Mesangial cell proliferation is an early pathological indicator of diabetic nephropathy (DN). Growing evidence highlights the pivotal role of paired-related homeobox 1 (Prrx1), a key regulator of cellular proliferation and tissue differentiation, in various disease pathogenesis. Notably, Prrx1 is highly expressed in mesangial cells under DN conditions. Both in vitro and in vivo studies have demonstrated that Prrx1 overexpression promotes mesangial cell proliferation and contributes to renal fibrosis in db/m mice. Conversely, Prrx1 knockdown markedly suppresses hyperglycemia-induced mesangial cell proliferation and mitigates renal fibrosis in db/db mice. Mechanistically, Prrx1 directly interacts with the Yes-associated protein 1 (YAP) promoter, leading to the upregulation of YAP expression. This upregulation promotes mesangial cell proliferation and exacerbates renal fibrosis. These findings emphasize the crucial role of Prrx1 upregulation in high glucose-induced mesangial cell proliferation, ultimately leading to renal fibrosis in DN. Therefore, targeting Prrx1 to downregulate its expression presents a promising therapeutic strategy for treating renal fibrosis associated with DN.

Objective To develop a nomogram for predicting the risks of early anastomotic recurrence(EAR)after primary bowel resection in patients with Crohn's disease(CD).Methods The patients with CD under-going preoperative magnetic resonance enterography(MRE)and primary bowel resection were enrolled in this retrospective study and divided into an EAR group(18 patients)and EAR-free group(12 patients).The EAR group included the patients having an endoscopic Rutgeerts score of≥I2 month or the need for anastomotic resection within 12 months after surgery.All the 38 indexes including preoperative demographic characteristics,laboratory examina-tions,multi-parameter MRE features of the resected intestine and its adjacent mesentery,histological findings,and postoperative pharmacotherapy were analyzed.Least absolute shrinkage and selection operator(LASSO)regression and multivariate binary logistic regression analysis were performed to identify independent risk factors to be incorpo-rated into the nomogram for predicting the risks of early anastomotic recurrence and the prediction performance was evaluated.Results Mesenteric creeping fat index on MRE and comb sign were independent risks of EAR,with a concordance index of 0.882(95%CI:0.764～1).The calibration plot revealed a strong relationship between actual observation and predicted probability of EAR.Conclusions The preoperative MRE-based nomogram may be a potential tool for predicting EAR following surgery in patients with CD,which is beneficial to individual management in those patients.It provides reference for the formulation of early postoperative individualized drug adjuvant therapy in patients at high risk of EAR.

BACKGROUND: The treatment mode of lung cancer is epidermal growth factor receptor-tyrosine kinase inhibitors (EGFR-TKIs) as a first-line treatment for patients with EGFR mutant in non-small cell lung cancer (NSCLC). At the same time programmed death receptor 1 (PD-1) and its programmed death receptor ligand 1 (PD-L1) inhibitors therapy as the representative immune checkpoint inhibitors (ICIs) has a significant effect in the treatment of lung cancer. The aim of this study was to investigate the correlation between the expression of PD-1 and PD-L1 in NSCLC and clinicopathologic feature, EGFR gene mutation. METHODS: The protein expression of PD-1 and PD-L1 was detected by immunohistochemistry from 127 patients with NSCLC and EGFR gene mutation was detected by quantitative polymerase chain reaction (qPCR) to analyze its relation with clinicopathologic feature. Also, the correlation between protein expression of PD-1 and PD-L1 and EGFR mutation. RESULTS: The PD-1 positive expression in NSCLC tumor cells and tumor infiltrating immune cells is 53.5% (68/127), PD-L1 is 57.5% (73/127). The PD-1 and PD-L1 expression significantly higher in well-differentiated and moderately-differentiated carcinoma than poorly differentiated carcinoma, I+II than III+IV in clinical staging (P<0.05). The EGFR mutation rate was 46.5% (59/127), correlate with female, without smoking history, adenocarcinoma and well-differentiated and moderately-differentiated patients respectively higher than male, smoking history, squamous carcinoma and poorly differentiated patients (P<0.05). The protein expression of PD-L1 and PD-1 had the consistency in NSCLC patients (kappa=0.107,5, P=0.487). There was a negative correlation between the EGFR mutation and PD-1 and PD-L1 expression (Φ=-0.209, Φ=-0.221, P<0.05). Follow-up of NSCLC patients, the median total survival in under the age of 65, adenocarcinoma, well-differentiated and moderately-differentiated, with PD-L1 expression patients respectively higher than over the age of 65, squamous carcinoma, poorly differentiated, without PD-L1 expression patients (P<0.05). The median survival of hypo expression patients of PD-L1 significantly higher than hyper expression patient (P=0.04). CONCLUSIONS According to the Chinese Expert Consensus on Standards of PD-L1 immunohistochemistry testing for NSCLC, we tested the PD-L1 expression in NSCLC and then the dominant population of anti-PD-1/PD-L1 treatment was screened out. Patients with EGFR mutation were also detected and EGFR mutation was negatively correlated with the expression of PD-1 and PD-L1 as well. On the basis of PD-L1 expression and EGFR mutation status, it may benefit NSCLC patients from individualized treatment. Meanwhile, patients who were under the age of 65, adenocarcinoma, well-differentiated and moderately-differentiated, hypo expression of PD-L1 have a relatively good prognosis, to provide reference for the prognosis evaluation of NSCLC.

Objective:To develop a mesenteric creeping fat index (MCFI) based on CT enterography (CTE) to characterize the degree of creeping fat wrapping around the inflamed gut in Crohn disease (CD), and to assess the relationship between MCFI and the inflammatory intestinal stricture.Methods:From December 2018 to July 2019, the patients with CD who underwent surgery in the First Affiliated Hospital of Sun Yat-Sen University were prospectively collected. The extent of perienteric mesenteric vessels wrapping around the gut was reconstructed to develop MCFI based on CTE images. The intestinal stricture index was obtained by calculating the ratio of the maximal upstream luminal diameter divided by the minimum luminal diameter apparent within the stricturing region. Using region-by-region correlation between CTE and surgical specimen, creeping fat score in intestinal specimen was obtained by assessing the extent of creeping fat wrapping around the resected bowel segment, and HE staining was performed on the bowel specimen corresponding to creeping fat to obtain the pathological inflammatory score. The Spearman correlation analysis was used to evaluate the correlation between MCFI, creeping fat score in intestinal specimen, and inflammatory score, intestinal stricture index. The ROC curve analysis was used to assess the accuracy of MCFI in distinguishing moderate-severe and mild inflammatory bowel walls.Results:Totally 30 CD patients were enrolled. The creeping fat score in intestinal specimen positively correlated with pathological inflammatory score ( r s=0.403, P=0.027) and with intestinal stricture index ( r s=0.642, P<0.001). MCFI positively correlated with creeping fat score in intestinal specimen ( r s=0.840, P<0.001), with pathological inflammatory score ( r s=0.497, P=0.005), and with intestinal stricture index ( r s=0.599, P<0.001). ROC analysis showed that the area under the curve of MCFI for differentiating moderate-severely from mildly inflammatory bowel walls was 0.718 (95%CI 0.522-0.913). Using MCFI≥4 as a cutoff value, the sensitivity and specificity were 81.8% and 47.4%, respectively. Conclusions:There was a correlation between creeping fat and inflammatory intestinal strictures in CD. MCFI can non-invasively depict the degree of creeping fat wrapping around the gut and assess the inflammatory intestinal stricture.

Objective:To explore the diagnostic efficacy of nomogram based on multi-parameter MRI for assessment of bowel fibrosis in patients with Crohn disease（CD).Methods:The clinical and imaging data of CD patients diagnosed by surgical histopathology in the First Affiliated Hospital of Sun Yat-sen University from June 2015 to March 2018 were prospectively collected. All the patients underwent conventional MRI and diffusion kurtosis imaging（DKI) within 2 weeks before surgery. Patients who underwent surgery between June 2015 and September 2017 were included in the model building group, and those who underwent surgery between October 2017 and March 2018 were included in the model validation group. We measured the apparent diffusion coefficient（ADC) from monoexponential model of diffusion-weighted imaging（DWI), apparent diffusional kurtosis（K app), and apparent diffusion for non-Gaussian distribution（D app) from non-Gaussian DKI model, and observed T 2WI signal intensity and enhancement pattern of the same segment. One to three intestinal specimens per patient were stained with Masson′s trichrome for the histological grading of fibrosis. Correlations between qualitative/quantitative MRI indexes and histological grades were evaluated using the Spearman rank test. Multivariate logistic regression analysis was performed to identify independent factors to be included into the nomogram for predicting the degree of bowel fibrosis and its diagnostic performance was assessed by internal and external validation. Results:A total of 40 CD patients were included, including 31 in the model construction group and 9 in the model verification group. A total of 81 intestinal specimens from 31 patients were graded as none-to-mild bowel fibrosis（ n=32) and moderate-to-severe bowel fibrosis（ n=49) according to a scoring system of fibrosis. In the training cohort, the K app value of moderate-to-severely fibrotic bowel walls was significantly higher than that of none-to-mildly fibrotic bowel walls, and the D appand ADC values of moderate-to-severely fibrotic bowel walls were significantly lower than those of none-to-mildly fibrotic bowel walls（ Z=-5.999, -4.521 and -3.893; P<0.001). There was no significant difference in T 2WI signal intensity or enhancement pattern between these two groups（χ2=1.571 and 0.103; P>0.05). Moderate and mild correlations of histological fibrosis grades with K appand D app( r=0.721 and -0.483; P<0.001), and a mild correlation with ADC（ r=-0.445, P<0.001) were found. Independent factors derived from multivariate logistic regression analysis to predict the degree of bowel fibrosis were K app and D app. Internal and external validation revealed good performance of the nomogram with concordance index of 0.901（95% confidence interval, 0.824-0.978) and 1.000, respectively, for differentiating none-to-mild from moderate-to-severe fibrosis. Conclusion:The DKI-based nomogram can be used to evaluate the bowel fibrosis in CD patients and provides a visual and simple prediction method for clinic.

Objective To explore the clinical features of congenital hepatic fibrosis (CHF) in children.MethodsA total of 111 patients diagnosed with CHF during January 2002 to June 2015 were included and divided into children group and adult group according to the age at diagnosis. The clinical data including gender, age, clinical symptoms, signs, laboratory examinations, and imaging characteristics were retrospectively analyzed and compared between two groups.ResultsThere were high incidences of splenomegaly and liver cirrhosis in both children and adult groups, and no difference was found between two groups (P>?0.05). The fatigue, jaundice, and hepatosplenomegaly were more common in children group while the renal cyst and liver cyst were more common in adult group, and the differences were statistically signiifcant (P all?

Objective To explore the effect of different ages on behavioral dimensions of anxiety animal models in Kunming mice.Methods Young/Old,male,Kunming mice were recorded twice,for five minutes,with a one-week inter-trial interval in open field test (OFT),elevated plus maze (EPM) and light/dark box (LDB).The following parameters were evaluated:percentage of time spent in the OFT central area (Ctime％),percentage of number of squares visited in the OFT central area (Ccross％),the total number of horizontal squares in OFT (Cross),the total number of rears in OFT (Rear),percentage of time spent in the EPM open arms (Otime％),percentage of number of entries into the EPM open arms (Oentries％),the total number of entries into the EPM open and closed arms (Entries),percentage of time exploring in the LDB light area (Ltime％),percentage of number of squares crossing in the LDB light area (Lcross％),percentage of rears in the LDB light area (Lrear％),the total number of transition in LDB (Transition),the total number of horizontal squares in LDB (Cross) and the total number of rears in LDB (Rear).Results OFT-Ctime％,OFT-Ccross％,EPM-Otime％,EPM-Oentries％,LDB-Ltime％,LDB-Lcross％ and LDB-Lrear％ had significant loadings on anxiety factor; OFTCross,EPM-Entries,LDB-Transition and LDB-Cross loaded on locomotion-exploration factor.Old mice had higher anxiety emotion (Ctime％,t =3.12,P＜ 0.01; Ccross％,t =2.37,P＜ 0.01; Otime％,t =1.31,P＜ 0.05; Oentries％,t=1.57,P＜0.05; Ltime％,t=4.15,P＜0.01 ; Lcross％,t=3.28,P＜0.01 ; Lrear％,t=2.73,P＜0.01) and lower locomotion and exploratory activity (Cross,t =2.05,P ＜ 0.01 ; Entries,t =2.09,P ＜ 0.05 ;Transition,t=2.51,P＜0.01; Cross,t=3.02,P＜0.01),compared with Young.Conclusion Ages have no effect on structural dimensions of anxiety animal models.With the growth of ages,old mice have higher anxiety emotion but lower locomotion and exploratory activity.

OBJECTIVETo identify differentially expressed genes between chronic phase and blast crisis in chronic myeloid leukemia, explore the mechanism and screen potential biomarkers of disease progression.

METHODSThe differences in the gene expression profiles of bone marrow mononuclear cells between chronic phase and blastic crisis were examined using DNA microarray. PANTHER database, Genomatix database and Bibliosphere software were used to analyze and predict the critical genes or transcription factors during disease progression. Some of the genes or transcription factors were selected for verification by semi-quantitative RT-PCR.

RESULTSIn blastic crisis, 68 of the 1176 tested genes were obviously up-regulated. Sixteen of these differential genes were selectively expressed in leukocyte membranes. CD40, CCR3, LGALS3, RGS3, CEACAM3 and the related transcription factors RAC1, CTNNB1, TP53, and NF-κB, all as the nodes of the entire regulatory network, were presumed to play key roles in disease progression. The results of RT-PCR were consistent with the microarray data and showed high expression of CEACAM3, RGS3, CTNNB1 and RAC1 in blastic crisis.

CONCLUSIONA group of genes have been identified to very likely play key roles or serve as biomarkers in the transition from the chronic phase to blastic crisis in chronic myeloid leukemia.

Blast Crisis ; genetics ; Computational Biology ; Gene Expression Profiling ; Gene Expression Regulation, Leukemic ; Humans ; Leukemia, Myelogenous, Chronic, BCR-ABL Positive ; genetics ; Oligonucleotide Array Sequence Analysis ; Transcriptome

OBJECTIVETo investigate the cytogenetic differences between children and adults with acute lymphoblastic leukemia (ALL) using eight-probe fluorescence in situ hybridization and karyotype analysis.

METHODSEight-probe (MYC, P16, E2A, TEL/AML1, BCR/ABL , MLL , IGH, and hyperdiploidy) fluorescence in situ hybridization and karyotype analysis were performed for 86 adults and 39 children with acute lymphoblastic leukemia.

RESULTSEight-probe fluorescence in situ hybridization showed significant differences in the positivity rate of TEL/AML1, BCR/ABL, and hyperdiploidy between adult patients and children with ALL. By karyotype analysis, the positivity rate of t(9;22) and hyperdiploidy differed significantly between the children and adult patients (P<0.05).

CONCLUSIONAdults and children with ALL have different expression profiles of the fusion genes. Eight-probe fluorescence in situ hybridization is time-saving, accurate and efficient in detecting common genetic abnormalities in ALL patients, and can be well complementary to karyotype analysis in clinical diagnosis of ALL.

Adolescent ; Adult ; Child ; Child, Preschool ; Cytogenetics ; Female ; Humans ; In Situ Hybridization, Fluorescence ; methods ; Infant ; Karyotype ; Karyotyping ; Male ; Middle Aged ; Precursor Cell Lymphoblastic Leukemia-Lymphoma ; diagnosis ; genetics ; Young Adult

Objective To investigate the feasibility of virtual touch tissue quantification(VTQ) for the assessment of chronic allograft nephropathy(CAN).Methods 48 patients with normal renal function and 50 patients with CAN were checked by color Doppler and VTQ technique.All the results were compared　between two groups.Results Mean VTQ-values were significantly different between the two groups( P ＜ 0.05).ROC curve displayed that VTQ value of 2.51 m/s could be used to diagnose CAN,the sensitivity,specificity,positive predictive value and negative predictive value were 76.0％,52.1％,60.3％ and 65.7％,respectively.The diagnostic efficiency was 62.2％.Conclusions Parenchymal stiffness measured by VTQ is stable and repeatable,which can be used to diagnose patients with CAN and to monitor renal function.