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Background:. Circulating tumor DNA (ctDNA) is a promising biomarker for non-invasive epidermal growth factor receptor mutations (EGFRm) detection in lung cancer patients, but existing methods have limitations in sensitivity and availability. In this study, we used the ΔCt value (mutant cycle threshold [Ct] value–internal control Ct value) generated during the polymerase chain reaction (PCR) assay to convert super-amplification-refractory mutation system (superARMS) from a qualitative method to a semi-quantitative method named reformed-superARMS (R-superARMS), and evaluated its performance in detecting EGFRm in plasma ctDNA in patients with advanced lung adenocarcinoma. Methods:. A total of 41 pairs of tissues and plasma samples were obtained from lung adenocarcinoma patients who had known EGFRm in tumor tissue and were previously untreated. EGFRm in ctDNA was identified by using superARMS. Through making use of ΔCt value generated during the detection process of superARMS, we indirectly transform this qualitative detection method into a semi-quantitative PCR detection method, named R-superARMS. Both qualitative and quantitative analyses of the data were performed. Kaplan–Meier analysis was performed to estimate the progression-free survival (PFS) and overall survival (OS). Fisher exact test was used for categorical variables. Results:. The concordance rate of EGFRm in tumor tissues and matched plasma samples was 68.3% (28/41). At baseline, EGFRm-positive patients were divided into two groups according to the cut-off ΔCt value of EGFRm set at 8.11. A significant difference in the median OS (mOS) between the two groups was observed (EGFRm ΔCt ≤8.11 vs. >8.11: not reached vs. 11.0 months; log-rank P = 0.024). Patients were divided into mutation clearance (MC) group and mutation incomplete clearance (MIC) group according to whether the ΔCt value of EGFRm test turned negative after 1 month of treatment. We found that there was also a significant difference in mOS (not reached vs. 10.4 months; log-rank P = 0.021) between MC group and MIC group. Although there was no significant difference in PFS between the two groups, the two curves were separated and the PFS of MC group tended to be higher than the MIC group (not reached vs. 27.5 months; log-rank P = 0.088). Furthermore, EGFRm-positive patients were divided into two groups according to the cut-off of the changes in ΔCt value of EGFRm after 1 month of treatment, which was set at 4.89. A significant difference in the mOS between the two groups was observed (change value of ΔCt >4.89 vs. ≤4.89: not reached vs. 11.0 months; log-rank P = 0.014). Conclusions:. Detecting EGFRm in ctDNA using R-superARMS can identify patients who are more likely sensitive to targeted therapy, reflect the molecular load of patients, and predict the therapeutic efficacy and clinical outcomes of patients.

Background This study sought to explore the clinical effects of vancomycin-loaded calcium phosphate cement (CPC) in the treatment of chronic osteomyelitis. Methods Ninety-eight patients with chronic osteomyelitis, who were treated at our Department from December 1st, 2014 to December 1st, 2015, were randomly allocated into the research group or the control group. Each group comprised 49 patients. Patients in the research group (Group A) received a 1-stage treatment of vancomycin-loaded CPC after debridement, while those in the control group (Group B) received an irrigation and drainage device that administered irrigated antibiotics. The treatment effects, recurrence rates, and safety outcomes of the two groups were observed. Results Patients in the two groups were followed up with for a period of 12 months. The control group without recurrence in one case. There was some systemic adverse postoperative effects and safety issues. The X-ray film showed that CPC filling is good and part of the degradation of osteogenesis. Some patients in the research group the CPC particles were absorbed, the bone defect area was healed, after One-year postoperatively. Further, the cure rate was high. Conclusions One-stage vancomycin-loaded CPC implantation osteomyelitis lesions fill the die cavity, enable patients to continue to fight infection, induce bone defect osteogenesis, reduce the recurrence of chronic osteomyelitis, and are an effective method for treating chronic osteomyelitis. Trial registration Chinese Clinical Trial Registry website (ChiCTR2100044724).

Hypoxia-induced inflammation is the critical pathological feature of acute kidney injury (AKI). Activation of hypoxia-inducible factor (HIF) signaling is considered as a central mechanism of body adapting to hypoxia. Hypoxia-inducible factor prolyl hydroxylase inhibitor FG-4592 (Roxadustat) is a first-in-class HIF stabilizer for the treatment of patients with renal anemia. The current study aimed to investigate whether FG-4592 could protect against ischemia/reperfusion (I/R)-induced kidney injury via inhibiting inflammation. Here, efficacy of FG-4592 was evaluated in a mice model of I/R-induced AKI. Interestingly, improved renal function and renal tubular injuries, combined with reduced kidney injury molecule-1 were observed in the mice with FG-4592 administration. Meanwhile, inflammation responses in FG-4592-treated mice were also strikingly attenuated, as evidenced by the decreased infiltration of macrophages and neutrophils and down-regulated expression of inflammatory cytokines. In vitro, FG-4592 treatment significantly protected the tubular epithelial cells against hypoxia-induced injury, with suppressed inflammation and cell injuries. In summary, FG-4592 treatment could protect against the I/R-induced kidney injury possibly through diminishing tubular cells injuries and suppression of sequence inflammatory responses. Thus, our findings definitely offered a clinical potential approach in treating AKI.

Background:. Extra-corporeal video telescope operating monitor system provides a necessary instrument to perform high-precision neurosurgical procedures that could substitute or supplement the traditional surgical microscope. The present study was designed to evaluate a compact high-definition two-dimensional exoscope system for assisting in surgical removal of large vestibular schwannoma (VS), as an alternative to a binocular surgical microscope. Methods:. Patients with Koos grade 3 and grade 4 VS undergoing surgery were enrolled in this prospective cohort study between January 2013 and June 2018. The demographics and tumor characteristics (size, Koos grade, composition [cystic or solid mass]) were matched between the two groups of patients. The following outcome measurements were compared between the two groups: duration of surgery, volume of blood loss, extent of tumor resection, number of operating field adjustments, pre- and post-operative facial and cochlear nerve function evaluated at 3 months post-surgery, complications and surgeons’ comfortability. Results:. A total of 81 patients received tumor resection through the retrosigmoid approach under either an exoscope (cases, n = 39) or a surgical microscope (control, n = 42). Patients in the two groups had comparable tumor location (P = 0.439), Koos grading (P = 0.867), and composition (P = 0.891). While no significant differences in the duration of surgery (P = 0.172), extent of tumor resection (P = 0.858), facial function (P = 0.838), and hearing ability (P = 1.000), patients operated on under an exoscope had less blood loss (P = 0.036) and a fewer field adjustments (P

Introduction: Low molecular weight heparin (LMWH), a natural sulfated glycosaminoglycan with an affinity for proangiogenic factors, is produced by chemical or enzymatic depolymerization of unfractionated heparin (UFH). Known for its anticoagulant effects, LMWH has recently been reported to have a strong anti-inflammatory effect on colitis, myocarditis, and airway inflammation. However, as a newly-developed drug, its anti-inflammatory mechanism in upper respiratory tract inflammation has not been well-studied.Methods: SD rats were randomly divided into control and experimental groups. The experimental group was established by building an acute nasal sinusitis model with expansion sponges mixed with Streptococcus pneumoniae. Then the experimental group rats were subcutaneously injected with different concentrations of LMWH. After seven consecutive days of injection, some rats were sacrificed, and blood and nasal mucosa samples were taken to determine their inflammation status. The remaining acute sinusitis rats were randomly selected for a week of nasal irrigation with normal saline or saline mixed with different concentrations of LMWH. One week later, rats were sacrificed, and samples of blood and nasal mucosa were taken to determine the inflammation status.Results: Rat nasal mucosa in the model group had obvious inflammation. The degree of nasal mucosa inflammation damage in the experimental group was lower than in the experimental control group, proving that LMWH has a protective effect on the nasal mucosa and that the effect correlates with dosage. Irrigation of the nose with saline mixed with LMWH can improve the anti-inflammatory effect. Protein related to the TLR4-MyD88-NF-κB signaling pathway was activated in the acute sinusitis rat model, and LMWH can significantly inhibit its expression.Conclusion: This is the first report of the anti-inflammatory effect of LMWH in acute upper respiratory tract inflammation, together with an explanation of its anti-inflammatory mechanism. The findings contribute a theoretical basis for its potential anti-tumor effect.

BACKGROUND Fabry disease is a kind of lysosomal storage disease resulting from deficient activity of the lysosomal hydrolase alpha-galactosidase A (GLA). A mutation in the GLA gene leads to a loss of activity of alpha-galactosidase A. Some drugs, such as hydroxychloroquine, can cause pathological changes similar to those usually seen in Fabry disease. CASE SUMMARY We report the case of a 41-year-old female patient who was diagnosed with undifferentiated connective tissue disease in 2008. Hydroxychloroquine treatment started 2 years ago, and proteinuria and hematuria increased. Renal biopsy demonstrated renal phospholipidosis. Zebra bodies and myelin figures were found by renal electron microscopy and were initially thought to be indicators of Fabry disease. A genetic analysis of the patient and her family members did not reveal mutations in the GLA gene, supporting a diagnosis of hydroxychloroquine-induced renal phospholipidosis. CONCLUSION This report reveals one of the adverse effects of hydroxychloroquine. We should pay more attention to hydroxychloroquine-induced renal phospholipidosis.

Background Tuberculosis (TB) patient management (TPM) is crucial to improve patient compliance to treatment. The coverage of TPM delivered by TB dispensaries or Centers for Disease Control and Prevention (CDC) was not high under the previous CDC model of TB control in China. In the integrated TB control model in China, TB patient management (TPM) was mainly delivered by lay health workers (LHWs) in primary health care (PHC) sectors. This study aims to investigate TPM delivery in resource-limited western China and to identify factors affecting TPM delivery by LHWs under the integrated TB control model. Methods A stratified random sampling was used to select study sites. Pulmonary TB (PTB) patients ≥15 years old from selected counties/districts in Guizhou Province were surveyed from August 2015 to May 2016. Structured questionnaires were used to collect data. A χ2 test and logistic regression were used to identify factors associated with self-administered treatment (non-TPM). Results In total, 638 PTB patients were included in the final analysis. Close to 30% of patients were ethnic minorities. More than 30% of patients were from counties with high TB burden, and 24.9% of patients had poor compliance to treatment. Only 37.1% of patients received TPM delivered by LHWs under the integrated TB control model throughout the treatment period. The main reasons for unwillingness to manage reported by patients included social stigma and no perceived need. Being ethnic minorities (OR = 3.35) was a main factor associated with lower likelihood of receiving TPM, while living in areas with middle or high TB burden may increase the likelihood of receiving TPM (OR = 0.17 and 0.25, respectively). Among current management approaches, more than 85% of patients chose phone reminder as their preferred TPM by LHWs. Conclusions TPM under the integrated model in West China is still low and need further improvement, and the impeding factors of TPM need to be addressed. Strengthening patient-centered and community-based TPM and developing more feasible approaches of TPM delivery should be explored in future research in this region. Electronic supplementary material The online version of this article (10.1186/s40249-019-0563-3) contains supplementary material, which is available to authorized users.

Isolated genital tuberculosis is rare. We present a case of bilateral tuberculous epididymo-orchitis showing high FDG uptake on FDG PET/CT. In addition, the patient had a prostatic FDG-avid lesion, consistent with tuberculous prostatitis. This case indicates tuberculous epididymo-orchitis, especially in tuberculosis-endemic regions, should be considered as a differential diagnosis in patients with hypermetabolic epididymal or testicular lesions, including benign and malignant tumors, bacterial epididymo-orchitis, abscess, idiopathic granulomatous orchitis, and sarcoidosis.

The extent of lymph node (LN) dissection has been a topic of interest in gastric cancer (GC) surgery. D2 lymphadenectomy is considered the standard surgical procedure for most resectable advanced GC cases. The value and indications of more extended lymphadenectomy than D2 remain unclear. Currently, the controversial stations beyond the D2 range are mainly focused on no. 14v, no. 16a2/b1 and no. 13 LN stations. The metastatic rate of no. 14v LN is relatively high in advanced distal GC, particularly in patients with suspicious no. 6 LN metastasis. D2 plus no. 14v LN dissection may be attributed to improved survival outcomes for patients with obvious no. 6 LN metastasis. Although GC with para-aortic lymph node (PALN) metastases is considered an M1 disease beyond surgical cure, patients with limited PALN metastases may benefit from the treatment strategy of adjuvant chemotherapy followed by D2 plus no. 16a2-b1 LN dissection. In addition, D2 plus no. 13 LN dissection may be an option in a potentially curative gastrectomy for GC with duodenal invasion. The present review discusses the current status and future perspectives of D2 plus lymphadenectomy.

Promising cancer treatment requires the assistant of drug delivery systems (DDS) with the aim to increase the accumulation of drugs in tumor tissue. Herein, a hybrid DDS was successfully developed to integrate chondroitin sulfate (CS) and calcium carbonate (CC) in to one system. Anticancer drug adriamycin (Adr) was preloaded into CC nanoparticles to obtain Adr‐loaded CC nanoparticles (CC/Adr). The resulted CS‐CC/Adr nanoparticles as a biocompatible DDS was able to specifically target cancer cells to enhance the chemotherapy of lung cancer due to the surface modification of CS. Intracellular uptake as well as in vivo imaging results revealed the obtained CS‐CC/Adr nanoparticles (size of ~100 nm) showed CS mediated tumor specific accumulation into A549 and LLC cells than unmodified CC/Adr, in which the CD44 receptor might be involved, which finally resulted in stronger anticancer capability than Adr or CC/Adr. As a result, CS‐CC/Adr nanoparticles could be further extended to clinical administration in our future works.

This review summarizes the results of clinical trials of cell therapy in patients with heart failure (HF). In contrast to acute myocardial infarction (where results have been consistently negative for more than a decade), in the setting of HF the results of Phase I–II trials are encouraging, both in ischaemic and non-ischaemic cardiomyopathy. Several well-designed Phase II studies have met their primary endpoint and demonstrated an efficacy signal, which is remarkable considering that only one dose of cells was used. That an efficacy signal was seen 6–12 months after a single treatment provides a rationale for larger, rigorous trials. Importantly, no safety concerns have emerged. Amongst the various cell types tested, mesenchymal stromal cells derived from bone marrow (BM), umbilical cord, or adipose tissue show the greatest promise. In contrast, embryonic stem cells are not likely to become a clinical therapy. Unfractionated BM cells and cardiosphere-derived cells have been abandoned. The cell products used for HF will most likely be allogeneic. New approaches, such as repeated cell treatment and intravenous delivery, may revolutionize the field. As is the case for most new therapies, the development of cell therapies for HF has been slow, plagued by multifarious problems, and punctuated by many setbacks; at present, the utility of cell therapy in HF remains to be determined. What the field needs is rigorous, well-designed Phase III trials. The most important things to move forward are to keep an open mind, avoid preconceived notions, and let ourselves be guided by the evidence.

Herein, we aimed to investigate the functions of ADAMTS6 in colon cancer and its potential mechanism. Based on the data acquired from TCGA database, we revealed that ADAMTS6 was highly expressed in colon cancer tissues, and high expression of ADAMTS6 predicted worse prognosis in patients with colon cancer. Moreover, qRT-PCR demonstrated that the levels of ADAMTS6 were higher in colon cancer cell lines (NCI-H508, Caco-2, CW-2 and HCT 116) than that in normal control cell line CCD-18Co. Functional experiments displayed that depletion of ADAMTS6 repressed NCI-H508 cell growth, invasion and migration whilst overexpression of ADAMTS6 facilitated Caco-2 cell growth, invasion and migration. Moreover, ADAMTS6 silencing enhanced the protein expression of E-cadherin and reduced the levels of N-cadherin, Vimentin and Snail in NCI-H508 cells, whereas ADAMTS6 overexpression showed the counter effects in Caco-2 cells. The protein levels of p-AKT and p-p65 were decreased by depletion of ADAMTS6 in NCI-H508 cells, while their levels were enhanced by overexpression of ADAMTS6 in Caco-2 cells. These consequences indicated that the accelerating effect of ADAMTS6 on colon cancer cell growth, migration and invasion might be achieved by modulating EMT and AKT/NF-κB signaling pathway, offering important foundations for colon cancer treatment.

Dural amyloidoma is an unusual presentation of central nervous system amyloidosis. A 49-year-old woman presented with 1-month history of repeated episodes of vertigo. Precontrast MRI showed dural thickening over right frontal convexity with signal intensity similar to white matter. Postcontrast T1-weighted images showed remarkable enhancement of the lesion. Dural amyloidoma was confirmed by partial resection of the lesion. The patient underwent no further treatment. A follow-up FDG PET/CT showed increased FDG uptake of the residual dural amyloidoma. This case indicates dural amyloidoma should be included in the differential diagnosis of abnormal FDG uptake in dural lesions.

Background Immediate early response gene 3 (IER3) is a stress-inducible gene, which exerts diverse effects in regulating cell apoptosis and cell cycle. Growing evidence shows that IER3 functions either as an oncogene or a tumor suppressor in various human cancers with a cancer type-dependent manner. However, the involvement of IER3 in human bladder cancer (BCa) has not been elucidated. In the current study, we aimed to investigate the expression pattern and the clinical significance of IER3 in BCa. Methods We performed immunohistochemistry analysis to examine the subcellular localization and the expression levels of IER3 protein in 88 BCa specimens obtained from Department of Pathology in Massachusetts General Hospital. The associations of IER3 protein expression with various clinicopathological features and patients’ overall survival were statistically evaluated. Results IER3 protein was mainly expressed in the cytoplasm in bladder cancer cell. Of 88 BCa tissue specimens, 39 (44.3%) showed high expression of IER3 protein and 49 (55.7%) showed low expression. High IER3 protein expression was significantly associated with high pathologic nodal stage (p = 0.018). Kaplan-Meier analysis revealed that the overall survival of BCa patients with overexpression of IER3 protein was shorter than that with low expression (p

This study aims to investigate the curative effect of synthetic treatment for refractory acute myocardial infarction (AMI).A total of 76 patients with coronary AMI accompanied by shock, who were treated with combined therapy from August 1999 to April 2017, were included into this study. Sixty patients received emergency percutaneous coronary intervention (PCI). Among these patients, 39 patients received intra-aortic balloon counterpulsation (IABP), eight patients had failed PCI underwent emergency off-pump coronary artery bypass (E-OPCAB), and eight patients were treated by hybrid cardiac surgery.All patients were successfully rescued. However, two patients died afterward due to postoperative complications.For AMI patients complicated with shock, especially when emergency PCI fails or is difficult to perform, PCI + IABP, emergency E-OPCAB and hybrid cardiac surgery should be carried out, in order to achieve a good outcome and improve the success rate of rescue for this group of patients.Acute myocardial infarction (AMI); emergency percutaneous coronary intervention (PCI); intra-aortic balloon counterpulsation (IABP); emergency off-pump coronary artery bypass (E-OPCAB); hybrid cardiac surgery.

Internal jugular vein thrombosis (IJVT) is a rare complication of cervical necrotizing fasciitis (CNF) which may lead to life threat. This article reports a patient with severe CNF complicated with IJVT, and combined with the literature to analyze the diagnosis and treatment of CNF and IJVT.

Background Computed tomography (CT)-guided percutaneous implantation of 125Iodine radioactive seeds requires the precise arrangement of seeds by tumor shape. We tested whether selecting target areas, including subclinical areas around tumors, can influence locoregional recurrence in patients with non-small cell lung cancer (NSCLC). Method We divided 82 patients with NSCLC into two groups. Target areas in group 1 (n = 40) were defined along tumor margins based on lung-window CT. Target areas in group 2 (n = 42) were extended by 0.5 cm in all dimensions outside tumor margins. Preoperative plans for both groups were based on a treatment plan system, which guided 125 I seed implantation. Six months later, patients underwent chest CT to evaluate treatment efficacy (per Response Evaluation Criteria in Solid Tumors version 1). We compared locoregional recurrences between the groups after a year of follow-up. We then used the treatment plan system to extend target areas for group 1 patients by 0.5 cm (defined as group 3 data) and compared these hypothetical group 3 planned seeds with the actual seed numbers used in group 1 patients. Results All patients successfully underwent implantation; none died during the follow-up period. Recurrence was significantly lower in group 2 than in group 1 ( P < 0.05). Group 1 patients and group 3 data significantly differed in seed numbers ( P < 0.01). Conclusion Our results imply that extending the implantation area for 125 I seeds can decrease recurrence risk by eradicating cancerous lymph-duct blockades within the extended areas.

Embryo implantation is essential to the successful establishment of pregnancy. A previous study has demonstrated that actinomycin D (ActD) could initiate the activation of mouse delayed implantation. However, the mechanism underlying this activation remains to be elucidated. A low dose of ActD is an inducer of nucleolar stress. This study was to examine whether nucleolar stress is involved in embryo implantation. We showed that nucleolar stress occurred when delayed implantation was activated by ActD in mice. ActD treatment also stimulated the Lif-STAT3 pathway. During early pregnancy, nucleolar stress was detected in the luminal epithelial cells during the receptive phase. Blastocyst-derived lactate could induce nucleolar stress in cultured luminal epithelial cells. The inhibition of nucleophosmin1 (NPM1), which was a marker of nucleolar stress, compromised uterine receptivity and decreased the implantation rates in pregnant mice. To translate these mouse data into humans, we examined nucleolar stress in human endometrium. Our data demonstrated that ActD-induced nucleolar stress had positive effects on the embryo attachment by upregulating IL32 expression in non-receptive epithelial cells rather than receptive epithelial cells. Our data should be the first to demonstrate that nucleolar stress is present during early pregnancy and is able to induce embryo implantation in both mice and humans.

Descending necrotizing mediastinitis (DNM) has been the most common life-threatening complication of multispace infection (MSI) in the maxillofacial region owing to the lack of a timely diagnosis and treatment. We assessed the clinical characteristics and diagnosis of odontogenic MSI and evaluated the risk factors for DNM caused by MSI.We performed a retrospective cohort study of inpatients with MSI in the maxillofacial region from January 2012 to October 2016. The patients were classified into a non-DNM group and a secondary DNM group. The information collected included gender, age, systemic comorbidities, source of maxillofacial infection, computed tomography imaging data, and laboratory test results. Univariate analysis (t test and χA total of 296 patients were included. The mortality was 6.3%. On univariate analysis, the following factors were statistically significant: gender (P = .001); age (P = .003); source of infection (P = .004); number of affected spaces (P .001); involvement of the parotid space (P .001), submandibular space (P .001), subgingival space (P .001), pterygomandibular space (P .001), parapharyngeal space (P .001), and retropharyngeal space (P .001); and percentage of neutrophils (P .001). On multivariate analysis, the parapharyngeal space (P = .008), source of infection (P = .037), and number of affected spaces (P .001) were statistically significant.Glandular infection, parapharyngeal space involvement, and the presence of multiple affected spaces were risk factors for DNM. Clinicians should vigilantly watch for these factors during clinical treatment and effective measures taken to prevent the occurrence of DNM as soon as possible.

BACKGROUND: Descending necrotizing mediastinitis (DNM) is an inflammation occurring in the oropharynx and descending to the deep cervical space and mediastinum, which is a serious infectious disease. The investigation of a new classification system and treatment methods for DNM is still necessary. METHODS: A total of 139 patients with DNM caused by odontogenic or pharyngeal infection were retrospectively analyzed in last 20 years in the Ninth People’s Hospital Affiliated to Shanghai Jiao Tong University School of Medicine. The patients were divided into the traditional treatment Group T (Group T: 43 patients) and the new classification Group N (Group N: 96 patients). A new DNM classification was developed based on the progression of mediastinal infection as follows: type Ia: infection in the anterosuperior mediastinum; type I: infection in the anterior mediastinum; type II: infection in the posterior mediastinum; and type III: infection of the whole mediastinum. RESULTS: There were 49, 8, 10, and 29 patients classified as type Ia, I, II, and III, respectively in the Group N. The type Ia DNM patients were managed with transcervical mediastinal drainage, and the patients with types I and II DNM underwent open (thoracoscopic) surgery, 1 patient within types I died. The 29 patients with type III were managed with unilateral or bilateral open (thoracoscopic) surgery, among them, 8 patients died. The mortality rate for patients with type III DNM was 27.6%. The overall mortality rate in Group N was 9.4%. The mortality rate for patients in the Group T was 25.6%. The mortality rate of Group N was significantly lower than that of Group T (P

OBJECTIVE The new tumor probe 5-([C]-methyloxy)-L-tryptophan ([C]-L-CMTP) had been found to show high uptake in tumor tissue in our previous report; however, the pharmacokinetic properties of [C]-L-CMTP have not been characterized. In this present study, we evaluated the potential of [C]-L-CMTP as a PET probe for tumor imaging. METHODS The biodistribution of [C]-L-CMTP was determined in healthy mice and the incorporation of [C]-L-CMTP into proteins was investigated. In-vitro competitive inhibition experiments were conducted with Hepa1-6 hepatoma cell lines. [C]-L-CMTP PET imaging was performed on S180 tumor-bearing mice and lung tumor-bearing mice. RESULTS Biodistribution studies showed high uptake of [C]-L-CMTP in the liver, kidney, and pancreas, but low uptake in brain. The transport assay studies in Hepa1-6 cells suggested that [C]-L-CMTP was mainly transported by the amino acid transport system B and LAT1. [C]-L-CMTP was not incorporated into proteins in vitro. PET imaging showed that [C]-L-CMTP had high uptake in S180 fibrosarcoma tumor and lung tumor. CONCLUSION [C]-L-CMTP was not incorporated into proteins and was mainly transported by the amino acid transport system B and LAT1, PET imaging showed that [C]-L-CMTP had high uptake in tumor models; it seemed to be a promising PET probe for tumor by LAT1 transport. Video abstract: http://links.lww.com/NMC/A70.

Rationale Gastric cancer usually spread via blood circulation to liver, lung, bone, and kidney after recurrence, but it is extremely rare in clinical practice that gastric carcinoma metastasizes to the skin and colon without metastasis to common sites like liver or lung. Patient concerns A 57-year-old man was admitted to the hospital with altered bowel habit and hematochezia for 2 weeks. Diagnoses The patient was diagnosed with advanced gastric cancer at stage IIIA (pT3N2M0) two and a half years ago. Cutaneous metastasis from gastric cancer was confirmed by cutaneous biopsy 2 years following curative gastrectomy. Unfortunately, colonic metastasis from gastric cancer was found by PET-CT 6 months after the diagnosis of cutaneous metastasis. Interventions The patient was given chemotherapy with docetaxel, cisplatin, and 5-fluorouracil for the skin metastasis. Right hemicolectomy was performed when the malignant tumor of the colon was found, in order to relieve the symptom, and improve the quality of life. Outcomes The patient was treated with chemoradiotherapy in a local hospital, the peritoneal carcinomatosis occurred 5 months after the second operation, and died 9 months after the diagnosis of colonic metastasis. Lessons Our case represents a rare condition that solitary cutaneous and colonic metastasis from gastric cancer can occur after surgical resection and systemic chemotherapy. Its unique clinicopathological features can extend our insights on gastric cancer, and it may provide clinicians with some positive clinical experience for identifying and treating this disease.

Abnormal expression of Holliday junction recognition protein (HJURP) in several types of tumor cells plays a vital role in the formation and progression of tumors. Few studies have investigated the role of HJURP in prostate cancer (PCa). The aim of this study was to analyze the expression levels of HJURP in PCa and to establish the association with clinicopathological data. Reverse transcription quantitative polymerase chain reaction and immunohistochemical analysis were used to detect the expression levels of HJURP in benign and PCa prostate tissues. The Taylor dataset was statistically analyzed to determine if HJURP expression levels were associated with PCa clinicopathological data. HJURP was overexpressed in PCa tissues compared with benign prostate tissues. Statistical analysis of the Taylor dataset indicated that upregulation of HJURP was significantly associated with positive prostate-specific antigen (PSA) levels (P=0.004), high Gleason score (P=0.005), advanced pathological stage (P=0.007), metastasis (P

Background The poorly differentiated renal cell carcinoma (RCC) with rhabdomyosarcomatous sarcomatoid differentiation shows a severely aggressive biological behavior characterized by rapid disease progression. Preoperative identification of the subtype with the prognostic factors and imaging features of sarcomatoid renal cell carcinoma (SRCC) would be of great clinical significance. Case presentation A 45-year-old male patient presented a nine day history of gross hematuria without any other symptoms. A computed tomography (CT) and a full-body fluorine-18 fluoro-2-deoxyglucose (FDG) positron emission tomography (PET) - computed tomography (CT) scan urogram were performed. An initial diagnosis identified a space-occupying lesion of the right kidney, retroperitoneal and right renal hulum lymph node metastases, as well as a space-occupying lesion of the third thoracic vertebra (T3). A right radical nephrectomy was performed. Pathologic analysis revealed poorly differentiated RCC with rhabdomyosarcomatous sarcomatoid differentiation that extends into the renal sinus and the ureteral (T3N1M1). Five days later, the Magnetic Resonance imaging (MRI) evidenced a diffused osseous metastatic disease in the thoracic and lumbar vertebra and multiple retroperitoneal lymph node metastases. The disease progressed quickly to multiple organ dysfunction syndrome (MODS) in half a month and the patient died of respiratory failure two days later. The patient refused any chemoradiotherapy in the hospital. Conclusions Our case presents a SRCC with severe, aggressive, and rapid disease progression. Classifying SRCC imaging features by CT, MRI as well as PET-CT techniques could potentially be helpful for preoperative identification of the subtype. The prognostic factors of SRCC would be of great clinical interest.

Progesterone is required for the establishment and maintenance of mammalian pregnancy and widely used for conservative treatment of luteal phase deficiency in clinics. However, there are limited solid evidences available for the optimal timing and dose of progesterone therapy, especially for the possible adverse effects on implantation and decidualization when progesterone is administrated empirically. In our study, mouse models were used to examine effects of excess progesterone on embryo implantation and decidualization. Our data indicate that excess progesterone is not only harmful for mouse implantation, but also impairs mouse decidualization. In excess progesterone-treated mice, the impaired LIF/STAT3 pathway and dysregulated endoplasmic reticulum stress may lead to the inhibition of embryo implantation and decidualization. It is possible that the decrease in birth weight of excess progesterone-treated mice is due to a compromised embryo implantation and decidualization. Furthermore, excess progesterone compromises in vitro decidualization of human endometrial stromal cells.

AT-rich interaction domain 4A (ARID4A) and AT-rich interaction domain 4B (ARID4B), which are both the AT-rich interaction domain (ARID) family, have been reported to be oncogene or tumor suppressor gene in various human malignances, but there is no involvement about their functions in prostate cancer (PCa). Our previous study has reported that microRNA-30d (miR-30d) expression can predicted poor clinical prognosis in PCa, however, the underlying mechanisms of miR-30d have not been fully described. The aim of our study is to investigate the expression relevance between miR-30d and ARID4A or ARID4B, and examine the clinical significance and biological function of ARID4A and AIRD4B in PCa. In this study, both ARID4A and ARID4B were identified as the target genes of miR-30d. In addition, the mRNA expression of miR-30d in PCa tissues were significantly negative correlated with ARID4A (Pearson correlation coefficient = -0.313, P = 0.001) and ARID4B (Pearson correlation coefficient = -0.349, P

Purpose Descending necrotizing mediastinitis (DNM) is a serious complication of head and neck infections and has an excessively high mortality rate owing to the lack of understanding of DNM. We assessed the clinical characteristics, diagnosis, treatment, and outcomes of odontogenic DNM and evaluated the risk factors affecting the prognosis of DNM to provide an up-to-date overview for clinical practice. Materials and Methods We performed a retrospective cohort study, enrolling a sample of patients with DNM due to odontogenic infection who had been referred from January 2013 to December 2016. The patients were classified into surviving and deceased groups. The primary predictors in the present study were the presence of multiple comorbidities, complications, demographic data (age, gender), laboratory tests (white blood cell count, percentage of neutrophils), and time (duration before diagnosis, length of hospital stay). The primary outcome variable was the patient outcome (dead or alive). The continuous variables were evaluated using Student's t test or the t test, and the categorical and binary variables were compared using the χ2 test or Fisher exact test. Results A total of 81 patients (68 men, 13 women; median age of 57.2 ± 12.2 years) were included. The mortality was 4.9%. The most frequent cause of DNM was periapical periodontitis (66.7%). The lower posterior molars were involved in 39.5% of the cases. Treatment consisted of antibiotic therapy, aggressive transcervical mediastinal drainage (n = 74), and thoracotomy (n = 7). The associated risk factors for mortality were complications (P Conclusions Septic shock and complications were the risk factors that correlated with a poor prognosis. A timely diagnosis and use of aggressive mediastinal drainage are fundamental to reducing the incidence of complications and the development of septic shock in odontogenic DNM patients.

As a member of helix–loop–helix protein family, transcription factor 12 functions as either an oncogene or a tumor suppressor in various human cancers. However, there are no reports on its involvement in prostate cancer. To investigate clinical relevance of transcription factor 12 in prostate cancer and to evaluate its roles in malignant phenotypes of this cancer in vitro and in vivo, we here examined expression patterns of transcription factor 12 protein in 50 prostate cancer tissue specimens by immunohistochemistry. Then, associations of transcription factor 12 expression with various clinicopathological characteristics and patients’ prognosis of prostate cancer were evaluated. Its involvements in cancer cell proliferation, migration, invasion, and tumor growth were determined by in vitro and in vivo experiments. As a result, the positive immunostaining of transcription factor 12 protein was localized in cytoplasm and/or nucleus of prostate cancer cells. Its expression levels were decreased with prostate cancer Gleason score increased. Statistically, the decreased expression of transcription factor 12 protein more frequently occurred in prostate cancer patients with high Gleason score, positive metastasis, prostate-specific antigen failure, and short biochemical recurrence–free survival (all p

Background Even though aberrant expression of microRNA (miR)-30d has been reported in prostate cancer (PCa), its associations with cancer progression remain contradictory. The aim of this study was to investigate clinical significance, biological functions and underlying mechanisms of miR-30d deregulation in PCa. Methods Involvement of miR-30d deregulation in malignant phenotypes of PCa was demonstrated by clinical sample evaluation, and in vitro and in vivo experiments. The mechanisms underlying its regulatory effect on tumor angiogenesis were determined. Results miR-30d over-expression was observed in both PCa cells and clinical specimens. High-miR-30d was distinctly associated with high pre-operative PSA and Gleason score, advanced clinical and pathological stages, positive metastasis and biochemical recurrence (BCR), and reduced overall survival of PCa patients. Through gain- and loss-of-function experiments, we found that miR-30d promoted PCa cell proliferation, migration, invasion, and capillary tube formation of endothelial cells, as well as in vivo tumor growth and angiogenesis in a mouse model. Simulation of myosin phosphatase targeting subunit 1 (MYPT1), acting as a direct target of miR-30d, antagonized the effects induced by miR-30d up-regulation in PCa cells. Notably, miR-30d/MYPT1 combination was identified as an independent factor to predict BCR of PCa patients. Furthermore, miR-30d exerted its pro-angiogenesis function, at least in part, by inhibiting MYPT1, which in turn, increased phosphorylation levels of c-JUN and activated VEGFA-induced signaling cascade in endothelial cells. Conclusions miR-30d and/or its target gene MYPT1 may serve as novel prognostic markers of PCa. miR-30d promotes tumor angiogenesis of PCa through MYPT1/c-JUN/VEGFA pathway.

The aim of this study is to evaluate uptake of 2-(18)F-fluoroethyl-bis(zinc(II)-dipicolylamine) ((18)F-FEN-DPAZn2) as a promising cell death imaging agent, a choline analog (18)F-fluoroethylcholine ((18)F-FECH), (18)F-fluoride as a bone imaging agent, and a glucose analog 2-(18)F-fluoro-2-deoxy-d-glucose ((18)F-FDG) in the combined S180 fibrosarcoma and turpentine-induced inflammation mice models. The results showed that (18)F-FDG had the highest tumor-to-blood uptake ratio and tumor-to-muscle ratio, and high inflammation-to-blood ratio and inflammation-to-muscle ratio. (18)F -FECH showed moderate tumor-to-blood ratio and tumor-to-muscle ratio, and low inflammation-to-blood ratio and inflammation-to-muscle ratio. However, accumulation of (18)F FEN-DPAZn2 in tumor was similar to that in normal muscle. Also, (18)F-FEN-DPAZn2 and (18)F-fluoride exhibited the best selectivity to inflammation. (18)F-FECH positron emission tomography (PET) imaging demonstrates some advantages over (18)F-FDG PET for the differentiation of tumor from inflammation. (18)F FEN-DPAZn2 and (18)F-fluoride can be used for PET imaging of aseptic inflammation.

Small-molecular probe 18F-labeled bis(zinc(II)-dipicolylamine) complex (18F-FB-DPAZn2) was evaluated for PET imaging of sterile inflammation. In comparison with 18F-2-deoxy-β-d-glucose (18F-FDG), 18F-radiolabeled Annexin V (18F-FB-Annexin V) showed rapid clearance of radioactivity from the kidney and low uptake in most tissues. Both the lower radioactivity accumulation in brain and heart and the higher uptakes in the lung, liver, and intestine were observed for the biodistribution of 18F-FB-DPAZn2. In PET imaging, 18F-FDG showed significantly higher tumor and inflammation uptake than did of 18F-FB-DPAZn2 and 18F-FB-Annexin V in the S-180 fibrosarcoma mouse model and sterile inflammation mouse model. Both 18F-FB-DPAZn2 and 18F-FB-Annexin V performed the specifically localization in inflammation, and the ratios of inflammatory lesion-to-muscle and tumor-to-muscle were 1.83 ± 0.20 and 0.90 ± 0.12 (P 0.05) for 18F-FB-Annexin V, respectively. Terminal deoxynucleotide end-labeling (TUNEL) assays performed on the dissected tissues showed the significantly more TUNEL-positive nuclei in the inflammatory muscle than in tumor and normal muscle, and these TUNEL results correlated with the uptake of 18F-FB-DPAZn2 in dissected tissues. Biodistribution and PET imaging studies showed that the 18F-FB-DPAZn2 is suitable for imaging sterile inflammation in vivo and is capable of the differentiating tumor from inflammation.

MicroRNA-30c (miR-30c) acts as a tumor suppressor or a tumor promoter in various human malignancies. However, the involvement of miR-30c in prostate cancer (PCa) is still unclear. The aim of this study was to investigate the molecular function and the clinical significance of miR-30c in PCa. Expression levels of miR-30c in PCa tissues and cells were detected by quantitative real-time-PCR (qRT-PCR). Additionally, the associations of miR-30c expression with clinicopathological features and prognosis in PCa patients were analyzed. The potential role of miR-30c in tumorigenesis of PCa cells was further evaluated by in vitro cell assays. MiR-30c was significantly down-regulated in PCa tissues and cells compared with the corresponding controls (P

Our previous microarray data showed that microRNA-224 (miR-224) was downregulated in human prostate cancer (PCa) tissues compared with adjacent benign tissues. However, the underlying mechanisms by which miR-224 is involved in PCa remain unclear. In this study, we identified TRIB1 as a target gene of miR-224. Forced expression of miR-224 suppressed PCa cell proliferation, invasion and migration, and promoted cell apoptosis by downregulating TRIB1. Moreover, the expression level of miR-224 in PCa tissues was negatively correlated with that of TRIB1. miR-224 downregulation was frequently found in PCa tissues with metastasis, higher PSA level and clinical stage, whereas TRIB1 upregulation was significantly associated with metastasis. Both miR-224 downregulation and TRIB1 upregulation were significantly associated with poor biochemical recurrence-free survival of patients with PCa. In conclusion, these findings reveal that the aberrant expression of miR-224 and TRIB1 may promote PCa progression and have potentials to serve as novel biomarkers for PCa prognosis.

As a typical crowded public place, fatal deaths are caused by ineffective evacuation action in large hospital on account of the special characteristics of occupants in hospital building, i.e., pathological, physiological and psychological behaviour, etc. Large amount of observation by camera and videos, as well as questionnaires were carried out in a SJ Hospital, which is the one of biggest hospitals in Shenyang. Based on that, correlation analysis was carried out between special behavioural characteristics of occupants in hospital and pedestrian walk velocity, as well as the correlation with their evacuation decision behaviour. Furthermore, evacuation simulation in the hospital building was done on the base of the fire dynamics simulation software FDS+Evac developed by NIST, USA. The investigation results illustrate that occupant walks slowly in hospital buildings at a ratio of 70%∼90% comparing with the healthy people in common public buildings. Occupants in hospital building tend to ask help to staffs of the hospital in wayfinding in the case of emergent situations. More than 1/3rd of the occupants are more likely inclined to lose their idea once emergent situation occurs. The evacuation simulation illustrates that egress width and efficient evacuation instructions are the most important strategies in the efficient evacuation in hospital buildings.

We investigated the associations of clinical and socioeconomic factors with delayed orchidopexy for cryptorchidism in China. A retrospective study was conducted on cryptorchid boys who underwent orchidopexy at Children's Hospital at Chongqing Medical University in China from January 2012 to December 2017. Of 2423 patients, 410 (16.9%) received timely repair by 18 months of age, beyond which surgery was considered delayed. Univariate analysis suggested that the laterality of cryptorchidism (P = 0.001), comorbidities including inguinal hernia/scrotal hydrocele (P < 0.001) or urinary tract disease (P = 0.016), and whether patients lived in a poverty county (P < 0.001) could influence whether orchidopexy was timely or delayed. Logistic regression analysis suggested that the following factors were associated with delayed repair: unilateral rather than bilateral cryptorchidism (odds ratio [OR] = 1.752, P < 0.001), absence of inguinal hernia or hydrocele (OR = 2.027, P = 0.019), absence of urinary tract disease (OR = 3.712, P < 0.001), and living in a poverty county (OR = 2.005, P < 0.001). The duration of postoperative hospital stay and hospital costs increased with the patient's age at the time of surgery.

Introduction N -position radiolabeled amino acids, such as N -(2-[ 18 F]fluoropropionyl)-L-methionine ([ 18 F]FPMET) as a derivative of L-methionine (MET), can potentially serve as a PET tracer for tumor imaging. In the current study, radiosynthesis and biological evaluation of [ 18 F]FPMET as a new PET tumor agent are performed. Methods [ 18 F]FPMET was synthesized by reacting 4-nitrophenyl 2-[ 18 F]fluoropropionate ([ 18 F]NFP) with MET. In vitro competitive inhibition and protein incorporation experiments were performed with Hepa1-6 hepatoma cell lines. The biodistribution of [ 18 F]FPMET was determined in S180 fibrosarcoma-bearing mice. PET/CT studies of [ 18 F]FPMET were conducted in S180 fibrosarcoma-bearing mice, A549 lung adenocarcinoma-bearing nude mice, and PC-3 prostate cancer-bearing nude mice. Results [ 18 F]FPMET was synthesized in 72% ± 4% uncorrected radiochemical yield (n = 10) from [ 18 F]NFP. In vitro experiments showed that [ 18 F]FPMET was primarily transported through Na + -dependent system A, system ASC, and system B 0,+ , and was not incorporated into protein. Biodistribution and PET/CT imaging studies indicated that [ 18 F]FPMET could delineate S180 fibrosarcoma, A549 lung adenocarcinoma, and PC-3 prostate cancer. Conclusion An efficient synthesis of N -position [ 18 F]labeled amino acids with a classic [ 18 F]NFP prosthetic group is developed. The results support that [ 18 F]FPMET seems to be a potential tracer for tumor imaging with PET.

A few case-control studies were performed to assess the association between X-ray repair cross-complementing group 3 (XRCC3) rs861539 C/T polymorphism and lung cancer susceptibility, but no consistent finding was reported. In the present study, we performed a meta-analysis of 14 case-control studies with a total of 7,869 lung cancer cases and 10,778 controls to provide a comprehensive assessment of the association between XRCC3 rs861539 C/T polymorphism and lung cancer risk. Pooled odds ratios (ORs) and corresponding 95 % confidence intervals (95 % CIs) were calculated to assess the strength of the association. Overall, there was no significant association between XRCC3 rs861539 C/T polymorphism and lung cancer risk under all genetic models [OR (95 % CI) for T versus C, 1.00 (0.89-1.13), P = 0.99; OR (95 % CI) for TT versus CC, 1.07 (0.81-1.41), P = 0.62; OR (95 % CI) for TT/CT versus CC, 0.95 (0.84-1.07), P = 0.39; OR (95 % CI) for TT versus CT/CC, 1.10 (0.86-1.39), P = 0.62]. In the subgroup analyses of both Asians and Caucasians, there was still no significant association between XRCC3 rs861539 C/T polymorphism and lung cancer risk under all genetic models (All P values were more than 0.05). However, there was an obvious association between XRCC3 rs861539 C/T polymorphism and decreased risk of lung cancer in the subgroup analysis of the mixed population (All P values were less than 0.05). In addition, there was some risk of publication bias in the meta-analysis, and there was obvious discrepancy in the findings between studies with large sample size and studies with small sample size in the meta-analysis. The meta-analysis indicates that the association between XRCC3 rs861539 C/T polymorphism and lung cancer risk is still uncertain owing to the obvious discrepancy in the findings between studies with large sample size and studies with small sample size. More studies with large sample size are needed to further assess the association.

A combination of hematoma aspiration and local delivery of chemicals may be more effective than either therapy in intracerebral hemorrhage (ICH). The aim of the present study was to develop a rat model of hematoma aspiration plus intralesional injection after ICH. ICH was induced in adult Sprague-Dawley rats by an intrastriatal injection of bacterial collagenase IV. Hematoma aspiration was performed 3.5 h after ICH onset. Following aspiration, normal saline was injected into the lesion cavity. Hematoma aspiration with or without subsequent saline injection significantly reduced the hematoma volume, lesion volume, and perihematomal neutrophil infiltration. Hematoma aspiration plus subsequent intralesional injection is simple, feasible, and safe. This ICH model can be used to assess the effectiveness of hematoma removal plus local delivery of chemicals.

Abnormal spindle microtubule assembly (ASPM) gene was known to be linked with poor clinical prognosis in various tumors. However, the clinical significance of ASPM in prostate cancer (PCa) has not yet been understood. The purpose of this study was to determine the association of ASPM with tumor progression and prognosis in PCa patients. The expression of ASPM at protein level in human PCa and non-cancerous prostate tissue was detected by immunohistochemical analysis, which was further validated by using microarray-based dataset (NCBI GEO: GSE21032 and The Cancer Genome Atlas (TCGA) dataset) at mRNA level. Subsequently, the association of ASPM expression with the clinicopathological characteristics of patients with PCa was then statistically analyzed. Immunohistochemistry and dataset analyses revealed that ASPM expression was significantly increased in the PCa tissues with high Gleason score. Additionally, as showed by two datasets, ASPM expression was significantly high expressed in the PCa tissues when compared with the non-cancerous tissues, especially in advanced PCa pathological stage. The upregulation of ASPM mRNA expression in the PCa tissues significantly correlated with the presence of tumor metastasis, shorter overall survival and prostate-specific antigen (PSA) failure. Furthermore, both univariate and multivariate analyses showed that the upregulation of ASPM was a potential predictor of poor biochemical recurrence (BCR)-free survival. Our data suggest that ASPM may play an important role in the progression of PCa. More importantly, the increased expression of ASPM may potentially predict poor BCR-free survival in patients with PCa.

Although rabies virus is widely distributed in the world, and has been the subject of extensive investigations with the objective of its ultimate prevention, control, and management, there is much less knowledge of the characteristics, distribution, and infectivity of other lyssaviruses. Since bats are known animal vectors for all but one of the known lyssavirus genotypes, we have performed an extensive survey of bats in the Guangxi Province to provide information on lyssavirus distribution in southern China. The lyssavirus nucleoprotein gene was detected in brains of 2.86 % of 2,969 bats. Nucleotide sequence homologies among isolates were 86.9–99.6 %, but only 70.0–85.0 % for lyssaviruses in GenBank. These infected bats were detected from a wide area, essentially forming a band running from the south-west to the north-east of Guangxi, and it appears that infection by new lyssaviruses is widespread in this region.

Hedgehog (Hh) pathway has been implicated in the tumorigenesis of a large number of human tumors. But its effects on the progression and prognosis of bladder cancer remain poorly understood. The aim of this study was to investigate expression patterns of Hh pathway components in bladder cancer and to elucidate their prognostic values in this tumor. The expression of sonic hedgehog (Shh), its receptor Patched (Ptch1), and downstream transcription factor Gli1 in 118 specimens of bladder cancer and 30 specimens of adjacent normal bladder tissue was determined by immunohistochemistry. Statistical analyses were applied to test the relationship between the expression of these three proteins and clinicopathologic features and prognosis. Immunohistochemical staining results showed the localizations of Shh and Ptch1 proteins to be mainly located in the cytoplasm of bladder cancer cells, whereas Gli1 was mainly localized in the nuclear of tumor cells. Additionally, positive expression of Shh, Ptch1 and Gli1 proteins was correlated with pathological stage (P = 0.006, 0.006 and 0.008, respectively), venous invasion (P = 0.01, 0.01 and 0.012, respectively) and lymph node metastasis (P = 0.009, 0.01 and 0.013, respectively), but not with other factors including age, gender, tumor grade and recurrence of superficial cancer. Moreover, patients with positive expression of Shh, Ptch1 and Gli1 proteins respectively showed poorer disease-free (P = 0.002, 0.002 and 0.001, respectively) and overall survival (all P

To observe the expression of Nav1.1 and the effect of electroacupuncture therapy (ET) on it after acute cerebral ischemia.Focal acute cerebral ischemic model was established by occluding right middle cerebral artery. One hundred and forty-five male adult Sprague-Dawley rats were randomly divided into four groups: sham operation group, middle cerebral artery occlusion (MCAO) group, ET group and riluzole group. Double immunofluorescence and real-time PCR were used to observe Nav1.1 expression, and TTC staining was used to detect infarct volume at 6 hours, 1 day, 2 days, 3 days and 7 days after ischemia.The expression of Nav1.1 in sham operation group had no change. After ischemia, the expression of Nav1.1 was up-regulated evidently at 6 hours compared with sham operation group, down-regulated at 1 day and up-regulated again from 2 to 7 days after ischemia; the expression at 7 days was lower than that at 6 hours. In ET group and riluzole group, Nav1.1 expression were down-regulated compared with that in MCAO group after ischemia, the infarct volume was smaller than that in MCAO group at the same time point, and the difference is significant (p0.05); however, the difference between ET group and riluzole group is not significant (p0.05).ET and riluzole could regulate the expression of Nav1.1 after ischemia, decrease the infarction volume and reduce cerebral ischemic injury. One of the important mechanisms for ET's cerebral protective function may be that it could regulate the expression of Nav1.1 after ischemia.

Genetic polymorphisms in DNA repair genes may influence individual variation in DNA repair capacity, which may be associated with risk of gastric antrum adenocarcinoma (GAA) related to Helicobacter pylori infection. This study, including 361 GAAs and 616 controls without any evidence of tumors, was designed to evaluate the association between the polymorphisms of DNA repair genes XPC Ala499Val (RS#2228000) and Lys939Gln (RS#2228001), XPD Lys751Gln (RS#13181), and XRCC4 Ala247Ser (RS#3734091) and Ser298Asn (RS#1805377), and GAA risk for Guangxi population by means of TaqMan-PCR analysis. Increased risks of GAA were found for individuals with H. pylori positive [odds ratio (OR), 2.48; 95% confidence interval (CI), 1.84–3.33] or cagA positive (OR, 7.34; 95% CI, 5.46–9.87). No differences were observed among the studied groups with regard to the genotype distribution of XPC codons 499 and 939 and of XRCC4 codon 247; but XPD codon 751 genotypes with Gln [ORs (95% CI) were 2.67 (1.98–3.58) and 3.97 (2.64–5.99) for Lys/Gln and Gln/Gln, respectively] and XRCC4 codon 298 genotypes with Asn [ORs (95% CI) were 3.01 (2.21–4.10) and 4.78 (3.24–7.05) for Ser/Asn and Asn/Asn, respectively] increased the risk of GAA. Interestingly, there was an interactive effect between the risk genotypes of these two genes and cagA-positive status in the GAA risk (ORinteract = 2.05 and 2.08, respectively). However, we did not find the gene–H. pylori-status interaction effects on the risk of GAA (Pinteract > 0.05). The results suggested that the polymorphisms of XPD codon 751 and XRCC4 codon 298 are associated with an increased risk of developing H. pylori-related GAA among Guangxi population. © 2010 Wiley-Liss, Inc.

Aberrant expression of CK20 and Ki-67 has been documented in many kinds of primary tumors and has proved useful as an ancillary diagnostic aid for those tumors. The aim of this study was to analyze the expression patterns of CK20 and Ki-67 in human bladder carcinomas (BCa) and to evaluate their clinical significance in the progression of BCa. CK20 and Ki-67 expression in BCa and normal bladder tissues were detected by immunohistochemical staining. The Spearman correlation was calculated between the expression of CK20 and Ki-67 in BCa tissues. The correlation of CK20 and Ki-67 expression with the clinicopathological characteristics and the prognosis of BCa were subsequently assessed. CK20 expression was positively expressed in 103/154 (66.9%) of BCa and 2/30 (6.67%) of normal bladder tissues, respectively. The positive expression rate of Ki-67 in BCa tissues was also significantly higher than those in normal bladder tissues (81.8 vs. 10%, p < 0.01). The Spearman analysis indicated that the expression level of CK20 has a significant positive correlation with that of Ki-67 (rs = 0.86, p = 0.02). Pathologic findings demonstrated that the intensity of CK20 and Ki-67 staining in cancerous tissues was associated significantly with tumor grades (p = 0.03, p < 0.01), distant metastasis (both p < 0.01) and TNM grades (p = 0.01, p = 0.03) of BCa. The progression-free survival of the patients with CK20 (+)/Ki-67 (+) expression was poorest (p < 0.01). The results suggest that the expression of CK20 and Ki-67 may be an important feature of BCa, and the detection of their co-expression may benefit the prediction of BCa prognosis.

To investigate the clinicopathologic characteristics of extracellular matrix (ECM) metalloproteinase inducer (CD147) and vascular endothelial growth factor (VEGF) expression in advanced renal cell carcinoma (RCC), and to evaluate the clinical significance of these two markers in the prognosis of advanced RCC.CD147 and VEGF expression in paraffin-embedded specimens gathered from 53 patients with advanced RCC and 12 healthy controls were detected by the method of immunohistochemistry. The Spearman correlation was calculated between the expression levels of CD147 and VEGF in advanced RCC tissues. The association of CD147 and VEGF expression with the clinicopathologic features and prognosis of advanced RCC was subsequently assessed.CD147 and VEGF were positively expressed in 47/53 (88.7%) and 45/53 (84.9%) of patients with advanced RCC, respectively. Positive expression of CD147 (p= 0.02) and VEGF (p0.01) was significantly correlated with TNM stage of advanced RCC. A significant correlation was found between the expression of CD147 and VEGF in advanced RCC (r= 0.629, p= 0.04). Additionally, tumor CD147 and tumor VEGF expressions were significantly associated with the prognosis of advanced RCC patients. The survival rate of the patients with CD147-/VEGF- expression was the lowest (p0.01), and conjoined expressions of CD147-/VEGF- and CD147+/VEGF+ were independent prognostic indicators of advanced RCC (both p0.01).The expression of CD147 or VEGF may be an important feature of advanced RCC. A combined detection of CD147/VEGF coexpression may benefit us in the prediction of the prognosis of advanced RCC.

Biomarkers of Hepatitis B Virus (HBV) infection, aflatoxin B1 (AFB1) exposure and oxidative stress were detected in 71 hepatocellular carcinoma (HCC) patients and 694 controls from southern China. Plasma level of AFB1-Albumin-Adducts (AAA) and protein carbonyl content (PCC) were significantly higher in the 71 HCC cases than in any age/gender matched HBV sero-status groups (P

The association between aflatoxin B1 (AFB1) exposure and oxidative stress was extensively examined in 84 adolescents from an area at high risk for hepatocellular carcinoma in China. Plasma level of aflatoxin B1-albumin adducts (AAAs) was associated with AFB1 excretion in urine (r = 0.394, P0.001). Urinary AFB1 was also associated with both the urinary excretion of 8-hydroxydeoxyguanosine (8-OHdG) (ror = 0.479, P0.001) and 8-OHdG and hOGG1 levels in peripheral leukocytes (ror = 0.308, Por = 0.005). Similarly, AAA was significantly associated with both the urinary excretion of 8-OHdG (ror = 0.259, Por = 0.018) and the 8-OHdG and hOGG1 levels in peripheral leukocytes (ror = 0.313, Por = 0.004). In addition, urinary 8-OHdG was correlated with both the level of DNA 8-OHdG (ror = 0.24, Por = 0.05) and the expression of hOGG1 in peripheral leukocytes (ror = 0.429, P0.001). Protein carbonyl content (PCC) level was significantly associated with not only the level of DNA 8-OHdG (ror = 0.366, P0.001) and the urinary 8-OHdG (ror = 0.258, Por = 0.018) but also the expression of hOGG1 in peripheral leukocytes (r = 0.485, P0.001). A significant but weak association was found between high-performance liquid chromatograph-electrochemical detection (HPLC-ECD) and enzyme-linked immunosorbent assay (ELISA) for urinary 8-OHdG (r = 0.334, P = 0.002) and between HPLC-ECD and flow cytometry assays for 8-OHdG in leucocytes (r = 0.395, P0.001). Significant associations were observed between AAA and PCC and liver function indices (alanine aminotransferase and aspartate aminotransferase). These findings suggest significant contribution from AFB1 exposure to oxidative stress and subsequent repair among adolescents that may impose substantial risk for hepatocarcinogenesis in adulthood in this region.

Increased expression of E2F1 has been reported to be associated with tumor growth and cell survival of prostate cancer (PCa). However, its roles and mechanisms on PCa have not been fully elucidated. The present study found that E2F1 overexpression in PCa tissues was significantly associated with high Gleason score (P=0.01) and advanced pathological stage (P=0.02). In addition, PCa patients with high E2F1 expression more frequently had shorter biochemical recurrence-free survival (P=0.047) than those with low E2F1 expression. Then, we confirmed that the knock-down of E2F1 expression was able to inhibit cell cycle progression, invasion and migration of PCa cell lines in vitro, along with tumor xenograft growth and epithelial-to-mesenchymal transition (EMT) in vivo. Moreover, we identified CD147 as a novel interaction partner for E2F1 through bio-informatic binding site prediction, combined with chromatin immunoprecipitation-PCR (ChIP-PCR) and western blot analysis. Taken together, our data delineate an as yet unrecognized function of E2F1 as enhancer of tumor invasion and migration of PCa via regulating the expression of CD147 in PCa. Importantly, E2F1 may function as a biomarker that can differentiate patients with biochemical recurrent and non-biochemical recurrent disease following radical prostatectomy, highlighting its potential as a therapeutic target.

Protein regulator of cytokinesis 1 (PRC1) has been reported to be implicated into the completion of cytokinesis and is dys-regulated in a cancer-specific manner. However, it roles in human prostate cancer (PCa) remain unclear. In the current study, we aimed to investigate the expression pattern of PRC1 and its clinical significance in this malignancy.PRC1 protein expression in human PCa and non-cancerous prostate tissues was detected by immunohistochemistry, which was validated by microarray-based Taylor data at mRNA level. Then, the associations of PRC1 expression with clinicopathological features and clinical outcome of PCa patients were statistically analyzed.PRC1 expression in PCa tissues, at both mRNA and protein levels, were significantly higher than those in non-cancerous prostate tissues. In addition, the PCa patients with PRC1 overexpression more frequently had high Gleason score, advanced pathological stage, positive metastasis, short overall survival time and positive PSA failure than those with low Gleason score, early pathological stage, negative metastasis, long overall survival time and negative PSA failure (all P0.05). Moreover, PRC1 expression was identified as an unfavorable prognostic factor of biochemical recurrence-free survival in PCa patients (P0.001).These findings suggest that the aberrant expression of PRC1 may predict biochemical recurrence in men with PCa highlighting its potential as a prognostic marker of this malignancy.

Purpose: To investigate the involvement of hsa-miRNA-195-5p (miR-195) in progression and prognosis of human prostate cancer. Experimental Design: qRT-PCR was performed to detect miR-195 expression in both prostate cancer cell lines and clinical tissue samples. Its clinical significance was statistically analyzed. The roles of miR-195 and its candidate target gene, ribosomal protein S6 kinase, 70 kDa, polypeptide 1 (RPS6KB1) in prostate cancer progression were confirmed on the basis of both in vitro and in vivo systems. Results: miR-195 downregulation in prostate cancer tissues was significantly associated with high Gleason score (P = 0.001), positive metastasis failure (P < 0.001), and biochemical recurrence (BCR, P < 0.001). Survival analysis identified miR-195 as an independent prognostic factor for BCR-free survival of prostate cancer patients (P = 0.022). Then, we confirmed the tumor suppressive role of miR-195 through prostate cancer cell invasion, migration, and apoptosis assays in vitro, along with tumor xenograft growth, angiogenesis, and invasion in vivo according to both gain-of-function and loss-of-function experiments. In addition, RPS6KB1 was identified as a novel direct target of miR-195 through proteomic expression profiling combined with bioinformatic target prediction and luciferase reporter assay. Moreover, the reexpression and knockdown of RPS6KB1 could respectively rescue and imitate the effects induced by miR-195. Importantly, RPS6KB1 expression was closely correlated with aggressive progression and poor prognosis in prostate cancer patients as opposed to miR-195. Furthermore, we identified MMP-9, VEGF, BAD, and E-cadherin as the downstream effectors of miR-195–RPS6KB1 axis. Conclusion: The newly identified miR-195–RPS6KB1 axis partially illustrates the molecular mechanism of prostate cancer progression and represents a novel potential therapeutic target for prostate cancer treatment. Clin Cancer Res; 21(21); 4922–34. ©2015 AACR.