Li-Fraumeni syndrome(LFS)is a rare autosomal dominant genetic disorder.Patients with LFS tend to develop tumors at a young age and are at risk of multiple types of cancer.The core pathogenic mechanism of LFS is germline mutation of the TP53 gene,which leads to loss of function of the p53 protein and an increase in the risk of tumor development.There are many tumor types closely related to LFS,including soft tissue sarcoma,osteosarcoma,brain tumors,breast cancer,and adrenocortical carcinoma.Although some common mutation sites of the TP53 gene in LFS patients have been identified,there are still differences in mutation sites among different patients,and the type of TP53 gene mutation may affect the clinical manifestations and prognosis of patients.Therefore,genetic testing for LFS patients to determine the specific mutation form of TP53 is of great significance.This article reviews the clinical patho-logical characteristics,treatment methods,and prognosis of LFS-related tumor patients,aiming to provide useful refer-ences for clinical practice.

Purpose To investigate the differential expression of proteins secreted by diffuse-type gastric cancer-associated fibroblasts(DGC-CAFs)and intestinal-type gastric cancer-associated fibroblasts(IGC-CAFs)according to Lauren classification of gastric cancer.Methods Fresh surgery samples were acquired to extract primary cancer-asso-ciated fibroblasts(CAFs)to obtain the conditional medium,including three cases of diffuse-type gastric cancer(DGC)and three cases of intestinal-type gastric cancer(IGC).Then high performance liquid chromatography-tandem mass spectrometry(HPLC-MS/MS)was used to detect the differences in secreted factors between DGC-CAFs and IGC-CAFs.Additionally,a total of 1 174 cases were collected from the GEO and TCGA databases,and the distribution of stromal cells was assessed via ESTIMATE to derive stromal scores for both DGC and GC.Furthermore,Kaplan-Meier survival analysis was performed to evaluate the relationship between high stromal scores,elevated CAFs proportions,and patient prognosis.Subsequently,GO enrichment analysis was performed to investigate associated genes and their bi-ological functions.Results HPLC-MS/MS analysis showed that only 10 proteins were identified to be expressed in both DGC-CAFs and IGC-CAFs,namely SPARC,COL6A1,COL1A2,COL1A1,COL3A1,FN1,DCN,ACTG1,TIMP1 and SHROOM3.There were 8 proteins expressed higher in DGC-CAFs than IGC-CAFs in all cases with ratio＞2,namely COL3A1(5.28),COL1A2(3.98),DCN(3.71),TIMP1(3.40),COL6A1(3.35),ACTG1(3.13),COL1A1(2.84)and SHROOM3(2.50).Two other proteins,TUBB and BASP1,were identified in all three cases of DGC-CAFs.The former was only identified in one case of IGC-CAFs,while the latter was not identified in all three cases of IGC-CAFs.The results of bioinformatics analysis showed that the stromal score of DGC was higher than IGC,which correlated with poor prognosis.Analysis of cell components revealed that the related genes were more enriched in ECM,collagen-containing extracellular matrix and cell-cell junction.Also,the biological process and molecular function was based on the components,which was consistent with HPLC-MS/MS analysis results.Conclusion There are differ-ences in secreted proteins of DGC-CAFs and IGC-CAFs,both on the types and the content.The differential proteins are mostly enriched in ECM-related signaling pathways.Presumably,the high content of CAFs in the stroma affects the prognosis of gastric cancer patients by influencing the gene expression and the function of receptor pathway of ECM.

BACKGROUND:With the increasing attention of scholars at home and abroad to children's cervical spine-related diseases,the demand for exploring the anatomical indicators and changes of cervical spine morphology and development in children of different ages is increasing.OBJECTIVE:To explore and analyze the morphological changes of children with different ages and vertebral sequences by measuring the anatomical position indexes of C2-C7 neurocentral synchondrosis in children aged 1-6 years.METHODS:Normal cervical spine CT images were retrospectively collected from 160 children aged 1-6 years at provincial tertiary hospitals.They were divided into six groups according to an age group of 1 year.The raw data of consecutively scanned cervical spine tomography images were imported into Mimics 16.0 software.The positional anatomical indexes of cervical spine segments C2-C7 in coronal and transverse planes were measured and analyzed under the two-dimensional image window by choosing the measurement tools under the toolbar of Measurements.RESULTS AND CONCLUSION:(1)The distance between the two sides of C2-C7 neurocentral synchondrosis and the distance between the left and right sides of neurocentral synchondrosis and the transverse process gradually increased with age.The overall development of vertebrae in each cervical vertebral segment was faster than the ossification of the neurocentral synchondrosis.(2)The cross-sectional angles on both sides of C2-C7 neurocentral synchondrosis gradually increased with age,and the angles between the left and right sides of neurocentral synchondrosis and the anterior and posterior edges of the vertebral body gradually decreased.Both sides of the neurocentral synchondrosis in cervical vertebral segments tended to grow toward the arch site,which mainly promoted the growth and development of the arch.(3)Except for C7,the angle between the coronal planes on both sides of the cervical spine changed little with the descending neurocentral synchondrosis of the cervical spine,and the neurocentral synchondrosis of the cervical spine was more inclined to longitudinal growth and ossification.(4)The neurocentral synchondrosis position changes in C7 were significantly different from those in the rest of the cervical vertebrae.(5)The anatomical indexes of C2-C7 neurocentral synchondrosis position in children have obvious development rules among different ages and vertebral bodies,and these rules are helpful for the clinical diagnosis and treatment of cervical spine diseases in children.

Li-Fraumeni syndrome(LFS)is a rare autosomal dominant genetic disorder.Patients with LFS tend to develop tumors at a young age and are at risk of multiple types of cancer.The core pathogenic mechanism of LFS is germline mutation of the TP53 gene,which leads to loss of function of the p53 protein and an increase in the risk of tumor development.There are many tumor types closely related to LFS,including soft tissue sarcoma,osteosarcoma,brain tumors,breast cancer,and adrenocortical carcinoma.Although some common mutation sites of the TP53 gene in LFS patients have been identified,there are still differences in mutation sites among different patients,and the type of TP53 gene mutation may affect the clinical manifestations and prognosis of patients.Therefore,genetic testing for LFS patients to determine the specific mutation form of TP53 is of great significance.This article reviews the clinical patho-logical characteristics,treatment methods,and prognosis of LFS-related tumor patients,aiming to provide useful refer-ences for clinical practice.

Purpose To investigate the differential expression of proteins secreted by diffuse-type gastric cancer-associated fibroblasts(DGC-CAFs)and intestinal-type gastric cancer-associated fibroblasts(IGC-CAFs)according to Lauren classification of gastric cancer.Methods Fresh surgery samples were acquired to extract primary cancer-asso-ciated fibroblasts(CAFs)to obtain the conditional medium,including three cases of diffuse-type gastric cancer(DGC)and three cases of intestinal-type gastric cancer(IGC).Then high performance liquid chromatography-tandem mass spectrometry(HPLC-MS/MS)was used to detect the differences in secreted factors between DGC-CAFs and IGC-CAFs.Additionally,a total of 1 174 cases were collected from the GEO and TCGA databases,and the distribution of stromal cells was assessed via ESTIMATE to derive stromal scores for both DGC and GC.Furthermore,Kaplan-Meier survival analysis was performed to evaluate the relationship between high stromal scores,elevated CAFs proportions,and patient prognosis.Subsequently,GO enrichment analysis was performed to investigate associated genes and their bi-ological functions.Results HPLC-MS/MS analysis showed that only 10 proteins were identified to be expressed in both DGC-CAFs and IGC-CAFs,namely SPARC,COL6A1,COL1A2,COL1A1,COL3A1,FN1,DCN,ACTG1,TIMP1 and SHROOM3.There were 8 proteins expressed higher in DGC-CAFs than IGC-CAFs in all cases with ratio＞2,namely COL3A1(5.28),COL1A2(3.98),DCN(3.71),TIMP1(3.40),COL6A1(3.35),ACTG1(3.13),COL1A1(2.84)and SHROOM3(2.50).Two other proteins,TUBB and BASP1,were identified in all three cases of DGC-CAFs.The former was only identified in one case of IGC-CAFs,while the latter was not identified in all three cases of IGC-CAFs.The results of bioinformatics analysis showed that the stromal score of DGC was higher than IGC,which correlated with poor prognosis.Analysis of cell components revealed that the related genes were more enriched in ECM,collagen-containing extracellular matrix and cell-cell junction.Also,the biological process and molecular function was based on the components,which was consistent with HPLC-MS/MS analysis results.Conclusion There are differ-ences in secreted proteins of DGC-CAFs and IGC-CAFs,both on the types and the content.The differential proteins are mostly enriched in ECM-related signaling pathways.Presumably,the high content of CAFs in the stroma affects the prognosis of gastric cancer patients by influencing the gene expression and the function of receptor pathway of ECM.

BACKGROUND:With the increasing attention of scholars at home and abroad to children's cervical spine-related diseases,the demand for exploring the anatomical indicators and changes of cervical spine morphology and development in children of different ages is increasing.OBJECTIVE:To explore and analyze the morphological changes of children with different ages and vertebral sequences by measuring the anatomical position indexes of C2-C7 neurocentral synchondrosis in children aged 1-6 years.METHODS:Normal cervical spine CT images were retrospectively collected from 160 children aged 1-6 years at provincial tertiary hospitals.They were divided into six groups according to an age group of 1 year.The raw data of consecutively scanned cervical spine tomography images were imported into Mimics 16.0 software.The positional anatomical indexes of cervical spine segments C2-C7 in coronal and transverse planes were measured and analyzed under the two-dimensional image window by choosing the measurement tools under the toolbar of Measurements.RESULTS AND CONCLUSION:(1)The distance between the two sides of C2-C7 neurocentral synchondrosis and the distance between the left and right sides of neurocentral synchondrosis and the transverse process gradually increased with age.The overall development of vertebrae in each cervical vertebral segment was faster than the ossification of the neurocentral synchondrosis.(2)The cross-sectional angles on both sides of C2-C7 neurocentral synchondrosis gradually increased with age,and the angles between the left and right sides of neurocentral synchondrosis and the anterior and posterior edges of the vertebral body gradually decreased.Both sides of the neurocentral synchondrosis in cervical vertebral segments tended to grow toward the arch site,which mainly promoted the growth and development of the arch.(3)Except for C7,the angle between the coronal planes on both sides of the cervical spine changed little with the descending neurocentral synchondrosis of the cervical spine,and the neurocentral synchondrosis of the cervical spine was more inclined to longitudinal growth and ossification.(4)The neurocentral synchondrosis position changes in C7 were significantly different from those in the rest of the cervical vertebrae.(5)The anatomical indexes of C2-C7 neurocentral synchondrosis position in children have obvious development rules among different ages and vertebral bodies,and these rules are helpful for the clinical diagnosis and treatment of cervical spine diseases in children.

OBJECTIVE To study the improvement effects and mechanism of proanthocyanidins （PACs） on steroid-induced osteonecrosis of the femoral head （SONFH） in rabbits based on the receptor-interacting protein kinase 1 （RIPK1）/RIPK3/mixed lineage kinase domain-like protein （MLKL） signaling pathway. METHODS SONFH model in rabbits was induced by injecting Escherichia coli endotoxin+methylprednisolone. The successfully modeled rabbits were randomly divided into Model group （normal saline）， low-dose PACs group （PACs-L group， 11 mg/kg）， high-dose PACs group （PACs-H group， 22 mg/kg）， high-dose PACs+ RIPK1 activator （rRIPK1） group （PACs-H+rRIPK1 group， 22 mg/kg PACs+4 μg/kg rRIPK1）， along with a control group （normal saline）， with 6 rabbits in each group. Each administration group was given relevant medicine once a day intragastrically/via injection， for 4 consecutive weeks. After the last administration， the levels of tumor necrosis factor-α （TNF-α） and interleukin-6 （IL-6） in rabbit serum were measured. The changes in the microstructure of rabbit femurs， including bone mineral density （BMD）， trabecular thickness （Tb.Th）， trabecular number （Tb.N）， and trabecular separation （Tb. Sp） were examined. The histopathological features of rabbit femoral tissues were observed， and the apoptotic status of cells within the rabbit femoral tissues was detected. The mRNA expressions of vascular endothelial growth factor （VEGF） and bone morphogenetic protein 2 （BMP2） in rabbit femoral tissues were determined. The expressions of RIPK1/RIPK3/MLKL signaling pathway-related proteins in femoral tissues were detected. RESULTS Compared with the Control group， serum contents of TNF-α and IL-6， Tb.Sp， empty bone cavity rate， cell apoptosis rate， phosphorylation levels of RIPK1， RIPK3 and MLKL in femoral tissue were significantly increased in the Model group （P＜0.05）. BMD， Tb.Th， Tb.N， as well as the mRNA expression of VEGF and BMP2， along with protein expression of caspase-8， in the femoral tissues were all decreased （P＜0.05）. The bone cells in the femoral tissue were unevenly distributed， and the trabeculae were arranged sparsely. Compared with the Model group， the aforementioned quantitative indicators （P＜0.05） and pathological changes in all dosage groups of PACs showed significant improvements. Compared with the PACs-H group， the aforementioned quantitative indicators （P＜0.05） and pathological changes in the PACs-H+rRIPK1 group showed significant reversal. CONCLUSIONS PACs can ameliorate SONFH in rabbits， and its mechanism of action may be related to the inhibition of the activation of the RIPK1/RIPK3/MLKL signaling pathway， suppression of apoptosis in femoral tissue cells， and promotion of angiogenesis.

Purpose To investigate the expression of Clau-din18.2 and its relationship with clinicopathological parameters and prognosis in Epstein-Barr virus-associated gastric cancer(EBVaGC),and also to analyze the correlation between the ex-pression of Claudin18.2 and PD-L1,ARID1A,and HER2.Methods Tissue samples of 694 patients received radical gas-trectomy,and 25 cases of EBVaGC were selected according to EBER results and matched one by one.Immunohistochemistry was employed to assess the expression levels of Claudin18.2,PD-L1,ARID1A and HER2 in EBVaGC and non-EBVaGC.Ka-plan-Meier survival analysis was performed for analyzing the re-lationship between the expression of Claudin18.2,PD-L1 and ARID1A and the prognosis of gastric cancer patients,and the survival curve was drawn.Spearman correlation analysis was used to assess the respective relationships between Claudin18.2 and PD-L1,ARID1A,and HER2.Results The positive/high expression rates of Claudin18.2 in EBVaGC were 76％and 64％respectively.Furthermore,the positive/high expression rates of Claudin18.2 in non-EBVaGC were 32％and 20％,respective-ly.Claudin18.2 expression showed positively correlations with the tumor site(proximal stomach)in gastric cancer patients.In addition,compared with non-EBVaGC,PD-L1 CPS score was higher in EBVaGC(P＜0.001),and the deletion rate of AR-ID1A expression was also higher in EBVaGC(P=0.012).But there was no significant difference,and so did not the expression level of HER2 between EBVaGC and non-EBVaGC.Survival a-nalysis revealed that positive/high expression of Claudin18.2 did not show a significant correlation with prognosis.Sperman corre-lation analysis indicated a positive correlation between Clau-din18.2 and PD-L1(r=0.338 4,P=0.016 2),while the ex-pression of Claudin18.2 was negatively correlated with ARID 1A(r=-0.354 5,P=0.011 5).Finally,there was no signifi-cant correlation between Claudin18.2 and HER2.Conclusion Claudin18.2 is highly expressed in EBVaGC,which is correla-ted with PD-L1 and ARID1A.It provides more options of combi-nation therapies for patients with advanced gastric cancer.

Purpose To investigate the expression of Clau-din18.2 and its relationship with clinicopathological parameters and prognosis in Epstein-Barr virus-associated gastric cancer(EBVaGC),and also to analyze the correlation between the ex-pression of Claudin18.2 and PD-L1,ARID1A,and HER2.Methods Tissue samples of 694 patients received radical gas-trectomy,and 25 cases of EBVaGC were selected according to EBER results and matched one by one.Immunohistochemistry was employed to assess the expression levels of Claudin18.2,PD-L1,ARID1A and HER2 in EBVaGC and non-EBVaGC.Ka-plan-Meier survival analysis was performed for analyzing the re-lationship between the expression of Claudin18.2,PD-L1 and ARID1A and the prognosis of gastric cancer patients,and the survival curve was drawn.Spearman correlation analysis was used to assess the respective relationships between Claudin18.2 and PD-L1,ARID1A,and HER2.Results The positive/high expression rates of Claudin18.2 in EBVaGC were 76％and 64％respectively.Furthermore,the positive/high expression rates of Claudin18.2 in non-EBVaGC were 32％and 20％,respective-ly.Claudin18.2 expression showed positively correlations with the tumor site(proximal stomach)in gastric cancer patients.In addition,compared with non-EBVaGC,PD-L1 CPS score was higher in EBVaGC(P＜0.001),and the deletion rate of AR-ID1A expression was also higher in EBVaGC(P=0.012).But there was no significant difference,and so did not the expression level of HER2 between EBVaGC and non-EBVaGC.Survival a-nalysis revealed that positive/high expression of Claudin18.2 did not show a significant correlation with prognosis.Sperman corre-lation analysis indicated a positive correlation between Clau-din18.2 and PD-L1(r=0.338 4,P=0.016 2),while the ex-pression of Claudin18.2 was negatively correlated with ARID 1A(r=-0.354 5,P=0.011 5).Finally,there was no signifi-cant correlation between Claudin18.2 and HER2.Conclusion Claudin18.2 is highly expressed in EBVaGC,which is correla-ted with PD-L1 and ARID1A.It provides more options of combi-nation therapies for patients with advanced gastric cancer.

Objective To investigate the effect of dietary intake on the childbirth outcomes of primipara women with full-term labor analgesia. Methods A total of 400 primipara women with full-term labor analgesia were randomly divided into observation group and control group. The observation group received intake management and individualized dietary guidance, while the control group ate and drank according to their own wishes. The childbirth quality, the incidence of vomiting, the use of oxytocin due to uterine atony, the rate of intrapartum fever, the rate of perineal incision, the rate of cesarean section, the rate of vaginal assisted delivery, and the rate of postpartum hemorrhage were compared between the two groups. The duration of the first stage of labor, the duration of the second stage of labor, the duration of labor analgesia, and the amount of postpartum hemorrhage within 2 hours were also compared. Neonatal Apgar score, random blood glucose, umbilical artery blood pH value, umbilical artery blood lactic acid (Lac) value, the incidence of neonatal asphyxia, the incidence of neonatal fever, and the incidence of neonatal hypoglycemia were compared between the two groups. Results The observation group had lower incidences of vomiting, oxytocin use rate due to uterine atony, intrapartum fever rate, perineal incision rate, transferring cesarean section rate, and vaginal assisted delivery compared to the control group(P < 0.05). The observation group had lower rates of postpartum hemorrhage, shorter duration of the first and second stages of labor, shorter duration of labor analgesia, and less postpartum hemorrhage within 2 hours compared to the control group, and the incidences of neonatal hyperglycemia and hypoglycemia in the observation group were lower than those in the control group (P < 0.05). There were no statistically significant differences in umbilical artery blood pH value, Lac value, neonatal Apgar score, random blood glucose, neonatal asphyxia rate, and neonatal fever rate between the two groups (P>0.05). Conclusion Intake management and individualized dietary guidance during labor can reduce the incidence of uterine atony, shorten the duration of labor, decrease the incidence of dystocia, reduce postpartum hemorrhage within 2 hours and decrease the incidence of neonatal glucose abnormality.