T 1, T 2, T 3 and T 4 respectively accounted for 18.5% (34/184), 34.2% (63/184), 30.4% (56/184) and 16.8% (31/184) according to the 8th edition UICC staging system. The T staging population distribution of the two staging systems showed moderate consistency (Kappa=0.58). There was a statistically significant difference in overall survival (OS) among patients with stage T 1, T 2, T 3, T 4 according to the 7th edition UICC staging system ( χ2=10.606, P=0.014). There were statistically significant differences in OS between stage T 1 and stage T 2, T 3, T 4 ( χ2=4.866, P=0.027; χ2=11.965, P=0.001; χ2=4.351, P=0.037). The OS curves of stage T 2 and T 4 could not be separated. Moreover, the OS curves of stage T 3 and T 4 were distributed in reverse order. There was a statistically significant difference in OS among patients with stage T 1, T 2, T 3, T 4 according to the 8th edition staging system ( χ2=8.663, P=0.034). There were statistically significant differences in OS between stage T 1 and stage T 3, T 4( χ2=8.746, P=0.003; χ2=7.580, P=0.006). The OS curves of stage T 1 to T 4 were distributed in order, but the curves of stage T 3 and T 4 could not be separated. There was a statistically significant difference in progression-free survival (PFS) among patients with stage T 1, T 2, T 3, T 4 according to the 7th edition UICC staging system ( χ2=11.289, P=0.010). There were statistically significant differences in PFS between stage T 1 and stage T 2, T 3, T 4 ( χ2=8.209, P=0.004; χ2=13.302, P<0.001; χ2=6.550, P=0.010). The PFS curves of stage T 2 and T 4 could not be separated. Moreover, the PFS curves of stage T 3 and T 4 were distributed in reverse order. There was a statistically significant difference in PFS among patients with stage T 1, T 2, T 3, T 4 according to the 8th edition staging system ( χ2=12.074, P=0.007). There were statistically significant differences in PFS between stage T 1 and stage T 2, T 3, T 4( χ2=5.182, P=0.023; χ2=11.217, P=0.001; χ2=10.174, P=0.001). The PFS curves of stage T 1 to T 4 were distributed in order, but the curves of stage T 3 and T 4 could not be separated. The results of Cox multivariate analysis showed that T staging of both staging systems were the independent prognostic factors of the OS ( P=0.013; P=0.026) and PFS ( P=0.031; P=0.012). However, T staging of the two editions were not the independent prognostic factors of the local recurrence-free survival (LRFS) ( P=0.351; P=0.167) and distant metastasis-free survival (DMFS) ( P=0.059; P=0.052). The age was the independent prognostic factor of the OS ( HR=2.70, 95% CI: 1.53-4.76, P=0.001; HR=2.74, 95% CI: 1.55-4.84, P=0.001), PFS ( HR=2.72, 95% CI: 1.46-5.08, P=0.002; HR=2.94, 95% CI: 1.57-5.52, P=0.001), LRFS ( HR=5.87, 95% CI: 1.62-21.27, P=0.007; HR=6.02, 95% CI: 1.61-22.49, P=0.008) and DMFS ( HR=2.40, 95% CI: 1.22-4.72, P=0.011; HR=2.63, 95% CI: 1.34-5.18, P=0.005). N staging was the independent prognostic factor of the OS ( P=0.031; P=0.028). Conclusion:The T staging population distribution of the 7th and 8th edition UICC staging system had moderate consistency, and the T staging of the 8th edition is more advantageous in predicting the prognosis of OS and PFS. In both editions, T staging is an independent prognostic factor for OS and PFS.