Background::Somatic copy number variations (SCNVs) in the CDKN2A gene are among the most frequent events in the dysplasia-carcinoma sequence of esophageal squamous cell carcinoma. However, whether CDKN2A SCNVs are useful biomarkers for the risk stratification and management of patients with esophageal squamous cell dysplasia (ESCdys) is unknown. This study aimed to investigate the characteristics and prognostic value of CDKN2A SCNVs in patients with mild or moderate (m/M) ESCdys. Methods::This study conducted a prospective multicenter study of 205 patients with a baseline diagnosis of m/M ESCdys in five high-risk regions of China (Ci County, Hebei Province; Yanting, Sichuan Province; Linzhou, Henan Province; Yangzhong, Jiangsu Province; and Feicheng, Shandong Province) from 2005 to 2019. Genomic DNA was extracted from paraffin biopsy samples and paired peripheral white blood cells from patients, and a quantitative polymerase chain reaction assay, P16-Light, was used to detect CDKN2A copy number. The cumulative regression and progression rates of ESCdys were evaluated using competing risk models. Results::A total of 205 patients with baseline m/M ESCdys were enrolled. The proportion of ESCdys regression was significantly lower in the CDKN2A deletion cohort than in the diploid and amplification cohorts (18.8% [13/69] vs. 35.0% [28/80] vs. 51.8% [29/56], P <0.001). In the univariable competing risk analysis, the cumulative regression rate was statistically significantly lower ( P = 0.008), while the cumulative progression rate was higher ( P = 0.017) in ESCdys patients with CDKN2A deletion than in those without CDKN2A deletion. CDKN2A deletion was also an independent predictor of prognosis in ESCdys ( P = 0.004) in the multivariable analysis. Conclusion::The results indicated that CDKN2A SCNVs are associated with the prognosis of ESCdys and may serve as potential biomarkers for risk stratification.

Humans ; Esophageal Squamous Cell Carcinoma/pathology* ; Esophageal Neoplasms/pathology* ; Carcinoma, Squamous Cell/pathology* ; Precancerous Conditions/pathology* ; Early Diagnosis

OBJECTIVE：To st udy the effects of Anchang decoction on TLR 4/NF-κB signaling pathway and the expression of fecal calprotectin （FC）in TNBS-induced ulcerative colitis （UC）model rats . METHODS ：SD rats were randomly divided into blank group ，model group ，positive control group [Live Bifidobacterium capsules ，5 mL（containing Bifidobacterium 0.35 g）]， Anchang decoction low -dose，medium-dose and high-dose groups （1，5，10 mL，each milliliter is approximately equivalent to 0.11 g of total crude drug ），with 15 rats in each group. Other groups were given TNBS combined with ethanol enema to establish UC model rat ，except blank group was given normal saline. Two days after successful modeling ，blank group and model group were given normal saline 5 mL，administration groups were given relevant medicine intragastrically ，once a day ，for consecutive 14 d. After last medication ，HE staining was used to observe the pathological change of colon tissue in rats. Western blotting assay was used to detect the protein expression of TLR 4，TRAF6 and NF-κB in colon tissues of rats；Real-time fluorescent quantitative PCR was used to detect mRNA expression of TLR 4，TRAF6，TNF-α and NF-κB；ELISA assay was adopted to detect serum level of TNF-α，IL-6 and FC in stool samples. RESULTS ：Compared with blank group ，the colonic mucosa of model group was severely damaged，and the protein expression of TLR 4，TRAF6 and NF-κB，mRNA expression of TLR 4，TRAF6，TNF-α and NF-κb as well as serum levels of TNF-α，IL-6 and FC level in stool samples were increased significantly （P＜0.05）. Compared with model group，the pathological changes of colon tissue in rats were improved in different administration groups to different extents ，and above indexes were all decreased significantly （P＜0.05）. CONCLUSIONS ：Anchang decoction may relieve the inflammation of UC model rats by regulating the TLR 4/NF-κB signaling pathway and the expression of FC.

Objective    To explore the application value of synchronous CT-guided percutaneous biopsy followed by radiofrequency ablation in the diagnosis and treatment of lung tumors. Methods    The clinical data of 21 patients with lung tumors were retrospectively analyzed. There were 8 males and 13 females aged 68 (51, 73) years. A total of 24 lesions underwent CT-guided percutaneous biopsy and concurrent radiofrequency ablation. The effectiveness and safety of this protocol were analyzed. Results    All 21 patients successfully completed the procedures. The diameter of 24 lesions was 17.0 (13.3, 19.0) mm. Biopsy specimens met the requirements of pathological diagnosis, and the effectiveness of specimens was 100.0%. The incidence of small amount of pneumothorax/pleural shrinkage after procedures was 19.0% (4/21) and the incidence of tension pneumothorax was 4.7% (1/21). There was no obvious bleeding or other complications. Conclusion    Synchronous CT-guided percutaneous biopsy followed by radiofrequency ablation combines two interventional techniques, which is safe and effective in the diagnosis and treatment of lung tumors, and it is worthy of popularization and application in clinic.

Shengmai Yin (SMY) is a Chinese herbal decoction that effectively alleviates the side effects of radio-therapy in various cancers and helps achieve radiotherapy's clinical efficacy.In this study,we explored the interaction mechanism among SMY,DNA methylation,and nasopharyngeal carcinoma (NPC).We identified differences in DNA methylation levels in NPC CNE-2 cells and its radioresistant cells (CNE-2R)using the methylated DNA immunoprecipitation array and found that CNE-2R cells showed genome-wide changes in methylation status towards a state of hypomethylation.SMY may restore its original DNA methylation status,and thus,enhance radiosensitivity.Furthermore,we confirmed that the dif-ferential gene Tenascin-C (TNC) was overexpressed in CNE-2R cells and that SMY downregulated TNC expression.This downregulation of TNC inhibited NPC cell radiation resistance,migration,and invasion.Furthermore,we found that TNC was hypomethylated in CNE-2R cells and partially restored to a hypermethylated state after SMY intervention.DNA methyltransferases 3a may be the key protein in DNA methylation of TNC.

Objective:To explore the learning guidance model and its influencing factors of undergraduates in medical schools.Methods:Based on the developmental learning guidance theory, 1 117 undergraduates from two undergraduate medical universities were selected as the research objects, through questionnaire surveys to collect their knowledge learning, curriculum learning and other core variables, and balanced guidance, compound guidance and other outcome variables, using Smart PLS 3.0 to test the validity of the samples.Results:There were statistical significance in the path relationship affecting the core variables and the outcome variables of the learning guidance model, P<0.05, indicating that the influencing factors of the learning guidance model had a significantly positive effect on the learning guidance model construction. Conclusion:Constructing a "balanced-compound-special" learning guidance model suitable for undergraduates' learning activities in medical universities provides a reference for the application and promotion of learning guidance model in medical undergraduate stage.

Renal cell carcinoma (RCC) is one of the most common malignant tumors affecting the urogenital system, accounting for 90% of renal malignancies. Traditional chemotherapy options are often the front-line choice of regimen in the treatment of patients with RCC, but responses may be modest or limited due to resistance of the tumor to anticarcinogen. Downregulated expression of organic cation transporter OCT2 is a possible mechanism underlying oxaliplatin resistance in RCC treatment. In this study, we observed that miR-489-3p and miR-630 suppress OCT2 expression by directly binding to the OCT2 3'-UTR. Meanwhile, 786-O-OCT2-miRNAs stable expression cell models, we found that miRNAs could repress the classic substrate 1-methyl-4-phenylpyridinium (MPP), fluorogenic substrate ,-dimethyl-4-(2-pyridin-4-ylethenyl) aniline (ASP), and oxaliplatin uptake by OCT2 both and in xenografts. In 33 clinical samples, miR-489-3p and miR-630 were significantly upregulated in RCC, negatively correlating with the OCT2 expression level compared to that in adjacent normal tissues, using tissue microarray analysis and qPCR validation. The increased binding of c-Myc to the promoter of pri-miR-630, responsible for the upregulation of miR-630 in RCC, was further evidenced by chromatin immunoprecipitation and dual-luciferase reporter assay. Overall, this study indicated that miR-489-3p and miR-630 function as oncotherapy-obstructing microRNAs by directly targeting OCT2 in RCC.

Objective    To explore the diagnostic value of circulating tumor cells (CTC) measured by magnetic nanoparticle method in lung cancer. Methods    (1) We measured binding capability of A549 or NCI-H1965 cell lines with recognition peptide and capture efficiency by adding tumor cells into the whole blood of healthy human. (2) We measured CTC of 34 patients suspected with lung cancer, and the counting results of CTC were compared with the following pathological results. Results    (1) The binding capability was 80.0%±6.0% for A549 and 70.1%±4.8% for H1957, while the capture efficiency was 57.3%±7.0% for A549 and 37.3%±6.1% for H1975. (2) CTCs were identified in 71.9% of patients with lung cancer. The specificity was 83.3%, and area under receiver operating characteristic (ROC) curve was 0.792 (P=0.003). Conclusion    CTC measured by magnetic nanoparticle method has promising application in the diagnosis of lung cancer.

Objective    To explore the efficacy of a novel detection technique of circulating tumor cells (CTCs) to identify benign and malignant lung nodules. Methods     Nanomagnetic CTC detection based on polypeptide with epithelial cell adhesion molecule (EpCAM)-specific recognition was performed on enrolled patients with pulmonary nodules. There were 73 patients including 48 patients with malignant lesions as a malignant group and 25 patients with benign lesion as a benign group. There were 13 males and 35 females at age of 57.0±11.9 years in the malignant group and 11 males and 14 females at age of 53.1±13.2 years in the benign group. e calculated the differential diagnostic efficacy of CTC count, and conducted subgroup analysis according to the consolidation-tumor ratio, while compared with PET/CT on the efficacy. Results     CTC count of the malignant group was significantly higher than that of the benign group  (0.50/ml vs. 0.00/ml, P<0.05). Subgroup analysis according to consolidation tumor ratio (CTR) revealed that the difference was statistically significant in pure ground glass (pGGO) nodules 1.00/ml vs. 0.00/ml, P<0.05), but not in part-solid or pure solid nodules. For pGGO nodules, the area under the receiver operating characteristic (ROC) curve of CTC count was 0.833, which was significantly higher than that of maximum of standardized uptake value (SUVmax) (P<0.001). Its sensitivity and specificity was 80.0% and 83.3%, respectively. Conclusion     The peptide-based nanomagnetic CTC detection system can differentiate malignant tumor and benign lesions in pulmonary nodules presented as pGGO. It is of great clinical potential as a noninvasive, nonradiating method to identify malignancies in pulmonary nodules.

Objective To investigate the feasibility and safety of portal 125I seed stent implantation combined with doxorubicin-eluting beads transcatheter arterial chemoembolization (DEB-TACE) for the treatment of hepatocellular carcinoma (HCC) associated with main portal vein tumor thrombus (MPVTF).Methods Prospective single-arm study was designed.Seven HCC patients with MPVTT were sequentially enrolled in this study to receive treatment.Portal pressure before and after portal vein stent implantation were determined,the liver function were tested before and 1-3 days,4 days,5-7 days after portal vein stent implantation,the results and the postoperative complications were analyzed.Results All 7 patients were in BCLC-C stage,with Child-Pugh classification being A-B level.All patients were diagnosed as massive type HCC complicated by portal vein tumor thrombus.The lesions were located in hepatic left lobe (n=l) and hepatic right lobe (n=6),tumor thrombus in left branch of portal vein was seen in one patient and tumor thrombus in right branch of portal vein was found in 6 patients,MPVTT was observed in all 7 patients.Portal 125I seed stent implantation plus DEB-TACE was successfully accomplished in all 7 patients.The portal pressure before and after stent implantation was 15.3 cmH2O and 10.2 cmH2O respectively,the postoperative pressure showed an obvious reduction.After stent implantation,a transient elevation of the serum total bilirubin (TB),alanine aminotransferase (ALT) and aspartate aminotransferase (AST) could be observed,which gradually decreased in 3-4 days;the recovery of TB level was slower than that of ALT and AST levels.Two patients had concomitant myocardial damage,which was gradually recovered in 2-3 days.Conclusion For the treatment of HCC associated with MPVTT,portal 125I seed stent implantation plus DEB-TACE is safe and feasible,although its long-term curative effect needs to be further clarified.