[Participation rate and detection of colorectal neoplasms based on multi-round fecal immunochemical testing for colorectal cancer screening in the Chinese population].

Objective: To evaluate the participation rate and detection of colorectal neoplasms based on annual fecal immunochemical testing (FIT) for three consecutive years in a population-based colorectal cancer screening program in China. Methods: Based on a population-based colorectal cancer screening program conducted from May 2018 to May 2021 in 6 centers in China, 7 793 eligible participants aged 50-74 were included and offered free FIT and colonoscopy (for those who were FIT-positive on initial screening). At baseline, all participants were invited to receive FIT. In subsequent screening rounds, only FIT-positive participants who did not undergo colonoscopy or FIT-negative participants were invited to have repeated FIT screening. FIT-positive participants were recommended to undertake colonoscopy and pathological examination (if abnormalities were found during colonoscopy). An overall of three rounds of annual FIT screening were conducted. The primary outcomes of the study were the participation rate of FIT screening, the compliance rate of colonoscopy for FIT-positive participants, and the detection rate of colorectal neoplasms. Results: Among the 7 793 participants included in this study, 3 310 (42.5%) were male, with age of (60.50±6.49) years. The overall participation rates for the first, second and third round of FIT screening were 94.0%(7 327/7 793), 86.8% (6 048/6 968) and 91.3% (6 113/6 693), respectively. Overall, 7 742 out of 7 793 participants (99.3%) attended at least one round of screening, and 5 163 out of 7 793 participants (66.3%) attended all three rounds of screening. The positivity rate was significantly higher in the first (14.6%, 1 071/7 327) round compared with the second (5.6%, 3 41/6 048) and third (5.5%, 3 39/6 113) screening rounds (P<0.001). The overall compliance rates of colonoscopy examination among FIT-positive subjects were over 70% in three rounds, which were 76.3% (817/1 071), 75.7% (258/341) and 71.7% (243/339), respectively. In a multivariate logistic regression model considering factors including sex, education background, smoking, alcohol drinking, previous colonoscopy examination, colonic polyp history and family history of colorectal cancer among first-degree relatives, gender and smoking status were related factors affecting the participation rate of FIT screening, with higher rate in males and non-smokers. In addition, logistic regression analysis also found that age was negatively correlated with the compliance rate of colonoscopy in FIT positive patients. The detection rate of advanced tumors (colorectal cancer + advanced adenoma) declined from the first round to subsequent rounds [1st round: 1.15% (90/7 793); 2nd round: 0.57% (40/6 968); and 3rd round: 0.58% (39/6 693)], however, the positive predictive value for advanced neoplasms increased round by round, and was 11.02% in the first screening round, 15.50% in the second screening round, and 16.05 % in the third screening round. In each screening round, the detection rate for advanced neoplasms was higher in men than that in women, and increased with age. Conclusions: Annual repeated FIT screening has high acceptance and satisfying detection rates in the Chinese population. To optimize and improve the effectiveness of colorectal cancer screening, multi-round repeated FIT screening should be implemented while ensuring high participation rates.

[Value of fecal immunochemical test in colorectal cancer screening].

Screening and early diagnosis and treatment have been proven effective in reducing the incidence and mortality of colorectal cancer. Colonoscopy combined with pathological examination is the gold standard for colorectal cancer screening. However, due to the invasiveness, high cost and the need for professional endoscopists of colonoscopy, it is not feasible to directly use this method for mass population screening. Fecal immunochemical test (FIT) is one of the screening techniques recommended by authoritative international guidelines for colorectal cancer screening, and has been widely used in population-based colorectal cancer screening programs in countries around the world. This paper elaborates on the value of FIT in colorectal cancer screening from different aspects, such as the technical principles, the screening efficiency, the screening strategies, and the population effects and benefits. Additionally, it describes the current situation of colorectal cancer screening in China and summarizes the challenges faced in colorectal cancer screening in order to optimize the FIT-based colorectal cancer screening strategies in the population and provide theoretical reference for effective colorectal cancer screening.

[Research on applying genetic and environmental risk score in risk-adapted colorectal cancer screening].

Objective: To evaluate the effectiveness of a risk-adapted colorectal cancer screening strategy constructed utilizing genetic and environmental risk score (ERS). Methods: A polygenic risk score (PRS) was constructed based on 20 previously published single nucleotide polymorphisms for colorectal cancer in East Asian populations, using 2 160 samples with MassARRAY test results from a multicenter randomized controlled trial of colorectal cancer screening in China. The ERS was calculated using the Asia-Pacific Colorectal Screening Score system. Logistic regression was used to analyze the association between PRS alone and PRS combined with ERS and colorectal neoplasms risk, respectively. We also designed a risk-adapted screening strategy based on PRS and ERS (high-risk participants undergo a single colonoscopy, low-risk participants undergo an annual fecal immunochemical test, and those with positive results undergo further diagnostic colonoscopy) and compared its effectiveness with the all-acceptance colonoscopy strategy. Results: The high PRS group had a 26% increased risk of colorectal neoplasms compared with the low PRS group (OR=1.26, 95%CI: 1.03-1.54, P=0.026). Participants with the highest PRS and ERS were 3.03 times more likely to develop advanced colorectal neoplasms than those with the lowest score (95%CI: 1.87-4.90, P<0.001). As the risk-adapted screening simulation reached the third round, the detection rate of the PRS combined with ERS strategy was not statistically different from the all-acceptance colonoscopy strategy (8.79% vs. 10.46%, P=0.075) and had a higher positive predictive value (14.11% vs. 10.46%, P<0.001) and lower number of colonoscopies per advanced neoplasms detected (7.1 vs. 9.6, P<0.001). Conclusion: The risk-adapted screening strategy combining PRS and ERS helps achieve population risk stratification and better effectiveness than the traditional colonoscopy-based screening strategy.

[Investigating the effects of Modified Sijunzi Decoction on the diversity of intestinal microflora of severe scald rabbits based on 16S ribosomal RNA high-throughput sequencing].

Objective: To investigate the effects of Modified Sijunzi Decoction on the diversity of intestinal microflora of in severe scald rabbits based on 16S ribosomal RNA (16S rRNA) high-throughput sequencing. Methods: The experimental research method was adopted. Ninety Japanese big-ear rabbits regardless gender, aged 6 to 8 months, were randomly divided into normal control group, scald alone group, scald+low-dose group, scald+medium-dose group, and scald+high-dose group, with 18 rabbits in each group. The rabbits in normal control group were free to eat and drink, and the rabbits in scald alone group, scald+low-dose group, scald+medium-dose group, and scald+high-dose group were intragastrically administered normal saline, 0.2 g/mL Modified Sijunzi Decoction, 1.0 g/mL Modified Sijunzi Decoction, and 5.0 g/mL Modified Sijunzi Decoction, respectively for 7 days after sustaining full-thickness scalding of 30% total body surface area. On the 1st, 3rd, and 7th day after grouping, the levels of tumor necrosis factor α (TNF-α), interleukin 1ß (IL-1ß), and IL-10 in ileal mucosa tissue of rabbits in each group were determined by enzyme-linked immunosorbent assay, and the number of samples in each group at each time point was 6. According to the above experimental results, another 9 rabbits were selected and divided into normal control group, scald alone group and scald+medium-dose group, with 3 rabbits in each group. The grouping and treatment methods of rabbits in each group were the same as before. On the 7th day after grouping, the V3, V4 region of 16S rRNA of ileum mucosa of rabbits in three groups were sequenced by high-throughput sequencing technology. The number of quality bacteria was counted by QIME software. The classifications of phylum, class, order, family and genus of microflora were analyzed by RDP Classifier software. The α diversity (Ace, Chao1, Simpson, and Shannon indexes) and ß diversity were analyzed by Illumina MiSeq sequencing technology, and the number of experiment samples in each group was 3. Data were statistically analyzed with analysis for variance of factorial design, SNK test, and Bonferroni correction. Results: Compared with that in normal control group, the levels of TNF-α of ileal mucosa tissue of rabbits in scald alone group, scald+low-dose group, and scald+high-dose group on the 1st, 3rd, and 7th day after grouping and scald+medium-dose group on the 1st and 3rd day after grouping were all significantly increased (P<0.01), the levels of IL-1ß in ileal mucosa tissue of rabbits in scald alone group, scald+low-dose group, scald+medium-dose group and scald+high-dose group on the 1st, 3rd, and 7th day after grouping were all significantly increased (P<0.05 or P<0.01), and the levels of IL-10 in ileal mucosa tissue of rabbits in scald alone group, scald+low-dose group, scald+medium-dose group, and scald+high-dose group on the 1st, 3rd, and 7th day after grouping were all significantly decreased (P<0.01). Compared with that in scald alone group, the levels of TNF-α in ileal mucosa tissue of rabbits in scald+low-dose group, scald+medium-dose group, and scald+high-dose group on the 3rd and 7th day after grouping, and scald+medium-dose group on the 1st day after grouping were all significantly decreased (P<0.01), and the levels of IL-1ß in ileal mucosa tissue of rabbits in scald+low-dose group, scald+medium-dose group, and scald+high-dose group on the 3rd and 7th day after grouping and scald+medium-dose group on the 1st day after grouping were all significantly decreased (P<0.01), and the levels of IL-10 in ileal mucosa tissue of rabbits in scald+low-dose group on the 7th day after grouping and scald+medium-dose group on the 1st, 3rd, and 7th day after grouping and scald+high-dose group on the 3rd and 7th day after grouping were all significantly increased (P<0.05 or P<0.01). Compared with that in scald+low-dose group, the levels of TNF-α in ileal mucosa tissue of rabbits in medium-dose scald alone group on the 1st, 3rd, and 7th day after grouping and in high-dose scald alone group on the 3rd and 7th day after grouping were significantly decreased (P<0.01), and the levels of IL-1ß in ileal mucosa tissue of rabbits in medium-dose scald alone group on the 1st, 3rd, and 7th day after grouping and in high-dose scald alone group on the 3rd and 7th day after grouping were all significantly decreased (P<0.05 or P<0.01), and the levels of IL-10 in ileal mucosa tissue of rabbits in scald+medium-dose group on the 1st, 3rd, and 7th day after grouping and in scald+high-dose group on the 7th day after grouping were all significantly increased (P<0.05 or P<0.01). Compared with that in scald medium-dose group, the levels of TNF-α in ileal mucosa tissue of rabbits in scald+high-dose group on the 1st, 3rd, and 7th day after grouping were all significantly increased (P<0.01), and the levels of IL-10 in ileal mucosa tissue of rabbits in scald+high-dose group on the 1st, 3rd, and 7th day after grouping were all significantly decreased (P<0.01), and the levels of IL-1ß in ileal mucosa tissue of rabbits in scald+high-dose group on the 7th day after grouping was significantly decreased (P<0.01). Compared with that on the 1st day after grouping, the levels of TNF-α in ileal mucosa tissue of rabbits in scald alone group on the 3rd and 7th day after grouping and in normal control group on the 3rd day after grouping were all significantly increased (P<0.05 or P<0.01), and the levels of IL-1ß in ileal mucosa tissue of rabbits in scald alone group both on the 3rd and 7th day after grouping were significantly increased (P<0.01), and the levels of IL-10 in ileal mucosa tissue of rabbits in both scald+low-dose group and scald+high-dose group on the 7th day after grouping and scald+medium-dose group both on the 3rd and 7th day after grouping were significantly increased (P<0.05 or P<0.01), and the levels of TNF-α in ileal mucosa tissue of rabbits in scald+high-dose group on the 3rd and 7th day after grouping and in scald+medium-dose group on the 7th day after grouping were all significantly decreased (P<0.05 or P<0.01), and the level of IL-1ß in ileal mucosa tissue of rabbits in scald+medium-dose group on the 7th day after grouping was significantly decreased (P<0.01), and the level of IL-10 in ileal mucosa tissue of rabbits in scald alone group on the 7th day after grouping was significantly decreased (P<0.01). Compared with that on the 3rd day after grouping, the levels of TNF-α and IL-1ß in ileal mucosa tissue of rabbits in scald alone group and the levels of IL-10 in ileal mucosa tissue of rabbits in normal control group, scald+low-dose group, scald+medium-dose group, and scald+high-dose group on the 7th day after grouping were all significantly increased (P<0.05 or P<0.01); and the levels of TNF-α in ileal mucosa tissue of rabbits in scald+low-dose group, scald+medium-dose group, and scald+high-dose group on the 7th day after grouping were all significantly decreased (P<0.05), and the levels of IL-1ß in ileal mucosa tissue of rabbits both in scald+medium-dose group and scald+high-dose group on the 7th day after grouping were significantly decreased (P<0.05 or P<0.01), and the levels of IL-10 in ileal mucosa tissue of rabbits in scald alone group on the 7th day after grouping was significantly decreased (P<0.01). On the 7th day after grouping, the high-quality sequences obtained from the microflora in ileum mucosa of rabbits in normal control group, scald alone group, and scald+medium-dose group were 96 023, 107 365, and 95 921, respectively. At the classification level of phylum, class, order, family, and genus of the microflora in ileum mucosa of rabbits in three groups were all Bacteroidetes and Firmicutes, Clostridium and Bacteroidetes, Clostridium and Bacteroidetes, Rumenobacteriaceae and Clostridium and Bacteroideaceae, Clostridium and Bacteroidetes and rumen bacteria mainly, while the percentage of microflora in each group was different. There were no significant differences in Ace, Chao1, Simpson, Shannon indices (P>0.05), and no obvious difference in ß diversity of microflora in ileal mucosa tissue of rabbits among three groups. Conclusions: After severe scalding, the inflammatory response of rabbit ileal mucosa tissue is obvious and increased in a time-dependent manner. Modified Sijunzi Decoction can reduce inflammation with optimal therapeutic concentration of 1.0 g/mL. The technology of high-throughput sequencing can reflect the structural composition of the intestinal microflora accurately. The ileal microflora of the severe scald rabbit can be regulated by the administration of Modified Sijunzi Decoction.

[On-pump total arterial revascularization in coronary artery disease patients with left ventricular dysfunction: a multi-center retrospective study].

Objective: To evaluate the clinical outcomes of on-pump total arterial revascularization with bilateral radial artery (BRA) and left internal mammary artery (LIMA) as conduits in coronary artery bypass grafting (CABG) patients with left ventricular dysfunction (LVD). Methods: All the perioperative medical records and follow-up results of coronary artery disease patients with left ventricular ejection fraction (LVEF) ≤ 40% undergoing CABG from 24 heart centers of 15 provinces and autonomous regions in China between July 2015 and December 2019 were retrospectively analyzed. Results: A total of 87 consecutive patients (55 males and 32 females) underwent on-pump CABG with BRA and LIMA, with a mean age of (57.5±9.1) years old. There were 22 patients complicated with primary hypertension, 12 with diabetes mellitus, 8 with peripheral vascular disease, 7 with chronic obstructive lung disease, 12 with mild renal injury and 3 with partial aortic calcification. There were 43 cases with in-stent stenosis, and 21 had left main disease. The mean LVEF and left ventricular end-diastolic diameter (LVEDD) was (35.5±7.3)% and (65.5±2.6) mm, respectively. The mean graft number, aortic cross-clamp time and cardiopulmonary bypass duration was 3.2±0.9, (90.5±22.7) min and (113.4±19.2) min, respectively. There were 32 mitral and 9 aortic valve replacements, and 5 tricuspid annuloplasties. Prophylactic intra-aortic balloon pumps were implanted in 27 patients. There were 2 operative deaths from acute heart failure. After surgery, there were 15 cases of atrial fibrillation, 1 case of acute kidney injury, 1 case of acute myocardial infarction, and 1 cases of stroke. All the patients fulfilled the follow-up, with a mean time of (39.5±7.7) months. At 3 months after surgery, LVEDD was decreased and LVEF was improved significantly compared with pre-operative indicators [(53.0±1.5) mm vs (65.5±2.6) mm, t=9.51 P=0.02; (45.2±3.3)% vs (35.5±7.3)%, t=13.79, P=0.001]. No major cardiac events were reported during the follow-up. At (30.5±7.4) months after surgery, 62.4% of patients (53/85) underwent coronary CT angiography examination, and the results indicated that the graft patency was 98.8%, with only one case of RA occlusion occurred. Conclusion: In selected patients of LVD, on-pump total arterial revascularization with BRA and LIMA conduits was proved to be safe and effective.

Analysis of a registry database for esophageal cancer from high-volume centers in China.

Esophageal cancer has a high incidence among malignancies in China, but a comprehensive picture of the status of its surgical management in China has hitherto not been available. A nationwide database has recently been established to address this issue. METHOD: A National Database was setup through a network platform, and data was collected from 70 high-volume centers (>100 esophagectomies/per year) across China. Data was entered between January 2009 and December 2014, and was analyzed in June 2015 after a minimal follow-up of 6 months for all patients. 8181 patients with complete data who received surgery for primary esophageal cancer on the Database were included in the analysis. RESULT: In this series, there were 6052 males and 2129 females, with a mean age of 60.5 years (range: 22-90 years). The pathology in 95.5% of patients was squamous cell carcinoma. The pathological stage distribution was 1.2% in stage 0, 2.5% in Ia, 11.5% in Ib, 14.8% in IIa, 36.1% in IIb, 19.3% in IIIa, 8.3% in IIIb, 6.2% in IIIc. 1800 patients (22.0%) with locally advanced disease received preoperative neoadjuvant therapy and 3592 patients (43.9%) underwent postoperative adjuvant chemotherapy and/or radiotherapy. The esophagectomies were performed through left thoracotomy approach in 5870 cases (72.6%), through right chest approach in 2215 cases (27.4%) including right thoracotomy (21.3%) and VATS (6.1%). The 30-day postoperative mortality rate was 0.6% (43 patients), and the overall postoperative complication rate was 11.6% (951 patients). The 1-, 3-, and 5-year overall survival rates were 82.6%, 61.6%, and 52.9%, respectively. CONCLUSION: This National Registry Database from high-volume centers provides a comprehensive picture of surgical management for esophageal cancer in China for the first time. Squamous cell carcinoma predominates, but there is heterogeneity with respect to the surgical approach and perioperative oncologic management. Overall, surgical mortality and morbidity rates are low, and good survival rates have been achieved due to improvement of surgical treatment technology in recent years.

Broadband reflective lens in visible band based on aluminum plasmonic metasurface.

We demonstrate a flat optical lens based on plasmonic reflectarray metasurface, which consists of a planar array of hyperbolic-shaped aluminum (Al) nanoantenna separated from an Al ground plane by a SiO2 spacer. The gradual change in the width of the Al nanoantenna enables unique broadband (400-700 nm) to focus on the visible band because of its hyperbolic reflection-phase profile. The focal length of metalens is quickly decreased with the increase of wavelength in the short wavelength region (400-550 nm), compensating the chromatic aberration in traditional lenses. In long wavelength region (550-700 nm), the focal length has only a slight change, thereby minimizing chromatic aberration. Furthermore, the proposed metalens creates a small focal spot beyond diffraction limit, while maintaining high focusing efficiency. Our method of simple and anisotropic nanoantenna is used to realize wide phase tuning range offers a novel strategy to design braodband metalens, and our metalens has widespread applications in compact camera, telescope, and microscope.

[The association between aflatoxin exposure and primary hepatocellular carcinoma risks: a case-control study in Chongqing].

Objective: To investigate the association between aflatoxin exposure and primary hepatocellular carcinoma (PHC) development. Methods: From December 2013 to May 2016, we selected 214 patients newly diagnosed with PHC as cases, and 214 patients as controls from three hospitals in Chongqing. Cases were confirmed with PHC diagnosis standard. And cases caused by clear reasons such as drug-induced liver injury, alcoholic liver damage, fatty liver and gallstones etiology, were excluded. Controls were included with no cancer and no digestive system disease, and recruited simultaneously with cases. Cases and controls were frequency-matched (1∶1) by same gender and age (±3 years). Peripheral blood and random urine samples were collected and analyzed for serum HBsAg status by biochemistry analyzer, and serum AFB(1)-ALB adduct and urinary AFB(1)-N(7)-GUA adduct by ELISA. Basic information, living habits and history of disease for patients were obtained by questionnaires. We used wilcoxon rank sum test to compare the median of serum AFB(1)-ALB adduct and urinary AFB(1)-N(7)-GUA adduct in cases and controls. Logistic regression analyses were performed to assess risk factors for PHC, and synergism index (S) of aflatoxin with other factors was estimated by the method of Andersson. Results: There was no significant difference in age between PHC cases (50.74±9.67) years and controls (51.15±9.90) years. Logistic regression showed that the odds ratio of HBV infection for PHC development was 46.3 (95% CI: 23.3-88.0). There was a significant difference in median concentrations of serum AFB(1)-ALB adduct (cases vs controls: 146.23 vs 74.42 ng/g albumin, P<0.001), but no difference in median concentrations of urinary AFB(1)-N(7)-GUA adduct was observed (cases vs controls: 0.17 vs 0.14 ng/mg creatinine, P<0.210). The odd ratios for PHC risk after adjustment were 1.9 (95%CI: 1.1-3.4) for AFB(1)-ALB adduct, and 2.1 (95%CI: 1.0-4.2) for AFB(1)-N(7)-GUA adduct. Moreover, we observed a positive interaction of aflatoxin exposure with HBV, alcohol drinking, and diabetes. The S was 4.7 (95%CI: 2.8-7.9), 3.5 (95%CI: 1.0-12.0), and 12.4 (95%CI: 1.8-84.2), respectively for serum AFB(1)-ALB adduct with each of the three factors mentioned, and was 1.9 (95%CI:1.1-3.1), 2.0 (95%CI: 1.1-3.6), and 2.0 (95%CI: 1.1-3.6), respectively for urinary AFB(1)-N(7)-GUA adduct with each of the three factors mentioned. Conclusion: HBV was still the main risk factor, and AFB(1) exposure was also an independent risk factor for PHC in Chongqing. There was a positive interaction of aflatoxin with HBV, alcohol drinking, and diabetes.

Oncogenic activity of amplified miniature chromosome maintenance 8 in human malignancies.

Miniature chromosome maintenance (MCM) proteins play critical roles in DNA replication licensing, initiation and elongation. MCM8, one of the MCM proteins playing a critical role in DNA repairing and recombination, was found to have overexpression and increased DNA copy number in a variety of human malignancies. The gain of MCM8 is associated with aggressive clinical features of several human cancers. Increased expression of MCM8 in prostate cancer is associated with cancer recurrence. Forced expression of MCM8 in RWPE1 cells, the immortalized but non-transformed prostate epithelial cell line, exhibited fast cell growth and transformation, while knock down of MCM8 in PC3, DU145 and LNCaP cells induced cell growth arrest, and decreased tumour volumes and mortality of severe combined immunodeficiency mice xenografted with PC3 and DU145 cells. MCM8 bound cyclin D1 and activated Rb protein phosphorylation by cyclin-dependent kinase 4 in vitro and in vivo. The cyclin D1/MCM8 interaction is required for Rb phosphorylation and S-phase entry in cancer cells. As a result, our study showed that copy number increase and overexpression of MCM8 may play critical roles in human cancer development.

Serum expression level of cytokine and chemokine correlates with progression of human ovarian cancer.

OBJECTIVE: This work was designed to determine the relationship between serum expression level of cytokines and chemokines and progression of human ovarian cancer, and to evaluate the utility and diagnostic value of target markers as risk indicators. MATERIALS AND METHODS: A set of candidate cytokines and chemokines (GM-CSF, IFN-γ, GRO, IL-1ß, IL-2, IL-6, IL-8, MCP-1, TNF-a, VEGF, EGF, RANTES, CCL21/6Ckine, and SDF-1/CXCL12) were measured using Luminex liquid chip technique in healthy women (n=75) and in women with ovarian cancer (n=77). RESULTS: EGF, IL-6, MCP-1, 6Ckine, RANTES, and IL-10 were significantly overexpressed in the tumor group compared to those in normal controls, while IL-2 was reduced. The combined markers (EGF, MCP- 1, 6Ckine, IL-6, and TNF-α) achieved 91.1% sensitivity, 65.8% specificity, and 83.3% area under the ROC curve (AUC) in distinguishing serous ovarian cancer from health controls. CONCLUSION: This study suggested that serum expression level of cytokines and chemokines correlate with progression of human ovarian cancer. The association of EGF, MCP-1, 6Ckine, IL-6, and TNF-α may contribute to increase diagnosis rate of malignant ovarian tumors.

[Clinical and genetic analysis of an infant with isolated 17, 20-lyase deficiency].

OBJECTIVE: To explore the clinical and genetic characteristics of an infant with isolated 17, 20-lyase deficiency. METHOD: The clinical, biochemical and genetic characteristics were analyzed in an 8-month-old infant with 46, XY gonadal dysgenesis who presented predominantly the female external genitalia. RESULT: The infant was referred because of"masses in bilateral inguinal region and 46, XY gonadal dysgenesis". He was normotensive. Laboratory tests revealed elevated levels of progesterone and 17-hydroxyprogesterone. The detailed parameters are as follows: progesterone 29.35(reference range 0.09-1.0)nmol/L, 17-hydroxyprogesterone 10.9(reference range 0.6-2.6)nmol/L, testosterone 0.7(reference range 0.1-3.1)nmol/L, dehydroepiandrosterone sulfate <0.15(reference range 0.80-5.6)mg/L, androstenedione <0.3 (reference range 0.6-3.1) µg/L, luteinizing hormone 6.6(reference range 0.6-1.7)U/L, follicle stimulating hormone 1.8 (reference range 0.5-3.7)U/L, estradiol 37.66(reference range 73.4-146.8)pmol/L. The patient had normal levels of serum sodium, potassium, corticosteroid and plasma adrenocorticotropic hormone. Genomic DNA was extracted from the leukocytes of peripheral blood of the patient and subjected to next generation sequencing (NGS) for testing more than 200 sexual development related genes. Sanger sequencing was used to confirm the results of NGS. Genetic analysis revealed that the patient harbored compound heterozygous mutations of c. 1226C>G (p.Pro409Arg, P409R) and c. 707T>G (p.Val236Gly, V236G) in CYP17A1 gene derived from paternal and maternal allele. V236G was a novel mutation predicted to be pathogenic. The infant was diagnosed as isolated 17, 20-lyase deficiency combined with clinical and molecular characteristics of CYP17A1 gene. CONCLUSION: We have identified the compound heterozygous mutations of P409R and V236G in the CYP17A1 gene in one infant with isolated 17, 20-lyase deficiency. He presented with 46, XY gonadal dysgenesis, normal blood pressure and elevated concentration of progesterone and 17-hydroxyprogesterone.

LZTFL1 suppresses lung tumorigenesis by maintaining differentiation of lung epithelial cells.

Lung cancer is the leading cause of cancer-related death in the United States, and metastatic behavior is largely responsible for this mortality. Mutations in multiple 'driver' oncogenes and tumor suppressors are known to contribute to the lung tumorigenesis and in some cases represent therapeutic targets. Leucine Zipper Transcription Factor-like 1 (LZTFL1) is located in the chromosome region 3p21.3 where allelic loss and genetic alterations occur early and frequently in lung cancers. Previously, we found that LZTFL1 is downregulated in epithelial tumors, including lung cancer, and functions as a tumor suppressor in gastric cancers. However, the functional role of LZTFL1 in lung oncogenesis is undefined. We show here that downregulation of LZTFL1 expression in non-small cell lung cancer is associated with recurrence and poor survival, whereas re-expression of LZTFL1 in lung tumor cells inhibited extravasation/colonization of circulating tumor cells to the lung and inhibited tumor growth in vivo. Mechanistically, we found that LZTFL1 is expressed in ciliated human bronchial epithelial cells (HBECs) and its expression correlates with HBEC differentiation. LZTFL1 inhibits transforming growth factor ß-activated mitogen-activated protein kinase and hedgehog signaling. Alteration of intracellular levels of LZTFL1 resulted in changes of expression of genes associated with epithelial-to-mesenchymal transition (EMT). We conclude that LZTFL1 inhibits lung tumorigenesis, possibly by maintaining epithelial cell differentiation and/or inhibition of signalings that lead to EMT and suggest that reactivation of LZTFL1 expression in tumor cells may be a novel lung cancer therapeutic approach.

EIF5A2 predicts outcome in localised invasive bladder cancer and promotes bladder cancer cell aggressiveness in vitro and in vivo.

BACKGROUND: EIF5A2, eukaryotic translation initiation factor 5A2, is associated with several human cancers. In this study, we investigated the role of EIF5A2 in the metastatic potential of localised invasive bladder cancer (BC) and its underlying molecular mechanisms were explored. METHODS: The expression pattern of EIF5A2 in localised invasive BC was determined by immunohistochemistry. In addition, the function of EIF5A2 in BC and its underlying mechanisms were elucidated with a series of in vitro and in vivo assays. RESULTS: Overexpression of EIF5A2 was an independent predictor for poor metastasis-free survival of localised invasive BC patients treated with radical cystectomy. Knockdown of EIF5A2 inhibited BC cell migratory and invasive capacities in vitro and metastatic potential in vivo and reversed epithelial-mesenchymal transition (EMT), whereas overexpression of EIF5A2 promoted BC cells motility and invasiveness in vitro and metastatic potential in vivo and induced EMT. In addition, we found that EIF5A2 might activate TGF-ß1 expression to induce EMT and drive aggressiveness in BC cells. EIF5A2 stabilized STAT3 and stimulated nuclear localisation of STAT3, which resulted in increasing enrichment of STAT3 onto TGF-ß1 promoter to enhance the transcription of TGF-ß1. CONCLUSIONS: EIF5A2 overexpression predicts tumour metastatic potential in patients with localised invasive BC treated with radical cystectomy. Furthermore, EIF5A2 elevated TGF-ß1 expression through STAT3 to induce EMT and promotes aggressiveness in BC.

AIB1 predicts bladder cancer outcome and promotes bladder cancer cell proliferation through AKT and E2F1.

BACKGROUND: We previously demonstrated that AIB1 overexpression is an independent molecular marker for shortened survival of bladder cancer (BC) patients. In this study, we characterised the role and molecular mechanisms of AIB1 in BC tumorigenicity. METHODS: AIB1 expression was measured by immunohistochemistry in non-muscle-invasive BC tissue and adjacent normal bladder tissue. In addition, the tumorigenicity of AIB1 was assessed with in vitro and in vivo functional assays. RESULTS: Overexpression of AIB1 was observed in tissues from 46 out of 146 patients with non-muscle-invasive BC and was an independent predictor for poor progression-free survival. Lentivirus-mediated AIB1 knockdown inhibited cell proliferation both in vitro and in vivo, whereas AIB1 overexpression promoted cell proliferation in vitro. The growth-inhibitory effect induced by AIB1 knockdown was mediated by G1 arrest, which was caused by reduced expression of key cell-cycle regulatory proteins through the AKT pathway and E2F1. CONCLUSION: Our results suggest that AIB1 promotes BC cell proliferation through the AKT pathway and E2F1. Furthermore, AIB1 overexpression predicts tumour progression in patients with non-muscle-invasive BC.

Laparoscopic excision of a large prostatic utricle revealed by haematuria: 1-year follow-up.

Prostatic utricles revealed by the presentation of haematuria are very rare. Only limited experience with laparoscopic surgery of prostatic utricle has been reported to date. Herein we report a 20-year-old male with frequently terminal haematuria and oligozoospermia who underwent successful laparoscopic excision of a large prostatic utricle. Haematuria disappeared and semen quality improved during 1-year follow-up.

Phosphorylation and interaction of myopodin by integrin-link kinase lead to suppression of cell growth and motility in prostate cancer cells.

Myopodin is a tumor-suppressor gene that suppresses growth of prostate and urothelial carcinomas. However, the mechanism of myopodin tumor-suppressor activity or signaling that leads to activation of myopodin remains unclear. In this report, we showed that the N-terminus of myopodin binds integrin-linked kinase (ILK) both in vivo and in vitro. An ILK interaction motif of 78 amino acids (amino acids 82-157) was identified in the N-terminus region of myopodin. Induction of ILK-dependent kinase activity by integrin α7 led to phosphorylation of myopodin both in vivo and in vitro. Knocking down ILK dramatically reduced the inhibition of cell growth and motility mediated by myopodin. A mutant of myopodin lacking the ILK interaction motif is inactive in suppressing the growth and motility of PC3 cells. As a result, this study showed a novel and critical signaling pathway that leads to activation of myopodin.

Inhibition of prostate cancer growth and metastasis using small interference RNA specific for minichromosome complex maintenance component 7.

Minichromosome complex maintenance component 7 (MCM7) is a critical component of DNA replication licensing. Amplification and overexpression of MCM7 leads to high rate of prostate cancer metastasis. Recent studies indicate that MCM7 genome encodes a putative 'super-oncogene' cluster including MCM7 oncogene and a miRNA cluster that knocks down the expression of several critical tumor-suppressor genes. In this study, we constructed a vector that constitutively expresses small interference RNA (siRNA) specific for MCM7. Introduction of this vector into prostate cancer cell lines PC3 or Du145 decreases the expression of MCM7 by 80%. The vector inhibits DNA synthesis and generates growth arrest of these cancer cells. Severe combined immunodeficient mice were xenografted PC3 or Du145 tumors, and subsequently treated with this vector through tail vein injection with polyethylenimine. The animals had dramatically smaller tumor volume, less metastasis and better survival rate in comparison with the controls. As a result, intervention of MCM7 expression using siRNA approach may hold the promise for treating androgen refractory prostate cancer.

CSR1 induces cell death through inactivation of CPSF3.

CSR1 (cellular stress response 1), a newly characterized tumor-suppressor gene, undergoes hypermethylation in over 30% of prostate cancers. Re-expression of CSR1 inhibits cell growth and induces cell death, but the mechanism by which CSR1 suppresses tumor growth is not clear. In this study, we screened a prostate cDNA library using a yeast two-hybrid system and found that the cleavage and polyadenylation-specific factor 3 (CPSF3), an essential component for converting heteronuclear RNA to mRNA, binds with high affinity to the CSR1 C terminus. Further analyses determined that the binding motifs for CPSF3 are located between amino acids 440 and 543. The interaction between CSR1 and CPSF3 induced CPSF3 translocation from the nucleus to the cytoplasm, resulting in inhibition of polyadenylation both in vitro and in vivo. Downregulation of CPSF3 using small interfering RNA induced cell death in a manner similar to CSR1 expression. A CSR1 mutant unable to bind to CPSF3 did not alter CPSF3 subcellular distribution, did not inhibit its polyadenylation activity and did not induce cell death. In summary, CSR1 appears to induce cell death through a novel mechanism by hijacking a critical RNA processing enzyme.

Pathological factors evaluating prostate cancer.

Prostate cancer is one of the most prevalent malignancies for men world wide. However, only a small fraction of prostate cancer cases are metastasizing and life-threatening. Even though the detection rate of prostate cancer has been steadily increased in the last two decades due to implementation of PSA screening, it is still not clear what factors govern its clinical outcomes. In this review, we will discuss several recent pathological advances that might contribute to the progression of prostate cancer. In addition, this review will cover a brief overview on conventional morphological evaluation of prostate cancer differentiation.