Vitamin D levels in the assessment of Crohn's disease activity and their relation to nutritional status and inflammation.

BACKGROUND: Crohn's disease (CD) is frequently associated with malnutrition, inflammation and a deficiency of vitamin D (VD) with the relationships between these symptoms being poorly defined. VD is a modulator of the immune system and is associated with the onset of CD and disease activity. The level of serum VD may have potential in the assessment of CD activity. This study aimed to evaluate the relationships between VD, nutritional status and inflammation, and to identify more accurate VD thresholds. METHODS: The study included 76 outpatients with CD diagnosed between October 2018 and October 2020 and 76 healthy volunteers. Levels of serum 25(OH)D and nutritional indicators, as well as biochemical and disease activity assessments, were conducted. RESULTS: Patients with CD and healthy participants were found to differ significantly in their 25(OH)D levels as well in levels of nutritional and inflammatory indicators. The optimal VD cut-off value was found to be 46.81 nmol/L for CD development and 35.32 nmol/L for disease activity. Levels of 25(OH)D were correlated with both nutritional status and inflammation. CONCLUSIONS: The VD level is likely to be a useful additional tool in the evaluation of CD patients and predicting the disease activity and clinical response. The VD level may relate both to the nutritional status and levels of inflammation in CD patients, and disease progression.

Lung cancer screening study from a smoking population in Kunming.

OBJECTIVE: Yunnan, China, is a central tobacco-producing region with a large smoking population and an increasing incidence of lung cancer in recent years. This study aimed to understand the incidence of lung cancer and the characteristics of lung nodules on low-dose computed tomography (LDCT) scans of the chest in a long-term smoking population in Kunming. PATIENTS AND METHODS: Long-term smokers in Kunming who were not at risk of evident lung disease symptoms were recruited through recommendation and publicity by the Kunming University of Science and Technology. RESULTS: Among 375 cases eligible for inclusion,14 cases of lung cancer were detected with a detection rate of 3.73% (95% CI: 2.55%-4.27%), including one case of squamous carcinoma, one case of small cell lung cancer, seven cases of adenocarcinoma of the lung and five cases of early-stage lung cancer (35.71%). In the group of < 6 mm solid nodules and < 5 mm non-solid nodules, no lung cancer was detected in 201 cases; lung cancer was detected in 14 cases in 61 cases, and there was a statistical difference between the two groups (p < 0.05). CONCLUSIONS: The lung cancer detection rate in long-term smokers was high, with the type predominantly adenocarcinoma and a high incidence of lung nodules, and increased when solid nodules≥6 mm or non-solid nodules ≥ 5 mm were present. It is recommended that screening for lung cancer by LDCT of the chest be introduced in the male smoking population who meet the risk factors and that screening for lung cancer in women should be redefined as a high-risk factor.

[Effect of occupational factors on pre-diabetes mellitus among iron and steel workers].

Objective: To investigate the prevalence of pre-diabetes mellitus (PDM) and the impact of occupation-related factors on PDM, among workers from a steel company in Tangshan city, Hebei province. Methods: Clustering sampling method was used to select a steel company and to carry out occupational health-related physical checkup programs for eligible workers who had working in this company for longer than one year. The study began in February and ended up in June, 2017. Workers who were with FPG level as ≤6.9 mmol/L, and free from diabetes, were selected as the subjects for this study. Questionnaires were used and physical examinations and FPG testing conducted. Results: The total number of subjects in this study was 4 173, of which 2 648 appeared as pre-diabetic, with the prevalence rate as 63.4%. Increase of the PDM prevalence was in parallel with the length of service, among the workers. The risk for the pre-diabetes in those who worked more than 8 hours per day was 1.696 times higher than those who worked less than or equal to 8 h/d (95%CI:1.517-1.937). Compared with those workers without exposures to heat, noise or carbon monoxides, the proportion of pre-diabetes appeared higher in workers exposed to heat, noise or CO with OR=1.782 (95%CI: 1.205-2.636), 1.815 (95%CI: 1.209-2.794) and 1.653 (95%CI: 1.158-2.361), respectively. Risks for those who were exposed to heat or noise were higher than those who were free from exposure to any occupational hazards (OR=2.098, 95%CI: 1.296-3.397). Prevalence rates of pre-diabetes in those who were exposed to heat, noise or CO, were higher than that those who were not. Conclusion: Working hours and exposures to heat, noise or CO appeared as influential factors on PDM.

Overexpression of maelstrom promotes bladder urothelial carcinoma cell aggressiveness by epigenetically downregulating MTSS1 through DNMT3B.

We have recently identified and characterized a novel oncogene, maelstrom (MAEL) from 1q24, in the pathogenesis of hepatocellular carcinoma. In this study, MAEL was investigated for its oncogenic role in urothelial carcinoma of the bladder (UCB) tumorigenesis/aggressiveness and underlying molecular mechanisms. Here, we report that overexpression of MAEL in UCB is important in the acquisition of an aggressive and/or poor prognostic phenotype. In UCB cell lines, knockdown of MAEL by short hairpin RNA is sufficient to inhibit cell growth, invasiveness/metastasis and suppressed epithelial-mesenchymal transition (EMT), whereas ectopic overexpression of MAEL promoted cell growth, invasive and/or metastatic capacity and enhanced EMT both in vitro and in vivo. We further demonstrate that MAEL could induce UCB cell EMT by downregulating a critical downstream target, the metastasis suppressor 1 (MTSS1) gene, ultimately leading to an increased invasiveness of cancer cells. Notably, overexpression of MAEL in UCB cells substantially enhanced the enrichment of DNA methyltrans-ferase (DNMT)3B and histone deacetylase (HDAC)1/2 on the promoter of the MTSS1, and thereby epigenetically suppressing the MTSS1 transcription. Downregulation of MTSS1 by MAEL in UCB cells is partially dependent on DNMT3B. Furthermore, we identify that beside the gene amplification of MAEL, miR-186 is a key negative regulator of MAEL and downregulation of miR-186 is another important mechanism for MAEL overexpression in UCBs. These data suggest that overexpression of MAEL, caused by gene amplification and/or decreased miR-186, has a critical oncogenic role in UCB pathogenesis by downregulation of MTSS1, and MAEL could be used as a novel prognostic marker and/or effective therapeutic target for human UCB.

Effects of flurbiprofen axetil on postoperative serum IL-2 and IL-6 levels in patients with colorectal cancer.

We explored the effects of flurbiprofen axetil on interleukin (IL)-2 and IL-6 levels in postoperative patients with colorectal cancer. A total of 120 patients (American Society of Anesthesiologists I and II) scheduled to undergo colorectal cancer surgery were randomly divided into 3 groups (N = 40 in each group): flurbiprofen axetil group (group F), morphine group (group M), and tramadol group (group T). Group M received 0.1 mg/kg morphine, group T received 1.5 mg/kg tramadol, and group F received 1.5 mg/kg flurbiprofen axetil. Patients in the 3 groups were administered treatments through intravenous injection 10 min before surgery. Serum IL-2 and IL-6 levels were detected. Postoperative adverse reactions were recorded, such as nausea, vomiting, and pruritus. The serum IL-6 level of the 3 groups increased 3 h after surgery. Compared with group M, IL-6 level was higher in group T and group F at 1 day after the surgery, and the differences between group M and the other groups were significant (P < 0.05). Moreover, the incidence of adverse reactions was significantly different among 3 groups (P < 0.05). Flurbiprofen axetil promoted the secretion of IL-2 and inhibited IL-6; additionally, flurbiprofen axetil may have a lower incidence of adverse reactions compared to other treatments.

A novel simple phantom for verifying the dose of radiation therapy.

A standard protocol of dosimetric measurements is used by the organizations responsible for verifying that the doses delivered in radiation-therapy institutions are within authorized limits. This study evaluated a self-designed simple auditing phantom for use in verifying the dose of radiation therapy; the phantom design, dose audit system, and clinical tests are described. Thermoluminescent dosimeters (TLDs) were used as postal dosimeters, and mailable phantoms were produced for use in postal audits. Correction factors are important for converting TLD readout values from phantoms into the absorbed dose in water. The phantom scatter correction factor was used to quantify the difference in the scattered dose between a solid water phantom and homemade phantoms; its value ranged from 1.084 to 1.031. The energy-dependence correction factor was used to compare the TLD readout of the unit dose irradiated by audit beam energies with (60)Co in the solid water phantom; its value was 0.99 to 1.01. The setup-condition factor was used to correct for differences in dose-output calibration conditions. Clinical tests of the device calibrating the dose output revealed that the dose deviation was within 3%. Therefore, our homemade phantoms and dosimetric system can be applied for accurately verifying the doses applied in radiation-therapy institutions.

MiR-29c mediates epithelial-to-mesenchymal transition in human colorectal carcinoma metastasis via PTP4A and GNA13 regulation of ß-catenin signaling.

BACKGROUND: Distant metastasis is the major cause of cancer-related death, and epithelial-to-mesenchymal transition (EMT) has a critical role in this process. Accumulating evidence indicates that EMT can be regulated by microRNAs (miRNAs). miR-29c has been implicated as a tumor suppressor in several human cancers. However, the role of miR-29c in the progression of colorectal cancer (CRC) metastasis remains largely unknown. PATIENTS AND METHODS: The expression of miR-29c was examined by qRT-PCR in a cohort of primary CRC (PC) and distant liver metastasis (LM) tissues. A series of in vivo and in vitro assays were carried out in order to elucidate the functions of miR-29c and the molecular mechanisms underlying the pathogenesis of metastatic CRC. RESULTS: miR-29c was markedly downregulated in PCs with distant metastasis and determined to be an independent predictor of shortened patient survival. But LM tissues showed higher levels of miR-29c than that in PC tissues. In CRC cells, miR-29c dramatically suppressed cell migration and invasion abilities in vitro and cancer metastasis in vivo. In addition, miR-29c inhibited EMT and negatively regulated Wnt/ß-catenin signaling pathway. Guanine nucleotide binding protein alpha13 (GNA13) and protein tyrosine phosphatase type IVA (PTP4A) were identified as direct targets of miR-29c, which acted through ERK/GSK3ß/ß-catenin and AKT/GSK3ß/ß-catenin pathways, respectively, to regulate EMT. Furthermore, significant associations between miR-29c, its target genes (GNA13 and PTP4A) and EMT markers were validated in both PC and LM tissues. CONCLUSION: Our findings highlight the important role of miR-29c in regulating CRC EMT via GSK-3ß/ß-catenin signaling by targeting GNA13 and PTP4A and provide new insights into the metastatic basis of CRC.

Dose distributions of an ¹9²Ir brachytherapy source in different media.

This study used MCNPX code to investigate the brachytherapy (192)Ir dose distributions in water, bone, and lung tissue and performed radiophotoluminescent glass dosimeter measurements to verify the obtained MCNPX results. The results showed that the dose-rate constant, radial dose function, and anisotropy function in water were highly consistent with data in the literature. However, the lung dose near the source would be overestimated by up to 12%, if the lung tissue is assumed to be water, and, hence, if a tumor is located in the lung, the tumor dose will be overestimated, if the material density is not taken into consideration. In contrast, the lung dose far from the source would be underestimated by up to 30%. Radial dose functions were found to depend not only on the phantom size but also on the material density. The phantom size affects the radial dose function in bone more than those in the other tissues. On the other hand, the anisotropy function in lung tissue was not dependent on the radial distance. Our simulation results could represent valid clinical reference data and be used to improve the accuracy of the doses delivered during brachytherapy applied to patients with lung cancer.

Longikaurin A, a natural ent-kaurane, induces G2/M phase arrest via downregulation of Skp2 and apoptosis induction through ROS/JNK/c-Jun pathway in hepatocellular carcinoma cells.

Hepatocellular carcinoma (HCC) is the most common form of primary liver cancer, and is also highly resistant to conventional chemotherapy treatments. In this study, we report that Longikaurin A (LK-A), an ent-kaurane diterpenoid isolated from the plant Isodon ternifolius, induced cell cycle arrest and apoptosis in human HCC cell lines. LK-A also suppressed tumor growth in SMMC-7721 xenograft models, without inducing any notable major organ-related toxicity. LK-A treatment led to reduced expression of the proto-oncogene S phase kinase-associated protein 2 (Skp2) in SMMC-7721 cells. Lower Skp2 levels correlated with increased expression of p21 and p-cdc2 (Try15), and a corresponding decrease in protein levels of Cyclin B1 and cdc2. Overexpression of Skp2 significantly inhibited LK-A-induced cell cycle arrest in SMMC-7721 cells, suggesting that LK-A may target Skp2 to arrest cells at the G2/M phase. LK-A also induced reactive oxygen species (ROS) production and apoptosis in SMMC-7721 cells. LK-A induced phosphorylation of c-Jun N-terminal kinase (JNK), but not extracellular signal-regulated kinase and P38 MAP kinase. Treatment with, the JNK inhibitor SP600125 prevented LK-A-induced apoptosis in SMMC-7721 cells. Moreover, the antioxidant N-acetylcysteine prevented phosphorylation of both JNK and c-Jun. Taken together, these data indicate that LK-A induces cell cycle arrest and apoptosis in cancer cells by dampening Skp2 expression, and thereby activating the ROS/JNK/c-Jun signaling pathways. LK-A is therefore a potential lead compound for development of antitumor drugs targeting HCC.

EZH2 supports nasopharyngeal carcinoma cell aggressiveness by forming a co-repressor complex with HDAC1/HDAC2 and Snail to inhibit E-cadherin.

The enhancer of zeste homolog 2 (EZH2) is upregulated and has an oncogenic role in several types of human cancer. However, the abnormalities of EZH2 and its underlying mechanisms in the pathogenesis of nasopharyngeal carcinoma (NPC) remain unknown. In this study, we found that high expression of EZH2 in NPC was associated closely with an aggressive and/or poor prognostic phenotype (P<0.05). In NPC cell lines, knockdown of EZH2 by short hairpin RNA was sufficient to inhibit cell invasiveness/metastasis both in vitro and in vivo, whereas ectopic overexpression of EZH2 supported NPC cell invasive capacity with a decreased expression of E-cadherin. In addition, ablation of endogenous Snail in NPC cells virtually totally prevented the repressive activity of EZH2 to E-cadherin, indicating that Snail might be a predominant mediator of EZH2 to suppress E-cadherin. Furthermore, co-immunoprecipitation (IP), chromatin IP and luciferase reporter assays demonstrated that in NPC cells, (1) EZH2 interacted with HDAC1/HDAC2 and Snail to form a repressive complex; (2) these components interact in a linear fashion, not in a triangular fashion, that is, HDAC1 or HDAC2 bridge the interaction between EZH2 and Snail; and (3) the EZH2/HDAC1/2/Snail complex could closely bind to the E-cadherin promoter by Snail, but not YY1, to repress E-cadherin. The data provided in this report suggest a critical role of EZH2 in the control of cell invasion and/or metastasis by forming a co-repressor complex with HDAC1/HDAC2/Snail to repress E-cadherin, an activity that might be responsible, at least in part, for the development and/or progression of human NPCs.

Anthracyclines disrupt telomere maintenance by telomerase through inducing PinX1 ubiquitination and degradation.

Telomere maintenance is essential for cancer growth. Induction of telomere dysfunction, for example, by inhibition of telomeric proteins or telomerase, has been shown to strongly enhance cancer cells' sensitivity to chemotherapies. However, it is not clear whether modulations of telomere maintenance constitute cancer cellular responses to chemotherapies. Furthermore, the manner in which anti-cancer drugs affect telomere function remains unknown. In this study, we show that anthracyclines, a class of anti-cancer drugs widely used in clinical cancer treatments, have an active role in triggering telomere dysfunction specifically in telomerase-positive cancer cells. Anthracyclines interrupt telomere maintenance by telomerase through the downregulation of PinX1, a protein factor responsible for targeting telomerase onto telomeres, thereby inhibiting telomerase association with telomeres. We further demonstrate that anthracyclines downregulate PinX1 by inducing this protein degradation through the ubiquitin-proteasome-dependent pathway. Our data not only reveal a novel action for anthracyclines as telomerase functional inhibitors but also provide a clue for the development of novel anti-cancer drugs based on telomerase/telomere targeting, which is actively investigated by many current studies.

Diagnosing the combination of renal dysgenesis, Gartner's duct cyst and ipsilateral müllerian duct obstruction.

PURPOSE: We describe the differential points in the diagnosis of the combination of renal dysgenesis, Gartner's duct cyst and ipsilateral müllerian duct obstruction. Various imaging studies and urological procedures were performed. We report our experience in detecting these anomalies in 10 girls and review the literature. MATERIALS AND METHODS: Ten girls, 7 to 13 years old, with this combination of anomalies were identified in the last 10 years. Imaging studies as well as urological procedures were selectively performed, especially at puberty following menarche. Patients received long-term followup with ultrasound. RESULTS: Cystic dilation of Gartner's duct protruded into the bladder and presented as a ureterocele in 5 patients and posterior to the bladder in 5. Surgical removal of a partial portion of a Gartner's duct cyst was performed in 5 patients for alleviation of urinary symptoms. Unilateral müllerian duct obstruction was demonstrated in all 10 patients. Excision of the vaginal septum was performed in 6 patients for relief of genital obstruction. CONCLUSIONS: When cystic dilatation of the pelvis, especially a ureterocele-like cyst without ureteral dilatation, is found in girls with ipsilateral renal dysgenesis, the possibility of a Gartner's duct cyst should be considered. For early detection and treatment of unilateral obstruction of duplicated müllerian ducts pelvic sonography should be performed at puberty, especially just after menarche, in girls with renal dysgenesis and ipsilateral Gartner's duct cyst.

A giant retroperitoneal ganglioneuroma with intraspinal involvement: report of one case.

A 9-year-old girl was discovered to have had a huge retroperitoneal mass causing moderate hydronephrosis and anterior displacement of the right kidney and which was found on a renal ultrasonographic examination. A series of examinations including (1)IVP, (2) abdominal computed tomography, (3) MRI and(4) incisional biopsy revealed a giant dumb-bell shaped retroperitoneal ganglioneuroma with intraspinal involvement. Secondary scoliosis was also noticed. We successfully resected the huge ganglioneuroma of the right retroperitoneum in a two stage procedure: her postoperative course was uneventful.

Ultrasonic demonstration of ectopic urethral ureter in duplex kidney: report of two cases.

Two cases of duplex kidney with ectopic urethral ureter are reported. Using abdominal ultrasound, the poorly functioning upper pole pelvis of the involved kidney was found to be sonolucent which may have been misinterpreted for a simple renal cyst. The corresponding ureter was dilated and drained into the proximal urethra. Ultrasound is an ideal imaging modality in the assessment of children with a duplicated renal system and may provide detailed information about this structural anomaly, such as the exact insertion of the ectopic ureter.

Splenic cysts in children.

Splenic cysts were found, incidentally, in eight children during the past nine years (1987-1995) in Taipei Municipal Women's and Children's Hospital. Five of the children were boys and three were girls. The age at diagnosis ranged from 8 to 15 years. Evidence of possible splenic cyst development was found initially by ultrasonography; six patients received further evaluation with computerized tomography (CT); one patient received radionuclide scanning. The cysts ranged from 2 cm to 14 cm in diameter. Four of the patients received surgical treatment (three partial splenectomy and one total splenectomy) because of huge splenic cysts (diameter > 10 cm). Subsequent pathological examination revealed that all cysts had epithelial cell lining in the cyst wall, meaning they were all congenital in origin. The remaining four cases were followed up at the Out-patient Clinic here. All cases had a benign clinical course.

Mediastinal lymphangioma in an infant.

Lymphangioma confined exclusively to the mediastinum occurs rarely in patients under 2 years of age. A 17-month-old girl presented with recurrent respiratory symptoms and signs. Chest radiographs taken at 9 and 17 months of age showed a large mediastinal mass, which had increased in size during the interval. Sonography revealed the mass to be cystic and multiloculated. Magnetic resonance imaging demonstrated a heterogeneous mass lying in the anterior and superior mediastinum and enveloping the great vessels. The child underwent a left thoracotomy and the tumor was almost completely removed. The pathologic diagnosis was cavernous lymphangioma. The postoperative course was uneventful. Lymphangioma, though rare, should be considered in the differential list of mediastinal tumors and cysts in infants.

Ultrasonic detection of single ectopic ureter inserted into the urethra in girls: report of two cases.

Two girls, each with a single ectopic ureter inserted into the proximal urethra, are reported. Abdominal ultrasonography showed that the involved kidneys were small and hydronephrotic. The associated ureters were dilated and opened into the proximal urethra. Diagnosis was confirmed by voiding cystourethrogram.