Objective: To explore the role and mechanism of epiregulin (EREG) in clear cell renal cell carcinoma (ccRCC)，and to find biomarkers and therapeutic targets for ccRCC. Methods: Based on the data from The Cancer Genome Atlas (TCGA) and Genotype-Tissue Expression (GTEx) databases，the correlation between the expression level of EREG in ccRCC tissues and the clinical staging and survival of ccRCC patients was analyzed. The samples of 6 ccRCC cases treated in the Second Affiliated Hospital of the Air Force Medical University were collected. The expression of EREG was confirmed with immunohistochemistry and quantitative real-time polymerase chain reaction (q-PCR). The effects of EREG overexpression on the proliferation，cell cycle and apoptosis of ACHN cells were verified with CCK-8 and flow cytometry. Finally，the expressions of EREG，epidermal growth factor receptor (EGFR) and the downstream pathway proteins were detected with Western blotting. Results: Based on the databases，it was found that the expression of EREG in ccRCC samples was higher than that in adjacent tissues，and there was a positive correlation with the clinical stage. Survival analysis showed that high expression of EREG was a risk factor affecting the prognosis. The results of immunohistochemical staining and qPCR revealed that EREG was highly expressed in ccRCC. Flow cytometry showed that EREG overexpression promoted the proliferation of ACHN cells，enhanced cell cycle，and inhibited apoptosis. In addition，Western blotting suggested that EREG promoted the expressions of EREG，EGFR and the downstream proteins. Conclusion: The expression of EREG is associated with the prognosis of ccRCC patients. In vitro cell experiments have shown that it can promote the proliferation of ccRCC cells and inhibit their apoptosis，thereby leading to the progression of ccRCC. It can serve as a potential biomarker for prognosis prediction and a drug development target for ccRCC patients.

OBJECTIVE To explore the pharmacodynamic related substances and mechanism of Weining San(WNS) against gastric ulcer(GU) according to fingerprint and network pharmacology. METHODS Twelve batches of WNS fingerprints were established by HPLC, and methodological investigation was carried out. Combined with reference substances, characteristic peaks were identified, pharmacodynamic related substances were screened, and network pharmacological analysis was carried out. Using TCMIP and Swiss Target Prediction database to retrieve component targets; Using OMIM, GeneCards and Drugbank databases to retrieve GU disease targets, taking the intersection targets of components and diseases, using String database to construct protein-protein interaction network diagram, and analyzing topological parameters; Using Cytoscape 3.8.2 software to construct "component-disease-target" network diagram; GO and KEGG enrichment analysis of intersection targets were carried out by Metascape website. Then the alcoholic GU mouse model was established by intragastric administration of absolute ethanol to verify the results of network pharmacology prediction. RESUITS　The precision, stability and repeatability of HPLC fingerprint method were good. By comparison and comprehensive analysis of control substances, notoginsenoside R1, ginsenoside Rg1, militarine, ginsenoside Rb1, schisandrin, schisandrol B, deoxyschizandrin and schisantherin A were identified as pharmacodynamic related substances in WNS, which may play their role by regulating core targets such as AKT1, IL-6, STAT3, TNF, IL1B and key signal pathways such as PI3K-Akt and JAK-STAT. The gastric ulcer index, ulcer inhibition rate and HE staining showed that WNS could improve gastric mucosal injury in GU mice. The results of ELISA, WST-1 and TBA showed that WNS could decrease the levels of TNF-α, IL-6, IL-1β and MDA, and increase the levels of SOD and PGE2, suggesting that the anti-GU effect of WNS was related to the inhibition of inflammatory reaction and oxidative stress mechanism, which further verified the prediction of network pharmacology. CONCLUSION This study combines fingerprint analysis, network pharmacology, and animal experimental validation to explore the pharmacodynamic related substances and mechanisms of WNS anti-GU efficacy, providing reference for quality control and clinical research of WNS.

The surveillance data of new cases of acute myocardial infarction (AMI) from January 1, 2013, to December 31, 2021, in Tengzhou City, Shandong Province, were used to analyze the incidence rate of AMI and its change trend among residents. The age and gender standardized incidence rate was calculated based on the 7th National Population Census 2020. The Cochran-Armitage trend test was used to analyze the trend of onset time and age. From 2013 to 2021, the crude and standardized incidence rate of total AMI in Tengzhou City declined from 130.07/100 000 and 161.12/100 000 to 76.15/100 000 and 72.77/100 000 ( Z=-13.785 and -20.822, both P<0.001). The crude and standardized incidence rates of males were higher than those of females. In 2016, males aged 45-54 years old and females aged 35-64 years old increased by 33.33%, 103.65%, 106.30%, and 95.75% compared to 2015, and the differences were statistically significant ( χ2=6.512, 4.965, 25.115, and 46.004, all P<0.05). The incidence rate of AMI in men aged<35 and 35-44 years old had an upward trend. From 2013 to 2021, the incidence rate of AMI decreased by 55.15% in urban areas and 36.59% in rural areas ( Z=-8.529 and -11.235, both P<0.001).

The surveillance data of new cases of acute myocardial infarction (AMI) from January 1, 2013, to December 31, 2021, in Tengzhou City, Shandong Province, were used to analyze the incidence rate of AMI and its change trend among residents. The age and gender standardized incidence rate was calculated based on the 7th National Population Census 2020. The Cochran-Armitage trend test was used to analyze the trend of onset time and age. From 2013 to 2021, the crude and standardized incidence rate of total AMI in Tengzhou City declined from 130.07/100 000 and 161.12/100 000 to 76.15/100 000 and 72.77/100 000 ( Z=-13.785 and -20.822, both P<0.001). The crude and standardized incidence rates of males were higher than those of females. In 2016, males aged 45-54 years old and females aged 35-64 years old increased by 33.33%, 103.65%, 106.30%, and 95.75% compared to 2015, and the differences were statistically significant ( χ2=6.512, 4.965, 25.115, and 46.004, all P<0.05). The incidence rate of AMI in men aged<35 and 35-44 years old had an upward trend. From 2013 to 2021, the incidence rate of AMI decreased by 55.15% in urban areas and 36.59% in rural areas ( Z=-8.529 and -11.235, both P<0.001).

OBJECTIVETo explore the genetic basis for a Chinese pedigree affected with congenital hypofibrinogenamia.

METHODSPeripheral blood samples were collected from 9 members from the pedigree. Routine coagulation tests including activated partial thromboplastin time (APTT), thrombin time (TT), the prothrombin time (PT) were carried out. The activity of fibrinogen (Fg: C) was measured using Clauss method, and fibrinogen antigen (Fg: Ag) was measured with immunoturbidimetry. All exons and exon-intron boundaries of the fibrinogen Aα, Bβ and γ chain genes were amplified using PCR, which was followed by direct sequencing. Suspected mutation was confirmed by reverse sequencing. The mutant fibrinogen was analyzed with Swiss-PdbViewer.

RESULTSThe proband showed prolonged APTT, PT and TT. Her functional fibrinogen (Fg: C) and antigen fibrinogen (Fg: Ag) levels were reduced to 0.69 g/L and 0.72 g/L, respectively. Her mother and grandmother also had a low levels of fibrinogen, which were 0.99 g/L and 0.83 g/L for Fg: C, 1.02 g/L and 0.87 g/L for Fg: Ag, respectively. The results of other members from the pedigree were all within the normal range. Genetic analysis reveled a heterozygous G>T mutation at nucleotide 7590 in exon 8 of γ gene in the proband, which was predicted to be a novel Ser313Ile mutation. The mutation was also found in her mother and grandmother. Model analysis showed that the Ser313Ile mutation disturbed the hydrogen bonds between Ser313, Asn319 and Asp320. Moreover, the mutation also altered the mutual electrostatic force and affected the folding and instability of the mutant fibrinogen.

CONCLUSIONThe heterozygous Ser313Ile mutation probably underlies the hypofibrinogenemia in this pedigree.

Adult ; Afibrinogenemia ; genetics ; Female ; Fibrinogen ; chemistry ; genetics ; Heterozygote ; Humans ; Male ; Middle Aged ; Mutation ; Pedigree

Objective To investigate the expression,clinicopathological significance and correlation of S100A4,EGFR and PI3K in lung adenocarcinoma.Methods Immunohistochemical method (EnVision two steps) was used to detect the expression of S100A4,EGFR and PI3K proteins in 84 lung adenocarcinoma tissue samples and 30 normal lung tissue samples.The relationship of S100A4,EGFR and PI3K expression with clinicopathologic factors,post-operative five-year survival and the correlations among the three proteins were analyzed.Results The positive expression rates of S100A4,EGFR and PI3Kin lung adenocarcinoma tissues were higher than those in normal tissues,respectively [(69.0 ％,58/84) vs (6.7 ％,2/30),(64.3 ％,54/84) vs (16.7 ％,5/30),(52.4 ％,44/84) vs (13.3 ％,4/30),P ＜ 0.01].The expression of S100A4,EGFR and PI3K proteins were positively correlated with the differentiated degree,lymph node metastasis,clinical stages,and five-year survival (P ＜ 0.05),but not correlated with other clinicopathologic factors (P ＞ 0.05).The expression of S100A4 was positively correlated with EGFR and PI3K in lung adenocarcinoma (P ＜ 0.01),and the expression of EGFR was positively correlated with PI3K (P＜ 0.01).Conclusions S100A4,EGFR and PI3K were closely related with the occurrence,development,metastasis and prognosis of lung adenocarcinoma.S100A4 might be an important marker in estimating biological behavior and metastasis tendence of lung adenocarcinoma.S100A4 may be correlated with EGFR and PI3K.

OBJECTIVETo detect the presence of ROS1 fusion gene in pulmonary adenocarcinoma and its clinicopathologic parameters.

METHODSFluorescence RT-PCR was used to detect the presence of ROS1 fusion gene in 369 surgical resection samples of pulmonary adenocarcinoma with known EGFR mutation status. The presence of ROS1 fusion gene in correlation with clinicopathologic features was analyzed. Sixteen positive and 20 negative samples by RT-PCR were further confirmed by direct sequencing.

RESULTSROS1 fusion gene was detected in 16 of 369 lung adenocarcinoma samples (4.3%). The presence of ROS1 fusion gene was not correlated to gender, age, smoking history, tumor site, size, histological subtype, tumor differentiation, T staging, lymph node metastasis, TNM staging and EGFR mutation (P > 0.05). The frequency of ROS1 fusion gene was similar in female and male patients, 4.4% (8/183) vs 4.3% (8/186), P > 0.05. The presence of ROS1 fusion gene in patients of ≤ 60 years of age was higher than that in patients of > 60 years, 5.1% (10/195) vs 3.4% (6/174), P > 0.05. The rate of ROS1 fusion gene of non-smokers was a slight higher than that of smokers, 4.4% (14/318) vs 3.9% (2/51), P > 0.05. Both positive and negative cases were confirmed by direct sequencing in all cases.

CONCLUSIONSROS1 fusion gene occurs more frequently in younger and non-smoking patients of pulmonary adenocarcinoma, and may coexist with EGFR mutations. ROS1 fusion gene seems to define a distinct subset of pulmonary adenocarcinoma.

Objective To detect the presence of ROS1 fusion gene in pulmonary adenocarcinoma and its clinicopathologic parameters.Methods Fluorescence RT-PCR was used to detect the presence of ROS1 fusion gene in 369 surgical resection samples of pulmonary adenocarcinoma with known EGFR mutation status.The presence of ROS1 fusion gene in correlation with clinicopathologic features was analyzed.Sixteen positive and 20 negative samples by RT-PCR were further confirmed by direct sequencing.Results ROS1 fusion gene was detected in 16 of 369 lung adenocarcinoma samples (4.3%).The presence of ROS1 fusion gene was not correlated to gender, age, smoking history, tumor site, size, histological subtype, tumor differentiation, T staging, lymph node metastasis, TNM staging and EGFR mutation ( P>0.05).The frequency of ROS1 fusion gene was similar in female and male patients,4.4%(8/183) vs 4.3%(8/186) , P>0.05.The presence of ROS1 fusion gene in patients of ≤60 years of age was higher than that in patients of >60 years,5.1%(10/195) vs 3.4%(6/174), P>0.05.The rate of ROS1 fusion gene of non-smokers was a slight higher than that of smokers, 4.4% ( 14/318 ) vs 3.9%( 2/51 ) , P>0.05.Both positive and negative cases were confirmed by direct sequencing in all cases.Conclusions ROS1 fusion gene occurs more frequently in younger and non-smoking patients of pulmonary adenocarcinoma, and may coexist with EGFR mutations.ROS1 fusion gene seems to define a distinct subset of pulmonary adenocarcinoma.

BACKGROUND:At present, the methods of treating unstable comminuted radial head fractures contain open reduction and internal fixation and metal prosthesis replacement. There were success cases treated by the two methods, but some shortcomings simultaneously existed.
OBJECTIVE:To compare the clinical therapeutic effects of replacement of the radial head with metal prosthesis with open reduction and internal fixation for the treatment of unstable comminuted radial head fractures.
METHODS:A prospective randomized control ed analysis was performed in 45 cases of unstable comminuted radial head fractures. These cases received open reduction and internal fixation and metal prosthesis replacement. This study compared the Broberg and Morrey elbow joint function score and the incidence of complications after fixation, and performed statistical analysis.
RESULTS AND CONCLUSION:The subjects were fol owed up for 1-5 years, averagely 2.8 years. According to Broberg and Morrey scores, the average score was 90.1 and the incidence of complications was 13.6%in the prosthesis replacement group. The average score was 76.8 and the incidence of complications was 47.9%in the open reduction. Significant differences were visible between the two groups (P<0.01). Compared with the open reduction group, prosthesis replacement for unstable comminuted radial head fractures obtained better joint function and lower incidence of complications.

Objective To explore the relationships between brain-derived neurotrophic factor gene G196A polymorphisms and psychopathology and the cognitive function in schizophrenic patients.Methods 224 patients and 220 normal controls were examined with polymerase chain reaction(PCR),denaturing polyacrylamide gel electrophoresis and silver staining to determine genotype and allele of G196A.Clinical symptoms were assessed with the Positive and Negative Symptom Scale (PANSS).Cognitive function was assessed with Wisconsin card sorting test (WCST) and Trail Making Test(CPT).To analyse the differences of the scores of Scale for the Assessment of Positive Symptoms(SAPS) and Scale for the Assessment of Negative Symptoms (SANS) among the patients with the genotype G/G,G/A and A/A.At the same time,the differences of the performance of WCST and CPT were analyzed.Results ①There were no significant differences of the genotypes G/G,G/A and A/A and allele G and A between patients and controls.②There were significant differences of the genotypes A/A between patients with Positive Symptoms and patients with Negative Symptoms (x2 =4.558,P ＜ 0.05).③There were no significant differences in the performances of complete categorizations and persistent wrong numbers of WCST and the performances of CPT among three groups of patients with genotype G/G,G/A and A/A (One-Way ANOVA,all P ＞ 0.05).Conclusion BDNF gene G196A polymorphisms are not associated with schizophrenia and the cognitive function but are associated with positive symptoms of schizophrenia.