Objective To study the expression of thyroid hormone receptor binding protein 4(TRIP4)and DNA damage inducing transcription factor 4(DDIT4)in glioma tissue and their relationship with clinical pathological characteristics and prognosis.Methods 94 glioma patients admitted to the First Hospital of Hebei Medical University from February 2018 to February 2019 were selected as the research subjects.The expression of TRIP4,DDIT4 proteins in tissues were detected by immunohistochemistry.The relationship between the expression of TRIP4,DDIT4 proteins in glioma tissues and clinical pathological characteristics were compared.The differences in survival prognosis of glioma patients with different levels of TRIP4,DDIT4 protein expression were analyzed by Kaplan-Meier survival curve.Univariate and multivariate COX regression analysis was conducted to analyze the factors affecting the survival prognosis of glioma patients.Results The positive rates of TRIP4(68.09%),DDIT4(65.96%)proteins in glioma tissues were higher than those in adjacent tissues(13.83%,10.64%),with statistically significant differences(χ2=57.212,60.866,all P<0.05).There was a significant positive correlation between TRIP4 and DDIT4 protein expression in glioma tissues(r=0.722,P<0.05).The positive rates of TRIP4(83.64%vs 46.15%,80.00%vs 51.28%)and DDIT4(80.00%vs 46.15%,76.36%vs 51.28%)proteins in glioma tissues with tumor diameter≥3cm,WHO grade Ⅲ were significantly higher than those in tissues with tumor diameter＜3cm,WHO grade Ⅰ～Ⅱ(χ2=6.393～14.754,P<0.05).The 3-year overall survival rates of the TRIP4 positive and negative expression groups were 37.50%(24/64)and 66.67%(20/30),respectively.The 3-year cumulative survival of the TRIP4 positive expression group was significantly lower than that in the TRIP4 negative expression group(Log-rank χ2=5.949,P=0.015).The 3-year overall survival rate of DDIT4 positive and negative expression group was 37.10%(23/62)and 70.00%(21/30),respectively.The 3-year cumulative survival of the DDIT4 positive expression group was significantly lower than that in the DDIT4 negative expression group(Log-rank χ2=7.642,P=0.006).Tumor diameter≥3cm(HR=1.614,P=0.000),WHO grade Ⅲ(HR=1.790,P=0.000),positive TRIP4(HR=1.665,P=0.000)and positive DDIT4(HR=1.476,P=0.000)were independent risk factors affecting the survival prognosis of glioma patients.Conclusion The expression of TRIP4 and DDIT4 protein in glioma tissue was increased.Both of them were related to tumor diameter and WHO grade,and are potential tumor markers for survival prognosis of glioma.

To compare and analyze the "same disease, same price" policy in the regionsimplementing diagnosis related group(DRG) payment reform, and to provide recommendations for further policy optimization and extension.

OBJECTIVE To evaluate the palatability and chewability of chewable tablets， and provide reference for the quality evaluation of various types of chewable tablets. METHODS Using self-made Glucosamine hydrochloride chewable tablets as the model drug， the quality test was conducted. The in vitro simulation system for chewable tablets was established by using a texture analyzer and rheometer， and an oral simulation experiment was conducted on chewable tablets. The texture analyzer was used to measure the force required for chewing and simulate the static disintegration process of chewable tablets； the rheometer was adopted to measure the viscoelasticity， thixotropy， and deformability of chewable tablets during the chewing process. RESULTS The disintegration time limit， principal component content， and dissolution of self-made Glucosamine hydrochloride chewable tablets all met the limit requirements. The in vitro simulation results of the texture analyzer showed that self-made chewable tablets were easy to chew in both axial and radial directions， and the force required for chewing was within the range of the chewing force of the teeth； chewable tablets could disintegrate at an appropriate time without being chewed and only taken in the oral cavity. The in vitro simulation results of the rheometer showed that the chewable tablets in the oral cavity exhibited a behavior of elasticity as the main factor and viscosity as the secondary factor through the continuous stirring of the tongue， and the viscosity of the chewable tablets gradually decreased with tongue stirring or tooth chewing； when chewing with teeth， the internal force of the chewing tablets decreased， causing plastic deformation and crushing. After being crushed， the shape couldn’t be restored， making it easy to chew and swallow. CONCLUSIONS The combination of texture analyzer and rheometer can be used to simulate the oral chewing process and evaluate the palatability and chewability of self-made Glucosamine hydrochloride chewable tablets. This model can provide reference for the evaluation of various chewable tablets.

Objective:To investigate the efficacy and safety of ab externo or ab interno transluminal trabeculotomy in the treatment of secondary glaucoma following pars plana vitrectomy (PPV).Methods:An observational case series method was performed.Seventeen eyes of 17 patients with glaucoma following PPV were enrolled in Henan Eye Hospital and Beijing Tongren Hospital from May 2016 to Feburary 2022.Primary conditions of patients receiving PPV included retinal detachment in 13 eyes, vitreous hemorrhage in 3 eyes, and entophthalmia in 1 eye.All the subjects underwent ab externo (11 eyes) or ab interno (6 eyes) transluminal trabeculotomy.The scope of all cases accepted trabeculotomy was ≥300°(11 cases of 360°, 4 cases of 330° and 2 cases of 300°).Before and at 1 week, 1 month, 6 months and 12 months after surgery, the intraocular pressure (IOP) was evaluated by Goldmann Tonometer and the best corrected visual acuity (BCVA) was measured using a standard visual acuity chart and converted to logrithm of minimal angle of resolution (LogMAR).The number of anti-glaucoma drug applications and surgery-related complications were recorded.The primary outcomes evaluated were IOP and surgical success rate.Secondary outcomes were medication quantity, BCVA (LogMAR) changes, and complications.Surgical success was defined as IOP reduction to <21 mmHg (1 mmHg=0.133 kPa) with or without the use of IOP-lowering medication.This study adhered to the Declaration of Helsinki.The study protocol was approved by the Ethics Committee of Henan Eye Hospital (No.HNEECKY-2021[41]).Written informed consent was obtained from each subject.Results:Preoperative, 1-week, 1-month, 6-month, and 12-month postoperative mean IOP was (34.41±5.11), (21.88±11.72), (20.77±7.67), (19.50±7.01), and (16.32±4.68)mmHg, respectively, with an statistically significant overall difference ( F=20.779, P<0.001).IOP at difference time points after surgery were lower than that before surgery, showing statistically significant differences (all at P<0.01).Compared with before surgery, IOP was reduced more than 40% at 12 months after surgery in 14 eyes.Surgical success rates at 6 and 12 months after surgery were both 76.5%.The number of IOP-lowing drugs decreased significantly after operation ( Z=-4.580, P<0.001).The difference in BCVA between before and 6 months after surgery was not statistically significant ( Z=-1.311, P=0.190).No serious complications were seen in any of the operated eyes postoperatively. Conclusions:Ab externo or ab interno transluminal trabeculotomy is safe and effective in the treatment of secondary glaucoma after PPV.

Objective:To analyze the expression of FAT1 gene in pancreatic adenocarcinoma and its relationship with clinicopathological features, prognosis, and immunotherapy for pancreatic adenocarcinoma.Methods:(1) Bioinformatics analysis: based on FAT1 mRNA expression and clinical data of 179 cases of pancreatic adenocarcinoma in the TCGA database, and FAT1 mRNA expression data of 328 cases of normal pancreatic tissues in the GTEx database. We analyzed the differences in FAT1 mRNA expression in pancreatic adenocarcinoma and normal pancreatic tissues and the relationship between FAT1 mRNA expression and the degree of differentiation, clinical stage, prognosis, immune cell infiltration, and immune checkpoint-associated genes in pancreatic adenocarcinoma. FAT1-related differentially expressed genes were analyzed by applying Limma 3.40.2 software package, and GO and KEGG enrichment analysis was performed on the differentially expressed genes. Immunohistochemical (IHC) of FAT1 in pancreatic adenocarcinoma and normal pancreatic tissues was analyzed by HPA database. (2) Validation of own tissue samples: tissue samples and clinical and prognostic data of 192 patients with pancreatic ductal adenocarcinoma admitted to Zhejiang Cancer Hospital from March 8, 2010 to September 30, 2020 were collected. IHC was performed on the tissue samples to verify the protein expression of FAT1 in pancreatic adenocarcinoma and its relationship with immune-related proteins, the degree of differentiation of pancreatic adenocarcinoma, clinical staging, and prognosis.Results:(1) Bioinformatics analysis: the FAT1 mRNA expression of 179 pancreatic adenocarcinoma tissues from the TCGA database was 5.55±1.04, which was higher than that of 328 normal pancreatic tissues with FAT1 mRNA from the GTEx database (2.95±0.53, P＜0.001). FAT1-specific IHC images showed that FAT1 expression was generally high in pancreatic adenocarcinoma tissues, and FAT1 expression shifted from the cell membrane to the cytoplasm. The FAT1 mRNA expression in the highly differentiated group (31 cases), the moderately differentiated group (96 cases), and the lowly differentiated group (52 cases) were 4.99±1.46, 5.51±0.80, and 5.68±1.08, the expression of pancreatic adenocarcinoma tissues were all higher than that of normal pancreatic tissues (all P＜0.001), and the FAT1 mRNA expression of the moderately differentiated group and the poorly differentiated group were all higher than that of the highly differentiated group (all P＜0.001). The median progression-free survival time (PFS) and median overall survival time (OS) of the 90 patients in the FAT1 mRNA low-expression group were 16.5 and 24 months, respectively, which were longer than those of the 89 patients in the FAT1 mRNA high-expression group (median PFS and OS were 13 and 18 months, respectively; P-values were 0.011 and 0.005, respectively). Multifactorial Cox regression analysis showed that FAT1 mRNA expression level was an independent influencing factor for OS in pancreatic adenocarcinoma patients ( HR=1.47, 95% CI: 1.09-1.99). Correlation analysis showed that FAT1 mRNA expression in pancreatic adenocarcinoma was positively correlated with B-cell infiltration, CD8+ T-cell infiltration, neutrophil infiltration, macrophage infiltration, and myeloid dendritic cell infiltration ( ρ=0.27, P＜0.001; ρ=0.28, P＜0.001; ρ=0.32, P＜0.001; ρ=0.21, P=0.004; ρ=0.32, P＜0.001), and also positively correlated with mRNA expression of CD274, HAVCR2, and PDCD1LG2 ( r=0.327, P＜0.001; r=0.231, P=0.002; r=0.258, P＜0.001). GO and KEGG enrichment analyses showed that FAT1 mRNA expression levels were associated with activation of the Wnt signaling pathway ( P=0.029), the PI3K/Akt pathway ( P<0.001), and other tumor microenvironment-related pathways. (2) Validation of own tissue samples: among 192 pancreatic adenocarcinoma tissues, FAT1 was highly expressed in 58 cases (30.21%), and the proportion of FAT1-expressing positive tumor cells was positively correlated with the combined positive score of PD-L1 and the number of CD3+ T-cells infiltration ( r=0.154, P=0.032; r=0.287, P＜0.001), and the protein expression of FAT1 had no correlation with the differentiation degree of pancreatic adenocarcinoma ( ρ=0.082, P=0.254). The median OS of 58 patients in the FAT1 high-expression group and 134 patients in the FAT1 low-expression group were 18.89 and 25.84 months, respectively, and the difference was not statistically significant (χ2=1.93, P=0.165). Conclusion:FAT1 gene is highly expressed in pancreatic adenocarcinoma tissues, may play an oncogenic role in pancreatic adenocarcinoma, may be an adverse influence on overall survival and progression-free survival of patients; FAT1 gene may be involved in multiple immune-related pathways and promote tumor immune escape.

Objective:To explore the genetic basis for a Chinese pedigree affected with Fragile X syndrome (FXS) through Nanopore long-read sequencing.Methods:A FXS pedigree who had undergone genetic counseling at the First Affiliated Hospital of Zhengzhou University in April 2023 was selected as the study subject. Nanopore long-read sequencing, triplet-repeat primed PCR (TP-PCR), methylation-specific multiplex ligation-dependent probe amplification (MS-MLPA) and trinucleotide polymorphism genotyping of androgen receptor (AR) gene were used to analyze the FMR1 CGG repeat number, methylation, and X chromosome inactivation of the pedigree members. This study has been approved by the Medical Ethics Committee of the First Affiliated Hospital of Zhengzhou University (No. KS-2018-KY-36). Results:Full mutation and CpG island hypermethylation were detected in the proband. The elder sister of the proband had full mutation of the FMR1 gene on one X chromosome and hypermethylation of CpG island, while the FMR1 gene on the other X chromosome was normal. FMR1 premutation was detected in the proband′s mother. Conclusion:Nanopore long-read sequencing can simultaneously detect the dynamic mutation and methylation status of the FMR1 gene on the two X chromosomes of females, which has important value for the diagnosis of FXS in different genders.

Objective:To analyze the expression of FAT1 gene in pancreatic adenocarcinoma and its relationship with clinicopathological features, prognosis, and immunotherapy for pancreatic adenocarcinoma.Methods:(1) Bioinformatics analysis: based on FAT1 mRNA expression and clinical data of 179 cases of pancreatic adenocarcinoma in the TCGA database, and FAT1 mRNA expression data of 328 cases of normal pancreatic tissues in the GTEx database. We analyzed the differences in FAT1 mRNA expression in pancreatic adenocarcinoma and normal pancreatic tissues and the relationship between FAT1 mRNA expression and the degree of differentiation, clinical stage, prognosis, immune cell infiltration, and immune checkpoint-associated genes in pancreatic adenocarcinoma. FAT1-related differentially expressed genes were analyzed by applying Limma 3.40.2 software package, and GO and KEGG enrichment analysis was performed on the differentially expressed genes. Immunohistochemical (IHC) of FAT1 in pancreatic adenocarcinoma and normal pancreatic tissues was analyzed by HPA database. (2) Validation of own tissue samples: tissue samples and clinical and prognostic data of 192 patients with pancreatic ductal adenocarcinoma admitted to Zhejiang Cancer Hospital from March 8, 2010 to September 30, 2020 were collected. IHC was performed on the tissue samples to verify the protein expression of FAT1 in pancreatic adenocarcinoma and its relationship with immune-related proteins, the degree of differentiation of pancreatic adenocarcinoma, clinical staging, and prognosis.Results:(1) Bioinformatics analysis: the FAT1 mRNA expression of 179 pancreatic adenocarcinoma tissues from the TCGA database was 5.55±1.04, which was higher than that of 328 normal pancreatic tissues with FAT1 mRNA from the GTEx database (2.95±0.53, P＜0.001). FAT1-specific IHC images showed that FAT1 expression was generally high in pancreatic adenocarcinoma tissues, and FAT1 expression shifted from the cell membrane to the cytoplasm. The FAT1 mRNA expression in the highly differentiated group (31 cases), the moderately differentiated group (96 cases), and the lowly differentiated group (52 cases) were 4.99±1.46, 5.51±0.80, and 5.68±1.08, the expression of pancreatic adenocarcinoma tissues were all higher than that of normal pancreatic tissues (all P＜0.001), and the FAT1 mRNA expression of the moderately differentiated group and the poorly differentiated group were all higher than that of the highly differentiated group (all P＜0.001). The median progression-free survival time (PFS) and median overall survival time (OS) of the 90 patients in the FAT1 mRNA low-expression group were 16.5 and 24 months, respectively, which were longer than those of the 89 patients in the FAT1 mRNA high-expression group (median PFS and OS were 13 and 18 months, respectively; P-values were 0.011 and 0.005, respectively). Multifactorial Cox regression analysis showed that FAT1 mRNA expression level was an independent influencing factor for OS in pancreatic adenocarcinoma patients ( HR=1.47, 95% CI: 1.09-1.99). Correlation analysis showed that FAT1 mRNA expression in pancreatic adenocarcinoma was positively correlated with B-cell infiltration, CD8+ T-cell infiltration, neutrophil infiltration, macrophage infiltration, and myeloid dendritic cell infiltration ( ρ=0.27, P＜0.001; ρ=0.28, P＜0.001; ρ=0.32, P＜0.001; ρ=0.21, P=0.004; ρ=0.32, P＜0.001), and also positively correlated with mRNA expression of CD274, HAVCR2, and PDCD1LG2 ( r=0.327, P＜0.001; r=0.231, P=0.002; r=0.258, P＜0.001). GO and KEGG enrichment analyses showed that FAT1 mRNA expression levels were associated with activation of the Wnt signaling pathway ( P=0.029), the PI3K/Akt pathway ( P<0.001), and other tumor microenvironment-related pathways. (2) Validation of own tissue samples: among 192 pancreatic adenocarcinoma tissues, FAT1 was highly expressed in 58 cases (30.21%), and the proportion of FAT1-expressing positive tumor cells was positively correlated with the combined positive score of PD-L1 and the number of CD3+ T-cells infiltration ( r=0.154, P=0.032; r=0.287, P＜0.001), and the protein expression of FAT1 had no correlation with the differentiation degree of pancreatic adenocarcinoma ( ρ=0.082, P=0.254). The median OS of 58 patients in the FAT1 high-expression group and 134 patients in the FAT1 low-expression group were 18.89 and 25.84 months, respectively, and the difference was not statistically significant (χ2=1.93, P=0.165). Conclusion:FAT1 gene is highly expressed in pancreatic adenocarcinoma tissues, may play an oncogenic role in pancreatic adenocarcinoma, may be an adverse influence on overall survival and progression-free survival of patients; FAT1 gene may be involved in multiple immune-related pathways and promote tumor immune escape.

Objective To detect the expression of p-ERK5 and WT-1 in cancer tissues of the patients with high-grade serous ovarian cancer(HSOC),and to analyze their relationship with the prognosis of the pa-tients to provide a basis for judging the prognosis of HSOC patients.Methods Fifty-four patients with HSOC visiting in the gynecology and obstetrics department of the Affiliated Hospital of North China University of Technology from January 2008 to December 2019 were selected as the study subjects.The age,clinical stage,lymph node metastasis,complicating ascites,recurrence within 3 years,platinum sensitive,interval debulking surgery(IDS)and CA125 level at first visit were collected.The ovarian cancer tissue samples were collected.The expression levels of p-ERK5 and WT-1 protein in ovarian cancer tissues were detected by immunohisto-chemistry.The expression situation of the two kinds of factors were compared among different clinicopatho-logical features.The Kaplan-Meier method and COX regression analysis were used to evaluate the prognosis of the patients with HSOC.Results The median progress free survival(PFS)in the p-ERK5 and WT-1 protein low-expression groups was 36.0 months and 37.0 months respectively,which in the high-expression groups was 17.0 months and 15.0 months respectively.The median overall survival(OS)in the p-ERK5 and WT-1 protein low expression group was 90.0 months,which in the high expression group was 40.0 months,and the difference was statistically significant(P＜0.001).Conclusion The high expression of p-ERK5 and WT-1 protein is associated with PFS time and OS time.

Objective:To explore the causes of self-management dilemma in young and middle-aged patients with recurrent acute pancreatitis from the perspectives of nurses, patients and patient caregivers, in order to provide reference for developing self-management intervention plans that meet the needs of patients.Methods:Using the descriptive phenomenological methods from qualitative research, 15 patients with recurrent acute pancreatitis, six nurses and nine caregivers from the Hepatobiliary Pancreatic Surgery Ward of the Second Norman Bethune Hospital of Jilin University from November 2021 to December 2022 were selected for semi-structured in-depth interviews. The Colaizzi 7-step method was used to analyze and refine the theme.Results:Two main themes were extracted to explain the difficulties in self-management of young and middle-aged patients with recurrent acute pancreatitis. The internal reasons for the self-management dilemma included cognitive biases in the importance of self-management, limited access to self-management knowledge and negative attitudes towards self-behavior management, and the external reasons for self-management dilemma included insufficient inclusiveness of the external environment towards diseases, fear of disease progression, multiple burdens caused by diseases and busy work.Conclusions:Young and middle-aged patients with recurrent acute pancreatitis experience multiple difficulties in the process of self-management. Clinical medical staff should explore self-management models with contemporary characteristics, enhance patient self-management ability and quality of life, reduce disease recurrence rate.

Objective To explore the research hotspots and development trends of pyrroloquinoline quinone(PQQ),and explore the research and application value of PQQ.Methods In this study,Web of Science was used as the retrieval database to search for literature related to PQQ published from 1985 to 2022,and VOSviewer software was used to include the keywords,countries and regions,journals,etc.Bibliometric analysis was performed on these literatures.Results A total of 1 512 articles were included,with an overall upward trend in the number of annual publications.The journal category with the highest number of publications was Biochemistry and Molecular Biology.Journal of Biological Chemistry had the highest total link strength.The high-frequency keywords mainly included dietary nutrition supplement,mitochondria,antioxidant,etc.The visualization results of countries and regions showed that although China started its research relatively late,and it had a strong connection intensity with other countries.Conclusion In recent years,the research heat of PQQ has gradually increased,and its antioxidant effects,improvement of mitochondrial function and action targets may be the hotpots of future research.PQQ still has broad development prospects,and will inject new vitality into the pharmaceutical and healthcare industry.