Thoracic SMARCA4-deficient undifferentiated tumor-pathological diagnosis and combined immune checkpoint inhibitor treatment / 北京大学学报(医学版)

We explored clinicopathological features and treatment strategies for thoracic SMARCA4-deficient undifferentiated tumor (SMARCA4-UT). Thoracic SMARCA4-UT is a new entity recently acknowledged in the 2021 edition of World Health Organization Classification of Thoracic Tumors, and doctors are relatively unfamiliar with its diagnosis, treatment, and prognosis. Taking a case of SMARCA4-UT treated in Peking University First Hospital as an example, this multi-disciplinary discussion covered several hot issues on diagnosing and treating thoracic SMARCA4-UT, including histological features, immu- nohistochemical and molecular phenotype, immune checkpoint inhibitor (ICI) therapy, and pathological assessment of neoadjuvant therapy response. The patient was an older man with a long history of smoking and was admitted due to a rapidly progressing solid tumor in the lower lobe of the right lung. Histologically, tumor cells were epithelioid, undifferentiated, diffusely positive for CD34, and partially positive for SALL4.The expression of BRG1 protein encoded by SMARCA4 gene was lost in all of tumor cells, and next-generation sequencing(NGS)confirmed SMARCA4 gene mutation (c.2196T>G, p.Y732Ter). The pathological diagnosis reached as thoracic SMARCA4-UT, and the preoperative TNM stage was T1N2M0 (ⅢA). Tumor proportion score (TPS) detected by immunohistochemistry of programmed cell death 1-ligand 1 (PD-L1, clone SP263) was 2%. Tumor mutation burden (TMB) detected by NGS of 1 021 genes was 16. 3/Mb. Microsatellite detection showed the tumor was microsatellite stable (MSS). Neo-adjuvant therapy was implemented with the combined regimen of chemotherapy and ICI. Right lower lobectomy was performed through thoracoscopy after the two weeks' neoadjuvant. The pathologic assessment of lung tumor specimens after neoadjuvant therapy revealed a complete pathological response (CPR). The post-neoadjuvant tumor TNM stage was ypT0N0M0. Then, five cycles of adjuvant therapy were completed. Until October 2022, neither tumor recurrence nor metastasis was detected, and minimal residual disease (MRD) detection was negative. At present, it is believed that if BRG1 immunohistochemical staining is negative, regardless of whether SMARCA4 gene mutation is detected, it should be classified as SMARCA4-deficient tumors. SMARCA4-deficient tumors include a variety of carcinomas and sarcomas. The essential criteria for diagnosing SMARCA4-UT includes loss of BRG1 expression, speci-fic histological morphology, and exclude other common thoracic malignant tumors with SMARCA4-deficiency, such as squamous cell carcinoma, adenocarcinoma and large cell carcinoma. SMARCA4-UT is a very aggressive malignant tumor with a poor prognosis. It has almost no targeted therapy mutations, and little response to chemotherapy, but ICI is currently the only effective drug. The successful diagnosis and treatment for this case of SMARCA4-UT should enlighten significance for various kinds of SMARCA4-deficient tumors.

Preliminary Study on the Relationship between the Developmental Stage of Multiple Myeloma Disease and the Results of Bone Marrow Whole Exome Sequencing / 中国实验血液学杂志

OBJECTIVE@#To investigate the genetic results of whole exome sequencing of bone marrow from new onset multiple myeloma (MM) patients to analyze the process of genetic clonal evolution in MM patients.@*METHODS@#Genomic DNA was extracted from bone marrow samples of 15 MM patients and the whole exomes sequencing was performed using next generation sequencing technology. Using own buccal cells as germline controls, combinated with clinical information, the mutation profile of genes from high-risk asymptomatic myeloma to symptomatic myeloma were analyzed, and genes that may be associated with the efficacy and side effects of bortezomib were screened.@*RESULTS@#Except for two patients in whom no peripheral neuropathy was observed after a short treatment period, other patients peripheral neuropathy developed of various degrees during treatment with bortezomib containing chemotherapy, and the vast majority of patients achieved remission after receiving this bortezomib-related chemotherapy regimen. All patients had comparable levels of the inherited mutations number, but the somatic mutations was correlated with disease evolution.@*CONCLUSION@#different gene "mutational spectra" exist in myeloma patients at different stages and are associated with progression through all stages of the disease.

A retrospective clinical analysis of 17 cases of renal cell carcinoma with Stauffer syndrome / 现代泌尿外科杂志

【Objective】 To explore the diagnosis, treatment and prognosis of renal cell carcinoma (RCC) patients with Stauffer syndrome. 【Methods】 The clinicopathological and follow-up data of 17 RCC patients with Stauffer syndrome who underwent operation during Sep.2014 and Aug.2019 were retrospectively analyzed. The survival was analyzed with Kaplan-Meier curve and log-rank, and related factors affecting the prognosis were determined with univariate and multivariate Cox regression model. 【Results】 The pathological results included clear cell RCC in 14 cases, papillary RCC in 2 cases, and poorly differentiated tissue in 1 case. The liver function recovered within 3 months after operation in 5 cases, within 6 months in 3 cases, within 1 year in 4 cases, and did not recover in 3 cases. During the follow up of 6 to 72 (average 54.1) months, the 1-, 3-, and 5-year survival rates were 88.2% (15/17), 76.5% (13/17) and 52.9% (9/17), respectively. Survival analysis showed that the cancer-specific survival (CSS) of RCC patients with Stauffer syndrome was low, and tumor size, AJCC stage, lymph node metastasis and Stauffer syndrome were predictors of poor prognosis. 【Conclusion】 The prognosis of RCC patients with Stauffer syndrome is poor, and early surgical intervention should be conducted. The liver function of most patients can return to normal gradually after surgery. Continuous examination of liver function has significant meaning for tumor recurrence, metastasis and prognosis.

Expression change and role of Kruppel-like factor 4 mRNA, microRNA-881-3p, circular RNA_20298 and circular RNA_14826 in the hepatocyte apoptosis during the rat liver regeneration / 解剖学报

[ Abstract] Objective To explore the role pathway and pattern of the Kruppel-like factor 4 (KLF4) and its mRNA interaction with microRNA (miRNAs) and circular RNA (circRNAs) at 0 hour and the 120 th hour in the rat liver regeneration. Methods The rat 2 / 3 hepatectomy (partial hepatectomy, PH) model was prepared as described by Higgins, the hepatocytes were isolated according to the method of Smedsrod et al, the expression changes of mRNA, miRNA and circRNA together named as competing endogenous RNA (ceRNA) were detected by the large-scale quantitative detection technology, the interaction network of ceRNA was constructed by Cytoscape 3. 2 software, and their correlation in expression and role were analyzed by ceRNA comprehensive analysis. Results It was found that at the 0 hour and the 120th hour PH, the ratio value of KLF4 mRNA showed 1. 00±0. 16 and 3. 14±0. 27, miR-881-3p displays 18. 30±1. 44 and 0. 47±0. 02, circRNA_20298 indicated 0. 32±0. 10 and 4. 24±0. 22, circRNA_14826 showed 0. 42±0. 13 and 0. 61±0. 08. At the same time, the four kinds of cell apoptosis-related genes adrenoceptor beta 2 (ADRB2), dimethylarginine dimethylaminohydrolase 2 (DDAH2), annexin A5 (ANXA5), ect, which were promoted in expression by KLF4, were down-regulated at 0 hour after PH, but the cell apoptosis-related genes synuclein gamma (SNCG), glutathione-disulfide reductase (GSR), FYVE, RhoGEF and PH domain containing 4 (FGD4), ect, which were inhibited in expression by KLF4, were up-regulated at 0 hour after PH. On the other hand, the cell apoptosis-related genes ANXA5 and thymosin beta 10 (TMSB10), which are promoted in expression by KLF4, were up-regulated at the 120th hour after PH, but the cell apoptosis-related genes chloride intracellular channel 4 (CLIC4) and ataxin 3 (ATXN3), ect, which were inhibited in expression by KLF4, were down-regulated at the 120th hour after PH. Conclusion The correlation in expression and role of the miRNAs, which are inhibited by circRNAs, KLF4, its mRNA is inhibited by miRNAs, and the cell apoptosis-related genes, which are regulated by KLF4, are helpful for the hepatocyte to be in active state 0 hour after PH and to be in apoptotic state 120-hour after PH.

Effect of Morus alba extract sanggenon C on growth and proliferation of glioblastoma cells / 中国中药杂志

Glioblastoma is the most common primary cranial malignancy, and chemotherapy remains an important tool for its treatment. Sanggenon C(San C), a class of natural flavonoids extracted from Morus plants, is a potential antitumor herbal monomer. In this study, the effect of San C on the growth and proliferation of glioblastoma cells was examined by methyl thiazolyl tetrazolium(MTT) assay and 5-bromodeoxyuridinc(BrdU) labeling assay. The effect of San C on the tumor cell cycle was examined by flow cytometry, and the effect of San C on clone formation and self-renewal ability of tumor cells was examined by soft agar assay. Western blot and bioinformatics analysis were used to investigate the mechanism of the antitumor activity of San C. In the presence of San C, the MTT assay showed that San C significantly inhibited the growth and proliferation of tumor cells in a dose and time-dependent manner. BrdU labeling assay showed that San C significantly attenuated the DNA replication activity in the nucleus of tumor cells. Flow cytometry confirmed that San C blocked the cell cycle of tumor cells in G_0/G_1 phase. The soft agar clone formation assay revealed that San C significantly attenuated the clone formation and self-renewal ability of tumor cells. The gene set enrichment analysis(GSEA) implied that San C inhibited the tumor cell division cycle by affecting the myelocytomatosis viral oncogene(MYC) signaling pathway. Western blot assay revealed that San C inhibited the expression of cyclin through the regulation of the MYC signaling pathway by lysine demethylase 4B(KDM4B), which ultimately inhibited the growth and proliferation of glioblastoma cells and self-renewal. In conclusion, San C exhibits the potential antitumor activity by targeting the KDM4B-MYC axis to inhibit glioblastoma cell growth, proliferation, and self-renewal.

Criminological Characteristics and Criminal Responsibility Capacity of Offenders with Alcoholism / 中山大学学报(医学科学版)

ObjectiveTo analyze the criminal behavior characteristics of alcohol-related crime offenders and explore the relationship between criminal behavior characteristics and criminal responsibility capacity. MethodsBasic information， alcohol use information， psychiatric symptoms before and after the crime， criminological behavioral characteristics and conclusion of judicial evaluation were collected. ResultsThe drinking history of the chronic alcoholism group 25.0 （13.3~30.0） years was significantly longer than that of the acute alcoholism group 1.2 （0~14.3） years. In the chronic alcoholism group， 85.0% drank alcohol at least once a day， 52.5% had morning or bedtime drinking habits， and 92.5% drank mainly alone. Violent crimes accounted for 57.6%. Delirium existed in 52.5% of the chronic alcoholics' mental state at the time of the crime， and 84.6% of the acute alcoholics' mental state was hazy. In the chronic alcoholism group， 42.5% committed the crime with pathological motive， and in the acute alcoholism group， 69.2% committed the crime with realistic motive. Acute alcoholism group 96.2% were assessed as complete criminal responsibility capacity， and chronic alcoholism group 50.0% were assessed as complete criminal responsibility capacity. ConclusionCompared with acute alcoholism offenders， chronic alcoholics had a longer drinking duration， more frequency drinking， and obvious morning drinking or bedtime drinking habits. The nature of alcoholism crime cases was mostly violent. Compared with the chronic alcoholism group， the acute alcoholism group had highly selective motives for committing crimes and were mostly rated as complete criminally responsibility.

Efficacy of Bevacizumab Combined with Paclitaxel and Platinum-Based Chemotherapy in Advanced Metastatic Cervical Cancer and Its Effect on T Lymphocyte Subsets and Tumor Markers / 肿瘤防治研究

Objective To investigate the efficacy of bevacizumab combined with paclitaxel and platinum-based chemotherapy in advanced metastatic cervical cancer and its effect on T lymphocyte subsets and tumor markers. Methods Sixty patients with advanced metastatic cervical cancer (treated in our hospital) were randomly divided into control (30 cases) and treatment (30 cases) groups. All patients were given radiotherapy; the control group received paclitaxel and platinum-based chemotherapy, whereas the treatment group received the same with added bevacizumab. The pain conditions (visual analog score (VAS)) and quality of life (Karl Fischer quality of life (KPS)), clinical efficacy, T lymphocyte subset levels (CD3+, CD4+, and CD8+), tumor markers (carbohydrate antigen 125 (CA125), carcinoembryonic antigen (CEA), and squamous epithelial carcinoma-associated antigen (SCCA)) and adverse reactions were compared between the two groups. Results The VAS score, serum CA125, CEA, SCCA, and CD8+ level were significantly reduced in both groups after treatment (P < 0.05), and it significantly decreased in the treatment group compared with the control group (P < 0.05). KPS score, CD3+, and CD4+ levels significantly increased after treatment in the two groups (P < 0.05), and compared with the control group, the treatment group significantly increased (P < 0.05). Moreover, the total effective rate (66.67%) was significantly higher than that in the control group (40.00%) (P < 0.05), and no significant difference existed in the incidence of adverse reactions between the two groups (P > 0.05). Conclusion Bevacizumab combined with paclitaxel and platinum-based chemotherapy can effectively reduce the pain and improve the immune function and quality of life of patients with advanced metastatic cervical cancer. This chemotherapy is also safe and effective.

EGFR mutation, expression of PD-L1/Ki-67 and their correlation with clinical features in elderly NSCLC patients / 中华检验医学杂志

Objective:To investigate the mutation of epidermal growth factor receptor (EGFR), the expression of programmed death ligand 1 (PD-L1), cell proliferation-associated antigen (Ki-67) in elderly patients with non-small cell lung cancer (NSCLC), and their correlation with clinical feature such as gender, histological type and TNM stage.Methods:The tissue samples of 340 elderly NSCLC patients with definite histopathological diagnosis were collected from January 2020 to December 2020 in Huadong Hospital Affiliated to Fudan University, including 195 males and 145 females, age between 68.9±6.0 years. Patients were grouped according to clinical features such as gender, histological type and TNM stage. The expression of EGFR mutation, PD-L1 and Ki-67 were detected by Super-ARMS and immunohistochemistry. The correlation between tnem and clinical features was statistically analyzed, and the correlation between EGFR mutation and PD-L1/Ki-67 expression was further analyzed separately.Results:In elderly NSCLC patients′ tissues, the positive rate of EGFR mutation was 48.53% (165/340). L858R and 19del mutations were the most common types, which were 56.36% (93/165), 30.30% (50/165) respectively. The mutation rate of EGFR was higher in women, lung adenocarcinoma, well-differentiated, and low-stage patients, which were 65.52% (95/145), 53.77% (164/305), 56.75% (143/252), 52.53% (135/257) respectively. In addition, the positive rate of PD-L1 expression was higher in elderly patients with non-adenocarcinoma lung cancer and poorly differentiated adenocarcinoma, which were 37.14% (13/35), 24.53% (13/53) respectively. The negative rate of PD-L1 expression was higher in elderly patients with NSCLC in stage Ⅰ+Ⅱ, no lymph node metastasis and weakly positive Ki-67, which were 89.11% (229/257), 87.63% (248/283), 94.71% (197/208) respectively. Correlation analysis showed that EGFR mutation was negatively correlated with the expression of PD-L1 and Ki-67 (PD-L1: r=-0.22, P<0.001; Ki-67: r=-0.32, P<0.001). Conclusion:There is a negatively correlation between EGFR mutation and the expression of PD-L1 and Ki-67 in elderly NSCLC, suggesting that the combined detection of EGFR mutation and PD-L1 expression could provide the basis for precise targeted therapy for elderly NSCLC patients.

Potential diagnostic and therapeutic targets and anti-tumor mechanisms of Neddylation pathway in digestive system tumors / 中华检验医学杂志

Neddylation,a novel post-translational modification of proteins, is overactivated in digestive system tumors and can be used as a potential anti-tumor molecular target. Targeting Neddylation pathway plays an anti-tumor role by inducing cell cycle arrest, apoptosis, senescence and autophagy of digestive system tumor cells, as well as enhancing the sensitivity of digestive system tumor cells to the radiotherapy and chemotherapy. Targeting Neddylation pathway and its inhibnitor MLN4924 can act as poential targets against digestive system tumors.

Practice of procedure rules of Party committee meeting at tertiary public hospitals based on information platform / 中华医院管理杂志

To strengthen the Party′s overall leadership over public hospitals is the cornerstone to ensure nonprofit and sustainable development of public hospitals.It is a vital guarantee to promote the Party construction work at public hospitals by establishing and improving the hospital′s internal management organization, management system, rules of procedure and handling system. This study aimed to establish the operation system of the rules of procedure of the Party committee meeting of public hospitals by building an office automation platform. This system could connect functions covering topics determination, meeting convening, resolution implementation, and supervision in an effort to achieve a closed-loop management and to realize the controllability, feedback and traceability of the decision-making process. The closed-loop management could not only ensures that the decision-making process be scientific and standardized, but also the decision-making efficiency, for reference in the Party committees of other public hospitals in improving their efficiency and quality of debate and decision making.

Thinking on PBL teaching for health inspection and quarantine undergraduate / 中华医学教育探索杂志

This paper discusses from two aspects of case writing and PBL implementation experience. PBL cases should be based on professional requirements and reflect professional characteristics. Health inspection and quarantine cases targeted at application-oriented talent cultivation can be integrated into relevant experimental skills items. At the same time, the forms of case writing are expanded according to the differences of theme forms, which are designed as parallel cases and serial cases, so as to be applicable to the curriculum integration in different areas. In the implementation of PBL teaching, students' learning status is the key to the efficiency of classroom discussion, which determines whether the implementation of PBL is completely autonomous learning or embedded instruction. Teachers should establish cooperative learning atmosphere to improve the efficiency of classroom discussion

Research on the anti-lung cancer effects of targeted Neddylation modifying pathway and its inhibitor MLN4924 and its mechanism / 国际肿瘤学杂志

Neddylation is overactivated in lung cancer, which promotes the development of lung cancer by activating its downstream CRL ubiquitin ligase and promoting the CRL tumor-suppressor protein substrate degradation. MLN4924, a small molecule inhibitor of Neddylation, plays an anti-lung cancer role by inducing cell cycle arrest, apoptosis and senescence. Furthermore, targeting the key enzymes of Neddylation and their substrates, Cullin family proteins, can inhibit the development of lung cancer.

Mechanism of Potentilla discolor in treating UC by regulating mitochondrial autophagy / 中国中药杂志

To evaluate the therapeutic effect of Potentilla discolor on 2,4,6-trinitrobenzensulfonic acid(TNBS)-induced experimental ulcerative colitis(UC) in rats and to determine its therapeutic mechanism through mitochondrial autophagy, immune cells, and cytokines. A rat model of UC was established by TNBS-ethanol enema. Rats were divided into six groups: control, UC model, sulfasalazine(positive drug), and high-dose, moderate-dose, and low-dose ethanol extract groups. After 14-day continuous administration of the corresponding drugs, the disease activity index(DAI) and hematoxylin and eosin(HE) were evaluated. The morphological structure of mitochondria was observed by using transmission electron microscope(TEM), mitophagy-related mRNA expression was detected by using Real-time quantitative polymerase chain reaction(qRT-PCR), immune cell differentiation in rat serum was detected by using flow cytometry(FCM), and cytokine expression in colon tissues of rats was detected by protein microarray. The results showed that compared with the model group, each dose group of P. discolor could significantly reduce the DAI of UC model rats, and decrease the degree of inflammatory cells infiltration in the colon tissue of UC model rats. Meanwhile the expressions of T cells and Th cells in the serum increased significantly, the expression of Tc cells in the serum decreased significantly. Transmission electron microscope found that there was fusion of mitochondria and lysosomes in the colon tissue of the administration group. The expressions of mitochondrial autophagy related genes NF-κB, p62 and parkin were significantly increased in colon tissues. The results of protein chip showed that compared with the model group, the high dose group of P. discolor could significantly regulate the expression of cytokines. In conclusion, these results suggested that P. discolor improved TNBS-induced acute ulcerative colitis in rats by regulating the mitochondrial autophagy and the inflammatory factor expression.

Progress of cell death induced by Neddylation modification pathway inhibitor MLN4924 / 肿瘤研究与临床

Protein ubiquitin-like modification of Neddylation is an important post-translational modification mode of protein to widely regulate cell cycle, growth, development and other biological processes. Recent studies have found that MLN4924, small molecule inhibitor of Neddylation modification, has a significant anti-tumor effect, which can inhibit the tumor growth by inducing cell cycle arrest, senescence and apoptosis, and inhibiting tumor angiogenesis. This paper reviews the related mechanism research of cell programmed death induced by Neddylation modification pathway inhibitor MLN4924.

Hypoglycemic effects of Tibetan medicine Huidouba in STZ-induced diabetic mice and db/db mice / 中草药·英文版

Objective: Huidouba (HDB) is a Chinese folk medicine used to treat diabetes in Sichuan Province, China. Therefore, we investigated the anti-diabetic effects of HDB and its underlying mechanisms. We hypothesized that HDB treatment could enhance glucose tolerance and insulin sensitivity, and thus prevent a hyperglycemia state. Methods: To test the hypothesis, streptozotocin (STZ)-induced diabetic mice and db/db mice, widely used models of hyperglycemia and insulin-resistant diabetes, were either treated with HDB, metformin, or acarbose. Blood glucose, oral glucose tolerance test, insulin tolerance test, pancreatic histopathology and serum biochemistry were detected to assess the hypoglycemic effect of HDB. Results: HDB treatments were found to show the effect in reducing glucose levels. HDB also resulted in a significant reduction in body weight and food intake in the STZ-induced diabetic mouse model. Furthermore, it significantly improved glucose and insulin tolerance in the two diabetic mouse models. Importantly, insulin, glucagon, pancreatic polypeptide, and somatostatin immunohistochemistry revealed that HDB treatment improved the function and the location of the cells in the islets compared with the other two treatments. HDB treatment resulted in significant restoration of islet function. Our results illustrated the underlying mechanism of HDB in the progression of diabetes, and HDB can be an effective agent for the treatment of diabetes. Conclusion: The results of this study suggested that HDB can reduce blood glucose levels in STZ-induced hyperglycemic mice and db/db mice.

Expression and role of CCAAT enhancer binding protein β mRNA, microRNA-369-3p and rno-Rmdn2_0006 of hepatocytes during the rat liver regeneration initiation / 解剖学报

Objective To explore the pathways and patterns which CCAAT/enhancer binding protein β(CEBPβ) mRNA, miR-369-3p and rno-Rmdn2_0006 regulate the hepatocytes in G

Effects of tetrandrine on proliferation, migration, and invasion of glioblastoma cells / 中国中药杂志

Glioblastoma is the most common intracranial primary malignant tumor, which leads to the poor quality of life of patients and has a high recurrence rate. Chemotherapy is a vital part in the treatment of this disease. Tetrandrine(Tet) is an active ingredient extracted from the root of the Chinese medicinal plant Stephania tetrandra, which has been proved with a wide range of pharmacological effects including anti-tumor. However, there are few studies regarding the effect of Tet on glioma. In this study, MTT and BrdU assays were employed to detect the effect of Tet on the proliferation of LN229 glioblastoma cells; flow cytometry was used to analyze the cycle distribution and apoptosis; plate cloning assay and soft agar colony formation assay were performed to study the colony formation ability of LN229 cells exposed to Tet; scratch assay and Transwell assay were conducted to detect the ability of migration and invasion; Western blot was adopted to the exploration of the molecular mechanism. The MTT and BrdU assays showed that Tet inhibited the proliferation of LN229 cells in a time-and dose-dependent manner. The plate cloning assay and soft agar colony formation assay showed that Tet weakened the colony formation of LN229 cells in vitro; cytometry assay showed that Tet blocked cells in the G_1 phase and promoted cell apoptosis; scratch and Transwell assays proved that Tet inhibited the migration and invasion of LN229 cells; Western blot results showed that Tet down-regulated the expression levels of CDK2, CDK6, cyclin D1, cyclin E1, snail, slug, vimentin, and N-cadherin, while up-regulated the level of E-cadherin. The results indicate that Tet has a certain inhibitory effect on the proliferation, migration, and invasion of LN229 glioblastoma cells, and such effect may be related to the participation of Tet in the regulation of c-Myc/p27 axis and snail signaling pathway.

Clinical application of circulating tumor cells in the diagnosis and treatment of urothelial carcinoma / 中华检验医学杂志

Objective:To study the correlation between circulating tumor cells (CTC) and the degree of pathological invasion, recurrence and metastasis of urothelial carcinoma, and so to explore the clinical value of CTC detection in bladder cancer.Methods:A total of 142 patients with urothelial carcinoma in Huadong Hospital Affiliated to Fudan University were enrolled as cancer group from July 2016 to January 2018. According to the degree of tumor invasion, cancer group was divided into the non-muscle-invasive group (49 cases) and the muscle-invasive group(93 cases). In addition, 52 patients with benign urinary tract lesions admitted were selected as the benign group and 56 patients with non-urinary tract diseases and non-tumor as the control group. A total of 3.2 ml of venous anticoagulant blood from each subject was collected. CTC was enriched by negative enrichment using the magnetic beads coated with monoclonal antibody Cluster 45 of differentiation (CD45) to capture and remove white blood cells, and identified by chromosome 8 probe(CEP8) fluorescence in situ hybridization (FISH) technique. CD45-/4′,6′-diamidino-2-phenylindole+/CEP8>2(CD45-/DAPI+/CEP8>2) cells were judged as CTC. SPSS22.0 statistical software was used for statistical analysis.Results:≥2 CTCs/3.2 ml in blood was set as cutoff value. CTC positive rates in bladder cancer group, benign group and control group were 70.42%(100/142), 28.85%(15/52) and 8.93%(5/56), respectively, and there was a significant difference (χ 2=70.496, P=0.000). There was a statistically difference ( U=2 863.5, P=0.011) in the mean count of CTC(2 CTCs/3.2 ml vs 4 CTCs/3.2 ml) between the two groups. The proportion of≥5 CTCs/3.2 ml in the muscle-invasive group was 40.86% (38/93), which was significantly higher than that in the non-muscle-invasive group, 18.37% (9/49) (χ 2=7.330, P=0.007). Cystoscope follow-up of 65 patients treated with transurethral resection of the bladder tumor showed that the recurrence and metastasis rate in patients with≥5 CTCs/3.2 ml was as high as 47.62% (10/21), compared with 11.36% (5/44) of patients with<5 CTCs/3.2 ml (χ 2=10.530, P=0.001). Among 59 patients undergoing radical cystectomy, no significant difference was found in tumor diameter >3 cm, positive surgical margins and positive lymph nodes among all groups according to CTC negative or positive and CTC number ( P>0.05). But the recurrence and metastasis rate of patients with ≥5 CTCs/3.2 ml (59.10%) was significantly higher than that of patients with <5 CTCs/3.2 ml (6/30)(χ 2=8.364, P=0.004). Conclusion:The number of CTC increased with the deepening of tumor invasion; Tumor recurrence and metastasis increased significantly in the patients with ≥5/3.2 ml CTCs in blood.

The prognostic value of concomitant carcinoma in situ in patients with upper tract urinary carcinoma after radical nephroureterectomy:an systematic review and Meta-analysis / 中华泌尿外科杂志

Objective The aim of this study was to evaluate the influence of concomitant carcinoma in situ (CCIS) on tumor survival for the upper tract urinary carcinoma (UTUC) through systematic review and meta-analysis.Methods In the light of Preferred Reporting Items for Systematic Reviews and Meta-analysis (PRISMA) guidelines,a systematic search of Web of Science,PubMed and EMBASE China National Knowledge Infrastructure (CNKI) and Wanfang database by key words "upper urinary tract urothelial carcinoma"" renal sputum cancer concomitant carcinoma in situ",and "radical ureterectomy" were performed for all reports that included detailed results on the predictors of CCIS.The search deadline is June 2019,and the search terms are English and Chinese.Methodological quality evaluation was performed using the QUIPS tool,and statistical analysis of the relevant data was performed using Stata 12.0 and RevMan 5.3 software.Results Sixteen articles were included in this study and all published between 2012 and 2019.A total of 11 131 patients with UTUC,including 1 774 (15.9％) patients with CCIS.According to our final results,there was a significant correlation of CCIS with worse cancer-specific survival (CSS) (HR =1.10,95％ CI 1.05-1.16,P ＜ 0.001),recurrence-free survival (RFS) (HR =1.15,95％ CI 1.09-1.21,P＜0.001) and overall survival (OS) (HR=1.10,95％CI 1.03-1.17,P=0.003).Begg's bias analysis showed no significant publication bias in CSS (P =0.822),RFS (P =0.348),and OS (P =0.452).Conclusions This study demonstrated that CCIS was associated with poor oncological outcome and could serve as a independent prognostic factor for patient with UTUC after radical nephroureterectomy.

The prognostic value of concomitant carcinoma in situ in patients with upper tract urinary carcinoma after radical nephroureterectomy: an systematic review and Meta-analysis / 中华泌尿外科杂志

Objective@#The aim of this study was to evaluate the influence of concomitant carcinoma in situ (CCIS) on tumor survival for the upper tract urinary carcinoma (UTUC) through systematic review and meta-analysis.@*Methods@#In the light of Preferred Reporting Items for Systematic Reviews and Meta-analysis (PRISMA) guidelines, a systematic search of Web of Science, PubMed and EMBASE China National Knowledge Infrastructure (CNKI) and Wanfang database by key words "upper urinary tract urothelial carcinoma" "renal sputum cancer" "concomitant carcinoma in situ" , and "radical ureterectomy" were performed for all reports that included detailed results on the predictors of CCIS. The search deadline is June 2019, and the search terms are English and Chinese. Methodological quality evaluation was performed using the QUIPS tool, and statistical analysis of the relevant data was performed using Stata 12.0 and RevMan 5.3 software.@*Results@#Sixteen articles were included in this study and all published between 2012 and 2019. A total of 11 131 patients with UTUC, including 1 774 (15.9%) patients with CCIS. According to our final results, there was a significant correlation of CCIS with worse cancer-specific survival (CSS) (HR=1.10, 95%CI 1.05-1.16, P<0.001), recurrence-free survival (RFS) (HR=1.15, 95%CI 1.09-1.21, P<0.001) and overall survival (OS) (HR=1.10, 95%CI 1.03-1.17, P=0.003). Begg′s bias analysis showed no significant publication bias in CSS (P=0.822), RFS (P=0.348), and OS (P=0.452).@*Conclusions@#This study demonstrated that CCIS was associated with poor oncological outcome and could serve as a independent prognostic factor for patient with UTUC after radical nephroureterectomy.