Renal fibrosis is a pathological process presented in all chronic kidney diseases and lacks effective treatment. Renal anti-aging protein Klotho displays impressive anti-renal fibrosis capacities, but sustainedly depressed during the initiation and progression of renal fibrosis due to aberrant epigenetic modifications, making Klotho a potential target of epigenetic intervention in anti-renal fibrosis therapy. The author has performed a series of studies and first established TGFb as an essential upstream pathological factor that causes Klotho suppression by inhibiting miR-152 and miR-30. This inhibition subsequently induces DNMT1 and DNMT3a and leads to Klothopromoter hypermethylation and Klotho suppression. Further, it has been found that Rhein from the Chinese medicinal herbal plant and a specific inhibitor of histone deacetylase (HDAC) 3 are capable of either inhibiting the aberrant DNMT1/3a induction and Klotho promoter DNA hypermethylation or enhancing PPARg acetylationat lysine 240/265 and its up-regulation of Klotho, resulting in Klotho restoration and reduced renal fibrosis and the associated renal and bone injuries. Therefore our findings have revealed the distinct epigenetic features of Klotho suppression in renal fibrosis and demonstrated the promising potentials of Klotho-targeted strategies in the treatment of renal fibrosis and the related disorders.

Exploration of the underlying mechanisms of tumor occurrence and development, as well as evaluation of the efficacy of anticancer drug treatments, relies on various research models both in vivo and in vitro. Over the past few decades, with the rapid advancement of biomedical technology, significant achievements have been made in this field. Gene detection technology has progressed from a single-gene perspective to multi-gene approaches, resulting in rapid development of bioinformatics and transformation of the conceptual understanding of malignant tumors. Moreover, in vitro cell research models have evolved from monolayer two-dimensional and primary cultures to three-dimensional configurations, which better imitate the cellular interactions and functions within tumor tissues. Furthermore, in vivo animal research models have transitioned from traditional carcinogen induction and cell or tissue xenografts to genetically engineered animal models or xenograft models, enabling targeted investigation into the roles of relevant genes in the occurrence and development of tumors. Clinical research has shifted from simple retrospective to prospective studies, including phase Ⅰ/Ⅱ/Ⅲ clinical trials, investigator-initiated clinical trials, and real-world clinical trials. The major shortcomings of current malignant tumor research models include their singularity, insufficient simulation of the tumor microenvironment, disparities between animal models and human tumors, and the lack of consideration for personalized medicine. Further research and optimization of the models are still needed in the future, along with more effective integration of different models to form an optimized comprehensive experimental model system. This review systematically examines and comprehensively overviews the evolution of malignant tumor research models with the aim of providing more references to researchers engaged in oncology research.

【Objective】 To compare the diagnostic efficacy of full-field digital mammography(FFDM), digital breast mammography(DBT) and dynamic enhanced magnetic resonance imaging(DCE-MRI) for breast tumors in different gland types. 【Methods】 Retrospective analyses of 56 breast lesions in 49 patients who underwent FFDM, DBT and MRI in the Department of Radiology, Sun Yat-sen Memorial Hospital, Sun Yat-sen University from October 2018 to December 2019 were performed. The breasts were divided into the non-dense or dense pattern, according to FFDM images. The breast lesions were diagnosed as benign(BI-RADS grade 4a and below) or malignant(BI-RADS grade 4b and above), based on the images of FFDM, DBT and MRI, respectively. All patients underwent surgery or biopsy to get a pathological diagnosis. The kappa consistency tests and receiver operating characteristics(ROC) analyses were used to compare the efficacy of FFDM, DBT and MRI in the diagnosis of breast tumor in different gland patterns. 【Results】 In all breasts, MRI (kappa = 0.66) was moderately consistent with pathological diagnosis, which was higher than DBT(kappa = 0.44), while there was no significant difference between FFDM(kappa = 0.14) and pathological diagnosis. In non-dense breasts, MRI (kappa = 0.88) was moderately consistent with pathological diagnosis, which was higher than DBT(kappa = 0.51), while there was no significant difference between FFDM(kappa = 0.18) and pathological diagnosis. In dense breasts, MRI(kappa = 0.54) was moderately consistent with pathological diagnosis, which was higher than DBT(kappa = 0.37), while there was no significant difference between FFDM(kappa = 0.10) and pathological diagnosis. In all breasts, the diagnostic efficacy of MRI, DBT and FFDM for breast tumor decreased gradually(AUC = 0.83; 0.73; 0.58). Specifically, the specificity of MRI, DBT and FFDM increased sequentially(77%, 82%, 86%), but the sensitivity decreased(88%, 65%, 29%). In non-dense breasts, the diagnostic efficacy of MRI, DBT and FFDM for breast tumor decreased gradually(AUC = 0.97; 0.84; 0.66). Specifically, the sensitivity of MRI(94%) was higher than that of DBT(69%) and FFDM(31%). In dense breasts, the diagnostic efficacy of MRI, DBT and FFDM for breast tumor decreased gradually(AUC = 0.77; 0.69; 0.55). Specifically, the specificity of MRI, DBT and FFDM increased sequentially(71%, 76%, 82%), but the sensitivity decreased(83%, 61%, 28%) . 【Conclusions】 In both dense and non-dense breasts, FFDM has the lowest diagnostic ability. In non-dense breasts, the diagnostic efficacy of MRI is higher than DBT. DBT shows its advantage over MRI in dense breasts, as it has a higher diagnostic specificity.

Adult ; Carrier Proteins ; metabolism ; Extracellular Matrix Proteins ; metabolism ; Female ; Glycoproteins ; metabolism ; Hepatitis B, Chronic ; metabolism ; pathology ; Humans ; Liver ; metabolism ; pathology ; Male ; Middle Aged

OBJECTIVETo compare the efficacy of preemptive epidural analgesia combined with postoperative epidural analgesia, postoperative epidural analgesia alone and intravenous analgesia for postoperative pain relief and their effects on plasma interleukin-6 (IL-6) concentration following radical surgery for gastric carcinoma.

METHODSSixty-six patients with gastric carcinoma scheduled for gastrectomy were randomly divided into 3 groups, namely group P (n=22), group E (n=22) and group V (n=22), to receive preemptive epidural analgesia combined with postoperative epidural analgesia, exclusive postoperative epidural analgesia, and exclusive postoperative intravenous analgesia, respectively. Hemodynamic data were recorded for all the patients during the operation, and visual analogue scale (VAS) was used to assess the pain intensity at 4, 8, 16, 24, 48 and 72 h after surgery. Plasma IL-6 concentration was determined before surgery and at 24, 48, 72 h after surgery.

RESULTSNo significant changes occurred in the hemodynamics during the preoperative periods. VAS and IL-6 were lower in group P than in group E and V, and group E had lower measurement than group V (P<0.05).

CONCLUSIONPreemptive epidural analgesia combined with postoperative epidural analgesia provides more satisfactory pain relief and more effectively prevents IL-6 increment than exclusive epidural analgesia or intravenous analgesia after gastrectomy for gastric carcinoma.

Adult ; Amides ; administration & dosage ; Analgesia, Epidural ; methods ; Analgesics ; administration & dosage ; Female ; Fentanyl ; administration & dosage ; Gastrectomy ; methods ; Humans ; Infusions, Intravenous ; Interleukin-6 ; blood ; Male ; Middle Aged ; Morphine ; administration & dosage ; Pain, Postoperative ; drug therapy ; Stomach Neoplasms ; blood ; surgery ; Treatment Outcome

Objective: This study aimed to evaluate the role of preoperative two-dimensional (2D) shear wave elastography (SWE) in assessing the stages of liver fibrosis in patients with suspected biliary atresia (BA) and compared its diagnostic performance with those of serum fibrosis biomarkers. Materials and Methods: This study was approved by the ethical committee, and written informed parental consent was obtained. Two hundred and sixteen patients were prospectively enrolled between January 2012 and October 2018. The 2D SWE measurements of 69 patients have been previously reported. 2D SWE measurements, serum fibrosis biomarkers, including fibrotic markers and biochemical test results, and liver histology parameters were obtained. 2D SWE values, serum biomarkers including, aspartate aminotransferase to platelet ratio index (APRi), and other serum fibrotic markers were correlated with the stages of liver fibrosis by METAVIR. Receiver operating characteristic (ROC) curves and area under the ROC (AUROC) curve analyses were used. Results: The correlation coefficient of 2D SWE value in correlation with the stages of liver fibrosis was 0.789 (p < 0.001). The cut-off values of 2D SWE were calculated as 9.1 kPa for F1, 11.6 kPa for F2, 13.0 kPa for F3, and 15.7 kPa for F4. The AUROCs of 2D SWE in the determination of the stages of liver fibrosis ranged from 0.869 to 0.941. The sensitivity and negative predictive value of 2D SWE in the diagnosis of ≥ F3 was 93.4% and 96.0%, respectively. The diagnostic performance of 2D SWE was superior to that of APRi and other serum fibrotic markers in predicting severe fibrosis and cirrhosis (all p < 0.005) and other serum biomarkers. Multivariate analysis showed that the 2D SWE value was the only statistically significant parameter for predicting liver fibrosis. Conclusion 2D SWE is a more effective non-invasive tool for predicting the stage of liver fibrosis in patients with suspected BA, compared with serum fibrosis biomarkers.

Objective: This study aimed to evaluate the role of preoperative two-dimensional (2D) shear wave elastography (SWE) in assessing the stages of liver fibrosis in patients with suspected biliary atresia (BA) and compared its diagnostic performance with those of serum fibrosis biomarkers. Materials and Methods: This study was approved by the ethical committee, and written informed parental consent was obtained. Two hundred and sixteen patients were prospectively enrolled between January 2012 and October 2018. The 2D SWE measurements of 69 patients have been previously reported. 2D SWE measurements, serum fibrosis biomarkers, including fibrotic markers and biochemical test results, and liver histology parameters were obtained. 2D SWE values, serum biomarkers including, aspartate aminotransferase to platelet ratio index (APRi), and other serum fibrotic markers were correlated with the stages of liver fibrosis by METAVIR. Receiver operating characteristic (ROC) curves and area under the ROC (AUROC) curve analyses were used. Results: The correlation coefficient of 2D SWE value in correlation with the stages of liver fibrosis was 0.789 (p < 0.001). The cut-off values of 2D SWE were calculated as 9.1 kPa for F1, 11.6 kPa for F2, 13.0 kPa for F3, and 15.7 kPa for F4. The AUROCs of 2D SWE in the determination of the stages of liver fibrosis ranged from 0.869 to 0.941. The sensitivity and negative predictive value of 2D SWE in the diagnosis of ≥ F3 was 93.4% and 96.0%, respectively. The diagnostic performance of 2D SWE was superior to that of APRi and other serum fibrotic markers in predicting severe fibrosis and cirrhosis (all p < 0.005) and other serum biomarkers. Multivariate analysis showed that the 2D SWE value was the only statistically significant parameter for predicting liver fibrosis. Conclusion 2D SWE is a more effective non-invasive tool for predicting the stage of liver fibrosis in patients with suspected BA, compared with serum fibrosis biomarkers.

OBJECTIVEIn an attempt to study the moleculr characterization and epidemiology of simian adenoviruses in nonhuman primate (NHP) populations.

METHODSWe examined a colony of captively bred rhesus macaques (Macaca mulatta) in China for the presence of adenoviral DNA in stool samples. This was done by using the PCR method that targeted the adenovirus polymerase gene, and the PCR positive fragments were cloned for sequencing and phylogenetic analyses.

RESULTSAmong the 57 animals analyzed, fecal samples from 12 animals were positive for the presence of adenoviral DNA. The results suggested that the viral DNA clones were primarily segregated into two large groups: SAdV-6 (2 non-redundant sequences) and SAdV-7 (9 non-redundant sequences). In addition, there were three clones with more similarity to SAdV-1, SAdV-3 and HAdV-52 respectively.

CONCLUSIONOur data confirmed the prevalence of adenoviral DNA in the feces of NHPs and revealed the adenoviruses in the gastrointestinal tract of the study animals. heterogeneity and phylogenetics of the adenoviruses in the gastrointestinal tract of the study animals.

Adenoviridae ; classification ; enzymology ; genetics ; isolation & purification ; Animals ; DNA-Directed DNA Polymerase ; genetics ; Feces ; virology ; Female ; Macaca mulatta ; virology ; Male ; Molecular Sequence Data ; Phylogeny ; Sequence Analysis, DNA ; Viral Proteins ; genetics

OBJECTIVETo compare differences between Crowe IV developmental dysplasia of the hip (DDH) with secondary acetabulum and Crowe IV DDH without secondary acetabulum,and determine whether it is necessary to divide Crowe IV DDH into two subtypes.

METHODSFrom June 2007 to May 2015,145 hips of 112 Crowe N patients who underwent total hip arthroplasty (THA) using S-ROM stem were divided into two groups: secondary acetabulum formaton group (group A) and no secondary acetabulum formaton group (group B). In group A,there were 12 females, 96 males,with an average age of (39.38 ± 11.19) years old. In group B, there were 2 females, 35 males, with an average age of (38.19 ± 10.92) years old. All the patients were evaluated by using Harris Hip Score. Radiographic evaluations were made preoperatively and during follow up. The differences between two groups were compared on dislocation height, canal flare index (CFI), subtrochanteric shortening osteotomy (SSTO) usage, pre- and post-operation Harris scores, complications.

RESULTSThe dislocation height for group A was (4.74 ± 1.57) cm, while the dislocation height for group B was (3.12 ± 1.15) cm. Significantly difference was detected between two groups. The CFI for group A was 2.69 ± 0.68, while the CFI for group B was 3.42 ± 0.79, and the significantly difference was detected between two groups. Harris scores were totally improved from 58.18 ± 15.67 preoperatively to 91.20 ± 3.79 post-operatively and the difference was significant. Pre-operative Harris scores was 58.1 ± 15.3 in group A, 58.3 ± 16.9 in group B. Post-operative Harris scores was 91.0 ± 4.1 in group A, 91.0 ± 5.1 in group B. No significant difference was found on Harris scores between A and B preoperatively and post-operatively. Complications of 4 cases peri-prosthesis fracture, 4 cases dislocation and 4 cases nerve injury occur in group A; While only one case dislocation and one case nerve injury occur in group B. No statistical significance was detected.

CONCLUSIONCrowe IV DDH with secondary acetabulum is significantly different from Crowe IV DDH without secondary acetabulum on dislocation height and femoral morphology, which causes the different selections of surgical techniques (SSTO usage or not). These important differences in fundamental parameters indicate the necessity to further divide Crowe IV DDH into IVA and IVB two subtypes.

Adolescent ; Adult ; Aged ; Female ; Hip Dislocation, Congenital ; classification ; surgery ; Humans ; Male ; Middle Aged ; Postoperative Complications ; therapy

OBJECTIVETransfusion transmitted virus (TTV) DNA was detected in serum samples obtained from healthy infants and volunteer blood donors living in Jiujiang city in an attempt to shed light on the prevalence of TTV infection and the transmission route of TTV infection in infants.

METHODSModified untranslated region, polymerase chain reaction (UTR PCR) and N22 PCR were performed to test TTV DNA in serum samples from 86 infants and 58 blood donors.

RESULTSTTV DNA was detected by UTR PCR in 51 (53.5%) infants and 58 (100%) in blood donors, while that tested by N22 PCR was 14 (16.3%) and 22 (37.3%) in infants and blood donors, respectively. Among infants younger than 30 days, 1 - 6 months and 7 - 12 months of age, TTV DNA was detected by UTR PCR and N22 PCR at rates of 0, 33.3%, 95.0% and 0, 7.4%, 30.0%, respectively.

CONCLUSIONThe prevalence rates of TTV DNA detected by UTR PCR were 95% in infants of 7 - 12 months after birth and 100% in healthy blood donors in Jiujiang city. However the results obtained by N22 PCR were much less frequently in the same population. Results showed that significant difference did exist in the prevalence of TTV DNA detected by the two different PCR systems. Age-dependent increase of TTV infection was observed in early childhood, while environmental sources were considered to be the most common route of TTV acquisition as the primary infection in infants. However, the prevalence of TTV in infants of 7 - 12 months was similar to that in healthy adults in the same region.

Base Sequence ; China ; epidemiology ; DNA Virus Infections ; epidemiology ; virology ; DNA, Viral ; chemistry ; genetics ; Humans ; Infant ; Infant, Newborn ; Molecular Sequence Data ; Polymerase Chain Reaction ; Prevalence ; Sequence Analysis, DNA ; Sequence Homology, Nucleic Acid ; Torque teno virus ; genetics